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Sample records for rituximab ifosfamide carboplatin

  1. A salvage chemotherapy of R-P-IMVP16/CBDCA consisting of rituximab, methylprednisolone, ifosfamide, methotrexate, etoposide, and carboplatin for patients with diffuse large B cell lymphoma who had previously received R-CHOP therapy as first-line chemotherapy.

    Science.gov (United States)

    Matsumoto, Takuro; Hara, Takeshi; Shibata, Yuhei; Nakamura, Nobuhiko; Nakamura, Hiroshi; Ninomiya, Soranobu; Kitagawa, Junichi; Kanemura, Nobuhiro; Goto, Naoe; Kito, Yusuke; Kasahara, Senji; Yamada, Toshiki; Sawada, Michio; Miyazaki, Tatsuhiko; Takami, Tsuyoshi; Takeuchi, Tamotsu; Moriwaki, Hisataka; Tsurumi, Hisashi

    2017-09-01

    We have reported the efficacy of the salvage chemotherapy P-IMVP16/CBDCA for patients with diffuse large B cell lymphoma (DLBCL) who had previously received CHOP before the availability of rituximab (R). Here, we confirmed the efficacy of R combined with P-IMVP16/CBDCA as a salvage chemotherapy for patients with DLBCL, who had previously received R-CHOP. We retrospectively analysed 59 patients with relapse or refractory DLBCL (38 male patients and 21 female patients) presenting between June 2004 and June 2013. The patients received R 375 mg/m 2 on day 1, methylprednisolone 1000 mg/body for 3 days (from day 3 to day 5), ifosfamide 1000 mg/m 2 for 5 days (from day 3 to day 7), methotrexate 30 mg/m 2 on day 5 and day 12, etoposide 80 mg/m 2 for 3 days (from day 3 to day 5), and carboplatin 300 mg/m 2 on day 3 every 21 days. Patients aged 70 years or older were given 75% of the standard dose. The overall response rate (complete response + partial response) was 64.4%. The 2-year overall survival rate was 55.3%. The 2-year progression free survival rate was 34.7%. The 2-year overall survival rate was 61.5% for the relapse patients, and 15.6% for the refractory patients (p effects were mild and tolerable. The R-P-IMVP-16/CBDCA regimen displayed a significant activity in relapsed DLBCL, with acceptable toxicity, and should be considered a candidate for salvage chemotherapy. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  2. Delayed rhabdomyolysis with paclitaxel, ifosfamide, carboplatin, and etoposide regimen: a case report.

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    Sokolova, Alexandra; Chan, Onyee; Ullah, Waqas; Hamdani, Auon Abbas; Anwer, Faiz

    2017-04-11

    High-dose chemotherapy with autologous stem cell rescue is commonly used for the treatment of relapsed germ cell tumors. We report the first case of delayed rhabdomyolysis with paclitaxel, ifosfamide, carboplatin, and etoposide regimen. We report a case of a 21-year-old African-American man diagnosed with relapsed non-seminomatous germ cell tumor who received high-dose chemotherapy with carboplatin and etoposide following TIGER trial arm B off-protocol. His course was complicated by muscle pain and rhabdomyolysis after cycle 4 on day +12 after infusion of autologous stem cells. To the best of our knowledge, this complication has not been reported with this regimen. A differential diagnosis of sepsis and neutropenic fever along with side effects of high-dose chemotherapy were considered, but based on the timing of events, it was concluded that the etiology of rhabdomyolysis is high-dose chemotherapy. Rhabdomyolysis was successfully treated with hydration and did not recur during subsequent cycle 5. Delayed rhabdomyolysis after high-dose chemotherapy with paclitaxel, ifosfamide, carboplatin, and etoposide regimen has not been previously reported and needs to be considered for preventive strategy and prompt diagnosis and treatment to avoid renal complications. Physicians should have a low threshold to check creatine kinase enzymes in patients with unexplained muscle pain or renal insufficiency after high-dose chemotherapy.

  3. Hematopoietic Progenitor Cell Mobilization with Ifosfamide, Carboplatin, and Etoposide Chemotherapy versus Plerixafor-Based Strategies in Patients with Hodgkin and Non-Hodgkin Lymphoma.

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    Dhakal, Binod; Veltri, Lauren Westfall; Fenske, Timothy S; Eastwood, Daniel; Craig, Michael D; Cumpston, Aaron; Shillingburg, Alexandra; Esselman, Jean; Watkins, Kathy; Pasquini, Marcelo C; D'Souza, Anita; Hari, Parameswaran; Kanate, Abraham Sebastian; Hamadani, Mehdi

    2016-10-01

    Studies comparing the efficacy and safety of chemo-mobilization with ifosfamide, carboplatin, and etoposide (ICE) ± rituximab with plerixafor-based approaches in lymphoma patients have not been performed. We analyzed hematopoietic progenitor cell mobilization outcomes in lymphoma patients undergoing chemo-mobilization with ICE (n = 35) compared with either routine plerixafor (n = 30) or "just in time" (JIT) plerixafor-based mobilization (n = 33). Chemo-mobilization provided a significantly higher total CD34(+) cell yield (median collection, 5.35 × 10(6) cells/kg for ICE versus 3.15 × 10(6) cells/kg for routine plerixafor and 3.6 × 10(6) cells/kg for JIT plerixafor, P JIT plerixafor, P = .20). There was no significant difference in the 3 groups in terms of total number of apheresis sessions performed (median, 2 in each group; P = .78). There were no mobilization failures (inability to collect at least 2 × 10(6) cells/kg) in the chemo-mobilization group, whereas 5 patients (16.7%) in the routine plerixafor and 3 patients (9.1%) in JIT group had mobilization failure (P = .04). Mean time to neutrophil engraftment was faster in the chemo-mobilization group, 10.3 days (±1.2) compared with 12.1 days (±3.6) in the routine plerixafor group and 11.6 days (±3.0) in the JIT group (P JIT group (P JIT, P < .001). Our data suggests that chemo-mobilization with ICE provides a higher total CD34(+) cell yield, lower rates of mobilization failure, faster engraftment, and lower cost compared to plerixafor-based approaches with comparable toxicity profile between the groups, except for higher transfusion requirements with chemo-mobilization. Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  4. Dose escalation of the hypoxic cell sensitizer etanidazole combined with ifosfamide, carboplatin, etoposide, and autologous hematopoietic stem cell support.

    Science.gov (United States)

    Elias, A D; Wheeler, C; Ayash, L J; Schwartz, G; Ibrahim, J; Mills, L; McCauley, M; Coleman, N; Warren, D; Schnipper, L; Antman, K H; Teicher, B A; Frei, E

    1998-06-01

    Multiple mechanisms of drug resistance contribute to treatment failure. Although high-dose therapy attempts to overwhelm these defenses pharmacologically, this approach is only successful in a fraction of treated patients. Many drug resistance mechanisms are shared between malignant and normal cells, but the expression of various drug resistance mechanisms associated with hypoxia is largely confined to tumor tissue. Thus, reversal of this mechanism is likely to provide a therapeutic advantage to the host. This study was designed to define the dose-limiting toxicities and maximum tolerated dose of etanidazole when it is given concurrently with high-dose ifosfamide, carboplatin, and etoposide (ICE), with hematopoietic stem cell support. The maximum tolerated doses of high-dose ICE were administered concurrently with dose escalations of etanidazole, a hypoxic cell sensitizer. All agents were given by 96-h continuous i.v. infusion beginning on day -7. Mesna uroprotection was provided. Autologous marrow and cytokine mobilized peripheral blood progenitor cells were reinfused on day 0. Granulocyte colony-stimulating factor was administered following reinfusion until the granulocytes recovered to > 1000/microliter. Fifty-five adults with advanced malignancies were enrolled in cohorts of five to nine patients. Four dose levels of etanidazole between 3 and 5.5 g/m2/day (12, 16, 20, and 22 g/m2 total doses) and two doses of carboplatin (1600 and 1800 mg/m2 total doses) were evaluated. Seven patients died of organ toxicity (13%); two each from veno-occlusive disease of liver and sepsis; and one each from sudden death, renal failure, and refractory thrombocytopenic hemorrhage. Five deaths occurred at the top dose level. One additional patient suffered a witnessed cardiorespiratory arrest from ventricular fibrillation and was resuscitated. Dose-dependent and largely reversible peripheral neuropathy was observed consisting of two syndromes: severe cramping myalgic/neuralgic pain

  5. Comparison of Nutrition-Related Adverse Events and Clinical Outcomes Between ICE (Ifosfamide, Carboplatin, and Etoposide) and MCEC (Ranimustine, Carboplatin, Etoposide, and Cyclophosphamide) Therapies as Pretreatment for Autologous Peripheral Blood Stem Cell Transplantation in Patients with Malignant Lymphoma

    Science.gov (United States)

    Imataki, Osamu; Arai, Hidekazu; Kume, Tetsuo; Shiozaki, Hitomi; Katsumata, Naomi; Mori, Mariko; Ishide, Keiko; Ikeda, Takashi

    2018-01-01

    Background The aim of this study was to compare nutrition-related adverse events and clinical outcomes of ifosfamide, carboplatin, and etoposide regimen (ICE therapy) and ranimustine, carboplatin, etoposide, and cyclophosphamide regimen (MCEC therapy) instituted as pretreatment for autologous peripheral blood stem cell transplantation. Material/Methods We enrolled patients who underwent autologous peripheral blood stem cell transplantation between 2007 and 2012. Outcomes were compared between ICE therapy (n=14) and MCEC therapy (n=14) in relation to nutrient balance, engraftment day, and length of hospital stay. In both groups, we compared the timing of nutrition-related adverse events with oral caloric intake, analyzed the correlation between length of hospital stay and duration of parenteral nutrition, and investigated the association between oral caloric intake and the proportion of parenteral nutrition energy in total calorie supply. Five-year survival was compared between the groups. Results Compared with the MCEC group, the ICE group showed significant improvement in oral caloric intake, length of hospital stay, and timing of nutrition-related adverse events and oral calorie intake, but a delay in engraftment. Both groups showed a correlation between duration of parenteral nutrition and length of hospital stay (P=0.0001) and between oral caloric intake (P=0.0017) and parenteral nutrition energy sufficiency rate (r=−0.73, P=0.003; r=−0.76, P=0.002). Five-year survival was not significantly different between the groups (P=0.1355). Conclusions Our findings suggest that compared with MCEC therapy, ICE therapy improves nutrition-related adverse events and reduces hospital stay, conserving medical resources, with no significant improvement in long-term survival. The nutritional pathway may serve as a tool for objective evaluation of pretreatment for autologous peripheral blood stem cell transplantation. PMID:29398693

  6. Combined carboplatin plus ifosfamide and cisplatin in patients with advanced ovarian carcinoma. A phase I-II study. GOCS (Gynecological Oncology Cooperative Study).

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    Lorusso, V; Leone, B; Di Vagno, G; Manzione, L; Palmeri, S; Vallejo, C; Machiavelli, M; Nacci, G; Bilancia, D; Leonardi, V; Catino, A; Gargano, G; Loverro, G; Selvaggi, L; De Lena, M

    1998-02-01

    Because of the relative lack of overlapping toxicity, carboplatin (PPL) and cisplatin (CDDP) can be easily combined for treatment of ovarian cancer to increase total platinum dose intensity. Ifosfamide (IFO), one of the most effective single agents in ovarian cancer, has a low hematological toxicity when administered in continuous infusion. From January 1991 to December 1993, 34 patients with advanced ovarian cancer, previously untreated with chemo- or radiotherapy, were enrolled in a phase I-II study with the aim of determining the maximum tolerated dose (MTD) of CDDP (on day 8 of a 28-day cycle) in combination with PPL (300 mg/m2 on day 1) and IFO (4,000 mg/m2/24 h by continuous infusion on day 1). The initial dose level of CDDP was 40 mg/m2, which was continuously increased by 10 mg/m2 up to the MTD defined as one dose level below that inducing dose-limiting toxicity (DLT) in at least two-thirds of treated patients; no dose escalation was allowed in the same patient. Grade 3-4 leukopenia and thrombocytopenia were observed in 54 and 49% of patients, respectively. The DLT was reached at 70 mg/m2 and therefore the dose recommended for the phase II study was 60 mg/m2. Complete (CR) plus partial response was observed in 88% of patients with a 21% pathological CR. With a minimum follow-up of 32 months (median 40 months), median progression-free survival and overall survival were 21 and 39 months, respectively. In conclusion, the combination of CDDP, PPL, and IFO provides an effective regimen for ovarian cancer with an acceptable toxicity profile.

  7. A Phase I Study of Pulse High-Dose Vorinostat (V) plus Rituximab (R), Ifosphamide, Carboplatin, and Etoposide (ICE) in Patients with Relapsed Lymphoma

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    Budde, Lihua E.; Zhang, Michelle M.; Shustov, Andrei R.; Pagel, John M.; Gooley, Ted A.; Oliveira, George R.; Chen, Tara L.; Knudsen, Nancy L.; Roden, Jennifer E.; Kammerer, Britt E.; Frayo, Shani L.; Warr, Thomas A.; Boyd, Thomas E.; Press, Oliver W.; Gopal, Ajay K.

    2013-01-01

    SUMMARY Given the poor outcomes of relapsed aggressive lymphomas and preclinical data suggesting that ≥2.5 μM concentrations of vorinostat synergize with both etoposide and platinums, we hypothesized that pulse high-dose vorinostat could safely augment the anti-tumour activity of (R)ICE [(rituximab), ifosphamide, carboplatin, etoposide] chemotherapy. We conducted a phase I dose escalation study using a schedule with oral vorinostat ranging from 400 mg/d to 700 mg bid for 5 days in combination with the standard (R)ICE regimen (days 3, 4 and 5). Twenty-nine patients (median age 56 years, median 2 prior therapies, 14 chemoresistant [of 27 evaluable], 2 prior transplants) were enrolled and treated. The maximally tolerated vorinostat dose was defined as 500 mg twice daily × 5 days. Common dose limiting toxicities included infection (n=2), hypokalaemia (n=2), and transaminitis (n=2). Grade 3 related gastrointestinal toxicity was seen in 9 patients. The median vorinostat concentration on day 3 was 4.5 μM (range 4.2–6.0 μM) and in vitro data confirmed the augmented antitumour and histone acetylation activity at these levels. Responses were observed in 19 of 27 evaluable patients (70%) including 8 complete response/unconfirmed complete response. High-dose vorinostat can be delivered safely with (R)ICE, achieves potentially synergistic drug levels, and warrants further study, although adequate gastrointestinal prophylaxis is warranted. PMID:23356514

  8. Vorinostat, Rituximab, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Relapsed or Refractory Lymphoma or Previously Untreated T-Cell Non-Hodgkin Lymphoma or Mantle Cell Lymphoma

    Science.gov (United States)

    2017-04-17

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Mycosis Fungoides/Sezary Syndrome; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Waldenström Macroglobulinemia

  9. A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1).

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    Booton, R; Lorigan, P; Anderson, H; Baka, S; Ashcroft, L; Nicolson, M; O'Brien, M; Dunlop, D; O'Byrne, K; Laurence, V; Snee, M; Dark, G; Thatcher, N

    2006-07-01

    Phase III studies suggest that non-small-cell lung cancer (NSCLC) patients treated with cisplatin-docetaxel may have higher response rates and better survival compared with other platinum-based regimens. We report the final results of a randomised phase III study of docetaxel and carboplatin versus MIC or MVP in patients with advanced NSCLC. Patients with biopsy proven stage III-IV NSCLC not suitable for curative surgery or radiotherapy were randomised to receive four cycles of either DCb (docetaxel 75 mg/m(2), carboplatin AUC 6), or MIC/MVP (mitomycin 6 mg/m(2), ifosfamide 3 g/m(2) and cisplatin 50 mg/m(2) or mitomycin 6 mg/m(2), vinblastine 6 mg/m(2) and cisplatin 50 mg/m(2), respectively), 3 weekly. The primary end point was survival, secondary end points included response rates, toxicity and quality of life. The median follow-up was 17.4 months. Overall response rate was 32% for both arms (partial response = 31%, complete response = 1%); 32% of MIC/MVP and 26% of DCb patients had stable disease. One-year survival was 39% and 35% for DCb and MIC/MVP, respectively. Two-year survival was 13% with both arms. Grade 3/4 neutropenia (74% versus 43%, P MVP. The MIC/MVP arm had significant worsening in overall EORTC score and global health status whereas the DCb arm showed no significant change. The combination of DCb had similar efficacy to MIC/MVP but quality of life was better maintained.

  10. Carboplatin binding to histidine

    Energy Technology Data Exchange (ETDEWEB)

    Tanley, Simon W. M. [University of Manchester, Brunswick Street, Manchester M13 9PL (United Kingdom); Diederichs, Kay [University of Konstanz, D-78457 Konstanz (Germany); Kroon-Batenburg, Loes M. J. [Utrecht University, Padualaan 8, 3584 CH Utrecht (Netherlands); Levy, Colin [University of Manchester, 131 Princess Street, Manchester M1 7DN (United Kingdom); Schreurs, Antoine M. M. [Utrecht University, Padualaan 8, 3584 CH Utrecht (Netherlands); Helliwell, John R., E-mail: john.helliwell@manchester.ac.uk [University of Manchester, Brunswick Street, Manchester M13 9PL (United Kingdom)

    2014-08-29

    An X-ray crystal structure showing the binding of purely carboplatin to histidine in a model protein has finally been obtained. This required extensive crystallization trials and various novel crystal structure analyses. Carboplatin is a second-generation platinum anticancer agent used for the treatment of a variety of cancers. Previous X-ray crystallographic studies of carboplatin binding to histidine (in hen egg-white lysozyme; HEWL) showed the partial conversion of carboplatin to cisplatin owing to the high NaCl concentration used in the crystallization conditions. HEWL co-crystallizations with carboplatin in NaBr conditions have now been carried out to confirm whether carboplatin converts to the bromine form and whether this takes place in a similar way to the partial conversion of carboplatin to cisplatin observed previously in NaCl conditions. Here, it is reported that a partial chemical transformation takes place but to a transplatin form. Thus, to attempt to resolve purely carboplatin binding at histidine, this study utilized co-crystallization of HEWL with carboplatin without NaCl to eliminate the partial chemical conversion of carboplatin. Tetragonal HEWL crystals co-crystallized with carboplatin were successfully obtained in four different conditions, each at a different pH value. The structural results obtained show carboplatin bound to either one or both of the N atoms of His15 of HEWL, and this particular variation was dependent on the concentration of anions in the crystallization mixture and the elapsed time, as well as the pH used. The structural details of the bound carboplatin molecule also differed between them. Overall, the most detailed crystal structure showed the majority of the carboplatin atoms bound to the platinum centre; however, the four-carbon ring structure of the cyclobutanedicarboxylate moiety (CBDC) remained elusive. The potential impact of the results for the administration of carboplatin as an anticancer agent are described.

  11. Nonconvulsive status epilepticus due to ifosfamide.

    Science.gov (United States)

    Kilickap, Saadettin; Cakar, Mustafa; Onal, Ibrahim K; Tufan, Abdurrahman; Akoglu, Hadim; Aksoy, Sercan; Erman, Mustafa; Tekuzman, Gulten

    2006-02-01

    To report 2 cases of nonconvulsive status epilepticus (NCSE) following infusion of ifosfamide. Two patients who received ifosfamide-containing chemotherapy developed NCSE. One woman received ifosfamide 1000 mg/m2 (1 h infusion on days 1-5); confusion, lethargy, and speech deterioration developed on day 3. The second patient developed similar symptoms on day 3 of treatment with 2500 mg/m2. Both patients responded to intravenous administration of diazepam 10 mg and were given levetiracetam as maintenance therapy. The severity and presentation of central nervous system toxicity due to ifosfamide varies greatly and involves a spectrum ranging from subclinical electroencephalogram changes to coma. NCSE, an epileptic disorder in which typical convulsive activity is absent, has previously been reported in only 4 patients receiving ifosfamide. Levetiracetam may be used for maintenance antiepileptic therapy after diazepam administration. Among the many presentations of ifosfamide neurotoxicity, clinicians should consider NCSE as a possible explanation for changes in consciousness in a patient receiving this agent. An objective causality assessment by use of the Naranjo probability scale revealed that NCSE due to ifosfamide was probable.

  12. Pharmacokinetics of ifosfamide and some metabolites in children

    NARCIS (Netherlands)

    Kaijser, G. P.; de Kraker, J.; Bult, A.; Underberg, W. J.; Beijnen, J. H.

    1998-01-01

    The pharmacokinetics of ifosfamide and some metabolites in children was investigated. The patients received various doses of ifosfamide, mostly by continuous infusion, over several days. The penetration of ifosfamide and its metabolites into the cerebrospinal fluid was also studied in four cases.

  13. Clinical status of carboplatin.

    Science.gov (United States)

    Canetta, R; Franks, C; Smaldone, L; Bragman, K; Rozencweig, M

    1987-07-01

    Carboplatin, a cisplatin derivative, shows promise of being an effective weapon against ovarian, cervical, and small-cell lung cancer, as well as epidermoid cancer of the head and neck, with fewer toxic effects than cisplatin. It has successfully completed phase III investigation and clinical trials continue.

  14. Clinical pharmacology of ifosfamide and metabolites

    NARCIS (Netherlands)

    Kerbusch, T.

    2000-01-01

    Introduction Ifosfamide is an alkylating agent, which is used in the treatment of various types of malignant diseases in adults and childeren. Its use, however, can be accompanied by severe haematological, neuro- and nephrotoxicities. Since its development in the middle of the 1960’s, most of its

  15. Discovery – Development of Rituximab

    Science.gov (United States)

    NCI funded the development of rituximab, one of the first monoclonal antibody cancer treatments. With the discovery of rituximab, more than 70 percent of patients diagnosed with non-hodgkin lymphoma now live five years past their initial diagnosis.

  16. Progress in immunotherapy Rituximab

    International Nuclear Information System (INIS)

    El-Habbash, Manal M.; Alwindi, Abukris M.

    2007-01-01

    Rituximab is an anti-CD-20 chimeric monoclonal antibody that has shown substantial activity. Since its discovery, rituximab has been used with great success in a variety of hematological malignancies. Its success in the management of aggressive lymphomas led to expansion of its use in other conditions such as stem cell transplantation, post- transplant lymphoproliferative disorder, and other non-malignant conditions where B cell activation is thought to be important, such as idiopathic thrombocytopenic purpura and rheumatoid arthritis. The side effects have been remarkably few, particularly, infection is not more common that chemotherapy alone. This article reviews the structure, mechanism of action and uses of rituximab as monotherapy or in combination with chemotherapy. (author)

  17. Evaluation of ifosfamide salvage therapy for metastatic canine osteosarcoma.

    Science.gov (United States)

    Batschinski, K; Dervisis, N G; Kitchell, B E

    2014-12-01

    A retrospective study was performed to assess toxicity and response rate of ifosfamide salvage treatment for dogs diagnosed with metastatic osteosarcoma (OSA). Dogs diagnosed with OSA and previously treated with standard chemotherapy were included in the study. Nineteen dogs met the inclusion criteria, and 17 dogs were evaluable for response. Ifosfamide doses ranged from 375 to 425 mg m(-2) (median dose 375 mg m(-2)), with a median of two doses administered per dog (range 1-7 doses). The overall response to ifosfamide was 11.8% [complete response (CR) = 1/17, partial response (PR) = 1/17, stable disease (SD) = 2/17, progressive disease (PD) = 13/17]. Two dogs were hospitalized due to ifosfamide toxicosis. The median survival duration from the first dose of ifosfamide to death was 95 days. Ifosfamide was well tolerated, but minor anti-tumour activity was observed. © 2012 Blackwell Publishing Ltd.

  18. Compound list: carboplatin [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available carboplatin CBP 00133 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in..._vitro/carboplatin.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo.../Liver/Single/carboplatin.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATES...T/Rat/in_vivo/Liver/Repeat/carboplatin.Rat.in_vivo.Liver.Repeat.zip ftp://ftp.bio...sciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Single/carboplatin.Rat.in_vivo.Kidney.Single.zip ftp:

  19. Rituximab desensitization in three patients with severe rituximab allergy.

    Science.gov (United States)

    Öztürk, Erman; Özyiğit, Leyla Pur; Öztürk, Ayşe Bilge; Akay, Meltem Olga; Çetiner, Mustafa; Ferhanoğlu, Burhan

    Rituximab is a chimeric monoclonal antibody that targets CD20 positive B cells and has a positive effect on both overall and progression-free survival in B-cell lymphoid malignancies. Combination rituximab with chemotherapy treatment provide survival improvement. Although rituximab is an important treatment option in hematological malignancies, the risk of allergic reactions is high. These reactions are usually IgE-mediated and can be varied in regard of severity from urticaria to anaphylaxis. It is an option to interrupt the treatment and ommit rituximab therapy who had allergic reactions. Drug desensitization is another option and successful results have been reported by applying desensitization to such reactions. Drug desensitization alters the immune response to induce a state of temporary clinical tolerance to the allergic drug by giving gradual increasing of doses of drug at fixed time intervals. Herein, we present 3 cases successfully treated with rituximab desensitization. The cases were using rituximab with the diagnosis of Burkitt lymphoma, follicular lymphoma, and marginal zone lymphoma, respectively. Two cases had grade 2 and 1 case had grade 3 systemic allergic reaction with rituximab. There was no known allergy history in all 3 cases. All patients tolerated the desensitization protocol. The subsequent treatments of the patients were also given by desensitization protocol. A total of 12 desensitizations were administered to 3 cases. No severe or life-threating reactions were observed in subsequent applications. To date applying desensitization protocols ensure rituximab treatment safely. Rituximab desensitization can be performed at trained allergy centers, and it may be an appropriate option for rituximab allergic patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Rituximab treatment for fibrillary glomerulonephritis.

    Science.gov (United States)

    Hogan, Jonathan; Restivo, Michaela; Canetta, Pietro A; Herlitz, Leal C; Radhakrishnan, Jai; Appel, Gerald B; Bomback, Andrew S

    2014-10-01

    Approximately 50% of patients with fibrillary glomerulonephritis (GN) progress to end-stage renal disease (ESRD) within 2 years of diagnosis, and no standard therapy exists. The data on rituximab therapy for fibrillary GN are limited and have inconsistent outcomes. Here, we report the largest case series to date using rituximab for fibrillary GN. Retrospective chart reviews were conducted on 12 patients with fibrillary GN who were treated with rituximab (1 g i.v. × 2 doses or 375 mg/m(2) × 4 doses) at the Center for Glomerular Diseases at Columbia University Medical Center. Non-progression of disease was defined as stable/improved serum creatinine (SCr) with a minimum of 1 year of follow-up. The median SCr was 2.1 (range 0.7-2.7) mg/dL, median estimated glomerular filtration rate (eGFR) 39 (range 21-98) mL/min/1.73 m(2) and median proteinuria 4497 (range 210-7542) mg/day at the time of rituximab initiation. Four patients had received immunosuppression before rituximab, and nine received immunosuppression after rituximab, with four receiving a second rituximab course. Four of 12 patients were non-progressors, 3 of 12 had progressive renal dysfunction without reaching ESRD, and 5 patients reached ESRD. The median follow-up for patients who did not reach ESRD was 38 (range 14-76) months after rituximab treatment. Non-progressors had lower SCr values, higher eGFRs and shorter median duration from diagnosis to treatment than progressors. No serious adverse events were noted. Rituximab therapy was associated with non-progression of renal disease in 4 of 12 patients. At the time of treatment, these non-progressors had better renal function and shorter time from diagnosis to treatment than progressors. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  1. Carboplatin hypersensitivity: evaluation and successful desensitization protocol.

    Science.gov (United States)

    Bruchim, Ilan; Goldberg, Arnon; Fishman, Ami; Confino-Cohen, Ronit

    2014-01-01

    Carboplatin-induced immediate hypersensitivity reactions are relatively common among patients with gynecological malignancies. Once this occurs, the patient might be at risk for future carboplatin-induced reactions. This study evaluated the efficacy of allergic consultation, carboplatin skin testing and desensitization as a single intervention strategy in this population. Patients with a well-documented immediate reaction to carboplatin were offered allergy consultation, carboplatin skin testing and a desensitization plan in a single visit between scheduled chemotherapy sessions. Fifty-five patients with an immediate reaction were evaluated. After allergist assessment, 44 (89%) of 49 patients skin tested had a positive result. A total of 207 carboplatin desensitization cycles were administered to 49 women. Among them, 10 patients had a mild immediate hypersensitivity reaction during desensitization. Five patients subsequently tolerated carboplatin administered in the prolonged desensitization protocol. In the data presented, we propose a strategy that is both cost effective and very convenient for the patient. The diagnostic procedure, including allergist consultation and skin test, can be completed in less than 2 h. In most cases where carboplatin is indispensable, desensitization can be administered without overnight hospitalization.

  2. Activity of intraarterial carboplatin as a single agent in the treatment of newly diagnosed extremity osteosarcoma.

    Science.gov (United States)

    Petrilli, A S; Kechichian, R; Broniscer, A; Garcia, R J; Tanaka, C; Francisco, J; Lederman, H; Odone Filho, V; Camargo, O P; Bruniera, P; Pericles, P; Consentino, E; Ortega, J A

    1999-08-01

    Chemotherapy has dramatically improved the rates of cure and survival of patients with localized and metastatic osteosarcoma. Nonetheless, the number of chemotherapeutic agents active against osteosarcoma is limited to doxorubicin, cisplatin, high-dose methotrexate, and ifosfamide. Carboplatin, a cisplatin analogue, has been tested as a single agent in patients with recurrent osteosarcoma or as part of multiagent chemotherapy in newly diagnosed patients. We tested the activity and toxicity of two cycles of intraarterial carboplatin as a "window therapy" (600 mg/m2 per cycle) in 33 consecutive patients with extremity osteosarcoma before the start of multiagent chemotherapy. Response was based on clinical (tumor diameter, local inflammatory signs, and range of motion) and radiological parameters (plain local films and arteriographic studies prior to drug administration). Patients' age ranged between 8 and 18 years (median age 13 years). Primary tumor originated from the femur (15 patients), tibia (10 patients), fibula (4 patients), humerus (3 patients), and calcaneus (1 patient). Only 7 patients (21%) had metastatic disease at diagnosis (5 in the lung and 2 in other bones). A favorable clinical and radiological response was documented in 81% and 73% of the patients, respectively. Clinical and radiological progression occurred in 12% and 9% of the patients, respectively. Seventeen of the patients remain alive and disease-free. Survival and event-free survival at 3 years for nonmetastatic patients are 71% (SE = 9%) and 65% (SE = 9%), respectively; for metastatic patients, the figures are 17% (SE = 15%) and 14% (SE = 13%), respectively. We conclude that carboplatin is an active agent in the treatment of newly diagnosed extremity osteosarcoma. Copyright 1999 Wiley-Liss, Inc.

  3. Desensitization with oxaliplatin in patients intolerant of carboplatin desensitization.

    Science.gov (United States)

    Rose, Peter G; Metz, Carol; Link, Nicolas

    2014-11-01

    The tolerance and efficacy of oxaliplatin desensitization in patients who were intolerant of carboplatin desensitization were determined. We retrospectively reviewed the Gynecologic Oncology patients who received carboplatin or oxaliplatin from December 2007 until August 2014. The number of treatments and number of patients of carboplatin standard infusions, carboplatin desensitizations, and oxaliplatin desensitizations were determined. Carboplatin infusions (2294) were administered to 281 patients. Twenty-eight (10%) of these patients developed carboplatin hypersensitivity and were treated with 205 carboplatin desensitizations. Nine (29%) patients were subsequently treated with 61 oxaliplatin desensitizations due to intolerance of carboplatin desensitization. Nine of the 10 patients tolerated this infusion well. Four of 9 evaluable patients had an objective response, 2 complete and 2 partial. Oxaliplatin desensitization seems well tolerated and effective in most patients who are intolerant of carboplatin desensitization.

  4. Carboplatin Dosing for Adult Japanese Patients

    OpenAIRE

    ANDO, YUICHI; SHIMOKATA, TOMOYA; YASUDA, YOSHINARI; HASEGAWA, YOSHINORI

    2014-01-01

    ABSTRACT Carboplatin is a platinum-based anticancer drug that has been long used to treat many types of solid cancer. Because the clearance of carboplatin strongly correlates with the glomerular filtration rate (GFR), its dosage is calculated with the Calvert formula on the basis of the patient?s GFR to achieve the target area under the plasma drug concentration-time curve (AUC) for each patient. However, many lines of evidence from previous clinical studies should be interpreted with caution...

  5. Carboplatin dosing for adult Japanese patients.

    Science.gov (United States)

    Ando, Yuichi; Shimokata, Tomoya; Yasuda, Yoshinari; Hasegawa, Yoshinori

    2014-02-01

    Carboplatin is a platinum-based anticancer drug that has been long used to treat many types of solid cancer. Because the clearance of carboplatin strongly correlates with the glomerular filtration rate (GFR), its dosage is calculated with the Calvert formula on the basis of the patient's GFR to achieve the target area under the plasma drug concentration-time curve (AUC) for each patient. However, many lines of evidence from previous clinical studies should be interpreted with caution because different methods were used to estimate drug clearance and derive the dosage of carboplatin. There is a particularly high risk of carboplatin overdosing when the dosage is determined on the basis of standardized serum creatinine values. When deciding the dose of carboplatin for adult Japanese patients, preferred methods to assess renal function instead of directly measuring GFR include (1) 24-h urinary collection-based creatinine clearance adjusted by adding 0.2 mg/dl to the serum creatinine concentration measured by standardized methods, and (2) equation-based GFR (eGFR) with a back calculation to units of ml/min per subject. Given the limitations of serum creatinine-based GFR estimations, the GFR or creatinine clearance should be directly measured in each patient whenever possible. To ensure patient safety and facilitate a medical-team approach, the single most appropriate method available at each institute or medical team should be consistently used to calculate the dose of carboplatin with the Calvert formula.

  6. Determination of urinary 2- and 3-dechloroethylated metabolites of ifosfamide by high-performance liquid chromatography.

    Science.gov (United States)

    Goren, M P

    1991-10-04

    In vivo oxidation of chloroethyl side-chains on ifosfamide produces the toxin chloroacetaldehyde. Production of this labile metabolite can be indirectly quantitated by monitoring the excretion of the residual 2- and 3-dechloroethylated ifosfamide. Urinary ifosfamide and the two dechloroethylated metabolites were extracted into chloroform from alkalinized salt-saturated urine, followed by high-performance liquid chromatographic separation using an acetonitrile gradient on a reversed-phase column and ultraviolet detection at 190 nm. In five patients given 1.6 g/m2 ifosfamide, 11-30% of the dose was excreted over 24 h as unchanged drug, 11-21% as 3-dechloroethylated and 3-10% as 2-dechloroethylated ifosfamide.

  7. Lupus nephritis, pregnancy and rituximab

    Directory of Open Access Journals (Sweden)

    Enrique Dorado

    2017-04-01

    Full Text Available La nefritis lúpica (NL proliferativa es una de las complicaciones más graves del LES. La respuesta terapéutica con los esquemas clásicos no existe en el 20 al 70% de los casos, siendo la amplitud de dicho rango explicada por variaciones étnicas, falta de consenso en la definición de remisión, diferencias en los tiempos de tratamiento, seguimiento y en la clase de NL. En presencia de NL recidivante o refractaria los tratamientos y el nivel de evidencia sobre su eficacia son más limitados. Rituximab es un anticuerpo monoclonal quimérico (ratón-humano dirigido contra el antígeno CD 20 localizado en la superficie celular de los linfocitos B. Estos participan en la patogénesis del LES a partir de su maduración en células plasmáticas, producción de anticuerpos, secreción de citoquinas proinflamatorias, presentación de autoantígenos a las células T y en la activación de células T. La administración de rituximab genera un rápido y sostenido descenso de los linfocitos B CD 20+ circulantes y una reducción de los títulos de auto-anticuerpos. Se reportó una disminución significativa en los niveles de antiDNA a partir de la semana 14 y de los niveles de IgM, sin compromiso de IgG ni de IgA. Se detectó droga activa en sangre periférica luego de la semana 24 de la última infusión. La depleción de linfocitos B se puede mantener por 6 meses, su reconstitución es heterogénea y puede tardar más de un año. Esta linfopenia selectiva tendría un valor predictivo de respuesta terapéutica, la remisión clínica prolongada tendría asociación con repoblación incompleta de células B de memoria varios años luego del tratamiento. En estudios observacionales realizados en pacientes con NL refractaria se reportó respuesta terapéutica con rituximab entre 67-77 % luego de 6 a 12 meses de seguimiento. Sin embargo los resultados del estudio Lupus Nephritis Assesment with Rituximab (LUNAR, randomizado controlado, a doble ciego

  8. Carboplatin: the clinical spectrum to date.

    Science.gov (United States)

    Canetta, R; Rozencweig, M; Carter, S K

    1985-09-01

    The existing literature data base on carboplatin updated to June, 1985 has been reviewed. The compound seems to retain the same spectrum of activity as cisplatin, and a definite set of efficacy data is available for ovarian cancer of epithelial origin, small cell carcinoma of the lung and epidermoid carcinoma of the head and neck. A yet unpublished toxicity data base on carboplatin suggests that the compound has an improved therapeutic index over the parent compound, cisplatin, and that it does not seem inferior to another platinum coordination compound currently in clinical trials, iproplatin.

  9. Gemcitabine Hydrochloride, Carboplatin, Dexamethasone, and Rituximab in Treating Patients With Previously Treated Lymphoid Malignancies

    Science.gov (United States)

    2017-05-28

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  10. Modulation of the cytochrome P450-mediated metabolism of ifosfamide by ketoconazole and rifampin

    NARCIS (Netherlands)

    Kerbusch, T.; Jansen, R. L.; Mathôt, R. A.; Huitema, A. D.; Jansen, M.; van Rijswijk, R. E.; Beijnen, J. H.

    2001-01-01

    The autoinducible metabolic transformation of the anticancer agent ifosfamide involves activation through 4-hydroxyifosfamide to the ultimate cytotoxic ifosforamide mustard and deactivation to 2- and 3-dechloroethylifosfamide with concomitant release of the neurotoxic chloroacetaldehyde. Activation

  11. Rituximab selectively suppresses specific islet antibodies.

    Science.gov (United States)

    Yu, Liping; Herold, Kevan; Krause-Steinrauf, Heidi; McGee, Paula L; Bundy, Brian; Pugliese, Alberto; Krischer, Jeff; Eisenbarth, George S

    2011-10-01

    The TrialNet Study Group evaluated rituximab, a B-cell-depleting monoclonal antibody, for its effect in new-onset patients with type 1A diabetes. Rituximab decreased the loss of C-peptide over the first year of follow-up and markedly depleted B lymphocytes for 6 months after administration. This article analyzes the specific effect of rituximab on multiple islet autoantibodies. A total of 87 patients between the ages of 8 and 40 years received either rituximab or a placebo infusion weekly for four doses close to the onset of diabetes. Autoantibodies to insulin (IAAs), GAD65 (GADAs), insulinoma-associated protein 2 (IA2As), and ZnT8 (ZnT8As) were measured with radioimmunoassays. The primary outcome for this autoantibody analysis was the mean level of autoantibodies during follow-up. Rituximab markedly suppressed IAAs compared with the placebo injection but had a much smaller effect on GADAs, IA2As, and ZnT8As. A total of 40% (19 of 48) of rituximab-treated patients who were IAA positive became IAA negative versus 0 of 29 placebo-treated patients (P 1 year in insulin-treated patients. For the patients receiving insulin for >2 weeks prior to rituximab administration, we cannot assess whether rituximab not only blocks the acquisition of insulin antibodies induced by insulin administration and/or also suppresses preformed insulin autoantibodies. Studies in prediabetic non-insulin-treated patients will likely be needed to evaluate the specific effects of rituximab on levels of IAAs.

  12. Enfermedad pulmonar intersticial asociada a rituximab

    Directory of Open Access Journals (Sweden)

    Marcelo Fernández Casares

    2013-08-01

    Full Text Available La introducción en la práctica clínica del anticuerpo anti-CD20 rituximab ha mejorado sustancialmente el pronóstico de diversas enfermedades autoinmunes y hematológicas. Con el incremento de su uso ha aumentado el registro de efectos adversos, entre ellos la toxicidad pulmonar. Una de sus complicaciones más serias es la enfermedad pulmonar intersticial, entidad potencialmente fatal que debe ser considerada en pacientes que han recibido rituximab y presentan disnea, fiebre y tos sin clara evidencia de infección. Presentamos un caso de enfermedad pulmonar intersticial asociada a rituximab.

  13. Carboplatin versus alternating carboplatin and doxorubicin for the adjuvant treatment of canine appendicular osteosarcoma: a randomized, phase III trial†

    Science.gov (United States)

    Skorupski, K. A.; Uhl, J. M.; Szivek, A; Allstadt Frazier, S. D.; Rebhun, R. B.; Rodriguez, C. O.

    2016-01-01

    Despite numerous published studies describing adjuvant chemotherapy for canine appendicular osteosarcoma, there is no consensus as to the optimal chemotherapy protocol. The purpose of this study was to determine whether either of two protocols would be associated with longer disease-free interval (DFI) in dogs with appendicular osteosarcoma following amputation. Dogs with histologically confirmed appendicular osteosarcoma that were free of gross metastases and underwent amputation were eligible for enrollment. Dogs were randomized to receive either six doses of carboplatin or three doses each of carboplatin and doxorubicin on an alternating schedule. Fifty dogs were included. Dogs receiving carboplatin alone had a significantly longer DFI (425 versus 135 days) than dogs receiving alternating carboplatin and doxorubicin (P = 0.04). Toxicity was similar between groups. These results suggest that six doses of carboplatin may be associated superior DFI when compared to six total doses of carboplatin and doxorubicin. PMID:24118677

  14. Carboplatin versus alternating carboplatin and doxorubicin for the adjuvant treatment of canine appendicular osteosarcoma: a randomized, phase III trial.

    Science.gov (United States)

    Skorupski, K A; Uhl, J M; Szivek, A; Allstadt Frazier, S D; Rebhun, R B; Rodriguez, C O

    2016-03-01

    Despite numerous published studies describing adjuvant chemotherapy for canine appendicular osteosarcoma, there is no consensus as to the optimal chemotherapy protocol. The purpose of this study was to determine whether either of two protocols would be associated with longer disease-free interval (DFI) in dogs with appendicular osteosarcoma following amputation. Dogs with histologically confirmed appendicular osteosarcoma that were free of gross metastases and underwent amputation were eligible for enrollment. Dogs were randomized to receive either six doses of carboplatin or three doses each of carboplatin and doxorubicin on an alternating schedule. Fifty dogs were included. Dogs receiving carboplatin alone had a significantly longer DFI (425 versus 135 days) than dogs receiving alternating carboplatin and doxorubicin (P = 0.04). Toxicity was similar between groups. These results suggest that six doses of carboplatin may be associated superior DFI when compared to six total doses of carboplatin and doxorubicin. © 2013 John Wiley & Sons Ltd.

  15. Fanconi's syndrome and nephrogenic diabetes insipidus in an adult treated with ifosfamide.

    Science.gov (United States)

    Ingemi, Amanda I; Bota, Vasile M; Peguero, Anyeri; Charpentier, Margaret

    2012-01-01

    Fanconi's syndrome is a serious condition characterized by type II proximal renal tubular dysfunction, with urinary loss of glucose, amino acids, phosphate, bicarbonate, and potassium. Ifosfamide-induced Fanconi's syndrome is reported in about 1.4-5% of children being treated for solid tumors, yet only a few cases have been reported in adults. We describe a 54-year-old man who came to the hospital with symptoms of neutropenic fever 4 days after his fourth cycle of ifosfamide and doxorubicin treatment for recurrent sarcoma with metastases to the lung. During admission, he was noted to have severe renal tubular dysfunction; ifosfamide-induced nephrogenic diabetes insipidus and Fanconi's syndrome were suspected. He received supportive therapy that resulted in incomplete resolution of signs and symptoms. The patient was discharged after a 5-day hospital stay when his white blood cell count increased from 0.1-2.5 × 10(3) /mm(3) and his fever had resolved. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 7) between the patient's development of diabetes insipidus and Fanconi's syndrome and his use of ifosfamide. This dual diagnosis of diabetes insipidus and Fanconi's syndrome in an adult makes this case unusual, as well as therapeutically challenging. We conducted a review of the existing literature regarding ifosfamide-induced Fanconi's syndrome and describe the proposed mechanisms and therapeutic options. This case suggests that patients treated with ifosfamide should be monitored closely for renal function to identify, and perhaps prevent, these rare adverse events. Preliminary animal models show promise for adding N-acetylcysteine to ifosfamide treatment, but more research is necessary before using this drug as a therapeutic option. © 2012 Pharmacotherapy Publications, Inc.

  16. Resveratrol improves ifosfamide-induced Fanconi syndrome in rats

    International Nuclear Information System (INIS)

    Sehirli, Ozer; Sakarcan, Abdullah; Velioglu-Oguenc, Ayliz; Cetinel, Sule; Gedik, Nursal; Yegen, Berrak C.; Sener, Goeksel

    2007-01-01

    Regarding the mechanisms of ifosfamide (IFO)-induced urinary toxicity, several hypotheses have been put forward, among which oxidative stress and depletion of glutathione are suggested. This investigation elucidates the role of free radicals in IFO-induced toxicity and the protection by resveratrol, a natural phytoalexin. Wistar albino rats were injected intraperioneally with saline (0.9% NaCl; control), saline + resveratrol (RVT; 10 mg/kg/day), ifosfamide (IFO; 50 mg/kg/day) or IFO + RVT for 5 days. Urine was collected for 24 h during the 5th day, and at the 120th h after the first injections, animals were killed by decapitation and trunk blood was collected. Lactate dehydrogenase (LDH) activity, total antioxidant capacity (AOC) and pro-inflammatory cytokines TNF-α, IL-β and IL-6 were assayed in plasma samples. Kidney and bladder tissues were obtained for biochemical and histological analysis. Formation of reactive oxygen species in the tissue samples was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probes. The results demonstrated that IFO induced a Fanconi syndrome characterized by increased urinary sodium, phosphate, glucose and protein, along with increased serum creatinine and urea levels. On the other hand, RVT markedly ameliorated the severity of renal dysfunction induced by IFO. Furthermore IFO caused a significant decrease in plasma AOC, which was accompanied with significant increases in the levels of the pro-inflammatory mediators and LDH activity, while RVT treatment reversed all these biochemical indices. In the saline-treated IFO group, glutathione levels were decreased significantly, while the malondialdehyde levels, myeloperoxidase activity and collagen content were increased in both tissues, which were in parallel with the increases in CL values. In the RVT-treated IFO group, all of these oxidant responses were prevented significantly. Our results suggest that IFO causes oxidative damage in the renal and bladder

  17. Rituximab-Induced Bronchiolitis Obliterans Organizing Pneumonia

    Directory of Open Access Journals (Sweden)

    Ahmet B. Ergin

    2012-01-01

    Full Text Available Rituximab-induced lung disease (R-ILD is a rare entity that should be considered in patients treated with rituximab who present with dyspnea, fever, and cough, but no clear evidence of infection. A variety of pathologic findings have been described in this setting. Bronchiolitis obliterans organizing pneumonia (BOOP is the most common clinicopathologic diagnosis, followed by interstitial pneumonitis, acute respiratory distress syndrome (ARDS, and hypersensitivity pneumonitis. Prompt diagnosis and treatment with corticosteroids are essential as discussed by Wagner et al. (2007. Here we present a case of an 82-year-old man who was treated with rituximab for recurrent marginal zone lymphoma. After the first infusion of rituximab, he reported fever, chills, and dyspnea. On computed tomography imaging, he was found to have bilateral patchy infiltrates, consistent with BOOP on biopsy. In our patient, BOOP was caused by single-agent rituximab, in the first week after the first infusion of rituximab. We reviewed the relevant literature to clarify the different presentations and characteristics of R-ILD and raise awareness of this relatively overlooked entity.

  18. Tandem mass spectrometric analysis of cyclophosphamide, ifosfamide and their metabolites.

    Science.gov (United States)

    Liu, Zhongfa; Chan, Kenneth K; Wang, Jeffrey J

    2005-01-01

    A detailed multi-stage (MSn) fragmentation study of cyclophosphamide (CP), ifosfamide (IF) and their major metabolites, using an ion-trap mass spectrometer and a Q-TOF mass spectrometer, was performed with the aid of specifically deuterium-labeled analogs. The analytes showed good responses in positive-ion electrospray mass spectrometry as [MH]+ ions. Tandem mass spectra revealed a wealth of structurally specific ions, allowing characterization of the fragmentation pathways of these analytes. The major fragmentation pathways of the protonated CP and IF are elimination of ethylene from C5 and C6 of 1,3,2-oxazaphosphorine-2-oxide via a McLafferty rearrangement, and cleavage of the P-N bond. However, their activated 4-OOH and 4-OH metabolites primarily underwent hydrogen peroxide elimination and dehydration, respectively, followed by fragmentation pathways similar to those of CP and IF. These results should prove useful in structural elucidation of future analogs of CP and IF, and/or of their metabolites. Copyright (c) 2005 John Wiley & Sons, Ltd.

  19. Ifosfamide and cisplatin as neoadjuvant chemotherapy for advanced cervical carcinoma.

    Science.gov (United States)

    Leone, B; Vallejo, C; Perez, J; Cuevas, M A; Machiavelli, M; Lacava, J; Focaccia, G; Ferreyra, R; Suttora, G; Romero, A; Castaldi, J; Arroyo, A; Rabinovich, M

    1996-04-01

    A phase II trial was performed to evaluate the efficacy and toxicity of a combination of cisplatin (CDDP) and ifosfamide (IFX) as neoadjuvant chemotherapy in advanced cervical carcinoma (ACC). Between August 1991 and September 1993, 57 untreated patients with stages IIB to IVA were entered into this study. Median age was 44 years (range, 25 to 74 years). The distribution by stages (International Federation of Gynecology and Obstetrics) was as follows: IIB, 31 patients; IIIB, 21 patients; and IVA, 5 patients. Therapy consisted of IFX 2000 mg/m(2) 1-h i.v. infusion days 1 to 3; mesna 400 mg/m(2) i.v. bolus at hours 0 and 4, and 800 mg p.o. at hour 8; and CDDP 100 mg/m(2) on day 3. Cycles were repeated every 28 days for a total of three courses. Both staging and response assessment were performed by a multidisciplinary team. An objective response was observed in 30 of 56 patients (54%; 95% confidence interval, 41 to 67%). Four patients (7%) had a complete response (CR) and 26(46%) had a partial response (PR). Patients with CR or operable PR underwent surgery, otherwise received definitive radiotherapy. Toxicity was mild to moderate. There were no toxicity related deaths. These results indicate that IFX/CDDP is an active combination for ACC with mild toxicity. The results of phase III studies that evaluate the real impact of neoadjuvant chemotherapy are awaited.

  20. Acute renal failure in high dose carboplatin chemotherapy

    NARCIS (Netherlands)

    Frenkel, J.; Kool, G.; de Kraker, J.

    1995-01-01

    Carboplatin has been reported to cause acute renal failure when administered in high doses to adult patients. We report a 4 1/2-year-old girl who was treated with high-dose carboplatin for metastatic parameningeal embryonal rhabdomyosarcoma. Acute renal failure developed followed by a slow partial

  1. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma

    DEFF Research Database (Denmark)

    Judson, Ian; Verweij, Jaap; Gelderblom, Hans

    2014-01-01

    BACKGROUND: Effective targeted treatment is unavailable for most sarcomas and doxorubicin and ifosfamide-which have been used to treat soft-tissue sarcoma for more than 30 years-still have an important role. Whether doxorubicin alone or the combination of doxorubicin and ifosfamide should be used...

  2. Desensitization to rituximab in a multidisciplinary setting.

    Science.gov (United States)

    Amorós-Reboredo, Patrícia; Sánchez-López, Jaime; Bastida-Fernández, Carla; do Pazo-Oubiña, Fernando; Borràs-Maixenchs, Núria; Giné, Eva; Valero, Antonio; Creus-Baró, Natàlia

    2015-10-01

    The need to offer first-line therapy to the increasing number of patients who have suffered an hypersensitivity reaction has stimulated the use of rapid desensitization protocols. To present our experience working as a multidisciplinary team using a rituximab rapid desensitization scheme. Patient demographics, allergic reaction, skin tests to rituximab, number of desensitizations, reactions during the desensitization protocol and actions taken, number of administered and completed cycles, were retrospectively collected in patients who received at least one desensitization to rituximab. Number of desensitizations successfully managed. Between 2012 and June 2013 five patients received a total of 19 desensitizations to rituximab using a 12 step rapid desensitization protocol. All patients received the scheduled chemotherapeutic cycles as inpatients, with no delay in administration dates. Three patients presented a hypersensitivity reaction during the first desensitization and in one patient the event occurred again during the second treatment cycle. All reactions occurred in the last step, when the infusion rate reached the maximum speed. The developed protocol for rapid desensitization was successful in five patients receiving rituximab. Patients could receive the full intended dose.

  3. Rituximab induced hypoglycemia in non-Hodgkin's lymphoma

    Directory of Open Access Journals (Sweden)

    Lali V

    2006-12-01

    Full Text Available Abstract Background Hypoglycemia is a vary rare toxicity of rituximab. The exact mechanism of rituximab induced hypoglycemia is not clear. Case presentation A 50 year old female presented with a left tonsillar non Hodgkin's lymphoma and was started on R-CHOP chemotherapy. Twenty four hours after the first rituximab infusion, she developed hypoglycemia which was managed by IV glucose infusion. Conclusion Hypoglycemia following rituximab administration is rare. Possibilities of hypoglycemia should be kept in mind in patients developing symptoms like fatigue, restlessness, and sweating while on rituximab therapy.

  4. Cyclophosphamide versus ifosfamide for paediatric and young adult bone and soft tissue sarcoma patients

    NARCIS (Netherlands)

    Mulder, Renée L.; Paulides, Marios; Langer, Thorsten; Kremer, Leontien C. M.; van Dalen, Elvira C.

    2010-01-01

    BACKGROUND: Alkylating agents, such as cyclophosphamide and ifosfamide, play a major role in the improved survival of children and young adults with bone and soft tissue sarcoma. However, there is still controversy as to their comparative anti-tumour efficacy and possible adverse effects.

  5. Cyclophosphamide versus ifosfamide for paediatric and young adult bone and soft tissue sarcoma patients

    NARCIS (Netherlands)

    Mulder, Renée L.; Paulides, Marios; Langer, Thorsten; Kremer, Leontien C. M.; van Dalen, Elvira C.

    2012-01-01

    Background Alkylating agents, such as cyclophosphamide and ifosfamide, play a major role in the improved survival of children and young adults with bone and soft tissue sarcoma. However, there is still controversy as to their comparative anti-tumour efficacy and possible adverse effects. This is an

  6. Cyclophosphamide versus ifosfamide for paediatric and young adult bone and soft tissue sarcoma patients

    NARCIS (Netherlands)

    Mulder, Renée L.; Paulides, Marios; Langer, Thorsten; Kremer, Leontien C. M.; van Dalen, Elvira C.

    2015-01-01

    Alkylating agents, such as cyclophosphamide and ifosfamide, play a major role in the improved survival of children and young adults with bone and soft tissue sarcoma. However, there is still controversy as to their comparative anti-tumour efficacy and possible adverse effects. This is the second

  7. Efficacy and safety of ifosfamide-based chemotherapy for osteosarcoma: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Fan XL

    2015-11-01

    Full Text Available Xiao-Liang Fan,1,* Guo-Ping Cai,2,* Liu-Long Zhu,1 Guo-Ming Ding1 1Department of Orthopaedics, Hangzhou First People’s Hospital, Nanjing Medical University, Hangzhou, 2Department of Orthopaedics, Jinshan Hospital, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: The efficacy of ifosfamide-based chemotherapy in the treatment of osteosarcoma has been investigated; however, results are inconsistent. Therefore, we reviewed the relevant studies and conducted a meta-analysis to assess the efficacy of ifosfamide-based chemotherapy in patients with osteosarcoma.Methods: A systematic literature search on PubMed, Embase, and Web of Science databases was performed. Eligible studies were clinical trials of patients with osteosarcoma who received ifosfamide-based chemotherapy. Hazard ratios (HRs were pooled to compare event-free survival (EFS and overall survival (OS. Risk ratios (RRs were pooled to compare good histologic response rates and adverse event incidence. Meta-analysis was performed using a fixed-effects model or a random-effects model according to heterogeneity.Results: A total of seven randomized controlled trials were included in this meta-analysis. Pooled results showed that ifosfamide-based chemotherapy significantly improved EFS (HR=0.72, 95% confidence interval [CI]: 0.63, 0.82; P=0.000 and OS (HR=0.83, 95% CI: 0.70, 0.99; P=0.034; furthermore, this form of chemotherapy increased good histologic response rate (RR=1.27, 95% CI: 1.10, 1.46; P=0.001. In addition, patients in the ifosfamide group exhibited a significantly higher incidence of fever (RR=2.23, 95% CI: 1.42, 3.50; P=0.000 and required more frequent platelet transfusion (RR=1.92, 95% CI: 1.23, 3.01; P=0.004.Conclusion: This meta-analysis confirmed that ifosfamide-based chemotherapy can significantly improve EFS and OS; this chemotherapy can also increase good histologic response rate in patients with osteosarcoma

  8. Carboplatin Hypersensitivity Reactions in Pediatric Low Grade Glioma Are Protocol Specific and Desensitization Shows Poor Efficacy.

    Science.gov (United States)

    Dodgshun, Andrew J; Hansford, Jordan R; Cole, Theresa; Choo, Sharon; Sullivan, Michael J

    2016-01-01

    The use of carboplatin for the treatment of pediatric low grade gliomas (PLGG) is often limited by the development of carboplatin hypersensitivity. Reported rates of carboplatin hypersensitivity reactions vary between 6% and 32% in these patients. Here we report the frequency of carboplatin hypersensitivity reactions depending on the treatment regimen used, and outcomes of carboplatin desensitization. The records of all patients in a single institution who were treated with carboplatin for PLGG were accessed and all patients receiving more than one dose of carboplatin are reported. Thirty four patients with PLGG were treated with carboplatin according to one of the two different regimens. Carboplatin hypersensitivity was documented in 47% of patients, but the frequency differed by treatment protocol. Those patients treated with 4-weekly single agent carboplatin had carboplatin allergy in 8% of cases whereas 68% of those treated with combined carboplatin and vincristine (every three weeks, according to the SIOP 2004 low grade glioma protocol) had carboplatin reactions (OR 23.6, P Desensitization was only successful in two out of 10 patients in whom it was attempted. Hypersensitivity reactions to carboplatin are more common in this cohort than previously reported and rates are protocol-dependent. Desensitization showed limited effectiveness in this cohort. © 2015 Wiley Periodicals, Inc.

  9. Carboplatin treatment of antiestrogen-resistant breast cancer cells

    DEFF Research Database (Denmark)

    Larsen, Mathilde S; Yde, Christina Westmose; Christensen, Ib J

    2012-01-01

    Antiestrogen resistance is a major clinical problem in current breast cancer treatment. Therefore, biomarkers and new treatment options for antiestrogen-resistant breast cancer are needed. In this study, we investigated whether antiestrogen‑resistant breast cancer cell lines have increased...... sensitivity to carboplatin, as it was previously shown with cisplatin, and whether low Bcl-2 expression levels have a potential value as marker for increased carboplatin sensitivity. Breast cancer cells resistant to the pure antiestrogen fulvestrant, and two out of four cell lines resistant...... to the antiestrogen tamoxifen, were more sensitive to carboplatin treatment compared to the parental MCF-7 cell line. This indicates that carboplatin may be an advantageous treatment in antiestrogen‑resistant breast cancer; however, a marker for increased sensitivity would be needed. Low Bcl-2 expression...

  10. Role of carbonate in the cytotoxicity of carboplatin.

    Science.gov (United States)

    Di Pasqua, Anthony J; Goodisman, Jerry; Kerwood, Deborah J; Toms, Bonnie B; Dubowy, Ronald L; Dabrowiak, James C

    2007-06-01

    Carboplatin, [Pt(NH3)2(CBDCA-O,O')], 1, where CBDCA is cyclobutane-1,1-dicarboxylate, is used against ovarian, lung, and other types of cancer. We recently showed (Di Pasqua et al. (2006) Chem. Res. Toxicol. 19, 139-149) that carboplatin reacts with carbonate under conditions that simulate therapy to produce carbonato carboplatin, cis-[Pt(NH3)2(O-CBDCA)(CO3)]2-, 2. We use 13C and 1H NMR and UV-visible absorption spectroscopy to show that solutions containing carboplatin that have been aged in carbonate buffer under various conditions contain 1, 2, and other compounds. We then show that aging carboplatin in carbonate produces compounds that are more toxic to human neuroblastoma (SK-N-SH), proximal renal tubule (HK-2) and Namalwa-luc Burkitt's lymphoma (BL) cells than carboplatin alone. Moreover, increasing the aging time increases the cytotoxicity of the platinum solutions as measured by the increase in cell death. Although HK-2 cells experience a large loss in survival upon exposure to carbonato forms of the drug, they have the highest values of IC50 of the three cell lines studied, so that HK-2 cells remain the most resistant to the toxic effects of the carbonato forms in the culture medium. This is consistent with the well-known low renal toxicity observed for carboplatin in therapy. The uptake rates for normal Jurkat cells (NJ) and cisplatin-resistant Jurkat cells (RJ), measured by inductively coupled plasma mass spectrometry (ICP-MS), are 16.6 +/- 4.2 and 12.3 +/- 4.8 amol of Pt h-1 cell-1, respectively, when exposed to carboplatin alone. However, when these cells are exposed to carboplatin that has been aged in carbonate media, normal Jurkat cells strongly bind/take up Pt at a rate of 14.5 +/- 4.1 amol of Pt h-1 cell-1, while resistant cells strongly bind/take up 5.1 +/- 3.3 amol of Pt h-1 cell-1. Collectively, these studies show that carboplatin carbonato species may play a major role in the cytotoxicity and uptake of carboplatin by cells.

  11. Rituximab-induced interstitial lung disease

    DEFF Research Database (Denmark)

    Naqibullah, Matiuallah; Shaker, Saher B; Bach, Karen S

    2015-01-01

    Rituximab (RTX), a mouse/human chimeric anti-CD20 IgG1 monoclonal antibody has been effectively used as a single agent or in combination with chemotherapy regimen to treat lymphoma since 1997. In addition, it has been used to treat idiopathic thrombocytopenic purpura, systemic lupus erythematous...

  12. Rituximab for nephrotic syndrome in children.

    Science.gov (United States)

    Iijima, Kazumoto; Sako, Mayumi; Nozu, Kandai

    2017-04-01

    Idiopathic nephrotic syndrome is the most common chronic glomerular disease in children. At least 20 % of children with this syndrome show frequent relapses and/or steroid dependence during or after immunosuppressive therapies, a condition defined as complicated frequently relapsing/steroid-dependent nephrotic syndrome (FRNS/SDNS). Approximately 1-3 % of children with idiopathic nephrotic syndrome are resistant to steroids and all immunosuppressive agents, a condition defined as refractory steroid-resistant nephrotic syndrome (SRNS); these SRNS children have a high risk of end-stage renal failure. Rituximab, a chimeric anti-CD20 monoclonal antibody, has been shown to be effective for patients with complicated FRNS/SDNS and refractory SRNS. This review describes the recent results of rituximab treatment applied to pediatric nephrotic syndrome, as well as those of our recent study, a multicenter, double-blind, randomized, placebo-controlled trial of rituximab for childhood-onset complicated FRNS/SDNS (RCRNS01). The overall efficacy and safety of rituximab for this disease are discussed.

  13. Fulminante, rituximab-resistente, mucocutane pemphigus vulgaris

    NARCIS (Netherlands)

    Gostyński, A.; Ammatuna, E.; Huls, G.; Wouthuyzen-Bakker, M.; Jonkman, M. F.; Horváth, B.

    2017-01-01

    Pemphigus vulgaris is an autoimmune disease mediated by auto-antibodies against desmoglein 1 and 3. First line treatment for pemphigus consists of systemic corticosteroids and anti-CD20 therapy (rituximab) to eliminate B-cells. Since 2005, more than 100 patients with pemphigus have been treated with

  14. Immunotherapy with rituximab in follicular lymphomas.

    Science.gov (United States)

    Saguna, Carmen; Mut, Ileana Delia; Lupu, Anca Roxana; Tevet, Mihaela; Bumbea, Horia; Dragan, Cornel

    2011-04-01

    Non-Hodgkin Lymphomas (NHL) represent a recent and fascinating domain of hemato-oncology, in which remarkable progress has been made. The conventional treatments of indolent lymphomas do not extend the survival rate, nor do they cure. Recent directions are centered on using several new drugs that are capable of overcoming the mechanisms that are resistant to recovery. The initiation of immunotherapy (Rituximab in 1997) seems to have changed the natural evolution of follicular lymphomas (FL). It is possible that resistance to healing in follicular lymphomas may be neutralized with Rituximab by suppressing STAT-1 positive macrophages that are present in the cellular microenvironment.Thereinafter, the re-evaluation of recent models of prognostic and therapeutic paradigmas that were used in FL became compulsory.The purpose of the paper is to compare the evolution of patients with follicular lymphoma and the period of response, according to the treatments. The study group consisted of the 71 patients diagnosed with follicular lymphoma, out of a total of 767 malignant lymphatic proliferations with B cells, for a period of 7 years (2002-2008), at the Hematology Department, Hospital Coltea, Bucharest and Hematology Department, Universitary Hospital, BucharestResults and conclusions: Combining chemotherapy with Rituximab had better results compared to the same chemotherapy, administered alone, both in induction and in case of relapse. The overall response rate in our study group was 74.7%, out of which 42.3% complete remissions. The overall response rate was 84.61% in the Rituximab group, compared to 68.88% in patients without Rituximab.

  15. Carboplatin hypersensitivity in children with glial tumors: a report of two cases

    Directory of Open Access Journals (Sweden)

    Tugce Kazgan

    2016-12-01

    Full Text Available Carboplatin, commonly used chemotherapeutic agent in treatment of pediatric cancers, can cause life-threatening hypersensitivty reactions. Carboplatin hypersensitivity is protocol-specific and associated with repeated doses and prolonged use of the drug. Vincristin and carboplatin combination is used efficiently in treatment of pediatric low-grade gliomas. However, hypersensitivity reactions are frequently observed during usage of this protocol. Desensitization strategies with variable success rates were reported. Failure of these strategies may lead to cessation of carboplatin Here, we report two cases with carboplatin hypersensitivity treated with epinephrine administration, in whom carboplatin was discontinued after hypersensitivity reaction. [Cukurova Med J 2016; 41(4.000: 796-798

  16. Carboplatin and pegylated liposomal doxorubicin versus carboplatin and paclitaxel in very platinum-sensitive ovarian cancer patients

    DEFF Research Database (Denmark)

    Mahner, Sven; Meier, Werner; du Bois, Andreas

    2015-01-01

    - and paclitaxel-based therapies. Patients were randomised to CD [carboplatin-pegylated liposomal doxorubicin (PLD)] or CP (carboplatin-paclitaxel) and stratified by treatment-free interval (TFI). In this analysis, patients with a TFI>24 months were analysed separately for progression free survival (PFS...... (8% versus 3.1%; P=0.082) sensory neuropathy (4.8% versus 2.3%; P=0.27) and grade 2 alopecia (88% versus 9.2%; P

  17. Rituximab in treatment of idiopathic glomerulopathy

    Directory of Open Access Journals (Sweden)

    Kamel El-Reshaid

    2012-01-01

    Full Text Available The aim of our study was to assess the role of rituximab (Mabthera in the treatment of patients with corticosteroid-resistant and calcineurin-inhibitors ± cellcept refractory idiopathic nephrotic syndrome (INS. A total of 83 patients who had required the previous treatment for a minimum of two years were included in the study. Our protocol included the use of rituximab in four-weekly slow infusions. Five patients were excluded as they could not tolerate rituximab infusion for allergic reaction. As expected, none of the patients had a decline in the total circulating lymphocyte counts yet all had achieved decline of their initially normal CD20 to < 0.5% one month after infusion. The decline persisted for eight to ten months later. In the minimal change disease (MCD group, 31 of the 32 patients had complete remission (CR and were off any immunosuppressive therapy and one of the previous non-responders (NR did not respond. Excluding two patients who had required retreatment, the others remained in CR (17 up to 28 months and six up to 36 months. Treatment with rituximab resulted in amelioration of NS in 17 of the 18 patients with focal segmental glomerulosclerosis (FSGS, while only one patient remained NR. Although renal function remained stable, proteinuria reappeared by eight to 12 months. Retreatment with rituximab resulted in a similar response with stable kidney function. In the 28 patients with membranous glomerulopathy (MG, 24 had achieved CR. Two patients failed to respond and two had partial remission. By 12 months, all patients relapsed. The response was within one month following treatment in patient with MCD, but was gradual within three months in FSGS and MG. Relapsers in all groups responded in a similar pattern to repeat dosing with the drug subsequently. Our prospective study represents an adequate number of patients with biopsy-proven subgroups of INS in both children and adults with long-term follow-up of treatment with rituximab

  18. A Population-Based Clinical Trial of Irinotecan and Carboplatin

    Directory of Open Access Journals (Sweden)

    Derick Lau

    2009-01-01

    Full Text Available Purpose. Phase I trials of anticancer drugs are commonly conducted using the method of modified Fibonacci. We have developed a population-based design for phase I trials of combining anticancer drugs such as irinotecan and carboplatin. Patients and Methods. Intrapatient dose escalation of irinotecan and carboplatin was performed according to a predetermined schema to reach individual dose-limiting toxicity (DLT in 50 patients with solid tumors refractory to previous chemotherapy. The individual toxicity-limiting dose levels were analyzed for normal distribution using the method of Ryan-Joiner and subsequently used to determine a population-based maximum tolerated dose (pMTD. For comparison, a simulation study was performed using the method of modified Fibonacci. Results. The most common dose-limiting toxicities (DLTs included neutropenia (58%, thrombocytopenia (16%, and diarrhea (8%. The frequency of individual toxicity-limiting dose levels of 50 patients approximated a normal distribution. The dose levels associated with individual limiting toxicities ranged from level 1 (irinotecan 100 mg/m2 and carboplatin AUC = 4 mg/mL x min to level 8 (irinotecan 350 mg/m2 and carboplatin AUC = 6. The pMTD was determined to be dose level 3 (150 mg/m2 for irinotecan and AUC = 5 for carboplatin. In contrast, the MTD was determined to be dose level 4 (200 mg/m2 for irinotecan and AUC 5 for carboplatin by modified-Fibonacci simulation. Conclusions. The population-based design of phase I trial allows optimization of dose intensity and derivation of a pMTD. The pMTD has been applied in phase II trial of irinotecan and carboplatin in patients with small-cell lung cancer.

  19. Multicenter study of environmental contamination with cyclophosphamide, ifosfamide, and methotrexate in 48 Canadian hospitals.

    Science.gov (United States)

    Poupeau, Céline; Tanguay, Cynthia; Caron, Nicolas J; Bussières, Jean-François

    2018-01-01

    Context Oncology workers are occupationally exposed to antineoplastic drugs. This exposure can induce adverse health effects. In order to reduce their exposure, contamination on surfaces should be kept as low as possible. Objectives To monitor environmental contamination with cyclophosphamide, ifosfamide, and methotrexate in oncology pharmacy and patient care areas in Canadian hospitals. To describe the impact of some factors that may limit contamination. Methods This is a descriptive study. Twelve standardized sites were sampled in each participating center (six in the pharmacy and six in patient care areas). Samples were analyzed for the presence of cyclophosphamide, ifosfamide, and methotrexate by ultra-performance liquid chromatography tandem mass spectrometry technology. Descriptive statistical analyses were done and results were compared with a Kolmogorov-Smirnov test for independent samples. Results In 2015, 48 hospitals participated in this study (48/202, 24%). Overall, 34% (181/525) of the samples were positive for cyclophosphamide, 8% (41/525) for ifosfamide, and 6% (31/525) for methotrexate. The 75th percentile value of cyclophosphamide surface concentration was 6.9 pg/cm 2 . For ifosfamide and methotrexate, they were lower than the limit of detection. Centers who prepared more antineoplastic drugs per year and centers who used more cyclophosphamide per year showed significantly higher surface contamination ( p contamination. Conclusion In comparison with other multicenter studies that were conducted in Canada, the concentration of antineoplastic drugs measured on surfaces is decreasing. Regular environmental monitoring is a good practice in order to maintain contamination as low as reasonably achievable.

  20. Prespecified candidate biomarkers identify follicular lymphoma patients who achieved longer progression-free survival with bortezomib-rituximab versus rituximab.

    Science.gov (United States)

    Coiffier, Bertrand; Li, Weimin; Henitz, Erin D; Karkera, Jayaprakash D; Favis, Reyna; Gaffney, Dana; Shapiro, Alice; Theocharous, Panteli; Elsayed, Yusri A; van de Velde, Helgi; Schaffer, Michael E; Osmanov, Evgenii A; Hong, Xiaonan; Scheliga, Adriana; Mayer, Jiri; Offner, Fritz; Rule, Simon; Teixeira, Adriana; Romejko-Jarosinska, Joanna; de Vos, Sven; Crump, Michael; Shpilberg, Ofer; Zinzani, Pier Luigi; Cakana, Andrew; Esseltine, Dixie-Lee; Mulligan, George; Ricci, Deborah

    2013-05-01

    Identify subgroups of patients with relapsed/refractory follicular lymphoma deriving substantial progression-free survival (PFS) benefit with bortezomib-rituximab versus rituximab in the phase III LYM-3001 study. A total of 676 patients were randomized to five 5-week cycles of bortezomib-rituximab or rituximab. The primary end point was PFS; this prespecified analysis of candidate protein biomarkers and genes was an exploratory objective. Archived tumor tissue and whole blood samples were collected at baseline. Immunohistochemistry and genetic analyses were completed for 4 proteins and 8 genes. In initial pairwise analyses, using individual single-nucleotide polymorphism genotypes, one biomarker pair (PSMB1 P11A C/G heterozygote, low CD68 expression) was associated with a significant PFS benefit with bortezomib-rituximab versus rituximab, controlling for multiple comparison corrections. The pair was analyzed under dominant, recessive, and additive genetic models, with significant association with PFS seen under the dominant model (G/G+C/G). In patients carrying this biomarker pair [PSMB1 P11A G allele, low CD68 expression (≤50 CD68-positive cells), population frequency: 43.6%], median PFS was 14.2 months with bortezomib-rituximab versus 9.1 months with rituximab (HR 0.47, P < 0.0001), and there was a significant overall survival benefit (HR 0.49, P = 0.0461). Response rates were higher and time to next antilymphoma therapy was longer in the bortezomib-rituximab group. In biomarker-negative patients, no significant efficacy differences were seen between treatment groups. Similar proportions of patients had high-risk features in the biomarker-positive and biomarker-negative subsets. Patients with PSMB1 P11A (G allele) and low CD68 expression seemed to have significantly longer PFS and greater clinical benefit with bortezomib-rituximab versus rituximab. ©2013 AACR.

  1. Rituximab and chemotherapy in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Sonet, Anne; Bosly, André

    2009-06-01

    Rituximab is an anti-CD20 chimeric monoclonal antibody with activity in nearly all subtypes of B-cell lymphomas. Association of rituximab with chemotherapy (mostly the cyclophosphamide, doxorubicin, vincristine and prednisolone [CHOP] regimen) in diffuse large B-cell lymphoma (DLBCL) represents an extraordinary revolution in the prognosis of DLBCL, and is the new standard of therapy in elderly and young, low-risk patients. Despite the lack of randomized, clinical trials in younger patients with high risk, rituximab is also a standard of care in these patients in clinical practice, at least in North America. The practice is based on observational trials (e.g., the British Columbia Registry) and the missing logic in classifying patients as 'younger' or 'older': 60 years old or 65 years old. In Europe, trials are ongoing to establish the best treatment for young, high-risk patients. Association of rituximab and chemotherapy deeply modifies prognostic factors defined before the rituximab era.

  2. Beneficial effect of tocilizumab in myasthenia gravis refractory to rituximab.

    Science.gov (United States)

    Jonsson, Dagur Ingi; Pirskanen, Ritva; Piehl, Fredrik

    2017-06-01

    Muscle fatigue associated with myasthenia gravis is caused by autoantibodies interfering with neuromuscular transmission. Immunomodulating treatment is widely used in moderate to severe myasthenia, although the use of newer biological drugs except rituximab is rare. We describe the effect of tocilizumab, a blocker of interleukin-6 signalling, in two female myasthenia patients with high titres of serum acetylcholine receptor antibodies and insufficient response to rituximab. The first patient had been treated with high dose immunoglobulins regularly for several years and the second patient had been treated both with different oral immune suppressants and immunoglobulins before testing a low dose of rituximab without significant clinical effect. Subsequent treatment with tocilizumab resulted in clinical improvement within a few months. The first patient was switched back to rituximab, which resulted in worsening until tocilizumab was restarted. Tocilizumab can be a therapeutic option in cases not responding to rituximab. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. B Cell Depletion: Rituximab in Glomerular Disease and Transplantation

    Directory of Open Access Journals (Sweden)

    S. Marinaki

    2013-12-01

    Full Text Available B cells play a central role in the pathogenesis of many autoimmune diseases. Selective targeting can be achieved with the use of the monoclonal antibody rituximab. In addition to being a drug for non-Hodgkin's lymphoma, rituximab is also an FDA-approved treatment for refractory rheumatoid arthritis and, since recently, ANCA vasculitis. It has shown efficacy in many autoimmune diseases. This review will discuss current evidence and the rationale of the use of rituximab in glomerular diseases, including randomized controlled trials. The focus will be on the use of rituximab in idiopathic membranous nephropathy, systemic lupus erythematosus and ANCA-associated vasculitis. The emerging role of rituximab in renal transplantation, where it seems to be important for the desensitization protocols for highly sensitized patients as well as for the preconditioning of ABO-incompatible recipients and the treatment of antibody-mediated rejection, will also be addressed.

  4. Adjuvant therapy with carboplatin and pamidronate for canine appendicular osteosarcoma.

    Science.gov (United States)

    Kozicki, A R; Robat, C; Chun, R; Kurzman, I D

    2015-09-01

    Amputation and chemotherapy are the mainstay of treatment for canine appendicular osteosarcoma (OSA). In vitro studies have demonstrated anti-tumour activity of pamidronate against canine OSA. The purpose of this study was to assess the safety of adding pamidronate to standard post-operative carboplatin chemotherapy in 17 dogs with appendicular OSA treated with limb amputation. Median disease-free interval (DFI) and median survival time (MST) were evaluated as secondary endpoints. Incidence of side effects and treatment outcomes were compared to 14 contemporary control patients treated with carboplatin alone. There were no identified side effects to the pamidronate treatment. The median DFI for the study group was 185 days compared to 172 days for the control group (P = 0.90). The MST of the study group was 311 days compared to 294 days for the control group (P = 0.89). Addition of pamidronate to carboplatin chemotherapy for the treatment of canine appendicular OSA is safe and does not impair efficacy of standard carboplatin treatment. © 2013 Blackwell Publishing Ltd.

  5. Preparation & in vitro evaluation of 90Y-DOTA-rituximab

    Science.gov (United States)

    Kameswaran, Mythili; Pandey, Usha; Dash, Ashutosh; Samuel, Grace; Venkatesh, Meera

    2016-01-01

    Background & objectives: Radioimmunotherapy is extensively being used for the treatment of non-Hodgkin's lymphoma (NHL). Use of rituximab, a chimeric anti-CD20 antibody directed against the CD20 antigen in combination with suitable beta emitters is expected to result in good treatment response by its cross-fire and bystander effects. The present work involves the conjugation of p-isothiocyanatobenzyl DOTA (p-SCN-Bn-DOTA) to rituximab, its radiolabelling with 90Y and in vitro and in vivo evaluation to determine its potential as a radioimmunotherapeutic agent. Methods: Rituximab was conjugated with p-SCN-Bn-DOTA at 1:1 antibody: DOTA molar ratio. The number of DOTA molecules linked to one molecule of rituximab was determined by radioassay and spectroscopic assay. Radiolabelling of rituximab with 90Y was carried out and its in vitro stability was evaluated. In vitro cell binding studies were carried out in Raji cells expressing CD20 antigen. Biodistribution studies were carried out in normal Swiss mice. Results: Using both radioassay and spectroscopic method, it was determined that about five molecules of DOTA were linked to rituximab. Radiolabelling of the rituximab conjugate with 90Y and subsequent purification on PD-10 column gave a product with radiochemical purity (RCP) > 98 per cent which was retained at > 90 per cent up to 72 h when stored at 37°C. In vitro cell binding experiments of 90Y-DOTA-rituximab with Raji cells exhibited specific binding of 20.7 ± 0.1 per cent with 90Y-DOTA-rituximab which reduced to 15.5 ± 0.2 per cent when incubated with cold rituximab. The equilibrium constant Kd for 90Y-DOTA-Rituximab was determined to be 3.38 nM. Radiolabelled antibody showed clearance via hepatobiliary and renal routes and activity in tibia was found to be quite low indicating in vivo stability of 90Y-DOTA-rituximab. Interpretation & conclusions: p-SCN-Bn-DOTA was conjugated with rituximab and radiolabelling with 90Y was carried out. In vitro studies carried

  6. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma.

    Science.gov (United States)

    Mok, Tony S; Wu, Yi-Long; Thongprasert, Sumitra; Yang, Chih-Hsin; Chu, Da-Tong; Saijo, Nagahiro; Sunpaweravong, Patrapim; Han, Baohui; Margono, Benjamin; Ichinose, Yukito; Nishiwaki, Yutaka; Ohe, Yuichiro; Yang, Jin-Ji; Chewaskulyong, Busyamas; Jiang, Haiyi; Duffield, Emma L; Watkins, Claire L; Armour, Alison A; Fukuoka, Masahiro

    2009-09-03

    Previous, uncontrolled studies have suggested that first-line treatment with gefitinib would be efficacious in selected patients with non-small-cell lung cancer. In this phase 3, open-label study, we randomly assigned previously untreated patients in East Asia who had advanced pulmonary adenocarcinoma and who were nonsmokers or former light smokers to receive gefitinib (250 mg per day) (609 patients) or carboplatin (at a dose calculated to produce an area under the curve of 5 or 6 mg per milliliter per minute) plus paclitaxel (200 mg per square meter of body-surface area) (608 patients). The primary end point was progression-free survival. The 12-month rates of progression-free survival were 24.9% with gefitinib and 6.7% with carboplatin-paclitaxel. The study met its primary objective of showing the noninferiority of gefitinib and also showed its superiority, as compared with carboplatin-paclitaxel, with respect to progression-free survival in the intention-to-treat population (hazard ratio for progression or death, 0.74; 95% confidence interval [CI], 0.65 to 0.85; P<0.001). In the subgroup of 261 patients who were positive for the epidermal growth factor receptor gene (EGFR) mutation, progression-free survival was significantly longer among those who received gefitinib than among those who received carboplatin-paclitaxel (hazard ratio for progression or death, 0.48; 95% CI, 0.36 to 0.64; P<0.001), whereas in the subgroup of 176 patients who were negative for the mutation, progression-free survival was significantly longer among those who received carboplatin-paclitaxel (hazard ratio for progression or death with gefitinib, 2.85; 95% CI, 2.05 to 3.98; P<0.001). The most common adverse events were rash or acne (in 66.2% of patients) and diarrhea (46.6%) in the gefitinib group and neurotoxic effects (69.9%), neutropenia (67.1%), and alopecia (58.4%) in the carboplatin-paclitaxel group. Gefitinib is superior to carboplatin-paclitaxel as an initial treatment for

  7. Carboplatin AUC 10 for IGCCCG good prognosis metastatic seminoma.

    Science.gov (United States)

    Tookman, Laura; Rashid, Sukaina; Matakidou, Athena; Phillips, Melissa; Wilson, Peter; Ansell, Wendy; Jamal-Hanjani, Mariam; Chowdhury, Simon; Harland, Stephen; Sarwar, Naveed; Oliver, Timothy; Powles, Thomas; Shamash, Jonathan

    2013-06-01

    Metastatic seminoma is a highly curable disease. Standard treatment comprises of combination chemotherapy. The short- and long-term toxicities of this treatment are increasingly recognised and the possibility of over treatment in such a curable disease should be considered. We have therefore assessed the use of single agent carboplatin at a dose of AUC 10 in patients with good prognosis metastatic seminoma. Patients with good prognosis metastatic seminoma treated with carboplatin (AUC 10) were identified at our institution and affiliated institutions. Treatment was three weekly for a total of three or four cycles. Outcome and toxicities were analysed. With a median follow-up of 36 months, 61 patients in total were treated with carboplatin AUC 10, all good prognosis by the IGCCCG criteria. Forty-eight percent had stage IIA/IIB disease and 52% had greater than stage IIB disease. Thirty-one patients (51%) had a complete response following treatment. Three-year survival was 96.3% with a three-year progression free survival of 93.2%. The main treatment toxicity was haematological with 46% having grade 3, 24% having grade 4 neutropenia and 54% experiencing grade 3/4 thrombocytopenia. There were no treatment related deaths. Single agent carboplatin at a dose of AUC 10 is an effective treatment for good prognosis metastatic seminoma. The outcome compares favourably to previously published outcomes of combination chemotherapy. Although haematological toxicity is a concern, single agent carboplatin treatment for good prognosis metastatic seminoma could be considered a treatment option and is associated with less toxicity than combination regimens currently used.

  8. Detection and quantification of rituximab in the human urine.

    Science.gov (United States)

    Jacobs, Roland; Langer-Jacobus, Thais; Duong, Michelle; Stahl, Klaus; Haller, Hermann; Schmidt, Reinhold E; Schiffer, Mario

    2017-12-01

    B cell depletion by rituximab treatment might be inefficient in patients suffering from nephrotic syndrome. Due to the impaired glomerular filtration barrier a significant portion of the therapeutic antibody might be lost into the urinary space. In order to determine the amount of rituximab in the urine of such patients, CD20+ Daudi cells were stained with the patients' urine followed by a fluorochrome-labeled secondary antibody. Mean fluorescence intensity of that way labeled Daudi cells was determined by flow cytometry. Control samples with defined rituximab concentrations were used to create standard curves. The analyses revealed that all nephelometric IgG+ urine samples tested also manifested rituximab at concentrations between 100 and 46,707μg/L. The flow cytometry-based approach is an easy and reliable method to assess rituximab in patients' urine samples for monitoring individual rituximab treatment courses in all patients co-presenting impaired renal filtration. Presence of such antibodies in the urine could be considered as criteria to modify the formulation or modality of rituximab delivery in order to prevent the loss of the therapeutic antibodies and thereby ensuring efficacy of the therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Urinary neutrophil gelatinase associated lipocalin as a biomarker in ifosfamide induced chronic renal failure.

    Science.gov (United States)

    Kesik, V; Demirkaya, E; Buyukpamukçu, M

    2015-12-01

    Neutrophil gelatinase associated lipocalin (NGAL) have been used with great success in acute renal failure and in some cases in chronic nephrotoxicity. In this work, we aimed to investigate urinary NGAL as an early marker of chronic renal failure (CRF). We investigated urinary NGAL of 29 children treated with ifosfamide chemotherapy and compared them with those of 12 healthy children. Urinary β2 microglobulin, serum cystatin C, and creatinine clearance analyses were also studied. The median age was 11 years (4-21) and median remission time was 4.3 years (1.8-14.4). The cumulative dose of ifosfamide was 36 g. Glomerular filtration rate was decreased in 41.4% and urine β2 microglobulin levels and serum cystatin C levels were elevated in 31% of the patients. As the remission time increased, serum creatinine and cystatin C levels were also increased. The sensitivity for β2 microglobulin and cystatin C in demonstrating CRF was 35.2% and 23% and specificity was 33.2% and 50% respectively. The 24-hour urine NGAL cut-off level for demonstrating CRF was found to be 1.065 ng/mL/24 hours. The sensitivity and specificity for this cut-off value were 83% and 77%, respectively. NGAL levels were significantly higher in the study group as compared with the control group. Although ifosfamide treatment was suggested to be safe with no complication of renal failure under a dose of 80 g/m2, chronic renal failure and deficits in glomerular and tubular function could be seen when the remission time increased. Elevated NGAL levels may be a good option in determining CRF.

  10. Ifosfamide: chemotherapy with new promise and new problems for the urologist.

    Science.gov (United States)

    Watson, R A

    1984-11-01

    Ifosfamide, a chemotherapeutic agent, offers new hope as well as new problems for the uro-oncologist. The "good news" is that this drug is achieving marked benefits in treating resistant testis tumors and may even hold hope for patients with renal cell carcinoma. The "bad news" is that a price must be paid in toxicity--predominantly a severe and restrictive hemorrhagic cystitis. A breakthrough is the finding that oral administration of acetylcysteine (Mucomyst) may, to a large extent, prevent this untoward side effect.

  11. Progressive outer retinal necrosis after rituximab and cyclophosphamide therapy

    Directory of Open Access Journals (Sweden)

    Mohit Dogra

    2018-01-01

    Full Text Available We report a case of progressive outer retinal necrosis (PORN in a patient of microscopic polyangitis (MPA, being treated with immunosuppressive drugs such as cyclophosphamide and rituximab. Her aqueous tap was positive for Varicella Zoster virus and she was treated with oral and intravitreal antivirals, along with discontinuation of one of the immunosuppressive agents, i.e. rituximab, which might have led to reactivation of the virus causing necrotizing retinitis lesions. Rituximab and cyclophosphamide are extremely potent drugs, which are necessary to manage immunological disorders such as MPA. However, they may predispose the patient to serious complications like viral infections, including PORN.

  12. Progressive outer retinal necrosis after rituximab and cyclophosphamide therapy.

    Science.gov (United States)

    Dogra, Mohit; Bajgai, Priya; Kumar, Ashok; Sharma, Aman

    2018-04-01

    We report a case of progressive outer retinal necrosis (PORN) in a patient of microscopic polyangitis (MPA), being treated with immunosuppressive drugs such as cyclophosphamide and rituximab. Her aqueous tap was positive for Varicella Zoster virus and she was treated with oral and intravitreal antivirals, along with discontinuation of one of the immunosuppressive agents, i.e. rituximab, which might have led to reactivation of the virus causing necrotizing retinitis lesions. Rituximab and cyclophosphamide are extremely potent drugs, which are necessary to manage immunological disorders such as MPA. However, they may predispose the patient to serious complications like viral infections, including PORN.

  13. EXPERIENCE OF TREATMENT WITH RITUXIMAB IN PATIENT WITH JUVENILE POLYARTERITIS

    Directory of Open Access Journals (Sweden)

    E.I. Alexeeva

    2011-01-01

    Full Text Available The article presents a case report of severe course of nodular polyarteritis. The disease was highly active, aggressive, and refractory to treatment with corticosteroids and cyclophosphamide combined with plasmapheresis and drugs for microcirculation improvement. The treatment with chimerical anti-CD20 monoclonal antibodies — rituximab — was successful. Symptoms of intoxication and tromboangiatic syndrome decreased in 4 weeks. Disease was stopped up to 16th week. The case report demonstrates high efficacy of rituximab: patient with severe nodular polyarteritis remains clinical and laboratory remission during 52 weeks.Key words: children, nodular polyarteritis, rituximab.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (2: 193–200

  14. Prolonged Remission in Neuromyelitis Optica Following Cessation of Rituximab Treatment.

    Science.gov (United States)

    Weinfurtner, Kelley; Graves, Jennifer; Ness, Jayne; Krupp, Lauren; Milazzo, Maria; Waubant, Emmanuelle

    2015-09-01

    Neuromyelitis optica is an autoimmune disease characterized by acute episodes of transverse myelitis and optic neuritis. Several small, open-label studies suggest rituximab, a monoclonal antibody against CD20, prevents relapses in neuromyelitis optica; however, there is little consensus on timing or duration of treatment. Here we report four patients with severe relapsing neuromyelitis optica who were stabilized on rituximab and, after discontinuing treatment, continued to experience prolonged remission of their disease. Remission ranged from 4.5 to 10.5 years total, including 3 to 9 years off all therapies. The patients had sustained clinical responses despite normal B-lymphocyte levels and, in at least 2 patients, continued seropositivity for aquaporin-4 antibodies. These cases suggest that rituximab may induce prolonged remission in certain neuromyelitis optica patients, and they highlight the need for further elucidation of rituximab's mechanism in neuromyelitis optica. © The Author(s) 2014.

  15. Parvovirus B19 reactivation presenting as neutropenia after rituximab treatment.

    Science.gov (United States)

    Klepfish, A; Rachmilevitch, E; Schattner, A

    2006-11-01

    A patient with primary biliary cirrhosis and associated refractory immune thrombocytopenic purpura was treated with 4 weekly courses of rituximab, a monoclonal antibody targeting B-cell surface antigen CD20. Her thrombocyte count and even cholestatic liver function tests improved. However, 17 weeks after rituximab treatment, she developed severe neutropenia (absolute neutrophil count 0.23x10(3)/mul) and recurrent thrombocytopenia with abnormal bone marrow of all three lineages. Although delayed-onset neutropenia has been reported after rituximab, reactivated viral infections have also been encountered. Parvovirus B19 was suspected and confirmed as the cause of neutropenia in our patient. The patient was supported by GCSF treatment and recovered uneventfully after several weeks. Neutropenia after rituximab can also be the predominant manifestation of reactivated parvovirus B19 infection and have a favorable prognosis.

  16. Clinical efficacy of preoperative chemotherapy with or without ifosfamide in patients with osteosarcoma of the extremity: meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Su, Wenmei; Lai, Zhennan; Wu, Fenping; Lin, Yanming; Mo, Yanli; Yang, Zhixiong; Wu, Jiayuan

    2015-02-01

    Ifosfamide has been used in neoadjuvant chemotherapy since the mid-1980s. Although several studies have been conducted, the results remain controversial. Randomized controlled trials have an improved balance of confounding factors and reliable results. Thus, we performed a meta-analysis based on randomized controlled trials to gather more evidence of the effect of ifosfamide on neoadjuvant chemotherapy for patients with osteosarcoma of the extremity. An electronic search was conducted via the Internet retrieval system to identify eligible trials until September 2014. Odds ratios (ORs) and 95 % confidence interval (CI) were calculated to compare the results of ifosfamide and ifosfamide-free therapies. Four trials with a total of 1,378 patients were eligible for our meta-analysis. Overall, compared with neoadjuvant chemotherapy without ifosfamide, the use of ifosfamide had no advantage in terms of histological response to chemotherapy (cHR; OR 1.36; 95 % CI 0.90-2.03, P = 0.140), 5-year event-free survival (EFS; OR 1.16; 95 % CI 0.789-1.75, P = 0.464), and 5-year overall survival (OS; OR 1.06; 95 % CI 0.70-1.59, P = 0.794). However, improvement was noted in the rate of limb salvage (OR 4.06; 95 % CI 2.04-8.10, P chemotherapy with ifosfamide for patients with extremity osteosarcoma might not increase the cHR and exhibited no significant effect on either EFS or OS. However, ifosfamide therapy could significantly increase the rate of limb salvage for osteosarcoma of the extremity, which suggests that the preoperative use of ifosfamide could increase the success rate of limb salvage operation.

  17. Clinical evaluation of rituximab treatment for neuromyelitis optica.

    Science.gov (United States)

    Fernández-Megía, M J; Casanova-Estruch, B; Pérez-Miralles, F; Ruiz-Ramos, J; Alcalá-Vicente, C; Poveda-Andrés, J L

    2015-10-01

    Neuromyelitis optica is an inflammatory and usually relapsing demyelinating autoimmune disease of the central nervous system that targets the optic nerves and spinal cord. Rituximab has been used for different neurological diseases that are probably immune-mediated or involving humoural immunity. The objective of this study is to evaluate the efficacy and safety of rituximab as treatment for neuromyelitis optica in a tertiary hospital. Retrospective study of patients with neuromyelitis optica treated with rituximab 1000mg on days 1 and 15, repeated every 6 to 8 months. We recorded EDSS score, relapse rate, overall condition, CD19+ count, presence of anti-NMO antibodies, and possible adverse reactions. Six patients were treated; all were women with a median age of 46 years (range, 38-58). Anti-NMO antibodies were detected in 3 patients (50%). Baseline EDSS was 4 (range 2.0-5.5). Two patients had previously been treated with an immunomodulatory drug. Median time from the first rituximab infusion to first relapse was 3.7 years (range 1.7-6.9). Two patients had infusion reactions after the first dose of rituximab. Four patients remained relapse-free and their EDSS score did not progress during rituximab treatment, one patient showed no clinical improvement, and one patient could not be evaluated. Rituximab can be considered an attractive therapeutic alternative for patients with neuromyelitis optica as there are no approved treatments for this disease. Further studies with rituximab are needed to establish the role of this drug in treating neuromyelitis optica. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  18. Rituximab: An emerging therapeutic agent for kidney transplantation

    Directory of Open Access Journals (Sweden)

    Joseph Kahwaji

    2009-10-01

    Full Text Available Joseph Kahwaji, Chris Tong, Stanley C Jordan, Ashley A VoComprehensive Transplant Center, Transplant immunology Laboratory, HLA Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, USAAbstract: Rituximab (anti-CD20, anti-B-cell is now emerging as an important drug for modification of B-cell and antibody responses in solid-organ transplant recipients. Its uses are varied and range from facilitating desensitization and ABO blood group-incompatible transplantation to the treatment of antibody-mediated rejection (AMR, post-transplant lymphoproliferative disorder (PTLD, and recurrent glomerular diseases in the renal allograft. Despite these uses, prospective randomized trials are lacking. Only case reports exist in regards to its use in de novo and recurrent diseases in the renal allograft. Recent reports suggests that the addition of rituximab to intravenous immunoglobulin (IVIG may have significant benefits for desensitization and treatment of AMR and chronic rejection. Current dosing recommendations are based on data from United States Food and Drug Administration-approved indications for treatment of B-cell lymphomas and rheumatoid arthritis. From the initial reported experience in solid organ transplant recipients, the drug is well tolerated and not associated with increased infectious risks. However, close monitoring for viral infections is recommended with rituximab use. The occurrence of progressive multifocal leukoencephalopathy (PML has been reported with rituximab use. However, this is rare and not reported in the renal transplant population. Here we will review current information regarding the effectiveness of rituximab as an agent for desensitization of highly human leukocyte antigen-sensitized and ABO-incompatible transplant recipients and its use in treatment of AMR. In addition, the post-transplant use of rituximab for treatment of PTLD and for recurrent and de novo glomerulonephritis in the allograft will be discussed. In

  19. Rituximab treatment in primary angiitis of the central nervous system.

    Science.gov (United States)

    Patel, Shreeya; Ross, Laura; Oon, Shereen; Nikpour, Mandana

    2018-06-01

    Primary angiitis of the central nervous system (PACNS) is a rare autoimmune vasculitis affecting the brain and spinal cord. Treatment with biological agents has revolutionised the treatment of many rheumatic conditions but there is scant literature regarding the use of biological agents in PACNS. We present three cases of PACNS treated with rituximab, including two cases of relapsed disease, and a literature review suggesting a role for rituximab in this condition. © 2018 Royal Australasian College of Physicians.

  20. Determination of ifosfamide, 2-and 3-dechloroethyifosfamide using gas chromatography with nitrogen-phosphorus or mass spectrometry detection

    NARCIS (Netherlands)

    Kerbusch, T; Jeuken, MJ; Derraz, J; van Putten, JWG; Huitema, ADR; Beijnen, JH

    2000-01-01

    A comparison was made between methods for determining ifosfamide (IF), 2- (2DCE) and 3-dechloroethylifosfamide (3DCE) using gas chromatography with nitrogen-phosphorus detection (GC-NPD) versus positive ion electron-impact ion-trap mass spectrometry (GC-MS'). Sample pretreatment involved

  1. Phase I and pharmacokinetic study of the combination of topotecan and ifosfamide administered intravenously every 3 weeks

    NARCIS (Netherlands)

    Kerbusch, T.; Groenewegen, G.; Mathôt, R. A. A.; Herben, V. M. M.; ten Bokkel Huinink, W. W.; Swart, M.; Ambaum, B.; Rosing, H.; Jansen, S.; Voest, E. E.; Beijnen, J. H.; Schellens, J. H. M.

    2004-01-01

    To determine the maximum-tolerated dose (MTD), dose-limiting toxicities, and pharmacokinetics of topotecan administered as a 30-min intravenous (i.v.) infusion over 5 days in combination with a 1-h i.v. infusion of ifosfamide (IF) for 3 consecutive days every 3 weeks. Patients with advanced

  2. Evaluation of toxicity after periocular and intravitreal administration of carboplatin in rabbit eyes

    Directory of Open Access Journals (Sweden)

    Denisa Darsová

    2011-01-01

    Full Text Available The aim of this study was to characterize the extent of toxicity of focal carboplatin administration and to identify the dose limiting toxicity in rabbit eyes depending on administered concentrations. New Zealand white male rabbits (n = 18 were treated with 1 of 3 regimens: a single periocular injection of 15 mg of carboplatin (group I, a single periocular injection of 30 mg of carboplatin (group II and a single transcorneal intravitreal injection of 0.05 mg of carboplatin (group III. Ophthalmologic examinations and vitreous samplings were performed under dissociative anaesthesia at regular intervals during next 2 (groups I and III or 3 (group II weeks. Carboplatin concentrations in vitreous samples were assessed by atomic absorption spectroscopy. At the end of experiments, all rabbit eyes were obtained for histopathologic examination. Clinical and histological evidence of toxicity was graded into four grades according to anatomical structures of the rabbit eye. The dose limiting toxicity was reached in group II after periocular injection of 30 mg of carboplatin and in group III after intravitreal injection of 0.05 mg of carboplatin. No systemic toxicity was observed in any group. Focal carboplatin administration may decrease systemic exposure to this cytotoxic drug in the retinoblastoma treatment. This moreover suggests that focal carboplatin administration is a promising approach and challenge for advanced retinoblastoma chemotherapy.

  3. Rituximab-related viral infections in lymphoma patients.

    Science.gov (United States)

    Aksoy, Sercan; Harputluoglu, Hakan; Kilickap, Saadettin; Dede, Didem Sener; Dizdar, Omer; Altundag, Kadri; Barista, Ibrahim

    2007-07-01

    Recently, a human/mouse chimeric monoclonal antibody, rituximab, has been successfully used to treat cases of B-cell non-Hodgkin's lymphoma and some autoimmune diseases. However, several viral infections related to rituximab have been reported in the literature, but were not well characterized. To further investigate this topic, relevant English language studies were identified through Medline. There were 64 previously reported cases of serious viral infection after rituximab treatment. The median age of the cases was 61 years (range: 21 - 79). The median time period from the start of rituximab treatment to viral infection diagnosis was 5.0 months (range: 1 - 20). The most frequently experienced viral infections were hepatitis B virus (HBV) (39.1%, n = 25), cytomegalovirus infection (CMV) (23.4%, n = 15), varicella-zoster virus (VZV) (9.4%, n = 6), and others (28.1%, n = 18). Of the patients with HBV infections, 13 (52.0%) died due to hepatic failure. Among the 39 cases that had viral infections other than HBV, 13 died due to these specific infections. In this study, about 50% of the rituximab-related HBV infections resulted in death, whereas this was the case in only 33% of the cases with other infections. Close monitoring for viral infection, particularly HBV and CMV, in patients treated with rituximab should be recommended.

  4. Carboplatin: molecular mechanisms of action associated with chemoresistance

    Directory of Open Access Journals (Sweden)

    Graziele Fonseca de Sousa

    2014-12-01

    Full Text Available Carboplatin is a derivative of cisplatin; it has a similar mechanism of action, but differs in terms of structure and toxicity. It was approved by the FDA in the 1980s and since then it has been widely used in the treatment of several tumor types. This agent is characterized by its ability to generate lesions in DNA through the formation of adducts with platinum, thereby inhibiting replication and transcription and leading to cell death. However, its use can lead to serious inconvenience arising from the development of resistance that some patients acquire during treatment, limiting the scope of its full potential. Currently, the biochemical mechanisms related to resistance are not precisely known. Therefore, knowledge of pathways associated with resistance caused by carboplatin exposure may provide valuable clues for more efficient rational drug design in platinum-based therapy and the development of new therapeutic strategies. In this narrative review, we discuss some of the known mechanisms of resistance to platinum-based drugs, especially carboplatin.

  5. Vinorelbine/carboplatin vs gemcitabine/carboplatin in advanced NSCLC shows similar efficacy, but different impact of toxicity

    DEFF Research Database (Denmark)

    Helbekkmo, N; Sundstrøm, S H; Aasebø, U

    2007-01-01

    This randomised phase III study in advanced non-small cell lung cancer (NSCLC) patients was conducted to compare vinorelbine/carboplatin (VC) and gemcitabine/carboplatin (GC) regarding efficacy, health-related quality of life (HRQOL) and toxicity. Chemonaive patients with NSCLC stage IIIB....../IV and WHO performance status 0-2 were eligible. No upper age limit was defined. Patients received vinorelbine 25 mg m(-2) or gemcitabine 1000 mg m(-2) on days 1 and 8 and carboplatin AUC4 on day 1 and three courses with 3-week cycles. HRQOL questionnaires were completed at baseline, before chemotherapy...... and every 8 weeks until 49 weeks. During 14 months, 432 patients were included (VC, n=218; GC, n=214). Median survival was 7.3 vs 6.4 months, 1-year survival 28 vs 30% and 2-year survival 7 vs 7% in the VC and GC arm, respectively (P=0.89). HRQOL, represented by global QOL, nausea/vomiting, dyspnoea...

  6. Advanced ovarian cancer: phase III randomized study of sequential cisplatin-topotecan and carboplatin-paclitaxel vs carboplatin-paclitaxel.

    Science.gov (United States)

    Hoskins, P; Vergote, I; Cervantes, A; Tu, D; Stuart, G; Zola, P; Poveda, A; Provencher, D; Katsaros, D; Ojeda, B; Ghatage, P; Grimshaw, R; Casado, A; Elit, L; Mendiola, C; Sugimoto, A; D'Hondt, V; Oza, A; Germa, J R; Roy, M; Brotto, L; Chen, D; Eisenhauer, E A

    2010-10-20

    Topotecan has single-agent activity in recurrent ovarian cancer. It was evaluated in a novel combination compared with standard frontline therapy. Women aged 75 years or younger with newly diagnosed stage IIB or greater ovarian cancer, Eastern Cooperative Oncology Group Performance Status of 1 or less, were stratified by type of primary surgery and residual disease, treatment center, and age; then randomly assigned to one of the two 21-day intravenous regimens. Patients in arm 1 (n = 409) were administered four cycles of cisplatin 50 mg/m(2) on day 1 and topotecan 0.75 mg/m(2) on days 1-5, then four cycles of paclitaxel 175 mg/m(2) over 3 hours on day 1 followed by carboplatin (area under the curve = 5) on day 1. Patients in arm 2 (n = 410) were given paclitaxel plus carboplatin as in arm 1 for eight cycles. We compared progression-free survival (PFS), overall survival, and cancer antigen-125 normalization rates in the two treatment arms. A stratified log-rank test was used to assess the primary endpoint, PFS. All statistical tests were two-sided. A total of 819 patients were randomly assigned. At baseline, the median age of the patients was 57 years (range = 28-78); 81% had received debulking surgery, and of these, 55% had less than 1 cm residual disease; 66% of patients were stage III and 388 (47.4%) patients had measurable disease. After a median follow-up of 43 months, 650 patients had disease progression or died without documented progression and 406 had died. Patients in arm 1 had more hematological toxicity and hospitalizations than patients in arm 2; PFS was 14.6 months in arm 1 vs 16.2 months in arm 2 (hazard ratio = 1.10, 95% confidence interval = 0.94 to 1.28, P = .25). Among patients with elevated baseline cancer antigen-125, fewer in arm 1 than in arm 2 had levels return to normal by 3 months after random assignment (51.6% vs 63.3%, P = .007) Topotecan and cisplatin, followed by carboplatin and paclitaxel, were more toxic than carboplatin and

  7. Ifosfamide, mesna and epirubicin as second-line chemotherapy in advanced breast cancer.

    Science.gov (United States)

    Kiraz, S; Baltali, E; Güler, N; Barista, I; Benekli, M; Celik, I; Güllü, I H; Kars, A; Tekuzman, G; Firat, D

    1996-08-01

    The ifosfamide, mesna and epirubicin (IMEpi) combination is administered to 16 patients having advanced metastatic breast carcinoma as second-line chemotherapy. We observed complete response in 6%, partial response in 44% (total overall response rate of 50%), stable disease in 12% and progressive disease in the remaining 38% of the patients. The median remission duration in responders was calculated to be 9.6 months. IMEpi regimen had a tolerable toxicity profile including alopecia, nausea and vomiting, microscopic hematuria, leukopenia and neurotoxicity in which serious complications necessitating discontinuation of the chemotherapy were not encountered. It might be concluded that IMEpi chemotherapy combination is an effective alternative among schedules in the management of patients with stage IV breast carcinoma without serious side effects.

  8. Exploiting the synergy between carboplatin and ABT-737 in the treatment of ovarian carcinomas.

    KAUST Repository

    Jain, Harsh Vardhan; Richardson, Alan; Meyer-Hermann, Michael; Byrne, Helen M

    2014-01-01

    that will achieve a predetermined level of tumor growth inhibition, thereby maximizing the synergy between the two drugs. Our simulations suggest that the infusion-duration of each carboplatin dose is a critical parameter, with an 8-hour infusion of carboplatin

  9. Ifosfamide, cisplatin, and etoposide (ICE) in the treatment of advanced non-small cell lung cancer.

    Science.gov (United States)

    Shepherd, F A; Evans, W K; Goss, P E; Latreille, J; Logan, D; Maroun, J; Stewart, D; Warner, E; Paul, K

    1992-02-01

    Forty-seven previously untreated patients with histologically or cytologically proven non-small cell lung cancer were treated with ICE (ifosfamide/cisplatin/etoposide). Patients received ifosfamide 4 g/m2 with mesna uroprotection on day 1, and cisplatin 25 mg/m2/d and etoposide 100 mg/m2/d on days 1, 2, and 3; courses were repeated every 28 days. Premedication with prochlorperazine, dexamethasone, and high-dose metoclopramide was given to prevent nausea; lorazepam was added on days 2 and 3 only. Thirty-four men and 13 women (median age, 60 years) received a total of 146 treatment cycles. One patient had stage IIIA disease, seven had IIIB disease, and 39 had hematogenous metastases. Forty-six patients were evaluable for response and toxicity. One patient suffered a myocardial infarction on day 7 that was judged unrelated to treatment. Two patients suffered early death from toxicity and have been classified as nonresponders. Three patients achieved complete response (median, 42+ weeks) and 14 patients achieved partial response (median, 29+ weeks; range, 10 to 82+), for an overall response rate of 37% (95% confidence limits, 23% to 51%). The median survival of the entire group is 26 weeks (1 to 82+). The median nadir granulocyte count was 0.275 x 10(9)/L (range, 0 to 2.3 x 10(9)/L), and there were 14 episodes (in 11 patients) or neutropenia-associated fever, one of which resulted in death. Seven of these patients had not had the required protocol dose reduction for nadir neutrophil count in the preceding cycle. The median nadir platelet count was 120 x 10(9)/L (range, 13 to 385 x 10(9)/L), and three patients required platelet transfusions. Eleven patients had RBC transfusions. Only ten patients had grade 2 gastrointestinal toxicity. Five patients had microscopic hematuria, and one patient had central nervous system toxicity.

  10. Randomized, phase II trial of pemetrexed and carboplatin with or without enzastaurin versus docetaxel and carboplatin as first-line treatment of patients with stage IIIB/IV non-small cell lung cancer.

    Science.gov (United States)

    Socinski, Mark A; Raju, Robert N; Stinchcombe, Thomas; Kocs, Darren M; Couch, Linda S; Barrera, David; Rousey, Steven R; Choksi, Janak K; Jotte, Robert; Patt, Debra A; Periman, Phillip O; Schlossberg, Howard R; Weissman, Charles H; Wang, Yunfei; Asmar, Lina; Pritchard, Sharon; Bromund, Jane; Peng, Guangbin; Treat, Joseph; Obasaju, Coleman K

    2010-12-01

    Enzastaurin is an oral serine/threonine kinase inhibitor that targets protein kinase C-beta (PKC-β) and the phosphatidylinositol-3-kinase/AKT pathway. This trial assessed pemetrexed-carboplatin ± enzastaurin to docetaxel-carboplatin in advanced non-small cell lung cancer. Patients with stage IIIB (with pleural effusion) or IV non-small cell lung cancer and performance status 0 or 1 were randomized to one of the three arms: (A) pemetrexed 500 mg/m and carboplatin area under the curve 6 once every 3 weeks for up to 6 cycles with a loading dose of enzastaurin 1125 or 1200 mg followed by 500 mg daily until disease progression, (B) the same regimen of pemetrexed-carboplatin without enzastaurin, or (C) docetaxel 75 mg/m and carboplatin area under the curve 6 once every 3 weeks for up to six cycles. The primary end point was time to disease progression (TTP). Between March 2006 and May 2008, 218 patients were randomized. Median TTP was 4.6 months for pemetrexed-carboplatin-enzastaurin, 6.0 months for pemetrexed-carboplatin, and 4.1 months for docetaxel-carboplatin (differences not significant). Median survival was 7.2 months for pemetrexed-carboplatin-enzastaurin, 12.7 months for pemetrexed-carboplatin, and 9.2 months for docetaxel-carboplatin (log-rank p = 0.05). Compared with the other arms, docetaxel-carboplatin was associated with lower rates of grade 3 thrombocytopenia and anemia but a higher rate of grade 3 or 4 febrile neutropenia. There was no difference in TTP between the three arms, but survival was longer with pemetrexed-carboplatin compared with docetaxel-carboplatin. Enzastaurin did not add to the activity of pemetrexed-carboplatin.

  11. Time Savings with Rituximab Subcutaneous Injection versus Rituximab Intravenous Infusion: A Time and Motion Study in Eight Countries

    Science.gov (United States)

    De Cock, Erwin; Kritikou, Persefoni; Sandoval, Mariana; Tao, Sunning; Wiesner, Christof; Carella, Angelo Michele; Ngoh, Charles; Waterboer, Tim

    2016-01-01

    Background Rituximab is a standard treatment for non-Hodgkin lymphoma. The SABRINA trial (NCT01200758) showed that a subcutaneous (SC) rituximab formulation did not compromise efficacy or safety compared with intravenous (IV) infusion. We aimed to quantify active healthcare professional (HCP) time and patient chair time for rituximab SC and IV, including potential time savings. Methods This non-interventional time and motion study was run in eight countries and 30 day oncology units. Rituximab SC data were collected alongside the MabCute trial (NCT01461928); IV data were collected per routine real-world practice. Trained observers recorded active HCP time for pre-specified tasks (stopwatch) and chair time (time of day). A random intercept model was used to analyze active HCP time (by task and for all tasks combined) in the treatment room and drug preparation area, drug administration duration, chair time and patient treatment room time by country and/or across countries. Active HCP and chair time were extrapolated to a patient’s first year of treatment (11 rituximab sessions). Results Mean active HCP time was 35.0 and 23.7 minutes for IV and SC process, respectively (-32%, p time was 27–58%. Absolute reduction in extrapolated active HCP time (first year of treatment) was 1.1–5.2 hours. Mean chair time was 262.1 minutes for IV, including 180.9 minutes infusion duration, vs. 67.3 minutes for SC, including 8.3 minutes SC injection administration (-74%, p time for the first year of treatment was 3.1–5.5 eight-hour days. Conclusions Compared with rituximab IV, rituximab SC was associated with reduced chair time and active HCP time. The latter could be invested in other activities, whereas the former may lead to more available appointments, reducing waiting lists and increasing the efficiency of day oncology units. Trial Registration ClinicalTrials.gov NCT01200758 PMID:27362533

  12. Progression of structural damage is not related to rituximab serum levels in rheumatoid arthritis patients

    NARCIS (Netherlands)

    Boumans, Maria; Teng, Onno; Thurlings, Rogier; Bijlsma, Johannes; Gerlag, Danielle; Huizinga, Tom; Vos, Koen; Stapel, Steven; Wolbink, Gertjan; Tekstra, Janneke; van Laar, Jaap; Tak, Paul P.

    2013-01-01

    The most cost-effective dosing regimen for rituximab treatment in RA is currently unknown. The objective of this study is to determine whether low rituximab serum levels are associated with progression of structural damage in RA patients. Sixty-two RA patients were treated with rituximab in three

  13. The Role of Rituximab in Lymphomas O papel do Rituximab nos linfomas

    Directory of Open Access Journals (Sweden)

    Bertrand Coiffier

    2002-01-01

    Full Text Available Over the last years the treatment of non-Hodgkin's lymphoma underwent a great advance in relation to the diagnosis, classification, high-dose chemotherapy, and hematopoietic stem cell transplantation. Simultaneously with this, there was the development of new drugs and support therapy which enabled an improvement in the evolution and survival of the patients. The use of monoclonal antibodies against cancer cells is an old idea and in this report the results of the role of the anti-CD20-Rituximab in lymphomas is discussed.Nos últimos anos o tratamento do linfomas não Hodgkin apresentou um grande avanço no diagnóstico, classificação, quimioterapia com altas doses e o transplante de células percursoras hematopoiéticas. Simultaneamente houve o desenvolvimento de novas drogas e no tratamento de suporte o que possibilita um avanço na evolução e sobrevida dos pacientes. A idéia do emprego de anticorpos monoclonais no tratamento do câncer é antiga e neste relato são apresentados os resultados e o papel do anti-CD20-Rituximab nos linfomas.

  14. Risk Factors of Hypersensitivity to Carboplatin in Patients with Gynecologic Malignancies.

    Science.gov (United States)

    Tai, Yu-Hsiao; Tai, Yi-Jou; Hsu, Heng-Cheng; Lee, Shu-Ping; Chen, Yun-Yuan; Chiang, Ying-Cheng; Chen, Yu-Li; Chen, Chi-An; Cheng, Wen-Fang

    2017-01-01

    We evaluated the prevalence of and risk factors for hypersensitivity reactions related to carboplatin, which is commonly used to treat gynecological malignancies. All women with pathologically documented ovarian, fallopian tube, or primary peritoneal cancer treated with carboplatin alone or a carboplatin-based combination chemotherapy regimen at a single hospital between January 2006 and December 2013 were retrospectively recruited. We analyzed the incidence, characteristics, risk factors, management, and outcomes of carboplatin-related hypersensitivity reactions among these patients. Among 735 eligible women, 75 (10.2%) experienced a total of 215 carboplatin-related hypersensitivity reaction events. The annual incidence of carboplatin-related hypersensitivity reactions gradually increased from 0.88% in 2006 to 5.42% in 2013. The incidence of carboplatin-related hypersensitivity was higher in patients with advanced stage disease ( P Kruskal-Wallis test), serous and mixed histological types ( P = 0.003, Kruskal-Wallis test), malignant ascites ( P = 0.009, chi-square test), and history of other drug allergy ( P test). Compared to women without hypersensitivity reactions, women who experienced hypersensitivity reactions had a significantly greater median cycle number (12 vs. 6, P test) and dose (6,816 vs. 3,844 mg, P test). The cumulative incidence of carboplatin-related hypersensitivity reactions dramatically increased with >8 cycles or dose >3,500 mg. Therefore, disease severity, histological type, malignant ascites, past drug allergies, and cumulative carboplatin dose are risk factors for carboplatin-related hypersensitivity reactions. Such reactions could potentially be reduced or prevented by slowing the infusion rate and using a desensitization protocol involving anti-allergy medications.

  15. Carboplatin-Induced Bilateral Papilledema: A Case Report

    Directory of Open Access Journals (Sweden)

    N. Fischer

    2009-04-01

    Full Text Available We report on a patient with carboplatin-induced bilateral papilledema, as it was described in the 1970s for cisplatin. Loss of visual accuracy up to full blindness, often loss of color vision and scotomas can be seen as a result of cortical blindness, macula degeneration, retrobulbar neuritis and papilledema. These symptoms are mostly unilateral and initially mild, so that more chemotherapy is given before the diagnosis is made. The symptoms are usually reversible within weeks to months after cessation of the platinum treatment. The therapeutic strategy is stopping the platinum treatment. In addition the empiric use of corticosteroids is suggested.

  16. [Castleman's disease: Rapid desensitization for hypersensitivity reaction to rituximab].

    Science.gov (United States)

    Boin, C; Lambert, S; Thomann, P; Aujoulat, O; Kieffer, P

    2016-06-01

    Rapid desensitization allows secure administration of a drug and is indicated when there is no therapeutic alternative. We report a 49-year-old patient who presented with a hypersensitivity reaction following an infusion of rituximab (375mg/m(2)) in the context of a Castleman's syndrome. After a clinical flare (splenomegaly, adenopathies) despite treatment with tocilizumab, anakinra and valganciclovir, the reintroduction of rituximab was decided, according to the rapid desensitization protocol. Four full dose desensitizations were successfully performed allowing immediate clinical improvement (apyrexia, loss of sweating and lymphadenopathy, splenomegaly partial regression) and biological (negativation of HHV8 viral load, and disappearance of neutropenia, anemia and thrombocytopenia). Rapid desensitization is a promising method for the pursuit of rituximab therapy after a hypersensitivity reaction and should be considered in patients with no acceptable therapeutic alternative. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  17. Multicenter study of environmental contamination with cyclophosphamide, ifosfamide, and methotrexate in 66 Canadian hospitals: A 2016 follow-up study.

    Science.gov (United States)

    Roland, C; Caron, N; Bussières, J F

    2017-08-01

    Oncology workers are occupationally exposed to antineoplastic drugs. This exposure can induce adverse health effects. To reduce their exposure, contamination on surfaces should be kept as low as possible. The main objective of this study was to monitor environmental contamination with cyclophosphamide, ifosfamide, and methotrexate in oncology pharmacy and patient care areas in Canadian centers. The secondary objective was to describe the impact of some factors that may limit contamination. This is a descriptive study. Twelve standardized sites were sampled in each participating center (six in the pharmacy and six in patient care areas). Samples were analyzed for the presence of cyclophosphamide, ifosfamide, and methotrexate by ultra-performance liquid chromatography-tandem mass spectrometry technology. Descriptive statistical analyses were done and results were compared with a Kolmogorov-Smirnov test for independent samples. In 2016, 66 centers participated in this study (66/202, 32.7%). Overall, 43.4% (326/752) of the samples were positive for cyclophosphamide, 13.2% (99/752) for ifosfamide and 6.9% (52/752) for methotrexate. The 75th percentile value of cyclophosphamide surface concentration was 6.8 pg/cm 2 and lower than the limit of detection for ifosfamide and methotrexate. Centers who prepared more antineoplastic drugs per year (p contamination to cyclophosphamide. Environmental surveillance is one part of a comprehensive approach for minimizing hazardous exposures in healthcare. This study highlights a low level of contamination of three hazardous drugs amongst 66 Canadian centers. Regular environmental monitoring is a good practice to maintain contamination as low as reasonably achievable.

  18. Outcome and Toxicity of an Ifosfamide-Based Soft Tissue Sarcoma Treatment Protocol in Children. The Importance of Local Therapy

    Directory of Open Access Journals (Sweden)

    S. Murray Yule

    1998-01-01

    Full Text Available Background. Although the survival of children with soft tissue sarcoma (STS has improved considerably, the outcome of patients with metastatic disease, and those with primary tumours of the extremities or parameningeal sites remains disappointing. We describe the clinical outcome of an ifosfamide-based regimen with local therapy directed only to children who failed to achieve a complete response to initial chemotherapy.

  19. Systemic high-dose methotrexate plus ifosfamide is highly effective for central nervous system (CNS) involvement of lymphoma

    OpenAIRE

    2008-01-01

    Abstract Patients with malignant central nervous system (CNS) involvement of lymphoma have a poor prognosis with intrathecal chemotherapy and radiation. In this paper, we report the results we obtained in such patients by intravenous chemotherapy with high-dose methotrexate and ifosfamide (HDMTX/IFO). The study involved a review of all patients who received HDMTX/IFO for CNS involvement of malignant lymphoma at our hospital. Therapy consisted of 4 g/m2 of MTX (4 h infu...

  20. Favourable response to rituximab by an ocular adnexal primary lymphoma.

    Science.gov (United States)

    Luque Valentin-Fernandez, M L; Alvarez Rodríguez, F; Rodríguez Jiménez, I

    2016-11-01

    A 70-year-old woman who presented with an extranodal marginal zone B-cell lymphoma in lacrimal gland and conjunctiva. Initial treatment with rituximab yielded an immediate good response. Five months later she showed lymphoid proliferation in her contralateral conjunctiva. Although no additional treatment was performed, the patient has been free of systemic symptoms and recurrences. Rituximab is a quite good therapeutic agent in low grade adnexal lymphomas. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. RITUXIMAB: NEW POTENTIALITIES OF THERAPY FOR RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    D E Karateev

    2008-01-01

    Full Text Available Some patients with rheumatoid arthritis (RA are unresponsive or intolerant to both synthetic first-line anti-inflammatory drugs (FLAID and tumor necrosis factor (TNF а inhibitors already included into all the treatment standards . Along with the conventional methods for overcoming drug resistance - switching to another FLAID or another TNF а blocker, the use of biologicals with another mechanism of action rather than suppression of TNF а gives a good account of itself. Prominent among these agents is the anti-B-cell drug rituximab. The new possibilities of the therapy, which open up the use of rituximab in patients with RA, are discussed.

  2. Rituximab as a possible cause of posterior reversible encephalopathy syndrome

    Directory of Open Access Journals (Sweden)

    Ahmed Imran Siddiqi

    2011-09-01

    Full Text Available A 66-year-old woman presented with new onset generalisedtonic-clonic seizures following her first dose ofchemotherapy comprising Rituximab, Cyclophosphamide,Hydroxydaunorubicin, Oncovin and Prednisolone (R-CHOP10 days earlier for non-Hodgkin’s lymphoma. On admission,computed tomography (CT scan of the cranium showed noabnormality. The CT was repeated within 48 hours as thepatient developed status epilepticus and papilledema; therepeat scan showed characteristics of posterior reversibleencephalopathy syndrome (PRES. Association of rituximabwith this condition was suspected as there was norecurrence of PRES after receiving two more cycles of CHOPwithout rituximab. Contrary to previously published casereports, this patient had a delayed clinical presentation.

  3. Combined chemoradiation of cisplatin versus carboplatin in cervical carcinoma: a single institution experience from Thailand

    International Nuclear Information System (INIS)

    Tharavichitkul, Ekkasit; Lorvidhaya, Vicharn; Kamnerdsupaphon, Pimkhuan; Sukthomya, Vimol; Chakrabandhu, Somvilai; Klunklin, Pitchayaponne; Onchan, Wimrak; Supawongwattana, Bongkoch; Pukanhaphan, Nantaka; Galalae, Razvan; Chitapanarux, Imjai

    2016-01-01

    To report the results of combined chemoradiation (CCRT) with cisplatin versus carboplatin in locally advanced cervical carcinoma. From 2009 to 2013, 255 patients with stage IIB-IVA cervical carcinoma, according to FIGO staging were prospectively assigned to be treated with pelvic radiotherapy followed by brachytherapy given concurrently with cisplatin or carboplatin in the treatment of locally advanced cervical cancer. Treatment outcomes and toxicitiy were evaluated. Two-hundred and thirteen patients could be evaluated. At a median follow-up time of 43 months (6–69 months), the 3-year local control, disease-free survival, metastasis-free survival and overall survival rates were 93, 80.8, 85.0 and 87.3 %, respectively. No statistical difference in terms of local control, disease-free survival, metastasis-free survival and overall survival rates between cisplatin and carboplatin treatments was observed in this study. Eighty-six percents of the patients in the carboplatin group could receive more than 4 cycles, while there were only 72 % in the cisplatin group who completed more than 4 cycles (p = 0. 02). In terms of acute toxicity, cisplatin caused significantly more anemia (p = 0.026), neutropenia (p = 0. 044) and nephrotoxicity (p = 0. 031) than carboplatin. No difference in late toxicity was observed in this study. Carboplatin yielded comparable results to cisplatin in concurrent chemo-radiation for locally advanced cervical cancer. In addition, carboplatin was associated with a better compliance rate and was associated with less of anemia, neutropenia and nephrotoxicity

  4. Rituximab (MabThera) til behandling af aktiv reumatoid artritis

    DEFF Research Database (Denmark)

    El Fassi, Daniel; Nielsen, Claus Henrik; Bendtzen, Klaus

    2006-01-01

    Rituximab (RTX) is a murine/human monoclonal antibody to CD20, a protein expressed almost exclusively on human B-lymphocytes. RTX induces rapid and marked B-cell depletion with beneficial clinical effects in 1/3 to 1/2 of rheumatoid arthritis patients. Treatment is given as two iv. infusions with...

  5. Rituximab-Based Treatment, HCV Replication, and Hepatic Flares

    Directory of Open Access Journals (Sweden)

    Evangelista Sagnelli

    2012-01-01

    Full Text Available Rituximab, a chimeric mouse-human monoclonal antibody directed to the CD20 antigen expressed on pre-B lymphocytes and mature lymphocytes, causes a profound B-cell depletion. Due to its peculiar characteristics, this drug has been used to treat oncohaematological diseases, B cell-related autoimmune diseases, rheumatoid arthritis, and, more recently, HCV-associated mixed cryoglobulinaemic vasculitis. Rituximab-based treatment, however, may induce an increased replication of several viruses such as hepatitis B virus, cytomegalovirus, varicella-zoster virus, echovirus, and parvovirus B19. Recent data suggest that rituximab-based chemotherapy induces an increase in HCV expression in hepatic cells, which may become a target for a cell-mediated immune reaction after the withdrawal of treatment and the restoration of the immune control. Only a few small studies have investigated the occurrence of HCV reactivation and an associated hepatic flare in patients with oncohaematological diseases receiving R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. These studies suggest that the hepatic flares are frequently asymptomatic, but life-threatening liver failure occurs in nearly 10% of cases.

  6. Rituximab-based treatment, HCV replication, and hepatic flares.

    Science.gov (United States)

    Sagnelli, Evangelista; Pisaturo, Mariantonietta; Sagnelli, Caterina; Coppola, Nicola

    2012-01-01

    Rituximab, a chimeric mouse-human monoclonal antibody directed to the CD20 antigen expressed on pre-B lymphocytes and mature lymphocytes, causes a profound B-cell depletion. Due to its peculiar characteristics, this drug has been used to treat oncohaematological diseases, B cell-related autoimmune diseases, rheumatoid arthritis, and, more recently, HCV-associated mixed cryoglobulinaemic vasculitis. Rituximab-based treatment, however, may induce an increased replication of several viruses such as hepatitis B virus, cytomegalovirus, varicella-zoster virus, echovirus, and parvovirus B19. Recent data suggest that rituximab-based chemotherapy induces an increase in HCV expression in hepatic cells, which may become a target for a cell-mediated immune reaction after the withdrawal of treatment and the restoration of the immune control. Only a few small studies have investigated the occurrence of HCV reactivation and an associated hepatic flare in patients with oncohaematological diseases receiving R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). These studies suggest that the hepatic flares are frequently asymptomatic, but life-threatening liver failure occurs in nearly 10% of cases.

  7. Microcosting Study of Rituximab Subcutaneous Injection Versus Intravenous Infusion

    NARCIS (Netherlands)

    Mihajloviç, Jovan; Bax, Pieter; van Breugel, Erwin; Blommestein, Hedwig M.; Hoogendoorn, Mels; Hospes, Wobbe; Postma, Maarten J.

    Purpose: The goal of this study is to identify and compare all direct costs of intravenous and subcutaneous rituximab given to patients with diffuse large B-cell lymphoma in the Netherlands.  Methods: Using a prospective, observational, bottom-up microcosting study, we collected primary data on the

  8. Kinetics of Rituximab Excretion into Urine and Peritoneal Fluid in Two Patients with Nephrotic Syndrome

    Directory of Open Access Journals (Sweden)

    Klaus Stahl

    2017-01-01

    Full Text Available Clinical observations suggest that treatment of Rituximab might be less effective in patients with nephrotic range proteinuria when compared to nonnephrotic patients. It is conceivable that the reason for this is that significant amounts of Rituximab might be lost in the urine in a nephrotic patient and that these patients require a repeated or higher dosage. However, this has not been systematically studied. In this case report we describe two different patients with nephrotic range proteinuria receiving Rituximab. The first patient received Rituximab for therapy resistant cryoglobulinemic membranoproliferative glomerulonephritis and the other for second line treatment of Felty’s syndrome. We employed flow cytometry to determine the amount of Rituximab excretion in both urine and peritoneal fluid specimens in these patients following administration of Rituximab. We found that a significant amount of Rituximab is lost from the circulation by excretion into the urine. Furthermore we saw a close correlation of the excretion of Rituximab to the excretion of IgG molecules suggesting selectivity of proteinuria as the determining factor of Rituximab excretion. Further larger scale clinical studies could have the potential to evaluate an optimal cut-off value of IgG urinary loss before a possible administration of Rituximab therefore contributing to a more individualized treatment approach in patients with nonselective and nephrotic range proteinuria.

  9. Kinetics of Rituximab Excretion into Urine and Peritoneal Fluid in Two Patients with Nephrotic Syndrome.

    Science.gov (United States)

    Stahl, Klaus; Duong, Michelle; Schwarz, Anke; Wagner, A D; Haller, Hermann; Schiffer, Mario; Jacobs, Roland

    2017-01-01

    Clinical observations suggest that treatment of Rituximab might be less effective in patients with nephrotic range proteinuria when compared to nonnephrotic patients. It is conceivable that the reason for this is that significant amounts of Rituximab might be lost in the urine in a nephrotic patient and that these patients require a repeated or higher dosage. However, this has not been systematically studied. In this case report we describe two different patients with nephrotic range proteinuria receiving Rituximab. The first patient received Rituximab for therapy resistant cryoglobulinemic membranoproliferative glomerulonephritis and the other for second line treatment of Felty's syndrome. We employed flow cytometry to determine the amount of Rituximab excretion in both urine and peritoneal fluid specimens in these patients following administration of Rituximab. We found that a significant amount of Rituximab is lost from the circulation by excretion into the urine. Furthermore we saw a close correlation of the excretion of Rituximab to the excretion of IgG molecules suggesting selectivity of proteinuria as the determining factor of Rituximab excretion. Further larger scale clinical studies could have the potential to evaluate an optimal cut-off value of IgG urinary loss before a possible administration of Rituximab therefore contributing to a more individualized treatment approach in patients with nonselective and nephrotic range proteinuria.

  10. A retrospective study on the management of patients with rituximab refractory follicular lymphoma.

    Science.gov (United States)

    Solal-Céligny, Philippe; Leconte, Pierre; Bardet, Aurélie; Hernandez, Juana; Troussard, Xavier

    2018-01-01

    Given that there are currently no clear recommendations regarding therapeutic options for rituximab refractory/relapsed follicular lymphoma patients, this study aimed to describe the real-life management of patients with refractory follicular lymphoma after systemic rituximab-containing regimens (rFL), and rFL patient characteristics. In this retrospective, national, multicentre study, descriptive analyses were mainly performed according to rituximab-containing regimen at rFL diagnosis [rituximab monotherapy (R-MONO), rituximab + chemotherapy (R-COMBO), and ongoing rituximab maintenance (R-MAINTAIN)]. The 459 analysed patients experienced rituximab-refractoriness between October 2013 and September 2015: R-MONO: 58 (13%), R-COMBO: 197 (43%), R-MAINTAIN: 204 (44%). Post-refractoriness strategies were heterogeneous: idelalisib ± rituximab (22%), without anti-lymphoma treatment (21%), rituximab-chemotherapy (21%) and stem cell transplantation (18%). Rituximab was continued in combination in 41% of cases. Chosen strategies varied according to patient age (without anti-lymphoma treatment: 28% of patients if ≥65 years vs. 12% if management and for the design of clinical trials in these patients. © 2017 John Wiley & Sons Ltd.

  11. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial

    DEFF Research Database (Denmark)

    Salles, Gilles; Seymour, John Francis; Offner, Fritz

    2011-01-01

    Patients with follicular lymphoma can have long survival times, but disease progression typically occurs 3-5 years after initial treatment. We assessed the potential benefit of 2 years of rituximab maintenance after first-line treatment in patients with follicular lymphoma receiving a rituximab...... plus chemotherapy regimen....

  12. Weekly Carboplatin Reduces Toxicity During Synchronous Chemoradiotherapy for Merkel Cell Carcinoma of Skin

    International Nuclear Information System (INIS)

    Poulsen, Michael; Walpole, Euan; Harvey, Jennifer; Dickie, Graeme; O'Brien, Peter; Keller, Jacqui; Tpcony, Lee; Rischin, Danny

    2008-01-01

    Purpose: The toxicity of radiotherapy (RT) combined with weekly carboplatin and adjuvant carboplatin and etoposide was prospectively assessed in a group of patients with high-risk Stage I and II Merkel cell carcinoma of the skin. This regimen was compared with the Trans-Tasman Radiation Oncology Group 96:07 study, which used identical eligibility criteria but carboplatin and etoposide every 3 weeks during RT. Patients and Methods: Patients were eligible if they had disease localized to the primary site and lymph nodes, with high-risk features. RT was delivered to the primary site and lymph nodes to a dose of 50 Gy and weekly carboplatin (area under the curve of 2) was given during RT. This was followed by three cycles of carboplatin and etoposide. A total of 18 patients were entered into the study, and their data were compared with the data from 53 patients entered into the Trans-Tasman Radiation Oncology Group 96:07 study. Results: Involved lymph nodes (Stage II) were present in 14 patients (77%). Treatment was completed as planned in 16 patients. The weekly carboplatin dose was delivered in 17 patients, and 15 were able to complete all three cycles of adjuvant carboplatin and etoposide. Grade 3 and 4 neutrophil toxicity occurred in 7 patients, but no cases of febrile neutropenia developed. Compared with the Trans-Tasman Radiation Oncology Group 96:07 protocol (19 of 53 cases of febrile neutropenia), the reduction in the febrile neutropenia rate (p = 0.003) and decrease in Grade 3 skin toxicity (p = 0.006) were highly statistically significant. Conclusion: The results of our study have shown that weekly carboplatin at this dosage is a safe way to deliver synchronous chemotherapy during RT for MCC and results in a marked reduction of febrile neutropenia and Grade 3 skin toxicity compared with the three weekly regimen

  13. [Circadian rhythm in susceptibility of mice to the anti-tumor drug carboplatin].

    Science.gov (United States)

    Lu, X H; Yin, L J

    1994-12-01

    The platinum-containing compounds has become a major chemical agent in the treatment of cancer. A circadian rhythm in the susceptibility of rodents and human being to cisplatin has been demonstrated, the maximal tolerance being found in the animal's active phase. Carboplatin is a second generation analog. Two studies were performed on mice with carboplatin under 12:12 light dark cycle to study its chronotoxicity and chronoeffectiveness. In study I, single intraperitoneal injection of 192mg/kg (LD50) carboplatin was given to four groups of mice at four different circadian stage. It was found that at 50% the overall mortality of mice, there was a mortality difference of 28% for mice receiving the drug at 9 a.m. to 71% for mice receiving drug at 9 p.m. It demonstrated that carboplatin was better tolerated in the animal's early sleep phase. In study II, S180 tumor-bearing mice were treated with 50mg/kg of carboplatin. The longest mean survival time and the lowest marrow toxicity occurred in the group which received the drug at the beginning of the sleep phase. It showed that the susceptibility of mice to carboplatin is circadian stage dependent. These data clearly demonstrate that, by timing the administration of drugs according to body rhythms, such as the host susceptibility-resistance rhythm to a drug, one can gain a therapeutic advantage over an approach which ignores such rhythms.

  14. Eficiency of different doses of rituximab in rheumatoid arthritis.

    Science.gov (United States)

    Mena-Vázquez, Natalia; Manrique-Arija, Sara; Ureña-Garnica, Inmaculada; Romero-Barco, Carmen M; Jiménez-Núñez, Francisco G; Coret, Virginia; Irigoyen-Oyarzábal, María Victoria; Fernández-Nebro, Antonio

    2016-01-01

    Evaluate the effectiveness, cost and safety of rituximab in patients with rheumatoid arthritis (RA) depending on the dose used. Retrospective observational study conducted on 52 patients with RA treated with at least one dose of rituximab for 135.3 patient-years were included. Three treatment groups were obtained: (G1) First course and following two 1g infusions separated by 15 days; (G2) First course 2 infusions of 1g followed by 2 infusions of 500mg; (G3) First course and followed by 2 infusions of 500mg separated by 15 days. Re-treatments were administered on-demand according to the clinical activity. The retention time (Log-Rank), retreats and adverse events rates (incidence rate ratio) and treatment costs per patient-month of rituximab were analysed by groups. Group 2 showed a better cost-effectiveness ratio than group 1, as it was associated with a longer retention of rituximab (mean [95% CI] 65.7 [60.8 to 70.7] months vs 33.5 [22.7 to 44.3]; P<.001) and a lower rate of severe adverse events with only a slight increase in the rate of retreatment (courses/patient-year [95% CI] 1.66 [1.39 to 1.93] vs. 1.01 [0.69 to 1.34]; P=.005), and in the costs (median/patient-month, €484.89 vs. €473.45). Although group 3 was €41.20/patient-month cheaper than group 2, it was associated with a higher rate of re-treatments and shorter retention of rituximab (P<.001). The use of full-dose rituximab at onset, followed by reduced doses in successive courses administered on-demand retreatment may be the most cost-effective option. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  15. Sequential rituximab and omalizumab for the treatment of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome).

    Science.gov (United States)

    Aguirre-Valencia, David; Posso-Osorio, Iván; Bravo, Juan-Carlos; Bonilla-Abadía, Fabio; Tobón, Gabriel J; Cañas, Carlos A

    2017-09-01

    Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome (CSS), is a small vessel vasculitis associated with eosinophilia and asthma. Clinical manifestations commonly seen in patients presenting with EGPA range from upper airway and lung involvement to neurological, cardiac, cutaneous, and renal manifestations. Treatment for severe presentations includes steroids, cyclophosphamide, plasmapheresis, and recently, rituximab. Rituximab is associated with a good response in the treatment of vasculitis, but a variable response for the control of allergic symptoms. Here, we report a 16-year-old female patient with severe EGPA (gastrointestinal and cutaneous vasculitis, rhinitis and asthma) refractory to conventional treatment. She was treated with rituximab, which enabled rapid control of the vasculitis component of the disease, but there was no response to rhinitis and asthma. Additionally, she developed severe bronchospasm during rituximab infusion. Sequential rituximab and omalizumab were initiated, leading to remission of all manifestations of vasculitis, rhinitis, and asthma, in addition to bronchospasm related to rituximab infusion.

  16. Single-dose Rituximab Therapy for Refractory Idiopathic Membranous Nephropathy: A Single-center Experience

    OpenAIRE

    Katsuno, Takayuki; Ozaki, Takenori; Kim, Hangsoo; Kato, Noritoshi; Suzuki, Yasuhiro; Akiyama, Shinichi; Ishimoto, Takuji; Kosugi, Tomoki; Tsuboi, Naotake; Ito, Yasuhiko; Maruyama, Shoichi

    2017-01-01

    To date, a recognized treatment for refractory membranous nephropathy (MN) has not been established. Recently, several reports have indicated the efficacy of rituximab as a novel treatment option. However, only a few published accounts exist of rituximab therapy for idiopathic MN (IMN) in the Asian population. We present the cases of three IMN patients who were treated with single-dose rituximab after they showed no response to conventional therapies, including corticosteroids, cyclosporine, ...

  17. Intralesional rituximab in primary conjunctival follicular lymphoma relapsed.

    Science.gov (United States)

    Rodríguez Villa, S; Ruiz Rodríguez, M J; Vargas Pabón, M

    2017-07-01

    A 49-year-old woman experienced a local relapse of a primary follicular lymphoma (FL) of the conjunctiva. She received 4 weekly intra-lesional injections followed by 6 monthly injections of rituximab (6mg/ml). A clinical response was achieved after first injection. No adverse ocular event or signs of lymphoma relapse were seen after 10 months of follow-up. Intralesional administration of rituximab for treating primary FL of the conjunctiva was an effective and safe therapeutic option; therefore it could be an alternative to other conventional treatments, such as radiotherapy or chemotherapy. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Ifosfamide and vinorelbine as first-line chemotherapy for metastatic breast cancer.

    Science.gov (United States)

    Leone, B A; Vallejo, C T; Romero, A O; Perez, J E; Cuevas, M A; Lacava, J A; Sabatini, C L; Dominguez, M E; Rodriguez, R; Barbieri, M R; Ortiz, E H; Salvadori, M A; Acuña, L A; Acuña, J M; Langhi, M J; Amato, S; Machiavelli, M R

    1996-11-01

    To evaluate the efficacy and toxicity of the combination of ifosfamide (IFX) and vinorelbine (VNB) as first-line chemotherapy in metastatic breast cancer (MBC). Between August 1993 and August 1995, 45 patients with untreated MBC received a regimen that consisted of IFX 2 g/m2 by 1-hour intravenous (i.v.) infusion on days 1 to 3, mesna 400 mg/m2 by i.v. bolus at hours 0 and 4 and 800 mg/m2 orally at hour 8 on days 1 to 3, and VNB 35 mg/m2 by 20-minute i.v. infusion on days 1 and 15. Courses were repeated every 28 days. During the first course only, half-dose VNB (17.5 mg/m2) was administered on days 8 and 22. The median age was 53 years and 30 patients (67%) were postmenopausal. Dominant sites of disease were soft tissue in nine patients, bone in seven, and visceral in 29. Objective responses (ORs) were recorded in 25 of 43 assessable patients (58%; 95% confidence interval, 43% to 73%). Complete remissions (CRs) occurred in six patients (14%) and partial remissions (PRs) in 19 (44%). No change (NC) was recorded in 10 patients (23%) and progressive disease (PD) in eight patients (19%). The median time to treatment failure was 12 months and the median survival duration 19 months. Myelosuppression was the limiting toxicity, mainly leukopenia in 32 patients (74%). In contrast, anemia and thrombocytopenia were mild. Other significant toxicities included peripheral neuropathy in nine patients (21%), constipation in 15 (35%), and myalgias in 11 (26%). IFX/VNB is an active combination against MBC with moderate toxicity and deserves further evaluation.

  19. Neoadjuvant chemotherapy with ifosfamide, cisplatin, and vinorelbine in advanced squamous cell carcinoma of the cervix.

    Science.gov (United States)

    Vallejo, C T; Pérez, J E; Domínguez, M E; Leone, B A; Machiavelli, M R; Lacava, J A; Romero, A O; Ortiz, E H; Grasso, S; Amato, S; Rodríguez, R; Barbieri, M; Romero Acuña, J; Focaccia, G; Suttora, G; Scenna, M; Boughen, J M; Romero Acuña, L A; Langhi, M J

    2000-10-01

    A phase II trial was performed to assess the efficacy and toxicity of a combination of ifosfamide (IFX), cisplatin (CDDP), and vinorelbine (VNB) as neoadjuvant chemotherapy (NAC) for untreated advanced cervical carcinoma (ACC). Between October 1995 and February 1998, 40 patients were entered in this study. Their median age was 43 years (range: 23-74 years). International Federation of Gynecology and Obstetrics stages were: IIB, 23; IIIB, 13; and IVA, 4. Therapy consisted of: IFX 2,000 mg/m2 1-hour (H) IV infusion days 1 to 3; 2-mercaptoethanesulfonic acid sodium salt (mesna) 400 mg/m2 IV bolus H 0 and 4, and 800 mg/m2 by mouth H 8, days 1 to 3; VNB 25 mg/m2 20-minute IV infusion days 1 and 8; and CDDP 75 mg/m2 IV day 3. Cycles were repeated every 28 days for a total of three courses. Both staging and response (R) assessment were performed by a multidisciplinary team. An objective response (OR) was observed in 24 of 40 patients (60%; 95% confidence interval, 45-75%). Four patients achieved complete response (CR) (10%); 20 partial response (50%); 12 patients stable disease (30%); and 4 progressive disease (10%). Eight of 24 patients (33%) with OR underwent radical surgery, and histologic CRs were recorded in 2 of them. The remaining patients received definitive radiotherapy after NAC. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 32 patients (80%) and was grade III or IV in 14 patients (36%). Peripheral neuropathy occurred in 9 patients (22%), whereas myalgias occurred in 10 (25%). Constipation was observed in 9 patients (23%); emesis occurred in 35 patients (88%). There were no therapy-related deaths. These results indicate that IFX/CDDP/VNB is an active combination for ACC with moderate toxicity. Implementation of this regimen in a multimodal therapy protocol deserves further study.

  20. Ifosfamide and mitoxantrone as first-line chemotherapy for metastatic breast cancer.

    Science.gov (United States)

    Perez, J E; Machiavelli, M; Leone, B A; Romero, A; Rabinovich, M G; Vallejo, C T; Bianco, A; Lacava, J A; Rodriguez, R; Cuevas, M A

    1993-03-01

    A phase II trial was performed to evaluate the efficacy and toxicity of a combination of ifosfamide (IFX) and mitoxantrone (MXN) as first-line chemotherapy for metastatic breast carcinoma. Between January 1990 and August 1991, 48 patients with metastatic breast cancer were entered onto the study. Therapy consisted of IFX 2 g/m2 given as a 1-hour intravenous (IV) infusion on days 1 to 3; mesna 400 mg/m2 as an IV bolus immediately before and 4 hours after IFX administration and 2,000 mg orally 8 hours after IFX administration on days 1 to 3; and MXN 12 mg/m2 as an i.v. bolus on day 3. Cycles were repeated every 21 days until progressive disease (PD) or severe toxicity developed. One patient was considered not assessable for response. Objective regression (OR) was observed in 28 of 47 patients (60%; 95% confidence interval, 46% to 74%). Six patients (13%) had a complete response (CR) and 22 (47%) had a partial response (PR). The median time to treatment failure for the whole group was 9 months (range, 1 to 28); median survival was 19 months (range, 2 to 28). There were no treatment-related deaths. The limiting toxicity was myelosuppression. Leukopenia occurred in 37 patients (77%) and was grade 3 or 4 in 19 patients (40%). Nausea and vomiting were observed in 38 patients (80%), mucositis in 16 patients (33%), and grade 2 hematuria in two patients (4%). Eight patients (16%) developed mild neurotoxicity. The combination of IFX plus MXN is an active regimen against metastatic breast cancer with moderate toxicity that deserves further evaluation.

  1. Ifosfamide and vinorelbine as first-line chemotherapy for advanced non-small cell lung carcinoma.

    Science.gov (United States)

    Vallejo, C; Romero, A; Perez, J; Cuevas, M; Lacava, J; Sabatini, C; Dominguez, M; Rodriguez, R; Barbieri, M; Romero Acuña, L; Romero Acuña, J; Langhi, M; Amato, S; Salvadori, M; Ortiz, E; Machiavelli, M; Leone, B

    1996-12-01

    We evaluated the efficacy and toxicity of the novel combination of ifosfamide (IFX) and vinorelbine (VNB) as first-line chemotherapy in patients with stage IIIB and IV non-small cell lung cancer (NSCLC). Between March 1993 and November 1994, 44 patients (17 stage IIIB; 27 stage IV) received a regimen consisting of IFX, 2 g/m2 in a 1-h infusion, days 1-3; mesna, 400 mg/m2 in an i.v. bolus at hours 0 and 4 and 800 mg orally at hour 8, days 1-3; and VNB, 35 mg/ m2 in a 20-min infusion, days 1 and 15. During the first course only, a half dose of VNB (17.5 mg/m2) was administered on days 8 and 22. Courses were repeated every 28 days. Forty patients were fully evaluable for response, and 44 were assessable for toxicity. Objective regression was recorded in 13 of 40 patients (33%). No patient achieved a complete response. Thirteen patients presented a partial response (33%); 17 (42%) had no change; and progressive disease was observed in 10 (25%). The median duration of response was 10 months, and the median time to treatment failure for the whole group was 4 months. Median survival was 11 months. The dose-limiting toxic effect was myelosuppression. Leukopenia occurred in 25 patients (57%) and was grade 3 or 4 in 8 patients (18%). Twelve patients (27%) developed peripheral neurotoxicity, while five had mild IFX-induced CNS toxicity. Phlebitis was observed in 15 of 30 patients (50%) who did not have central implantable venous systems. The IFX-VNB combination exhibited an activity against NSCLC that was among the highest reported for non-cisplatin-containing regimens, with a toxicity profile that was easily managed.

  2. Rapid-Infusion Rituximab in Lymphoma Treatment: 2-Year Experience in a Single Institution

    Science.gov (United States)

    Atay, Sevcan; Barista, Ibrahim; Gundogdu, Fatma; Akgedik, Kiymet; Arpaci, Afey

    2012-01-01

    Purpose: Rituximab is a chimeric anti-CD20 monoclonal antibody. We aimed to explore the safety and tolerability of rapid infusion rituximab, (over 90 minutes) in patients with non-Hodgkin's lymphoma at Hacettepe University Department of Medical Oncology. Patients and Methods: Adult patients diagnosed with non-Hodgkin's lymphoma who were to receive rituximab were included in the study. The schedule of administration for cycle 1 was unaltered and delivered according to the product monograph. All subsequent cycles were administered over a total infusion time of 90 minutes (20% of the dose in the first 30 minutes, then the remaining 80% over 60 minutes, total dose delivered in 500 mL). All patients were observed for infusion-related reactions during the rituximab infusion, and vital signs were recorded every 15 minutes. Results: From July 2006 to December 2008, 75 patients with non-Hodgkin's lymphoma were treated with rituximab-based chemotherapy. A total of 372 infusions were administered. The majority of patients were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, or rituximab only. The 90-minute rituximab infusion schedule was well tolerated, with no grade 3 or 4 infusion-related adverse events observed. Conclusion: A rapid infusion rituximab over 90 minutes is well tolerated and safe when administered as the second and subsequent infusions in the course of therapy. PMID:22942806

  3. Rapid-infusion rituximab in lymphoma treatment: 2-year experience in a single institution.

    Science.gov (United States)

    Atay, Sevcan; Barista, Ibrahim; Gundogdu, Fatma; Akgedik, Kiymet; Arpaci, Afey

    2012-05-01

    Rituximab is a chimeric anti-CD20 monoclonal antibody. We aimed to explore the safety and tolerability of rapid infusion rituximab, (over 90 minutes) in patients with non-Hodgkin's lymphoma at Hacettepe University Department of Medical Oncology. Adult patients diagnosed with non-Hodgkin's lymphoma who were to receive rituximab were included in the study. The schedule of administration for cycle 1 was unaltered and delivered according to the product monograph. All subsequent cycles were administered over a total infusion time of 90 minutes (20% of the dose in the first 30 minutes, then the remaining 80% over 60 minutes, total dose delivered in 500 mL). All patients were observed for infusion-related reactions during the rituximab infusion, and vital signs were recorded every 15 minutes. From July 2006 to December 2008, 75 patients with non-Hodgkin's lymphoma were treated with rituximab-based chemotherapy. A total of 372 infusions were administered. The majority of patients were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, or rituximab only. The 90-minute rituximab infusion schedule was well tolerated, with no grade 3 or 4 infusion-related adverse events observed. A rapid infusion rituximab over 90 minutes is well tolerated and safe when administered as the second and subsequent infusions in the course of therapy.

  4. Treatment of rheumatoid arthritis with biologic DMARDS (Rituximab and Etanercept).

    Science.gov (United States)

    Gashi, Afrim A; Rexhepi, Sylejman; Berisha, Idriz; Kryeziu, Avni; Ismaili, Jehona; Krasniqi, Gezim

    2014-01-01

    To determine efficacy and safety of treatment with Rituximab and Etanercept plus Methotrexate in patients with active Rheumatoid Arthritis (RA), who had an inadequate response to nonbiologic DMARDS therapies and to explore the pharmacogenetics and pharmacodynamics of Rituximab and Etanercept in our populations. Study was done at Rheumatology Clinic of University Clinical Centre in Prishtina during 2009-2011 years. We evaluated primary efficacy and safety at 24 weeks in patients enrolled in the study of long-term efficacy of Rituximab and Etanercept. Patients with active Rheumatoid Arthritis and an inadequate response to 1 or more non biologic DMARDS were randomized to receive intravenous Rituximab (1 course consisting of 2 infusions of 1.000 mg each -one group, and Etanercept 25 mg twice weekly -second group, but both groups with background MTX. The primary efficacy end point was a response on the ACR 20%, improvement criteria at 24 weeks, Secondary end points were responses on the ACR 50 and ACR 70, improvement criteria, the DAS 28, and EULAR response criteria at 24 weeks. During our investigations we treated 20 patients, 15 females and 5 males, in the treated group with RTX and 13 patients 8 females and 5 males in the treated group with ETN. Patients of group 1 and group 2 were of ages 37-69 years old and 19-69 years old (average 47-44) Most of the patients belong in 2nd and 3rd functional stage according to Steinbrocker. All ACR response parameters were significantly improved in RTX treated patients who also had clinically meaningful improvement in fatigue, disability and quality of life. Patients showed a trend less progression in radiographic end points. Most adverse events occurred with the first RTX infusion and were mild to moderate severity. At 24 weeks, a single course of RTX and ETN provided significant and clinically meaningful improvements in disease activity in patients with active, longstanding RA who had an inadequate response to 1 or more

  5. Rituximab: a novel treatment for refractory Riedel’s thyroiditis

    Directory of Open Access Journals (Sweden)

    Leanne Hunt

    2018-02-01

    Full Text Available This case report reviews the rare condition of Riedel’s thyroiditis via a patient case. The report highlights the difficulties that one may encounter when managing such a case in regards to patient symptoms, side effects of medications and the relapsing nature of the condition. The case report also highlights novel treatment in the treatment of Riedel’s thyroiditis, rituximab, how this works and the resolution of symptoms that we have achieved with our patient on this treatment.

  6. Rituximab does not reset defective early B cell tolerance checkpoints

    Science.gov (United States)

    Chamberlain, Nicolas; Massad, Christopher; Oe, Tyler; Cantaert, Tineke; Herold, Kevan C.; Meffre, Eric

    2015-01-01

    Type 1 diabetes (T1D) patients show abnormalities in early B cell tolerance checkpoints, resulting in the accumulation of large numbers of autoreactive B cells in their blood. Treatment with rituximab, an anti-CD20 mAb that depletes B cells, has been shown to preserve β cell function in T1D patients and improve other autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. However, it remains largely unknown how anti–B cell therapy thwarts autoimmunity in these pathologies. Here, we analyzed the reactivity of Abs expressed by single, mature naive B cells from 4 patients with T1D before and 52 weeks after treatment to determine whether rituximab resets early B cell tolerance checkpoints. We found that anti–B cell therapy did not alter the frequencies of autoreactive and polyreactive B cells, which remained elevated in the blood of all patients after rituximab treatment. Moreover, the limited proliferative history of autoreactive B cells after treatment revealed that these clones were newly generated B cells and not self-reactive B cells that had escaped depletion and repopulated the periphery through homeostatic expansion. We conclude that anti–B cell therapy may provide a temporary dampening of autoimmune processes through B cell depletion. However, repletion with autoreactive B cells may explain the relapse that occurs in many autoimmune patients after anti–B cell therapy. PMID:26642366

  7. [Rituximab: a new therapeutic alternative in Grave's disease].

    Science.gov (United States)

    Tello-Winniczuk, Nina; Díaz-Jouanen, Efraín

    2011-01-01

    Graves' disease is the most frequent cause of hyperthyroidism, affecting mainly young aged women, with an etiology of autoimmune basis. One of its manifestations, Graves' ophthalmopathy whose pathophysiology is unknown, represents one of the greatest therapeutic challenges in these patients, because they require aggressive treatment with steroids and multiple subsequent reconstructive surgeries in certain cases. It also represents a high burden to the health system. Drugs targeting B cells have been very effective for many autoimmune diseases. Rituximab is a murine humanized monoclonal antibody against CD20 + cells currently being studied in various autoimmune diseases including Graves' disease. The objective of this paper is to expose possible mechanisms by which rituximab could act in both hyperthyroidism and ophthalmopathy of Graves' disease, as well as the experience with its use acquired so far. The employment of rituximab in recently diagnosed patients or with mild ophthalmopathy is questionable with the evidence available today however, we think that it may have a role in refractory cases or those who have a contraindication for steroid use.

  8. Carboplatin enhances the production and persistence of radiation-induced DNA single-strand breaks

    International Nuclear Information System (INIS)

    Yang, L.; Douple, E.B.; O'Hara, J.A.; Wang, H.J.

    1995-01-01

    Fluorometric analysis of DNA unwinding and alkaline elution were used to investigate the production and persistence of DNA single-strand breaks (SSBs) in Chinese hamster V79 and xrs-5 cells treated with the chemotherapeutic agent carboplatin in combination with radiation. Carboplatin was administered to cells before irradiation in hypoxic conditions, or the drug was added immediately after irradiation during the postirradiation recovery period in air. The results of DNA unwinding studies suggest that carboplatin enhances the production of radiation-induced SSBs in hypoxic V79 cells and xrs-5 cells by a factor of 1.86 and 1.83, respectively, when combined with radiation compared to the SSBs produced by irradiation alone. Carboplatin alone did not produce a measureable number of SSBs. Alkaline elution profiles also indicated that the rate of elution of SSBs was higher in cells treated with the carboplatin is present after irradiation and during the postirradiation recovery period, the rejoining of radiation-induced SSBs by a factor of 1.46 in V79 cells with 20 Gy irradiation and by a factor of 2.02 in xrs-5 cells with 20 Gy irradiation. When carboplatin is present after irradiation and during the postirradiation recovery period, the rejoining of radiation-induced SSBs is inhibited during this postirradiation incubation period (radiopotentiation) with a relative inhibition factor at 1 h postirradiation of 1.25 in V79 cells and 1.15 in xrs-5 cells. An increased production and persistence of SSBs resulting from the interaction of carboplatin with radiation may be an important step in the mechanism responsible for the potentiated cell killing previously from studies in animal tumors and in cultured cells. 31 refs., 7 figs

  9. Doxorubicin and ifosfamide combination chemotherapy in previously treated acute leukemia in adults: a Southwest Oncology Group pilot study.

    Science.gov (United States)

    Ryan, D H; Bickers, J N; Vial, R H; Hussein, K; Bottomley, R; Hewlett, J S; Wilson, H E; Stuckey, W J

    1980-01-01

    The Southwest Oncology Group did a limited institutional pilot study of the combination of doxorubicin and ifosfamide in the treatment of previously treated adult patients with acute leukemia. Thirty-four patients received one or two courses of the combination. All patients had received prior chemotherapy and 32 had received prior anthracycline chemotherapy. Three patients died before their responses could be fully evaluated. Fourteen patients achieved complete remission (41%) and one patient achieved partial remission. The complete remission rate was 27% for patients with acute myeloblastic leukemia (myelomonoblastic leukemia, monoblastic leukemia, and erythroleukemia) and 89% for patients with acute lymphocytic and undifferentiated leukemia (ALL). Toxic effects included severe hematologic reactions in 33 of 34 patients, hematuria in six patients, altered sensorium in one patient, and congestive heart failure in one patient. The safety of the combination was established and toxic side effects of this therapy were tolerable. The 89% complete remission rate for previously treated patients with ALL suggests that the combination of doxorubicin and ifosfamide may be particularly effective in ALL.

  10. Ifosfamide in previously untreated disseminated neuroblastoma. Results of Study 3A of the European Neuroblastoma Study Group.

    Science.gov (United States)

    Kellie, S J; De Kraker, J; Lilleyman, J S; Bowman, A; Pritchard, J

    1988-05-01

    A prospective study of the effectiveness of ifosfamide as a single agent in the management of previously untreated patients with Evans stage IV neuroblastoma was undertaken. Eighteen children aged more than 1 year were treated with ifosfamide (IFX) 3 g/m2 daily for 2 days immediately after diagnosis and 3 weeks later. Treatment was continued with combination chemotherapy using vincristine, cyclophosphamide, cisplatinum and etoposide (OPEC) or a variant. Mesna (2-mercaptoethane sulphonate) was given to all patients during IFX treatment to prevent urotoxicity. Eight of the 18 patients (44%) responded to IFX. Nine had greater than 66% reduction in baseline tumor volume. Of 15 evaluable patients with raised pre-treatment urinary catecholamine excretion, six (40%) achieved greater than 50% reduction in pretreatment levels. Two of 10 patients evaluable for bone marrow response had complete clearance. Toxicity was mild in all patients. Upon completing 'first line' therapy, only four patients (22%) achieved a good partial remission (GPR) or complete response (CR). Median survival was 11 months. There was a lower rate of attaining GPR and shortened median survival in patients receiving phase II IFX before OPEC or variant, compared to patients with similar pre-treatment characteristics treated with OPEC from diagnosis in an earlier study.

  11. Investigating the heterogeneity of alkylating agents' efficacy and toxicity between sexes: A systematic review and meta-analysis of randomized trials comparing cyclophosphamide and ifosfamide (MAIAGE study)

    NARCIS (Netherlands)

    Fresneau, Brice; Hackshaw, A.; Hawkins, D. S.; Paulussen, M.; Anderson, J. R.; Judson, I.; Litière, S.; Dirksen, U.; Lewis, I.; van den Berg, H.; Gaspar, N.; Gelderblom, H.; Whelan, J.; Boddy, A. V.; Wheatley, K.; Pignon, J. P.; de Vathaire, F.; Le Deley, M. C.; Le Teuff, G.

    2017-01-01

    A marginal interaction between sex and the type of alkylating agent was observed for event-free survival in the Euro-EWING99-R1 randomized controlled trial (RCT) comparing cyclophosphamide and ifosfamide in Ewing sarcoma. To further evaluate this interaction, we performed an individual patient data

  12. Population pharmacokinetics of ifosfamide and its 2-and 3-dechloroethylated and 4-hydroxylated metabolites in resistant small-cell lung cancer patients

    NARCIS (Netherlands)

    Kerbusch, T; vanPutten, JWG; Groen, HJM; Huitema, ADR; Mathot, RAA; Beijnen, JH

    The aim of this study was to develop a population pharmacokinetic model that could describe the pharmacokinetics of ifosfamide, 2- and 3-dechloroethylifosfamide and 4-hydroxyifosfamide, and calculate their plasma exposure and urinary excretion. A group of 14 patients with small-cell lung cancer

  13. Paclitaxel, ifosfamide and cisplatin with granulocyte colony-stimulating factor or recombinant human interleukin 3 and granulocyte colony-stimulating factor in ovarian cancer : A feasibility study

    NARCIS (Netherlands)

    Veldhuis, GJ; Willemse, PHB; Beijnen, JH; Piersma, H; vanderGraaf, WTA; deVries, EGE; Boonstra, J.

    1997-01-01

    The tolerability and efficacy of four courses of paclitaxel and ifosfamide plus cisplatin every 3 weeks was evaluated in patients with residual or refractory ovarian cancer. Additionally, supportive haematological effects of recombinant human interleukin 3 (rhIL-3) and recombinant human granulocyte

  14. IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin

    Directory of Open Access Journals (Sweden)

    Zhi-Yong Wang

    2016-01-01

    Full Text Available Recent studies suggest that tumor-associated macrophage-produced IL-6 is an important mediator within the tumor microenvironment that promotes tumor growth. The activation of IL-6/STAT3 axis has been associated with chemoresistance and poor prognosis of a variety of cancers including colorectal carcinoma and thus serves as a potential immunotherapeutic target for cancer treatment. However, it is not fully understood whether anticytokine therapy could reverse chemosensitivity and enhance the suppressive effect of chemotherapy on tumor growth. In this study, we aimed to investigate the effect of IL-6 inhibition therapy on the antitumor effect of carboplatin. Enhanced expression of IL-6 and activation of STAT3 were observed in human colorectal carcinoma samples compared to normal colorectal tissue, with higher levels of IL-6/STAT3 in low grade carcinomas. Treatment of carboplatin (CBP dose-dependently increased IL-6 production and STAT3 activation in human colorectal LoVo cells. Blockade of IL-6 with neutralizing antibody enhanced chemosensitivity of LoVo cells to carboplatin as evidenced by increased cell apoptosis. IL-6 blockade abolished carboplatin-induced STAT3 activation. IL-6 blockade and carboplatin synergistically reduced cyclin D1 expression and enhanced caspase-3 activity in LoVo cells. Our results suggest that inhibition of IL-6 may enhance chemosensitivity of colon cancers with overactive STAT3 to platinum agents.

  15. Achieving a satisfactory clinical and biochemical response in antiphospholipid syndrome and severe thrombocytopenia with rituximab: two case reports.

    Science.gov (United States)

    Gamoudi, Donia; Cutajar, Melanie; Gamoudi, Nadia; Camilleri, David James; Gatt, Alex

    2017-06-01

    In AP syndrome (APS) with severe thrombocytopenia, rituximab represents a unique drug which can balance the effect of bleeding and thrombosis. By reducing the production of autoantibodies, rituximab can simultaneously raise the platelets and reduce the chance of thrombosis by suppressing APL antibodies. Rituximab can supersede splenectomy as second-line therapy in similar patients.

  16. Successful pregnancy after rituximab in a women with recurrent in vitro fertilisation failures and anti-phospholipid antibody positive.

    LENUS (Irish Health Repository)

    Ng, C T

    2012-02-01

    We report a case of successful pregnancy after rituximab in a patient with a history of in vitro fertilisation (IVF) failures and positive anti-cardiolipin antibody (ACA). Following a course of rituximab, her ACA became negative and she successfully conceived with IVF treatment. This is the first case in literature describing the use of rituximab therapy in this clinical scenario.

  17. A New Method to Quantify Ifosfamide Blood Levels Using Dried Blood Spots and UPLC-MS/MS in Paediatric Patients with Embryonic Solid Tumours.

    Directory of Open Access Journals (Sweden)

    Luz-María Torres

    Full Text Available Ifosfamide blood concentrations are necessary to monitor its therapeutic response, avoiding any adverse effect. We developed and validated an analytical method by UPLC-MS/MS to quantify ifosfamide in dried blood spots (DBS. Blood samples were collected on Whatman 903® filter paper cards. Five 3 mm disks were punched out from each dried blood spot. Acetonitrile and ethyl acetate were used for drug extraction. Chromatographic separation was carried out in an Acquity UPLC equipment with a BEH-C18 column, 2.1 x 100 mm, 1.7 μm (Waters®. The mobile phase consisted in 5 mM ammonium formate and methanol:acetonitrile (40:48:12 v/v/v at 0.2 mL/min. LC-MS/MS detection was done by ESI+ and multiple reaction mode monitoring, ionic transitions were m/z1+ 260.99 > 91.63 for ifosfamide and 261.00 > 139.90 for cyclophosphamide (internal standard. This method was linear within a 100-10000 ng/mL range and it was accurate, precise and selective. Ifosfamide samples in DBS were stable for up to 52 days at -80°C. The procedure was tested in 14 patients, ages 1 month to 17 years (9 males and 5 females, with embryonic tumours treated with ifosfamide, alone or combined, at a public tertiary referral hospital. Ifosfamide blood levels ranged from 11.1 to 39.7 μmol/L at 12 hours after the last infusion, while 24-hour levels ranged from 0.7-19.7 μmol/L. The median at 12 hours was 19.5 μmol/L (Q25 14.4-Q75 29.0 and 3.8 μmol/L (Q25 1.5-Q75 9.9 at 24 hours, p<0.001. This method is feasible to determine ifosfamide plasma levels in paediatric patients.

  18. Progressive multifocal leukoencephalopathy in rituximab-treated rheumatic diseases: a rare event.

    Science.gov (United States)

    Berger, Joseph R; Malik, Vineeta; Lacey, Stuart; Brunetta, Paul; Lehane, Patricia B

    2018-03-05

    This report assesses the observed risk of PML in patients treated with the anti-CD20 monoclonal antibody rituximab in the regulatory authority-approved autoimmune indications rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA). This was a cumulative analysis of confirmed PML cases in patients receiving rituximab for RA or GPA/MPA from both spontaneous reports and clinical trial sources, as captured in the manufacturer global company safety and clinical databases. Overall reporting rates were calculated and patient case details were summarized. As of 17 November 2015, there were nine confirmed PML cases among patients who had received rituximab for RA and two for GPA. Corresponding estimated reporting rates were 2.56 per 100,000 patients with RA (estimated exposure ≈ 351,396 patients) and < 1 per 10,000 patients with GPA/MPA (estimated exposure 40,000-50,000 patients). In all cases, patients had ≥ 1 potential risk factor for PML independent of rituximab treatment. In the RA population, the estimated reporting rate of PML generally remained stable and low since 2009 despite increasing rituximab exposure. There was no pattern of latency from time of rituximab initiation to PML development and no association of PML with the number of rituximab courses. Global post-marketing safety and clinical trial data demonstrated that the occurrence of PML is very rare among rituximab-treated patients with RA or GPA/MPA and has remained stable over time.

  19. Rituximab para la oftalmopatía asociada a la tiroides

    Directory of Open Access Journals (Sweden)

    Neda Minakaran

    2013-09-01

    Conclusiones de los autores: Actualmente no hay pruebas suficientes para apoyar la administración de rituximab en los pacientes con OAT. Se necesitan ECA grandes que investiguen rituximab versus placebo o corticosteroides en pacientes con OAT activo para hacer valoraciones adecuadas sobre la eficacia y la seguridad de este tratamiento nuevo para esta enfermedad.

  20. Micro-costing study of rituximab subcutaneous injection versus intravenous infusion in dutch setting

    NARCIS (Netherlands)

    Mihajlović, J.; Bax, P.; Van Breugel, E.; Blommestein, H.M.; Hoogendoorn, M.; Hospes, W.; Postma, M.J.

    2015-01-01

    Background: Rituximab for subcutaneous (SC) administration has recently been approved for use in common forms of diffuse large B-cell lymphoma (DLBCL). This form of rituximab is supplied in ready-to-use vials that do not require individual dose adjustment. It is expected that SC-injection will

  1. CUTANEOUS SQUAMOUS CELL CARCINOMA IN A PANTHER CHAMELEON (FURCIFER PARDALIS) AND TREATMENT WITH CARBOPLATIN IMPLANTABLE BEADS.

    Science.gov (United States)

    Johnson, James G; Naples, Lisa M; Chu, Caroline; Kinsel, Michael J; Flower, Jennifer E; Van Bonn, William G

    2016-09-01

    A 3-yr-old male panther chameleon (Furcifer pardalis) presented with bilateral raised crusted skin lesions along the lateral body wall that were found to be carcinoma in situ and squamous cell carcinoma. Similar lesions later developed on the caudal body wall and tail. A subcutaneous implantable carboplatin bead was placed in the first squamous cell carcinoma lesion identified. Additional new lesions sampled were also found to be squamous cell carcinomas, and viral polymerase chain reaction was negative for papillomaviruses and herpesviruses. Significant skin loss would have resulted from excision of all the lesions, so treatment with only carboplatin beads was used. No adverse effects were observed. Lesions not excised that were treated with beads decreased in size. This is the first description of cutaneous squamous cell carcinoma and treatment with carboplatin implantable beads in a panther chameleon.

  2. Muscle myeloid type I interferon gene expression may predict therapeutic responses to rituximab in myositis patients.

    Science.gov (United States)

    Nagaraju, Kanneboyina; Ghimbovschi, Svetlana; Rayavarapu, Sree; Phadke, Aditi; Rider, Lisa G; Hoffman, Eric P; Miller, Frederick W

    2016-09-01

    To identify muscle gene expression patterns that predict rituximab responses and assess the effects of rituximab on muscle gene expression in PM and DM. In an attempt to understand the molecular mechanism of response and non-response to rituximab therapy, we performed Affymetrix gene expression array analyses on muscle biopsy specimens taken before and after rituximab therapy from eight PM and two DM patients in the Rituximab in Myositis study. We also analysed selected muscle-infiltrating cell phenotypes in these biopsies by immunohistochemical staining. Partek and Ingenuity pathway analyses assessed the gene pathways and networks. Myeloid type I IFN signature genes were expressed at higher levels at baseline in the skeletal muscle of rituximab responders than in non-responders, whereas classic non-myeloid IFN signature genes were expressed at higher levels in non-responders at baseline. Also, rituximab responders have a greater reduction of the myeloid and non-myeloid type I IFN signatures than non-responders. The decrease in the type I IFN signature following administration of rituximab may be associated with the decreases in muscle-infiltrating CD19(+) B cells and CD68(+) macrophages in responders. Our findings suggest that high levels of myeloid type I IFN gene expression in skeletal muscle predict responses to rituximab in PM/DM and that rituximab responders also have a greater decrease in the expression of these genes. These data add further evidence to recent studies defining the type I IFN signature as both a predictor of therapeutic responses and a biomarker of myositis disease activity. Published by Oxford University Press on behalf British Society for Rheumatology 2016. This work is written by US Government employees and is in the public domain in the US.

  3. Exploiting the synergy between carboplatin and ABT-737 in the treatment of ovarian carcinomas.

    KAUST Repository

    Jain, Harsh Vardhan

    2014-01-06

    Platinum drug-resistance in ovarian cancers mediated by anti-apoptotic proteins such as Bcl-xL is a major factor contributing to the chemotherapeutic resistance of recurrent disease. Consequently, concurrent inhibition of Bcl-xL in combination with chemotherapy may improve treatment outcomes for patients. Here, we develop a mathematical model to investigate the potential of combination therapy with ABT-737, a small molecule inhibitor of Bcl-xL, and carboplatin, a platinum-based drug, on a simulated tumor xenograft. The model is calibrated against in vivo experimental data, wherein xenografts established in mice were treated with ABT-737 and/or carboplatin on a fixed periodic schedule. The validated model is used to predict the minimum drug load that will achieve a predetermined level of tumor growth inhibition, thereby maximizing the synergy between the two drugs. Our simulations suggest that the infusion-duration of each carboplatin dose is a critical parameter, with an 8-hour infusion of carboplatin given weekly combined with a daily bolus dose of ABT-737 predicted to minimize residual disease. The potential of combination therapy to prevent or delay the onset of carboplatin-resistance is also investigated. When resistance is acquired as a result of aberrant DNA-damage repair in cells treated with carboplatin, drug delivery schedules that induce tumor remission with even low doses of combination therapy can be identified. Intrinsic resistance due to pre-existing cohorts of resistant cells precludes tumor regression, but dosing strategies that extend disease-free survival periods can still be identified. These results highlight the potential of our model to accelerate the development of novel therapeutics such as BH3 mimetics.

  4. A randomized phase II study of carboplatin plus pegylated liposomal doxorubicin versus carboplatin plus paclitaxel in platinum sensitive ovarian cancer patients: a Hellenic Cooperative Oncology Group study

    Directory of Open Access Journals (Sweden)

    Briasoulis Evangelos

    2010-01-01

    Full Text Available Abstract Background Platinum-based combinations are the standard second-line treatment for platinum-sensitive ovarian cancer (OC. This randomized phase II study was undertaken in order to compare the combination of carboplatin and pegylated liposomal doxorubicin (LD with carboplatin and paclitaxel (CP in this setting. Methods Patients with histologically confirmed recurrent OC, at the time of or more than 6 months after platinum-based chemotherapy, were randomized to six cycles of CP (carboplatin AUC5 + paclitaxel 175 mg/m2, d1q21 or CLD (carboplatin AUC5 + pegylated LD 45 mg/m2, d1q28. Results A total of 189 eligible patients (CP 96, CLD 93, with a median age of 63 years, median Performance Status (PS 0 and a median platinum free interval (PFI of 16.5 months, entered the study. Discontinuation due to toxicity was higher in the CP patients (13.5% versus 3%, P = 0.016. The overall response rate was similar: CP 58% versus CLD 51%, P = 0.309 (Complete Response; CR 34% versus 23% and there was no statistical difference in time-to-progression (TTP or overall survival (OS; TTP 10.8 months CP versus 11.8 CLD, P = 0.904; OS 29.4 months CP versus 24.7 CLD, P = 0.454. No toxic deaths were recorded. Neutropenia was the most commonly seen severe toxicity (CP 30% versus CLD 35%. More frequent in CLD were severe thrombocytopenia (11% versus 2%, P = 0.016, skin toxicity and Palmar-plantar erythrodysesthesia (PPE grade 1-2 (38% versus 9%, PP = 0.029, 20% versus 5%, P = 0.003. PS and PFI were independent prognostic factors for TTP and OS. Conclusions The combination of pegylated LD with carboplatin is effective, showing less neurotoxicity and alopecia than paclitaxel-carboplatin. It thus warrants a further phase III evaluation as an alternative treatment option for platinum-sensitive OC patients. Trial Registration Australian New Zealand Clinical Trials Registry: ACTRN12609000436279

  5. Refractory myasthenia gravis - clinical profile, comorbidities and response to rituximab.

    Science.gov (United States)

    Sudulagunta, Sreenivasa Rao; Sepehrar, Mona; Sodalagunta, Mahesh Babu; Settikere Nataraju, Aravinda; Bangalore Raja, Shiva Kumar; Sathyanarayana, Deepak; Gummadi, Siddharth; Burra, Hemanth Kumar

    2016-01-01

    Introduction: Myasthenia gravis (MG) is an antibody mediated autoimmune neuromuscular disorder characterized by fatigable muscle weakness. A proportion of myasthenia gravis patients are classified as refractory due to non responsiveness to conventional treatment. This retrospective study was done to evaluate clinical profile, epidemiological, laboratory, and features of patients with MG and mode of management using rituximab and complications. Methods: Data of myasthenia gravis patients admitted or presented to outpatient department (previous medical records) with MG between January 2008 and January 2016 were included. A total of 512 patients fulfilled the clinical and diagnostic criteria of myasthenia gravis of which 76 patients met the diagnostic certainty for refractory myasthenia gravis and were evaluated. Results: Out of 76 refractory MG patients, 53 (69.73%) patients fulfilled all the three defined criteria. The median age of onset of the refractory MG group was 36 years with a range of 27-53 years. In our study 25 patients (32.89%) belonged to the age group of 21-30 years. Anti-MuSK antibodies were positive in 8 non-refractory MG patients (2.06%) and 36 refractory MG patients (47.36%). Mean HbA 1C was found to be 8.6±2.33. The dose of administered prednisone decreased by a mean of 59.7% ( p =3.3x10 -8 ) to 94.6% ( p =2.2x10 -14 ) after the third cycle of rituximab treatment. Conclusion: The refractory MG patients are most commonly female with an early age of onset, anti-MuSK antibodies, and thymomas. Refractory MG patients have higher prevalence and poor control (HbA 1C >8%) of diabetes mellitus and dyslipidemia probably due to increased steroid usage. Rituximab is very efficient in treatment of refractory MG with adverse effects being low.

  6. Vorinostat increases carboplatin and paclitaxel activity in non-small cell lung cancer cells

    OpenAIRE

    Owonikoko, Taofeek K.; Ramalingam, Suresh S.; Kanterewicz, Beatriz; Balius, Trent; Belani, Chandra P.; Hershberger, Pamela A.

    2010-01-01

    We observed a 53% response rate in non-small cell lung cancer (NSCLC) patients treated with vorinostat plus paclitaxel/carboplatin in a Phase I trial. Studies were undertaken to investigate the mechanism (s) underlying this activity. Growth inhibition was assessed in NSCLC cells by MTT assay after 72 h of continuous drug exposure. Vorinostat (1 µM) inhibited growth by: 17±7% in A549, 28±6% in 128-88T, 39±8% in Calu1, and 41±7% in 201T cells. Vorinostat addition to carboplatin or paclitaxel le...

  7. Study on the Preparation and Quality Control of 131I-Rituximab and 90Y-Rituximab for Non-Hodgkin-Lymphoma Therapy

    International Nuclear Information System (INIS)

    NguyenThi Thu; Duong Van Dong; Vo Thi Cam Hoa; Chu Van Khoa; Bui Van Cuong; Pham Ngoc Dien; Mai Phuoc Tho; Nguyen Thanh Binh; Dang Ho Hong Quang; Phan Quoc Thong; Mai Trong Khoa

    2009-01-01

    In recent years, radioimmunotherapy (RIT) has become a highly promising oncologic therapeutic modality with established clinically efficacy, particularly in the therapy of haematological malignancies. Rituximab, a chimeric monoclonal antibody targeted against the cluster designation (CD20) antigen was labelled with 131 I used in the treatment of B cell non Hodgkin's Lymphoma (NHL), B cell leukemia. In this study, the monoclonal antibody Rituximab was labelled with 131 I using chloramin T method (ChT). The optimized ChT concentration for the oxidation of 185 MBq of Na 131 I solution and 750□g of Rituximab was 20□g/20□l. The reaction time was 3 minutes at room temperature. The labeling reaction has stopped using sodiummetabisulphite (SMB). Labelling efficacy was controlled by ITLC. The reaction mixture was purified through the Sephadex G-25 PD10 Pharmacia column. The collected 131 I-Rituximab was filtered through a 0.20'm milipore sterile filter. The radiochemical labeling yield was more than 95%. Radiochemical purity of the radiopharmaceutical after purification was more than 99%. The product has been passed the test for sterility, bacterial endotoxins, to be sufficiency invivo and invitro stable and stability after labeling. 131 I-Rituximab was used for radioimmunoscintigraphy biodistribution in clinical. Rituximab was bound to the DTPA chelating agent using Hnatowich methods. Cyclic anhydride DTPA (cDTPAa, 0.1 mg/ml) was dissolved in chloroform and was degassed under a stream of nitrogen for 30 min. Rituximab solution in 0.05M bicarbonate buffer was immediately added and mixed for one minute at room temperature. The antibody Rituximab at different concentration (5mg/ml and 10mg/ml) was coupled with the cyclic DTPA anhydride, at molar ratios (cDTPAa : Rituximab) of 1:1, 3:1, 5:1, 10:1 and 20:1. The conjugation DTPA-Rituximab mixture was labelled with Y- 90 and purified and determinate of coupling efficiency. Coupling efficiency of cDTPA - to - Rituximab molar

  8. Preparation & in vitro evaluation of ⁹⁰Y-DOTA-rituximab.

    Science.gov (United States)

    Kameswaran, Mythili; Pandey, Usha; Dash, Ashutosh; Samuel, Grace; Venkatesh, Meera

    2016-01-01

    Radioimmunotherapy is extensively being used for the treatment of non-Hodgkin's lymphoma (NHL). Use of rituximab, a chimeric anti-CD20 antibody directed against the CD20 antigen in combination with suitable beta emitters is expected to result in good treatment response by its cross-fire and bystander effects. The present work involves the conjugation of p-isothiocyanatobenzyl DOTA (p-SCN-Bn-DOTA) to rituximab, its radiolabelling with [90] Y and in vitro and in vivo evaluation to determine its potential as a radioimmunotherapeutic agent. Rituximab was conjugated with p-SCN-Bn-DOTA at 1:1 antibody: DOTA molar ratio. The number of DOTA molecules linked to one molecule of rituximab was determined by radioassay and spectroscopic assay. Radiolabelling of rituximab with 90 Y was carried out and its in vitro stability was evaluated. In vitro cell binding studies were carried out in Raji cells expressing CD20 antigen. Biodistribution studies were carried out in normal Swiss mice. Using both radioassay and spectroscopic method, it was determined that about five molecules of DOTA were linked to rituximab. Radiolabelling of the rituximab conjugate with [90] Y and subsequent purification on PD-10 column gave a product with radiochemical purity (RCP) > 98 per cent which was retained at > 90 per cent up to 72 h when stored at 37°C. In vitro cell binding experiments of 90 Y-DOTA-rituximab with Raji cells exhibited specific binding of 20.7 ± 0.1 per cent with [90] Y-DOTA-rituximab which reduced to 15.5 ± 0.2 per cent when incubated with cold rituximab. The equilibrium constant K d for 90 Y-DOTA-Rituximab was determined to be 3.38 nM. Radiolabelled antibody showed clearance via hepatobiliary and renal routes and activity in tibia was found to be quite low indicating in vivo stability of [90] Y-DOTA-rituximab. p-SCN-Bn-DOTA was conjugated with rituximab and radiolabelling with 90 Y was carried out. In vitro studies carried out in Raji cells showed the specificity of the

  9. Ecotoxicity and genotoxicity of cyclophosphamide, ifosfamide, their metabolites/transformation products and their mixtures

    International Nuclear Information System (INIS)

    Česen, Marjeta; Eleršek, Tina; Novak, Matjaž; Žegura, Bojana; Kosjek, Tina; Filipič, Metka; Heath, Ester

    2016-01-01

    Cyclophosphamide (CP) and ifosfamide (IF) are commonly used cytostatic drugs that repress cell division by interaction with DNA. The present study investigates the ecotoxicity and genotoxicity of CP, IF, their human metabolites/transformation products (TPs) carboxy-cyclophosphamide (CPCOOH), keto-cyclophosphamide (ketoCP) and N-dechloroethyl-cyclophosphamide (NdCP) as individual compounds and as mixture. The two parent compounds (CP and IF), at concentrations up to 320 mg L −1 , were non-toxic towards the alga Pseudokirchneriella subcapitata and cyanobacterium Synecococcus leopoliensis. Further ecotoxicity studies of metabolites/TPs and a mixture of parent compounds and metabolites/TPs performed in cyanobacteria S. leopoliensis, showed that only CPCOOH (EC 50  = 17.1 mg L −1 ) was toxic. The measured toxicity (EC 50  = 11.5 mg L −1 ) of the mixture was lower from the toxicity predicted by concentration addition model (EC 50  = 21.1 mg L −1 ) indicating potentiating effects of the CPCOOH toxicity. The SOS/umuC assay with Salmonella typhimurium revealed genotoxic activity of CP, CPCOOH and the mixture in the presence of S9 metabolic activation. Only CPCOOH was genotoxic also in the absence of metabolic activation indicating that this compound is a direct acting genotoxin. This finding is of particular importance as in the environment such compounds can directly affect DNA of non-target organisms and also explains toxicity of CPCOOH against cyanobacteria S. leopoliensis. The degradation study with UV irradiation of samples containing CP and IF showed efficient degradation of both compounds and remained non-toxic towards S. leopoliensis, suggesting that no stable TPs with adverse effects were formed. To our knowledge, this is the first study describing the ecotoxicity and genotoxicity of the commonly used cytostatics CP and IF, their known metabolites/TPs and their mixture. The results indicate the importance of toxicological evaluation and

  10. [Clinical efficacy and adverse effects of taxol plus carboplatin or gemcitabine plus carboplatin in patients with advanced non-small-cell lung carcinoma].

    Science.gov (United States)

    Wang, Xiao-Yun; Zhao, Yu-Liang

    2010-12-21

    To observe the clinical efficacy and adverse effects of taxol plus carboplatin (TP) or gemcitabine plus carboplatin (GP) in patients with advanced non-small-cell lung carcinoma. A total of 86 patients with advanced non-small-cell lung carcinoma with a histologically confirmed diagnosis at our department were treated with at least two cycles of drug therapy according to the WHO standard. There were 43 cases in TP group and 43 cases in GP group. TP group: taxol 150 mg/m(2), d1, carboplatin 300 mg/m(2) in d1; GP group: gemcitabine 1000 mg/m(2), 30 min, d1, 8, carboplatin 300 mg/m(2) in d1, 3 weeks a cycle. The efficacy and side effects were analyzed after two cycles of chemotherapy. When TP and GP groups were compared, the effective rate was 44.2% vs 39.5%; disease control rate (CR + PR + SD): 81.4% vs 74.4%; median time to progress (TTP): 4.6 vs 4.5 months; medium survivals: 8.6 vs 8.8 months; 1-year survival rates: 17.2% vs 18.1%; 2-year survival rates: 8% vs 10%. The statistic analysis showed that the two groups had no significant difference. The main cytotoxicities of GP and TP groups were predominantly thrombocytopenia and leucopenia respectively. The two groups had no significant statistical difference. The incidences of allergen, alopecia and peripheral neurotoxicity were higher in the TP group. The two groups had statistical difference. Tolerance was excellent in both groups. The therapeutic effect and tolerance are excellent for advanced non-small cell lung carcinoma. The efficacy and survival rate of two groups show no statistical difference.

  11. Molecular mechanisms of resistance to Rituximab and pharmacologic strategies for its circumvention.

    Science.gov (United States)

    Stolz, Claudia; Schuler, Martin

    2009-06-01

    The introduction of Rituximab has greatly improved therapeutic options for patients with B-cell non-Hodgkin lymphoma (B-NHL). However, a substantial fraction of patients with aggressive B-NHL fails first-line therapy, and most patients with relapsing indolent B-NHL eventually acquire Rituximab resistance. Molecular understanding of the underlying mechanisms facilitates the development of pharmacologic strategies to overcome resistance. Rituximab exerts its activity on CD20-expressing B-cells by indirect and direct effector mechanisms. Indirect mechanisms are complement-dependent cytotoxicity (CDC), and antibody-dependent cell-mediated cytotoxicity (ADCC). Direct activities, such as growth inhibition, induction of apoptosis and chemosensitisation, have been reported, but are less defined. Moreover, the relative contribution of CDC, ADCC and direct mechanisms to the activity of Rituximab in vivo is unclear. Down-regulation of CD20 and expression of complement inhibitors have been described as escape mechanisms in B-NHL. Recent reports suggest that deregulated phosphoinositide-3-kinase (PI3K)/Akt, mitogen-activated kinases (MAPK) and nuclear-factor kappaB (NF-kappaB), as well as up-regulation of anti-apoptotic proteins may determine the efficacy of Rituximab to kill B-NHL cells in vitro and in vivo. The latter signalling pathways are attractive targets for pharmacologic modulation of resistance to Rituximab. With the advent of new inhibitors and antibodies, rationally designed clinical trials addressing Rituximab resistance are feasible.

  12. Study On The Preparation Of 90Y-DTPA-Rituximab For Non-Hodgkin Lymphoma Treatment

    International Nuclear Information System (INIS)

    Nguyen Thi Thu; Duong Van Dong; Bui Van Cuong; Vo Thi Cam Hoa; Chu Van Khoa; Phan Quoc Thong

    2011-01-01

    Yttrium is one of the most useful radionuclides for radioimmunotherapeutic applications, especially labelling with monoclonal antibodies. Rituximab was bound to the DTPA chelating agent using Hnatowich methods. Cyclic anhydride DTPA (cDTPAa, 0.1 mg/ml) was dissolved in chloroform and was degassed under a stream of nitrogen for 30 minutes. Rituximab solution in 0.05 M bicarbonate buffer was immediately added and mixed for one minute at room temperature. The antibody Rituximab at different concentration (5 mg/ml and 10 mg/ml) was coupled with the cDTPAa, at molar ratios (cDTPAa : Rituximab) of 1:1, 3:1, 5:1, 10:1 and 20:1. The conjugation of DTPA-Rituximab mixture was labelled with Y-90, then using Sephadex G25 in order to determine coupling efficiency. Coupling efficiency at a 3:1 mole ratio was 70%. After purification, the conjugation DTPA-Rituximab was labeled with Y-90 in 0.5 M acetate buffer, pH 5, at room temperature. The labeling yield was about 99%. The radiochemical purity of 90 Y-DTPA-Rituximab was more than 98 % which determined by ITLC in 0.1 M acetate at pH 6 as mobile phase. The radiopharmaceuticals have been test for sterility, apyrogenicity and biodistribution. This is a potential radiopharmaceutical for clinical application in therapeutic Non Hodgkin Lymphoma treatments. (author)

  13. Neurophysiological and clinical responses to rituximab in patients with anti-MAG polyneuropathy.

    Science.gov (United States)

    Zara, Gabriella; Zambello, Renato; Ermani, M

    2011-12-01

    Rituximab treatment has shown clinical improvement in anti-myelin associated glycoprotein (MAG) polyneuropathy. We analyzed scores of clinical scales and the most sensitive electrophysiological parameters before and after immunomodulating treatment with rituximab in a group of patients affected by anti-MAG demyelinating polyneuropathy. Clinical scores, the percentage of CD20 B-lymphocytes, anti-MAG antibody titers and electrophysiological data in 7 patients with anti-MAG polyneuropathy were analyzed. The patients were examined before a cycle with rituximab, 6, 12 and 24 months after the end of the treatment. Two patients were treated with rituximab additional cycles and re-evaluated 48 months after the first treatment. There were no evident correlation between anti-MAG serum antibody titers or clinical scales and electrodiagnostic data. Significant decrease in the proportion of CD20 B-lymphocytes was observed. Significant anti-MAG antibodies titers reduction was detected after re-treatment. At follow-up, pinprik sensation and two point discrimination presented a significant improvement compared with the score before treatment. In our patients, rituximab did not improve any electrophysiological data. No correlation with anti-MAG serum antibodies course was found. With rituximab only pin sensibility improved. Rituximab re-treatment significantly reduces anti-MAG serum antibodies titers but improves only small fibers sensibility. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  14. Comparative effectiveness and safety of nab-paclitaxel plus carboplatin vs gemcitabine plus carboplatin in first-line treatment of advanced squamous cell non-small cell lung cancer in a US community oncology setting

    Directory of Open Access Journals (Sweden)

    Mudad R

    2017-10-01

    Full Text Available Raja Mudad,1 Manish B Patel,2 Sandra Margunato-Debay,2 David Garofalo,3 Lincy S Lal4 1University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, Hollywood, FL, USA; 2Celgene Corporation, Summit, NJ, USA; 3Cardinal Health, Dallas, TX, USA; 4University of Texas School of Public Health, Houston, TX, USA Introduction: Real-world comparative effectiveness, safety, and supportive care use of nab-paclitaxel plus carboplatin vs gemcitabine plus platinum were analyzed in patients with advanced or metastatic squamous cell non-small cell lung cancer (NSCLC.Materials and methods: Patients who received ≥ 1 cycle of first-line nab-paclitaxel plus carboplatin or gemcitabine plus platinum were identified from the Navigating Cancer database. Clinical effectiveness endpoints included overall survival (OS and time to treatment discontinuation (TTD. Other endpoints included safety and utilization of supportive care. Cox proportional hazards models were used to control for potential confounding effects of baseline characteristics.Results: In total, 193 patients were included (nab-paclitaxel plus carboplatin, n = 61; gemcitabine plus platinum, n = 132. Baseline characteristics were generally similar between the cohorts. Patients receiving nab-paclitaxel plus carboplatin had a significantly longer OS than those receiving gemcitabine plus carboplatin (median, 12.8 vs 9.0 months; P = 0.03. However, the adjusted difference was not statistically significant (adjusted HR 1.55; 95% CI, 0.99–2.42; P = 0.06. nab-Paclitaxel plus carboplatin-treated patients had significantly longer TTD than gemcitabine plus carboplatin-treated patients (median, 4.3 vs 3.5 months; P = 0.03; adjusted HR 1.39; 95% CI, 1.01–1.90; P = 0.04. Grade 3 or 4 anemia and neutropenia were significantly lower in patients treated with nab-paclitaxel plus carboplatin vs gemcitabine plus carboplatin. Nausea and neuropathy (grade not specified were significantly higher in the

  15. Comparative Pharmacokinetics and Allometric Scaling of Carboplatin in Different Avian Species.

    Directory of Open Access Journals (Sweden)

    Gunther Antonissen

    Full Text Available The use of chemotherapeutics as a possible treatment strategy in avian oncology is steadily increasing over the last years. Despite this, literature reports regarding dosing strategies and pharmacokinetic behaviour of chemotherapeutics in avian species are lacking. The aim of the present study was to investigate the pharmacokinetics of carboplatin in a representative species of the order of Galliformes, Anseriformes, Columbiformes and Psittaciformes. Eight chickens, ducks and pigeons and twenty-eight parakeets were administered carboplatin intravenously (5 mg/kg body weight. A specific and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for quantification of the free carboplatin in plasma of the four birds species (limit of quantification: 20 ng/mL for chicken and duck, 50 ng/mL for pigeon and 100 ng/mL for parakeets. Non-compartmental pharmacokinetic analysis and allometric scaling demonstrated a significant correlation (R² = 0.9769 between body weight (BW and elimination half-life (T1/2el. T1/2el ranged from 0.41 h in parakeets (BW: 61 ± 8 g to 1.16 h chickens (BW: 1909 ± 619 g. T1/2el is a good parameter for dose optimization of carboplatin in other avian species, since also the previously reported T1/2el in cockatoos (average BW: 769 ± 68 g of 1.00 h corresponds to the results obtained in the present study.

  16. Evaluation of formulas using the serum creatinine level to calculate the optimal dosage of carboplatin.

    Science.gov (United States)

    van Warmerdam, L J; Rodenhuis, S; ten Bokkel Huinink, W W; Maes, R A; Beijnen, J H

    1996-01-01

    Carboplatin is a chemotherapeutic agent frequently used in the treatment of various malignancies. An individual dosing strategy has been recommended to yield the most optimal exposure, expressed as the area under the concentration-time curve (AUC). The formula developed by Calvert et al. (dose = target-AUC x [GFR + 25]) can be used to achieve this. However, due to the inconvenient [51Cr]-ethylenediamine-tetraacetic acid ([51Cr]-EDTA)-based measurement of the glomerular filtration rate (GFR), its application in the clinic has thus far been limited. Chatelut and co-workers have recently proposed a formula to estimate carboplatin clearance using the serum creatinine concentration. We retrospectively tested the Chatelut equation and the Calvert formula using either the creatinine clearance based on 24-h urine collection or the creatinine clearance based on the formula of Cockcroft and Gault. The latter equations were shown to predict the carboplatin clearance reasonably well, although systematic overprediction and underprediction occurred. However, the formula proposed by Chatelut and co-workers had no significant bias and was precise. It is proposed that this formula be used to calculate the optimal carboplatin dosage after prospective validation has been performed.

  17. Delivery of carboplatin by carbon-based nanocontainers mediates increased cancer cell death

    Energy Technology Data Exchange (ETDEWEB)

    Arlt, M; Fuessel, S; Kraemer, K; Wirth, M P [Department for Urology, University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Fetscherstrasse 74, 01307 Dresden (Germany); Haase, D; Hampel, S; Oswald, S; Bachmatiuk, A; Klingeler, R; Ritschel, M; Leonhardt, A; Buechner, B [Leibniz Institute for Solid State and Materials Research (IFW), Helmholtzstrasse 20, 01069 Dresden (Germany); Schulze, R, E-mail: kai.kraemer@uniklinikum-dresden.de [Bioanalytical Chemistry, Technische Universitaet Dresden, Bergstrasse 66, 01069 Dresden (Germany)

    2010-08-20

    Since the activity of several conventional anticancer drugs is restricted by resistance mechanisms and dose-limiting side-effects, the design of nanocarriers seems to be an efficient and promising approach for drug delivery. Their chemical and mechanical stability and their possible multifunctionality render tubular nanomaterials, such as carbon nanotubes (CNTs) and carbon nanofibres (CNFs), promising delivery agents for anticancer drugs. The goal of the present study was to investigate CNTs and CNFs in order to deliver carboplatin in vitro. No significant intrinsic toxicity of unloaded materials was found, confirming their biocompatibility. Carboplatin was loaded onto CNTs and CNFs, revealing a loading yield of 0.20 mg (CNT-CP) and 0.13 mg (CNF-CP) platinum per milligram of material. The platinum release depended on the carrier material. Whereas CNF-CP marginally released the drug, CNT-CP functioned as a drug depot, constantly releasing up to 68% within 14 days. The cytotoxicity of CNT-CP and CNF-CP in urological tumour cell lines was dependent on the drug release. CNT-CP was identified to be more effective than CNF-CP concerning the impairment of proliferation and clonogenic survival of tumour cells. Moreover, carboplatin, which was delivered by CNT-CP, exhibited a higher anticancer activity than free carboplatin.

  18. Chemical conversion of cisplatin and carboplatin with histidine in a model protein crystallized under sodium iodide conditions

    Energy Technology Data Exchange (ETDEWEB)

    Tanley, Simon W. M.; Helliwell, John R., E-mail: john.helliwell@manchester.ac.uk [University of Manchester, Brunswick Street, Manchester M13 9PL (United Kingdom)

    2014-08-29

    Crystals of HEWL with cisplatin and HEWL with carboplatin grown in sodium iodide conditions both show a partial chemical transformation of cisplatin or carboplatin to a transiodoplatin (PtI{sub 2}X{sub 2}) form. The binding is only at the N{sup δ} atom of His15. A further Pt species (PtI{sub 3}X) is also seen, in both cases bound in a crevice between symmetry-related protein molecules. Cisplatin and carboplatin are platinum anticancer agents that are used to treat a variety of cancers. Previous X-ray crystallographic studies of carboplatin binding to histidine in hen egg-white lysozyme (HEWL) showed a partial chemical conversion of carboplatin to cisplatin owing to the high sodium chloride concentration used in the crystallization conditions. Also, the co-crystallization of HEWL with carboplatin in sodium bromide conditions resulted in the partial conversion of carboplatin to the transbromoplatin form, with a portion of the cyclobutanedicarboxylate (CBDC) moiety still present. The results of the co-crystallization of HEWL with cisplatin or carboplatin in sodium iodide conditions are now reported in order to determine whether the cisplatin and carboplatin converted to the iodo form, and whether this took place in a similar way to the partial conversion of carboplatin to cisplatin in NaCl conditions or to transbromoplatin in NaBr conditions as seen previously. It is reported here that a partial chemical transformation has taken place to a transplatin form for both ligands. The NaI-grown crystals belonged to the monoclinic space group P2{sub 1} with two molecules in the asymmetric unit. The chemically transformed cisplatin and carboplatin bind to both His15 residues, i.e. in each asymmetric unit. The binding is only at the N{sup δ} atom of His15. A third platinum species is also seen in both conditions bound in a crevice between symmetry-related molecules. Here, the platinum is bound to three I atoms identified based on their anomalous difference electron densities

  19. Acute neurological worsening after Rituximab treatment in patients with anti-MAG neuropathy.

    Science.gov (United States)

    Sala, Emilie; Robert-Varvat, Florence; Paul, Stéphane; Camdessanché, Jean-Philippe; Antoine, Jean-Christophe

    2014-10-15

    Patients with peripheral neuropathy and anti-MAG monoclonal IgM may respond to Rituximab, a humanized monoclonal anti-CD20 antibody. We report on three patients with peripheral neuropathy and anti-MAG monoclonal IgM who deteriorated under Rituximab and reviewed seven previously published cases. Worsening was acute and severe, and occurred during the treatment period. All the patients improved after deterioration but at final evaluation only one was improved comparatively to baseline, five were worsened and four were stabilized. Deterioration was not clearly associated with an increase of the anti-MAG antibody titer. Two patients received Rituximab prior or after the course which induced worsening without adverse reaction. Although rare, acute worsening of the neuropathy can occur after Rituximab. The deterioration is however reversible within some weeks to several months. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Treatment of Graves' disease with rituximab specifically reduces the production of thyroid stimulating autoantibodies

    DEFF Research Database (Denmark)

    El Fassi, Daniel; Banga, J Paul; Gilbert, Jacqueline A

    2008-01-01

    involving Chinese hamster ovary cells transfected with the human thyrotropin receptor, we found that the stimulatory capacity of TRAbs was reduced markedly, by 66+/-22%, upon treatment with rituximab and methimazole for 21 days (p

  1. Four cases of recalcitrant pemphigus vulgaris salvaged with rituximab

    Directory of Open Access Journals (Sweden)

    Samyak Ganjre

    2017-01-01

    Full Text Available Although the long-term use of immunosuppressives – supplemented with more aggressive treatments such as immunoadsorption, intravenous immunoglobulins, or plasmapheresis in recalcitrant cases has dramatically improved the prognosis of pemphigus vulgaris, opportunistic infections secondary to immunosuppression continue to cause significant mortality. We report four cases– three old ones, who had accumulated significant morbidities over their disease duration ranging from 5 to 10 years, and the fourth, a teenage female intolerant to corticosteroids and idiosyncratic to methotrexate– who achieved complete remission on administration of rituximab by the lymphoma protocol. One of the old cases who had recalcitrant mucositis experienced its complete subsidence without any adjuvant whatsoever. All continue to remain asymptomatic for 11–20 months. None had infusion reactions or any delayed side effects.

  2. Severe antiphospholipid antibody syndrome - response to plasmapheresis and rituximab.

    Science.gov (United States)

    Gkogkolou, Paraskevi; Ehrchen, Jan; Goerge, Tobias

    2017-09-01

    Antiphospholipid antibody syndrome (APS) is a systemic autoimmune disease characterized by arterial and/or venous thrombosis, recurrent abortions and detection of antiphospholipid antibodies. In fulminant cases, involvement of multiple organs can lead to significant morbidity and even fatal outcomes, so that a rapid, interdisciplinary treatment is needed. Here, we describe the case of a 39-year-old woman with a severe hard-to-treat APS with arterial occlusion and progressive skin necrosis, who was successfully treated with a combination therapy with plasmapheresis and rituximab. The treatment led to complete remission of the skin lesions for over a year. Clinical response correlated with a long-lasting reduction of antiphospholipid antibodies and B-cell depletion. This case demonstrates the use of antiphospholipid antibodies for monitoring APS-activity and shows that this severe vascular disease requires rigorous therapeutic approaches.

  3. USE OF RITUXIMAB IN AUTOIMMUNE DISEASES: NEW ASPECTS

    Directory of Open Access Journals (Sweden)

    Dmitry Evgenyevich Karateyev

    2010-01-01

    Full Text Available It has been noted that off-label indication for Rituximab (RTX in rheumatological care indubitably requires its confirmation in the randomized clinical trials. A particular cautious approach should be taken in extending the indications for therapy with gene-engineering biologicals because of the intricacy and interaction of different immunoregulatory mechanisms. Nonetheless, it is stated that much clinical experience with RTX used in most severely ill therapy-resistant patients may serve as a basis for its prescription in a number of most complex inflammatory rheumatic diseases (RDs. There is new evidence for the use of RTX in various RDs differing in their clinical picture, course, and pathogenesis, such as spondyloarthritis, systemic lupus erythematosus, systemic vasculitis.

  4. Rituximab in anti-GBM disease: A retrospective study of 8 patients.

    Science.gov (United States)

    Touzot, Maxime; Poisson, Johanne; Faguer, Stanislas; Ribes, David; Cohen, Pascal; Geffray, Loic; Anguel, Nadia; François, Helene; Karras, Alexandre; Cacoub, Patrice; Durrbach, Antoine; Saadoun, David

    2015-06-01

    Anti-glomerular basement membrane (GBM) disease is a rare autoantibody-mediated disorder presenting as rapidly progressive glomerulonephritis, and often with pulmonary hemorrhage. Antibody removal with plasmapheresis and immunosuppressive drugs are the cornerstones of the treatment. Data regarding the use of specific B-cell depleting therapy such as rituximab are lacking. We conducted a retrospective observational study of 8 patients with severe and/or refractory GBM disease that received rituximab therapy. Eight patients (2 men, 6 women) with a mean age of 26 ± 13.1 years old were included. Seven had severe renal involvement [median creatinin level was 282 μmol/l, range (65-423)] requiring high immunosuppressive or plasmapheresis dependent, and two had relapse of pulmonary hemorrhage including one with renal failure. Patients received an initial immunosuppressive treatment including steroid and cyclosphosphamide (n = 8) and plasmapheresis (n = 5). Except one late relapse, rituximab therapy was started within two months after diagnosis. All patients except one received 4 weekly dose of rituximab (375 mg(2)). Anti-GBM antibodies were still present in 6/8 patients, at rituximab initiation. Complete remission was observed in 7 out of 8 patients, mostly 3 months after rituximab therapy. After a mean follow-up of 25.6 months (range 4-93), patient and renal survival were 100% and 75% respectively, but rituximab use did not improve GFR. Anti-GBM antibodies remained negative for all patients during follow-up. Only one patient developed a severe bacterial infection but no opportunistic or viral infections were reported. Rituximab may represent an additional and/or alternative therapy in the induction treatment of anti-GBM disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Long-term treatment with rituximab in severe juvenile idiopathic arthritis-associated uveitis.

    Science.gov (United States)

    Miserocchi, Elisabetta; Modorati, Giulio; Berchicci, Luigi; Pontikaki, Irene; Meroni, Pierluigi; Gerloni, Valeria

    2016-06-01

    To evaluate retrospectively the long-term efficacy of rituximab in patients with severe juvenile idiopathic arthritis (JIA)-associated uveitis. Eight patients (15 eyes) with severe and longstanding JIA uveitis, who had an inadequate response in controlling uveitis to one or more biologic agents including tumour necrosis factor blockers and abatacept, received rituximab therapy. Rituximab was given at a dose of 1000 mg per infusion on days 1 and 15 and then every 6 months. Clinical responses to treatment, including decrease in uveitis activity, visual acuity changes, reduction of concomitant local and systemic corticosteroid and/or immunosuppressants, and occurrence of adverse events, were assessed. Eight patients with a mean±SD age of 22.8±5.5 years were treated. The mean ocular disease duration was 17.7 years; the mean±SD follow-up time on rituximab was 44.75±4.9 months; and the mean number of rituximab infusions received was 8.75 (range 6-12). All patients achieved complete control of uveitis, but in two patients rituximab was discontinued due to inefficacy in treating arthritis. The decrease in uveitis activity was evident 4-5 months after the first infusion. Systemic corticosteroids and immunosuppressants used in association with rituximab were discontinued in five patients at the end of follow-up. None of the patients experienced visual worsening during the follow-up. No drug-related complications were encountered. Rituximab may be a promising effective treatment option for refractory uveitis associated with JIA leading to long-term quiescence of uveitis, particularly for patients who have not previously responded to other biologic therapies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  6. Critical appraisal of rituximab in the maintenance treatment of advanced follicular lymphoma

    Directory of Open Access Journals (Sweden)

    Aguiar-Bujanda D

    2015-10-01

    Full Text Available David Aguiar-Bujanda, María Jesús Blanco-Sánchez, María Hernández-Sosa, Saray Galván-Ruíz, Samuel Hernández-Sarmiento Department of Medical Oncology, Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain Abstract: Rituximab is an IgG1, chimeric monoclonal antibody specifically designed to recognize the CD20 antigen expressed on the surface of normal and malignant B-lymphocytes, from the B-cell precursor to the mature B-cells of the germinal center, and by most neoplasms derived from B-cells. After 2 decades of use, rituximab is firmly positioned in the treatment of follicular lymphoma (FL, both in the front line and in the relapsing disease, improving previous results by including it in classical chemotherapy regimens. However, the pharmacology of rituximab continues to generate controversial issues especially regarding the mechanisms of action in vivo. The contribution of rituximab as a maintenance treatment in FL has been significant progress in the management of this disease without an increase in side effects or a decrease in the quality of life of patients. With the widespread use of rituximab, there are new security alerts and side effects not previously detected in the pivotal trials that clinicians should learn to recognize and manage. In this article, we will review the pharmacokinetics and pharmacodynamics of rituximab, the management issues in the treatment of advanced FL focusing on maintenance rituximab, its long-term efficacy and safety profile, and its effect on the quality of life. Keywords: follicular lymphoma, long-term efficacy, maintenance, rituximab, toxicity

  7. Rituximab in the treatment of shrinking lung syndrome in systemic lupus erythematosus.

    Science.gov (United States)

    Peñacoba Toribio, Patricia; Córica Albani, María Emilia; Mayos Pérez, Mercedes; Rodríguez de la Serna, Arturo

    2014-01-01

    Shrinking lung syndrome (SLS) is a rare manifestation of systemic lupus erythematosus. We report the case of a patient with non-responding SLS (neither to glucocorticoids nor immunosupresors), who showed remarkable improvement after the onset of treatment with rituximab. Although there is a little evidence, treatment with rituximab could be proposed in SLS when classical treatment fails. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  8. Retrospective analysis of rituximab therapy and splenectomy in childhood chronic and refractory immune thrombocytopenic purpura.

    Science.gov (United States)

    Ay, Yilmaz; Karapinar, Tuba H; Oymak, Yesim; Toret, Ersin; Demirag, Bengu; Ince, Dilek; Ozcan, Esin; Moueminoglou, Nergial; Koker, Sultan A; Vergin, Canan

    2016-06-01

    Immune thrombocytopenic purpura (ITP) results from accelerated platelet destruction mediated by autoantibodies to platelet glycoproteins. Some patients with chronic ITP are refractory to all therapies [steroids, intravenous immunoglobulin (IVIG), anti-D and immunosuppresive drugs] and have chronic low platelet counts and episodic bleeding. We retrospectively evaluated the efficacy and safety of rituximab treatment and splenectomy in paediatric patients diagnosed with chronic and refractory ITP who were unresponsive to steroids, IVIG, cyclosporine and mycophenolate mofetil. Records of patients with chronic and refractory ITP in 459 patients with primary ITP who were followed up in our hospital from January 2005 to December 2014 were reviewed. Fifteen of patients received rituximab and/or applied splenectomy. Fifteen chronic ITP patients (10 boys, five girls) with a mean age of 10 years were enrolled in the study. Two of these patients were suffering from Evans syndrome. The median time since diagnosis of ITP was 10 years. The median follow-up duration after starting Rituximab and splenectomy were 13 and 9.5 months, respectively.None of the seven patients who were treated with rituximab achieved a response. A splenectomy was performed in six of the seven patients who had been treated with rituximab. Complete and partial responses were achieved in 67 and 33% of the patients, respectively. We evaluated the clinical characteristics and responses of chronic ITP patients who did not receive rituximab therapy and underwent a splenectomy. The success rate was 100% in the eight patients with chronic and refractory ITP. Rituximab therapy might not be beneficial for some children with severe chronic ITP who are refractory to standard agents. A splenectomy might be useful and preferable to rituximab.

  9. A Case of Rituximab-Induced Necrotizing Fasciitis and a Review of the Literature

    OpenAIRE

    Abdulkareem, Abdullateef; D’Souza, Ryan S.; Shogbesan, Oluwaseun; Donato, Anthony

    2017-01-01

    Necrotizing fasciitis is a fulminant soft tissue infection characterized by rapid progression and high mortality. Rituximab is a generally well-tolerated immunosuppresive medication used for B-cell malignancies and some rheumatological disorders. We report a case of a 69-year-old male with chronic lymphocytic leukemia who suffered necrotizing fasciitis of his left lower extremity secondary to Clostridium septicum 7 weeks after treatment with rituximab. Despite immediate intravenous antimicrob...

  10. Intermediate doses of rituximab used as adjuvant therapy in refractory pemphigus

    Directory of Open Access Journals (Sweden)

    Pradnya J Londhe

    2014-01-01

    Full Text Available Background: Rituximab, a monoclonal anti-CD20 antibody, has been used with encouraging results in pemphigus. We describe herein refractory cases of pemphigus vulgaris (n = 23 and pemphigus foliaceus (n = 1 treated with rituximab in addition to steroids and immunosuppressants. Aims: To assess the response to treatment, the duration of clinical remission, serology of the response and adverse effects of rituximab in pemphigus patients. Methods: We recorded observations of 24 patients with pemphigus having either refractory disease in spite of high dose of steroids and immunosuppressants, corticosteroid-dependent disease, strong contraindications to corticosteroids, or severe disease. The patients were treated with infusions of one injection per week for three consecutive weeks of 375 mg of rituximab per m 2 of body-surface area. One similar infusion was repeated after 3 months of 3 rd dose. We observed the clinical outcome after 6 months of 3 rd dose of rituximab and looked for complete healing of cutaneous and mucosal lesions (complete remission. Observations: After follow-up of 7-24 months, five patients showed only partial improvement while 19 of 24 patients had a complete remission 3 months after rituximab. Of these 19 patients, 12 patients achieved complete remission and are off all systemic therapy, and the rest are continuing with no or low dose of steroids with immunosuppressants. Two patients relapsed after initial improvement; one was given moderate dose of oral steroids and immunosuppressant and the other was given repeat single dose of rituximab to control relapse. Conclusion: Rituximab is able to induce a prolonged clinical remission in pemphigus after a single course of four infusions. The high cost and limited knowledge of long term adverse effects are limitations to the use of this biologic agent.

  11. Advanced non-small cell lung cancer in elderly patients: The standard every 3-weeks versus weekly paclitaxel with carboplatin

    Directory of Open Access Journals (Sweden)

    Hala Mohamed El-Shenshawy

    2012-10-01

    Conclusions: Efficacy was similar between the weekly regimen and the standard regimen of carboplatin and paclitaxel for elderly patients with advanced NSCLC and may be advantageous based on its favorable tolerability profile.

  12. Relationship between irreversible alopecia and exposure to cyclophosphamide, thiotepa and carboplatin (CTC) in high-dose chemotherapy

    NARCIS (Netherlands)

    de Jonge, M. E.; Mathôt, R. A. A.; Dalesio, O.; Huitema, A. D. R.; Rodenhuis, S.; Beijnen, J. H.

    2002-01-01

    Reversible alopecia is a commonly observed, important and distressing complication of chemotherapy. Permanent alopecia, however, is rare after standard-dose therapy, but has occasionally been observed after high-dose chemotherapy with cyclophosphamide, thiotepa and carboplatin (CTC). We evaluated

  13. Radiolabeling parameters of {sup 177}Lu-DOTA-RITUXIMAB

    Energy Technology Data Exchange (ETDEWEB)

    Massicano, Adriana V.F.; Alcarde, Lais F.; Oliveira, Ricardo S.; Mengatti, Jair; Araujo, Elaine B. de, E-mail: adriana.avfernandes@gmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    Cancer treatment using radioimmunotherapy (RIT) has been the focus of much research in the last two decades. In RIT, a radioisotope is coupled to a monoclonal antibody (mAb) to form a tumor-specific target agent to improve the cytocidal effect of the mAbs. RIT allows the systemic delivery of radiation to disease target by mAbs while sparing normal tissues. Rituximab® (Mabthera - Roche) is a chimeric mouse-human monoclonal antibody; it selectively binds with high affinity to the CD20 antigen, a hydrophobic transmembrane protein, which is expressed on B-lymphocytes and in more than 90% of B cell non-Hodgkin's lymphomas (NHL). The conjugation and radiolabeling process involve special conditions of pH and temperature, long processes of manipulation and mixing. All this process can damage the antibody structure and compromise its clinical application. Therefore, these parameters must be largely studied. The aim of this work was to evaluate the best radiolabeling conditions of DOTA-rituximab. Briefly, 10 mg of antibody previously purified by ultrafiltration device was conjugated with DOTA-NHS-ester (Macrocyclics) in 50 fold molar excess. The reaction was conducted for 1 hour in phosphate buffer pH 8.0 and gently mixing at room temperature, remaining for 24 hours under refrigeration. The immunoconjugated was purified by size exclusion column and ultrafiltration device. The radiolabeled parameters studied were: immunoconjugated mass, activity of {sup 177}LuCl{sub 3}, reaction time, temperature and pH. The radiochemical purity of the preparations was determined using analysis by thin layer chromatography (TLC-SG plates). The best studied condition presented radiochemical purity above 95% and the integrity of antibody was preserved. (author)

  14. Radiolabeling parameters of 177Lu-DOTA-RITUXIMAB

    International Nuclear Information System (INIS)

    Massicano, Adriana V.F.; Alcarde, Lais F.; Oliveira, Ricardo S.; Mengatti, Jair; Araujo, Elaine B. de

    2013-01-01

    Cancer treatment using radioimmunotherapy (RIT) has been the focus of much research in the last two decades. In RIT, a radioisotope is coupled to a monoclonal antibody (mAb) to form a tumor-specific target agent to improve the cytocidal effect of the mAbs. RIT allows the systemic delivery of radiation to disease target by mAbs while sparing normal tissues. Rituximab® (Mabthera - Roche) is a chimeric mouse-human monoclonal antibody; it selectively binds with high affinity to the CD20 antigen, a hydrophobic transmembrane protein, which is expressed on B-lymphocytes and in more than 90% of B cell non-Hodgkin's lymphomas (NHL). The conjugation and radiolabeling process involve special conditions of pH and temperature, long processes of manipulation and mixing. All this process can damage the antibody structure and compromise its clinical application. Therefore, these parameters must be largely studied. The aim of this work was to evaluate the best radiolabeling conditions of DOTA-rituximab. Briefly, 10 mg of antibody previously purified by ultrafiltration device was conjugated with DOTA-NHS-ester (Macrocyclics) in 50 fold molar excess. The reaction was conducted for 1 hour in phosphate buffer pH 8.0 and gently mixing at room temperature, remaining for 24 hours under refrigeration. The immunoconjugated was purified by size exclusion column and ultrafiltration device. The radiolabeled parameters studied were: immunoconjugated mass, activity of 177 LuCl 3 , reaction time, temperature and pH. The radiochemical purity of the preparations was determined using analysis by thin layer chromatography (TLC-SG plates). The best studied condition presented radiochemical purity above 95% and the integrity of antibody was preserved. (author)

  15. Relapse of nephrotic syndrome during post-rituximab peripheral blood B-lymphocyte depletion.

    Science.gov (United States)

    Sato, Mai; Kamei, Koichi; Ogura, Masao; Ishikura, Kenji; Ito, Shuichi

    2018-02-01

    Rituximab is effective against complicated childhood steroid-dependent nephrotic syndrome (SDNS). Peripheral blood B-lymphocyte (B-cell) depletion is strongly correlated with persistent remission, relapse rarely occurring during B-cell depletion; however, we have encountered several such patients. We retrospectively analyzed the characteristics and clinical course of 82 patients with SDNS treated with rituximab from January 2007 to December 2012 in our institution. Six of 82 patients (7.3%) had relapses during B-cell depletion after receiving rituximab (relapsed group). The remaining 76 patients did not have relapses during B-cell depletion (non-relapsed group). The median time to initial relapse during B-cell depletion was 85 days after receiving rituximab, which is significantly shorter than in the non-relapsed group (410 days, p = 0.0003). The median annual numbers of relapses after receiving rituximab were 2.5 and 0.9 in the relapsed and non-relapsed groups, respectively (p depletion did not differ between the two groups. Relapse during B-cell depletion after receiving rituximab suggests that various pathophysiological mechanisms play a part in childhood nephrotic syndrome.

  16. Hepatitis B reactivation and rituximab: a new boxed warning and considerations for solid organ transplantation.

    Science.gov (United States)

    Martin, S T; Cardwell, S M; Nailor, M D; Gabardi, S

    2014-04-01

    Use of rituximab, a chimeric monoclonal antibody directed at the CD20 antigen, continues to increase in solid organ transplantation (SOT) for several off-label uses. In September 2013, the United States Food and Drug Administration (FDA) issued a Drug Safety Communication to oncology, rheumatology and pharmacy communities outlining a new Boxed Warning for rituximab. Citing 109 cases of fatal hepatitis B virus (HBV) reactivation in persons receiving rituximab therapy with previous or chronic HBV infection documented in their Adverse Event Reporting System (AERS), the FDA recommends screening for HBV serologies in all patients planned to receive rituximab and antiviral prophylaxis in any patient with a positive history of HBV infection. There is a lack of data pertaining to this topic in the SOT population despite an increase in off-label indications. Previous reports suggest patients receiving rituximab, on average, were administered six doses prior to HBV reactivation. Recommendations on prophylaxis, treatment and re-challenging patients with therapy after resolution of reactivation remain unclear. Based on data from the FDA AERS and multiple analyses in oncology, SOT providers utilizing rituximab should adhere to the FDA warnings and recommendations regarding HBV reactivation until further data are available in the SOT population. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

  17. Kinetics of carboplatin-DNA binding in genomic DNA and bladder cancer cells as determined by accelerator mass spectrometry

    International Nuclear Information System (INIS)

    Hah, S S; Stivers, K M; Vere White, R; Henderson, P T

    2005-01-01

    Cisplatin and carboplatin are platinum-based drugs that are widely used in cancer chemotherapy. The cytotoxicity of these drugs is mediated by platinum-DNA monoadducts and intra- and interstrand diadducts, which are formed following uptake of the drug into the nucleus of cells. The pharmacodynamics of carboplatin display fewer side effects than for cisplatin, albeit with less potency, which may be due to differences in rates of DNA adduct formation. We report the use of accelerator mass spectrometry (AMS), a sensitive detection method often used for radiocarbon quantitation, to measure both the kinetics of [ 14 C]carboplatin-DNA adduct formation with genomic DNA and drug uptake and DNA binding in T24 human bladder cancer cells. Only carboplatin-DNA monoadducts contain radiocarbon in the platinated DNA, which allowed for calculation of kinetic rates and concentrations within the system. The percent of radiocarbon bound to salmon sperm DNA in the form of monoadducts was measured by AMS over 24 h. Knowledge of both the starting concentration of the parent carboplatin and the concentration of radiocarbon in the DNA at a variety of time points allowed calculation of the rates of Pt-DNA monoadduct formation and conversion to toxic cross-links. Importantly, the rate of carboplatin-DNA monoadduct formation was approximately 100-fold slower than that reported for the more potent cisplatin analogue, which may explain the lower toxicity of carboplatin. T24 human bladder cancer cells were incubated with a subpharmacological dose of [ 14 C]carboplatin, and the rate of accumulation of radiocarbon in the cells and nuclear DNA was measured by AMS. The lowest concentration of radiocarbon measured was approximately 1 amol/10 (micro)g of DNA. This sensitivity may allow the method to be used for clinical applications

  18. Poly (ɛ-caprolactone) nanoparticles of carboplatin: Preparation, characterization and in vitro cytotoxicity evaluation in U-87 MG cell lines.

    Science.gov (United States)

    Karanam, Vamshikrishna; Marslin, Gregory; Krishnamoorthy, Balakumar; Chellan, Vijayaraghavan; Siram, Karthik; Natarajan, Tamilselvan; Bhaskar, Balaji; Franklin, Gregory

    2015-06-01

    Carboplatin is a platinum based drug used in the treatment of several malignancies. Due to poor cellular uptake, generally, a larger dose of drug is administered to achieve therapeutic levels, causing harmful side-effects such as hematologic toxicity. In order to enhance the cellular uptake of carboplatin, we have developed carboplatin loaded nanoparticles using the biodegradable polymer poly (ɛ-caprolactone) (PCL). Nanoparticles ranging from the size of 23.77±1.37 to 96.73±2.79 nm with positive zeta potential and moderate entrapment efficiency (54.21±0.98%) were obtained. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) confirmed the spherical morphology and smooth surface of all nanoformulations. The concentrations of PCL and the stabilizer (DMAB) are found to play a role in determining the size and the entrapment efficiency of the nanoparticles. Drug release from nanoparticles followed a biphasic pattern with an initial burst release followed by a sustained release for 10h. Results of in vitro cellular uptake and cytotoxicity studies revealed that carboplatin in the form of PCL-nanoparticles were efficiently up taken and displayed profound cytotoxicity to U-87 MG (human glioma) cells than the free drug. Importantly, unlike the free carboplatin, carboplatin in the form of PCL nanoparticles did not present any haemolytic activity in rat erythrocytes, a major side effect of this chemotherapeutic drug. This suggests that poly (ɛ-caprolactone) nanoencapsulation of carboplatin might be an efficient approach to treat cancer, while reducing carboplatin induced haemolysis. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Kinetics of carboplatin-DNA binding in genomic DNA and bladder cancer cells as determined by accelerator mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Hah, S S; Stivers, K M; Vere White, R; Henderson, P T

    2005-12-29

    Cisplatin and carboplatin are platinum-based drugs that are widely used in cancer chemotherapy. The cytotoxicity of these drugs is mediated by platinum-DNA monoadducts and intra- and interstrand diadducts, which are formed following uptake of the drug into the nucleus of cells. The pharmacodynamics of carboplatin display fewer side effects than for cisplatin, albeit with less potency, which may be due to differences in rates of DNA adduct formation. We report the use of accelerator mass spectrometry (AMS), a sensitive detection method often used for radiocarbon quantitation, to measure both the kinetics of [{sup 14}C]carboplatin-DNA adduct formation with genomic DNA and drug uptake and DNA binding in T24 human bladder cancer cells. Only carboplatin-DNA monoadducts contain radiocarbon in the platinated DNA, which allowed for calculation of kinetic rates and concentrations within the system. The percent of radiocarbon bound to salmon sperm DNA in the form of monoadducts was measured by AMS over 24 h. Knowledge of both the starting concentration of the parent carboplatin and the concentration of radiocarbon in the DNA at a variety of time points allowed calculation of the rates of Pt-DNA monoadduct formation and conversion to toxic cross-links. Importantly, the rate of carboplatin-DNA monoadduct formation was approximately 100-fold slower than that reported for the more potent cisplatin analogue, which may explain the lower toxicity of carboplatin. T24 human bladder cancer cells were incubated with a subpharmacological dose of [{sup 14}C]carboplatin, and the rate of accumulation of radiocarbon in the cells and nuclear DNA was measured by AMS. The lowest concentration of radiocarbon measured was approximately 1 amol/10 {micro}g of DNA. This sensitivity may allow the method to be used for clinical applications.

  20. 4-step 4-h carboplatin desensitization protocol for patients with gynecological malignancies showing platinum hypersensitivity: a retrospective study.

    Science.gov (United States)

    Takase, Naoto; Matsumoto, Koji; Onoe, Takuma; Kitao, Akihito; Tanioka, Maki; Kikukawa, Yoshitaka; Yamaguchi, Satoshi; Fujiwara, Kiyoshi; Negoro, Shunichi

    2015-06-01

    Platinum agents are essential for treating gynecological malignancies, particularly ovarian cancer. However, multiple carboplatin doses may cause hypersensitivity reactions (HSRs). Carboplatin desensitization prevents life-threatening HSRs and promotes the successful completion of planned chemotherapy. Since January 2010, carboplatin desensitization was performed at our institution. Solutions with 1/1000, 1/100, and 1/10 dilutions of carboplatin and an undiluted solution were prepared in 250 mL of 5% glucose. Each solution was administered as a 1-h intravenous infusion (4-step 4-h protocol). This retrospective analysis was approved by the institutional review board. From January 2010 to December 2013, 20 patients with gynecological malignancies (median age 62 years, range 43-74 years) received desensitization treatment. The International Federation of Gynecology and Obstetrics stages at presentation were I, II, III, and IV in 1, 1, 15, 13 patients, respectively. During first-line and second-line treatments, 3 and 17 patients, respectively, experienced carboplatin-induced HSRs. The median carboplatin cycle number was 11 (range 2-16). In the first desensitization cycle, 17 (85%) patients completed treatment without adverse events, 2 experienced Grade 1 HSRs but completed treatment, and 1 experienced Grade 3 HSR and discontinued treatment. The first desensitization cycle completion rate was 95%. Of 83 desensitization cycles administered, 79 (95.2%) were completed. No treatment-related deaths occurred. Most patients completed the planned chemotherapy. Our protocol could be conducted safely with shorter duration and simpler procedures than previous protocols. Carboplatin desensitization seems beneficial for patients with a history of carboplatin-induced HSRs; however, the risk of HSR recurrence still remains. Desensitization should therefore be performed only by well-trained staff.

  1. Socioeconomic inequality in the use of rituximab therapy among non-Hodgkin lymphoma patients in Chinese public hospitals.

    Science.gov (United States)

    Yu-Wen, Huang; Mei-Bian, Zhang; Xiang, Xu; Xiao-Hua, Xu; Quan, Zhou; Le, Jian

    2014-03-01

    Rituximab is a patient-paid effective monoclonal-antibody drug for non-Hodgkin lymphoma (NHL). Little is known in China, a country with unequal distribution of wealth and medical insurance systems, about the impact of socioeconomic status (SES) on selecting rituximab therapy in NHL patients. A total of 328 NHL inpatients in 2 public hospitals in Hangzhou were recruited and divided into 2 equal groups: with rituximab therapy and with no rituximab therapy group. Selection and frequency of rituximab therapy increased with duration of education and in urban citizens (P inequality in provision of rituximab therapy among Chinese NHL patients, and this was associated with differences in SES status. Effective measures are suggested to ameliorate the inequality issue.

  2. Effectiveness of disease-modifying antirheumatic drug co-therapy with methotrexate and leflunomide in rituximab-treated rheumatoid arthritis patients

    DEFF Research Database (Denmark)

    Chatzidionysiou, Katerina; Lie, Elisabeth; Nasonov, Evgeny

    2012-01-01

    is an effective and safe alternative to methotrexate as concomitant treatment with rituximab. Slightly better results were obtained by the combination of rituximab and leflunomide than rituximab and methotrexate, raising the possibility of a synergistic effect of leflunomide and rituximab.......OBJECTIVES: To compare the effectiveness and safety of rituximab alone or in combination with either methotrexate or leflunomide.METHODS: 10 European registries submitted anonymised datasets with baseline, 3, 6, 9 and 12-month clinical data from patients who started rituximab.RESULTS: 1195 patients...

  3. Linfoma hepático primario: Evolución favorable con quimioterapia combinada con rituximab Primary hepatic lymphoma: favorable outcome with chemotherapy plus rituximab

    Directory of Open Access Journals (Sweden)

    I. Serrano-Navarro

    2008-11-01

    Full Text Available Comunicamos el caso de una paciente con un linfoma hepático primario tratado con éxito con quimioterapia combinada con rituximab. Utilizando los "encabezamientos estándar para búsquedas bibliográficas informatizadas" (Medical Subject Heading revisamos los casos publicados hasta la fecha de esta infrecuente entidad.This article describes the case of a patient with a non-Hodgkin primary hepatic lymphoma who was successfully treated with chemotherapy combined with rituximab. Using the Medical Subject Headings the published reports of this rare entity were reviewed.

  4. Bendamustine and rituximab (BR) versus dexamethasone, rituximab, and cyclophosphamide (DRC) in patients with Waldenström macroglobulinemia.

    Science.gov (United States)

    Paludo, Jonas; Abeykoon, Jithma P; Shreders, Amanda; Ansell, Stephen M; Kumar, Shaji; Ailawadhi, Sikander; King, Rebecca L; Koehler, Amber B; Reeder, Craig B; Buadi, Francis K; Dispenzieri, Angela; Lacy, Martha Q; Dingli, David; Witzig, Thomas E; Go, Ronald S; Gonsalves, Wilson I; Kourelis, Taxiarchis; Warsame, Rahma; Leung, Nelson; Habermann, Thomas M; Hayman, Suzanne; Lin, Yi; Kyle, Robert A; Rajkumar, S Vincent; Gertz, Morie A; Kapoor, Prashant

    2018-04-03

    The treatment approaches for Waldenstrom macroglobulinemia (WM) are largely based upon information from single-arm phase II trials, without comparative data. We compared the efficacy of two commonly used regimens in routine practice (bendamustine-rituximab (BR) and dexamethasone, rituximab plus cyclophosphamide (DRC)) and evaluated their activity with respect to the patients' MYD88 L265P mutation status. Of 160 consecutive patients, 60 received BR (43 with relapsed/refractory WM) and 100 received DRC (50 had relapsed/refractory WM). In the treatment-naïve setting, overall response rate (ORR) was 93% with BR versus 96% with DRC (p = 0.55). Two-year progression-free survival (PFS) with BR and DRC was 88 and 61%, respectively (p = 0.07). In salvage setting, ORR was 95% with BR versus 87% with DRC, p = 0.45; median PFS with BR was 58 versus 32 months with DRC (2-year PFS was 66 versus 53%; p = 0.08). Median disease-specific survival was not reached with BR versus 166 months with DRC (p = 0.51). The time-to-event endpoints and depth of response were independent of the MYD88 mutation status. Grade ≥ 3 adverse events of both regimens were comparable. A trend for longer PFS was observed with BR although the regimens have comparable toxicities. The activity of BR and DRC appears to be unaffected by patients' MYD88 mutation status.

  5. Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer.

    Science.gov (United States)

    O'Shaughnessy, Joyce; Schwartzberg, Lee; Danso, Michael A; Miller, Kathy D; Rugo, Hope S; Neubauer, Marcus; Robert, Nicholas; Hellerstedt, Beth; Saleh, Mansoor; Richards, Paul; Specht, Jennifer M; Yardley, Denise A; Carlson, Robert W; Finn, Richard S; Charpentier, Eric; Garcia-Ribas, Ignacio; Winer, Eric P

    2014-12-01

    There is a lack of treatments providing survival benefit for patients with metastatic triple-negative breast cancer (mTNBC), with no standard of care. A randomized phase II trial showed significant benefit for gemcitabine, carboplatin, and iniparib (GCI) over gemcitabine and carboplatin (GC) in clinical benefit rate, response rate, progression-free survival (PFS), and overall survival (OS). Here, we formally compare the efficacy of these regimens in a phase III trial. Patients with stage IV/locally recurrent TNBC who had received no more than two previous chemotherapy regimens for mTNBC were randomly allocated to gemcitabine 1,000 mg/m(2) and carboplatin area under the curve 2 (days 1 and 8) alone or GC plus iniparib 5.6 mg/kg (days 1, 4, 8, and 11) every 3 weeks. Random assignment was stratified by the number of prior chemotherapies. The coprimary end points were OS and PFS. Patients receiving GC could cross over to iniparib on progression. Five hundred nineteen patients were randomly assigned (261 GCI; 258 GC). In the primary analysis, no statistically significant difference was observed for OS (hazard ratio [HR] = 0.88; 95% CI, 0.69 to 1.12; P = .28) nor PFS (HR = 0.79; 95% CI, 0.65 to 0.98; P = .027). An exploratory analysis showed that patients in the second-/third-line had improved OS (HR = 0.65; 95% CI, 0.46 to 0.91) and PFS (HR = 0.68; 95% CI, 0.50 to 0.92) with GCI. The safety profile for GCI was similar to GC. The trial did not meet the prespecified criteria for the coprimary end points of PFS and OS in the ITT population. The potential benefit with iniparib observed in second-/third-line subgroup warrants further evaluation. © 2014 by American Society of Clinical Oncology.

  6. Comparison of the short-term efficacy between docetaxel plus carboplatin and 5-fluorouracil plus carboplatin in locoregionally advanced nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Lv X

    2016-08-01

    Full Text Available Xing Lv,1,2,* Wei-Xiong Xia,1,2,* Liang-Ru Ke,1,2 Jing Yang,1,2 Wen-Zhe Qiu,1,2 Ya-Hui Yu,1,2 Hu Liang,1,2 Xin-Jun Huang,1,2 Guo-Yin Liu,1,2 Qi Zeng,1,2 Xiang Guo,1,2 Yan-Qun Xiang1,2 1Key Laboratory of Oncology in South China, 2Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China *These authors contributed equally to this work Objective: Platinum-based chemotherapy in combination with radiotherapy is a standard treatment strategy for locoregionally advanced nasopharyngeal carcinoma (NPC. This study aimed to investigate the long-term efficacy and tolerability of inductive chemotherapy with docetaxel plus carboplatin (TC or 5-fluorouracil plus carboplatin (FC followed by concurrent radiation therapy in patients with NPC. Methods: Patients (N=88 were randomized to receive TC or FC as inductive therapy followed by concurrent radiotherapy (60–70 Gy with two cycles of carboplatin (area under the curve =5 mg·h/L. Patients were followed up for 8 years. Primary end point was progression-free survival (PFS. Secondary end points included overall survival (OS, toxicity, tumor response, distant metastasis-free survival, and local recurrence-free survival. Results: At the end of the follow-up period, 31 patients died, 32 had disease progression, eleven had cancer recurrence, and 25 had distant metastasis. Overall, there was no difference between treatment groups with regard to response or survival. We found that following induction and concurrent chemoradiotherapy, the majority of patients showed a complete response (~96%–98% for induction therapy and 82%–84% for comprehensive therapy to both therapies. PFS and OS were also similar between groups. The rate of PFS was 63.6% for both FC and TC and that of OS was 65.9% and 63.5%, respectively. The overall incidence of grade 3–4 adverse events in the TC group (20.5% was higher than in the FC group (10.7%. Neutropenia and leukopenia

  7. Effect of Rituximab in Patients With Leucine-Rich, Glioma-Inactivated 1 Antibody–Associated Encephalopathy

    Science.gov (United States)

    Irani, Sarosh R.; Gelfand, Jeffrey M.; Bettcher, Brianne M.; Singhal, Neel S.; Geschwind, Michael D.

    2015-01-01

    IMPORTANCE This observational study describes the efficacy and safety of rituximab in 5 patients with voltage-gated potassium channel (VGKC)–complex/leucine-rich, glioma-inactivated 1 (LGI1) antibody–associated encephalopathy. Rituximab is a monoclonal antibody that targets CD20 and is used to treat other neurologic and nonneurologic diseases. OBSERVATIONS This case series reports sequential seizure frequencies, modified Rankin Scale scores, and VGKC-complex antibody titers in 5 adult patients (median age, 65 years; range, 48–73 years) treated with rituximab. Median time from symptom onset to rituximab initiation was 414 days (range, 312–851 days). One patient showed a rapid clinical improvement after treatment with rituximab alone and experienced a rituximab-responsive clinical relapse. Another showed possible improvement on neuropsychometric memory indexes after rituximab therapy. In contrast, all patients showed robust responses to treatment with glucocorticoids, intravenous immunoglobulins, and/or plasma exchange at some point in their illness. Treatment with glucocorticoids—less so with intravenous immunoglobulins and plasma exchange—was associated with the most marked reductions in VGKC-complex antibodies. The only patient who did not receive glucocorticoids showed the poorest clinical and serologic responses. CONCLUSIONS AND RELEVANCE Rituximab was well tolerated in this predominantly older adult patient population and may be an effective option for some patients with LGI1 antibody–associated encephalopathy. Glucocorticoid therapy appears particularly efficacious. Earlier rituximab administration and randomized trials are required to formally assess efficacy. PMID:24842754

  8. Definitive chemoradiotherapy with carboplatin for squamous cell carcinoma of the head and neck.

    Science.gov (United States)

    Nagasaka, Misako; Zaki, Mark; Issa, Majd; Kim, Harold; Abrams, Judith; Sukari, Ammar

    2017-10-01

    Definitive concurrent chemoradiotherapy (CRT) is considered the standard of care for organ preservation and is the only potentially curative therapy for surgically unresectable patients with stage III to IVb locally advanced squamous cell carcinoma of the head and neck. In patients with high risks for adverse events utilizing cisplatin, carboplatin has been empirically substituted. The objective of this study was to estimate the locoregional control rate, progression-free survival, overall survival, and adverse events in locally advanced squamous cell carcinoma of the head and neck patients treated with CRT utilizing carboplatin. A retrospective single-arm analysis. Data on consecutive patients who fit the eligibility criteria were collected. Eligible patients were treated with 70 Gy of radiation therapy and at least two cycles of carboplatin (area of curve [AUC] of 5 between January 2007 to December 2013. Fifty-four patients were identified. Overall locoregional control rate was 50% (95% confidence interval [CI] 37%-63%). Median progression-free and overall survival were 21 (CI 11-33) and 40 (CI 33-NA) months, respectively. One-, 3-, and 5-year overall survival were 81% (CI 67%-89%), 59% (CI 41%-73%), and 42% (CI 22%-61%), respectively. Stage III/IVa patients (n = 45) had a median survival of 62 (CI 37-NA months) and 3 years of 71% (CI 53%-84%), whereas stage IVb (n = 9) had a median survival of 31 (CI 4-NA) months and none survived to 3 years. Definitive CRT with carboplatin for locally advanced squamous cell carcinoma of the head and neck was well tolerated and demonstrated comparable results to CRT with cisplatin. 4. Laryngoscope, 127:2260-2264, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  9. Phase I trial of verubulin (MPC-6827) plus carboplatin in patients with relapsed glioblastoma multiforme.

    Science.gov (United States)

    Grossmann, Kenneth F; Colman, Howard; Akerley, Wallace A; Glantz, Michael; Matsuoko, Yuko; Beelen, Andrew P; Yu, Margaret; De Groot, John F; Aiken, Robert D; Olson, Jeffrey J; Olsen, Jeffery J; Evans, Brent A; Jensen, Randy L

    2012-11-01

    Verubulin (MPC-6827) is a microtubule-destabilizing agent that achieves high concentrations in the brain. Verubulin disrupts newly formed blood vessels in xenografts. We determined the safety and tolerability of verubulin administered in combination with carboplatin in patients with relapsed glioblastoma multiforme (GBM). Three pre-selected doses of verubulin were tested: 2.1, 2.7, and 3.3 mg/m(2) in a standard "3+3" design. Verubulin was given every second week of a 6-week cycle in the 2.1 mg/m(2) cohort or weekly for 3 weeks of a 4-week cycle in subsequent cohorts. Carboplatin was administered intravenously at an area under the curve (AUC) dosage 4 every 2 weeks for the 2.1 mg/m(2) cohort or on day 1 of each 4-week cycle in subsequent cohorts. Nineteen patients with GBM in first or second relapse were enrolled. Four patients (21 %) experienced a grade 3 or greater verubulin- or carboplatin-related adverse event, including hypesthesia, cerebral ischemia, anemia, and thrombocytopenia. The mean plasma half life of verubulin was 3.2 h (SD = 0.82). Two patients achieved at least a partial response by Macdonald criteria. One of these patients remains progression free and off treatment more than 24 months beyond his initiation of verubulin. Five patients had stable disease. Median progression-free survival (PFS) across all patients was 8 weeks, and the 6-month PFS rate was 21 %. The combination of verubulin at the previously determined single-agent maximum tolerated dose of 3.3 mg/m(2) with carboplatin in patients with recurrent/refractory GBM is safe and well tolerated. In this patient population with a highly vascularized tumor, no cerebral hemorrhage was observed.

  10. Elevated β-catenin activity contributes to carboplatin resistance in A2780cp ovarian cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Barghout, Samir H. [Department of Obstetrics and Gynecology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB (Canada); Zepeda, Nubia; Xu, Zhihua [Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB (Canada); Steed, Helen [Department of Obstetrics and Gynecology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB (Canada); Lee, Cheng-Han [Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB (Canada); Fu, YangXin, E-mail: yangxin@ualberta.ca [Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB (Canada); Department of Obstetrics and Gynecology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB (Canada)

    2015-12-04

    Ovarian cancer is the fifth leading cause of cancer-related mortalities in women. Epithelial ovarian cancer (EOC) represents approximately 90% of all ovarian malignancies. Most EOC patients are diagnosed at advanced stages and current chemotherapy regimens are ineffective against advanced EOC due to the development of chemoresistance. It is important to better understand the molecular mechanisms underlying acquired resistance to effectively manage this disease. In this study, we examined the expression of the Wnt/β-catenin signaling components in the paired cisplatin-sensitive (A2780s) and cisplatin-resistant (A2780cp) EOC cell lines. Our results showed that several negative regulators of Wnt signaling are downregulated, whereas a few Wnt ligands and known Wnt/β-catenin target genes are upregulated in A2780cp cells compared to A2780s cells, suggesting that Wnt/β-catenin signaling is more active in A2780cp cells. Further analysis revealed nuclear localization of β-catenin and higher β-catenin transcriptional activity in A2780cp cells compared to A2780s cells. Finally, we demonstrated that chemical inhibition of β-catenin transcriptional activity by its inhibitor CCT036477 sensitized A2780cp cells to carboplatin, supporting a role for β-catenin in carboplatin resistance in A2780cp cells. In conclusion, our data suggest that increased Wnt/β-catenin signaling activity contributes to carboplatin resistance in A2780cp cells. - Highlights: • Wnt ligands and target genes are upregulated in cisplatin resistant A2780cp cells. • Negative regulators of Wnt signaling are down-regulated in A2780cp cells. • β-catenin transcriptional activity is higher in A2780cp cells compared to A2780s cells. • Inhibition of β-catenin activity increases carboplatin cytotoxicity in A2780cp cells.

  11. Synergistic Effect of Carboplatin and Piroxicam on Two Bladder Cancer Cell Lines.

    Science.gov (United States)

    Silva, Jéssica; Arantes-Rodrigues, Regina; Pinto-Leite, Rosário; Faustino-Rocha, Ana I; Fidalgo-Gonçalves, Lio; Santos, Lúcio; Oliveira, Paula A

    2017-04-01

    This study aimed to evaluate the in vitro efficacy of carboplatin and piroxicam, both in isolation and combined, against T24 and 5637 human urinary bladder cancer cell lines. Cell viability, drug interaction, cell morphology, cell proliferation, apoptosis and autophagy were analyzed after 72 h of drug exposure. Statistical analysis was performed and values of ppiroxicam produced a more potent antiproliferative effect when compared to single drugs. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  12. Elevated β-catenin activity contributes to carboplatin resistance in A2780cp ovarian cancer cells

    International Nuclear Information System (INIS)

    Barghout, Samir H.; Zepeda, Nubia; Xu, Zhihua; Steed, Helen; Lee, Cheng-Han; Fu, YangXin

    2015-01-01

    Ovarian cancer is the fifth leading cause of cancer-related mortalities in women. Epithelial ovarian cancer (EOC) represents approximately 90% of all ovarian malignancies. Most EOC patients are diagnosed at advanced stages and current chemotherapy regimens are ineffective against advanced EOC due to the development of chemoresistance. It is important to better understand the molecular mechanisms underlying acquired resistance to effectively manage this disease. In this study, we examined the expression of the Wnt/β-catenin signaling components in the paired cisplatin-sensitive (A2780s) and cisplatin-resistant (A2780cp) EOC cell lines. Our results showed that several negative regulators of Wnt signaling are downregulated, whereas a few Wnt ligands and known Wnt/β-catenin target genes are upregulated in A2780cp cells compared to A2780s cells, suggesting that Wnt/β-catenin signaling is more active in A2780cp cells. Further analysis revealed nuclear localization of β-catenin and higher β-catenin transcriptional activity in A2780cp cells compared to A2780s cells. Finally, we demonstrated that chemical inhibition of β-catenin transcriptional activity by its inhibitor CCT036477 sensitized A2780cp cells to carboplatin, supporting a role for β-catenin in carboplatin resistance in A2780cp cells. In conclusion, our data suggest that increased Wnt/β-catenin signaling activity contributes to carboplatin resistance in A2780cp cells. - Highlights: • Wnt ligands and target genes are upregulated in cisplatin resistant A2780cp cells. • Negative regulators of Wnt signaling are down-regulated in A2780cp cells. • β-catenin transcriptional activity is higher in A2780cp cells compared to A2780s cells. • Inhibition of β-catenin activity increases carboplatin cytotoxicity in A2780cp cells.

  13. Platinum desensitization in patients with carboplatin hypersensitivity: A single-institution retrospective study.

    Science.gov (United States)

    Altwerger, Gary; Gressel, Gregory M; English, Diana P; Nelson, Wendelin K; Carusillo, Nina; Silasi, Dan-Arin; Azodi, Masoud; Santin, Alessandro; Schwartz, Peter E; Ratner, Elena S

    2017-01-01

    The carboplatin desensitization (CD) protocol presented here allows patients with either a positive skin test or a prior hypersensitivity reaction (HSR) to safely, rapidly and effectively continue with carboplatin infusions. Newly described factors can identify patients at risk for developing adverse events during CD. A retrospective review was performed on patients with gynecologic cancer who underwent CD between 2005 and 2014. The CD protocol uses a four-step dilution process over 3.5h. 129 patients underwent CD and completed a total of 788cycles. The desensitization protocol prevented HSRs in 96% (753 out of 788) of these cycles. Patients achieved an average of 6.1cycles (SD±4.55, range 0-23) with CD. The CD protocol allowed 73% (94 of 129) of the patients to undergo carboplatin infusion without reaction. Patients with moderate to life-threatening HSRs (grade 2 through 4) were 10.5years younger at initial CD than patients with grades 0 or 1 HSRs (52.3 vs. 63, P = 0.0307). One patient death occurred during her thirteenth desensitization cycle. The HSR in this case was complicated by pre-exisiting pulmonary hypertension. This is the largest study of its kind showing a safe, effective and rapid (3.5h) CD protocol. The majority of patients with a history of either carboplatin hypersensitivity reaction or a positive skin test completed the CD protocol without HSRs. Age was identified as a risk factor for HSR severity during CD. Age can be employed along with pre-load dependent cardiac conditions as a way to help risk stratify patients undergoing CD. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Antitumor carboplatin is more toxic in tumor cells when photoactivated: enhanced DNA binging

    Czech Academy of Sciences Publication Activity Database

    Mlčoušková, Jarmila; Štěpánková, Jana; Brabec, Viktor

    2012-01-01

    Roč. 17, č. 6 (2012), s. 891-898 ISSN 0949-8257 R&D Projects: GA ČR(CZ) GD301/09/H004; GA ČR(CZ) GAP301/10/0598 Institutional research plan: CEZ:AV0Z50040702 Keywords : carboplatin * photodynamic therapy * DNA Subject RIV: BO - Biophysics Impact factor: 3.353, year: 2012

  15. Occurrence of cyclophosphamide and ifosfamide in aqueous environment and their removal by biological and abiotic wastewater treatment processes.

    Science.gov (United States)

    Česen, Marjeta; Kosjek, Tina; Laimou-Geraniou, Maria; Kompare, Boris; Širok, Brane; Lambropolou, Dimitra; Heath, Ester

    2015-09-15

    Cytostatic drug residues in the aqueous environment are of concern due to their possible adverse effects on non-target organisms. Here we report the occurrence and removal efficiency of cyclophosphamide (CP) and ifosfamide (IF) by biological and abiotic treatments including advanced oxidation processes (AOPs). Cyclophosphamide was detected in hospital wastewaters (14-22,000 ng L(-1)), wastewater treatment plant influents (19-27 ng L(-1)) and effluent (17 ng L(-1)), whereas IF was detected only in hospital wastewaters (48-6800 ng L(-1)). The highest removal efficiency during biological treatment (attached growth biomass in a flow through bioreactor) was 59 ± 15% and 35 ± 9.3% for CP and IF, respectively. Also reported are the removal efficiencies of both compounds from wastewater using hydrodynamic cavitation (HC), ozonation (O3) and/or UV, either individually or in combination with hydrogen peroxide (H2O2). Hydrodynamic cavitation did not remove CP and IF to any significant degree. The highest removal efficiencies: 99 ± 0.71% for CP and 94 ± 2.4% for IF, were achieved using UV/O3/H2O2 at 5 g L(-1) for 120 min. When combined with biological treatment, removal efficiencies were >99% for both compounds. This is the first report of combined biological and AOP treatment of CP and IF from wastewater with a removal efficiency >99%. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. A Randomized, Controlled Trial of Rituximab in IgA Nephropathy with Proteinuria and Renal Dysfunction.

    Science.gov (United States)

    Lafayette, Richard A; Canetta, Pietro A; Rovin, Brad H; Appel, Gerald B; Novak, Jan; Nath, Karl A; Sethi, Sanjeev; Tumlin, James A; Mehta, Kshama; Hogan, Marie; Erickson, Stephen; Julian, Bruce A; Leung, Nelson; Enders, Felicity T; Brown, Rhubell; Knoppova, Barbora; Hall, Stacy; Fervenza, Fernando C

    2017-04-01

    IgA nephropathy frequently leads to progressive CKD. Although interest surrounds use of immunosuppressive agents added to standard therapy, several recent studies have questioned efficacy of these agents. Depleting antibody-producing B cells potentially offers a new therapy. In this open label, multicenter study conducted over 1-year follow-up, we randomized 34 adult patients with biopsy-proven IgA nephropathy and proteinuria >1 g/d, maintained on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers with well controlled BP and eGFR<90 ml/min per 1.73 m 2 , to receive standard therapy or rituximab with standard therapy. Primary outcome measures included change in proteinuria and change in eGFR. Median baseline serum creatinine level (range) was 1.4 (0.8-2.4) mg/dl, and proteinuria was 2.1 (0.6-5.3) g/d. Treatment with rituximab depleted B cells and was well tolerated. eGFR did not change in either group. Rituximab did not alter the level of proteinuria compared with that at baseline or in the control group; three patients in each group had ≥50% reduction in level of proteinuria. Serum levels of galactose-deficient IgA1 or antibodies against galactose-deficient IgA1 did not change. In this trial, rituximab therapy did not significantly improve renal function or proteinuria assessed over 1 year. Although rituximab effectively depleted B cells, it failed to reduce serum levels of galactose-deficient IgA1 and antigalactose-deficient IgA1 antibodies. Lack of efficacy of rituximab, at least at this stage and severity of IgA nephropathy, may reflect a failure of rituximab to reduce levels of specific antibodies assigned salient pathogenetic roles in IgA nephropathy. Copyright © 2017 by the American Society of Nephrology.

  17. Long-term safety of rituximab induced peripheral B-cell depletion in autoimmune neurological diseases.

    Directory of Open Access Journals (Sweden)

    Anza B Memon

    Full Text Available B-cells play a pivotal role in several autoimmune diseases, including patients with immune-mediated neurological disorders (PIMND, such as neuromyelitis optica (NMO, multiple sclerosis (MS, and myasthenia gravis (MG. Targeting B-cells has been an effective approach in ameliorating both central and peripheral autoimmune diseases. However, there is a paucity of literature on the safety of continuous B-cell depletion over a long period of time.The aim of this study was to examine the long-term safety, incidence of infections, and malignancies in subjects receiving continuous therapy with a B-cell depleting agent rituximab over at least 3 years or longer.This was a retrospective study involving PIMND who received continuous cycles of rituximab infusions every 6 to 9 months for up to 7 years. The incidence of infection related adverse events (AE, serious adverse events (SAE, and malignancies were observed.There were a total of 32 AE and 4 SAE with rituximab treatment. The 3 SAE were noted after 9 cycles (48 months and 1 SAE was observed after 11 cycles (60 months of rituximab. There were no cases of Progressive multifocal leukoencephalopathy (PML and malignancies observed throughout the treatment period. Rituximab was well tolerated without any serious infusion reactions. Also, rituximab was found to be beneficial in treating PIMND over a 7-year period.This study demonstrates that long-term depletion of peripheral B-cells appears safe and efficacious in treating PIMND. Longer and larger prospective studies with rituximab are needed to carefully ascertain risks associated with chronic B-cell depletion, including malignancies. Recognizing that this is a small, retrospective study, such data nonetheless complement the growing literature documenting the safety and tolerability of B-cell depleting agents in neurological diseases.

  18. Efficacy and safety of rituximab in neuromyelitis optica: Review of evidence

    Directory of Open Access Journals (Sweden)

    Masoud Etemadifar

    2017-01-01

    Full Text Available Neuromyelitis optica (NMO is an autoimmune inflammatory disease of the central nervous system with preferential involvement in the optic nerve and spinal cord with a widespread spectrum of clinical features; multiple therapeutic agents have been used with different results. Recent evidence points to B-cell-mediated humoral immunity in the pathogenesis of NMO. Rituximab targets the CD20 antigen on B-cells. Treatment leads to profound B-cell depletion, principally over an antibody-dependent cell cytotoxicity mechanism. The aim of our study was to review clinical trials to elucidate the impact of rituximab on the relapse rate, Expanded Disability Status Scale (EDSS, and progression of disability in NMO. We performed a comprehensive review of all studies that evaluated clinical and paraclinical effects of rituximab on NMO. MEDLINE-PubMed, Web of Sciences, EMBASE, and Cochrane databases up to June 2016 included in our searches. In addition, reference lists from articles identified by search as well as a key review article to identify additional articles included in the study. Rituximab targets the CD20 antigen on B-cells and decreases attack frequency and severity in patients with NMO; however, it does not remove attacks, even when modifying treatment to achieve B-cell depletion. Most of the investigations revealed that EDSS significantly in all patients with rituximab treatment will be decreased after treatment with rituximab. No new or enlarged lesions or pathological gadolinium enhancement was observed in serial brain and spinal cord magnetic resonance imaging, except for those observed concomitantly with clinical relapses and the median length of spinal cord lesions was significantly reduced after therapy. Rituximab targets the CD20 antigen and decreases attack frequency and severity in patients with NMO.

  19. Use of adjuvant carboplatin for treatment of dogs with oral malignant melanoma following surgical excision.

    Science.gov (United States)

    Dank, G; Rassnick, K M; Sokolovsky, Y; Garrett, L D; Post, G S; Kitchell, B E; Sellon, R K; Kleiter, M; Northrup, N; Segev, G

    2014-03-01

    Melanoma is the most common oral malignancy in dogs. This retrospective study evaluated adjuvant carboplatin chemotherapy (with or without radiation therapy) in 17 dogs with malignant oral melanoma following surgical resection. The median dosage and number of doses of carboplatin administered to the 17 dogs was 300 mg m(-2) (range, 150-300 mg m(-2)) and 4 (range, 2-11), respectively. The overall median progression-free survival for all dogs was 259 days [95% confidence interval (CI95), 119-399 days]. The first progression-free survival event was local recurrence in seven dogs (41%) and metastases in seven dogs (41%). The median overall survival for all dogs was 440 days (CI95, 247-633 days). The tumour was the cause of death in 10 dogs (59%). On the basis of this study, systemic therapy with carboplatin may be an appropriate adjunct to local treatment for canine malignant melanoma, although future prospective controlled studies are needed to compare treatment modalities for this aggressive neoplasia. © 2012 John Wiley & Sons Ltd.

  20. Evaluation of Weight Change During Carboplatin Therapy in Dogs With Appendicular Osteosarcoma.

    Science.gov (United States)

    Story, A L; Boston, S E; Kilkenny, J J; Singh, A; Woods, J P; Culp, W T N; Skorupski, K A; Lu, X

    2017-07-01

    The prevalence of cancer cachexia in veterinary medicine has not been studied widely, and as of yet, no definitive diagnostic criteria effectively assess this syndrome in veterinary patients. (1) To determine the patterns of weight change in dogs with appendicular osteosarcoma treated with amputation and single-agent carboplatin during the course of adjuvant chemotherapy; and (2) to determine whether postoperative weight change is a negative prognostic indicator for survival time in dogs with osteosarcoma. Eighty-eight dogs diagnosed with appendicular osteosarcoma. Animals were accrued from 3 veterinary teaching hospitals. Retrospective, multi-institutional study. Dogs diagnosed with appendicular osteosarcoma and treated with limb amputation followed by a minimum of 4 doses of single-agent carboplatin were included. Data analyzed in each patient included signalment, tumor site, preoperative serum alkaline phosphatase activity (ALP), and body weight (kg) at each carboplatin treatment. A slight increase in weight occurred over the course of chemotherapy, but this change was not statistically significant. Weight change did not have a significant effect on survival. Institution, patient sex, and serum ALP activity did not have a significant effect on survival. Weight change was not a prognostic factor in these dogs, and weight loss alone may not be a suitable method of determining cancer cachexia in dogs with appendicular osteosarcoma. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  1. nab-Paclitaxel in Combination with Carboplatin for a Previously Treated Thymic Carcinoma

    Directory of Open Access Journals (Sweden)

    Go Makimoto

    2014-01-01

    Full Text Available We present the case of a 40-year-old man with previously treated thymic carcinoma, complaining of gradually worsening back pain. Computed tomography scans of the chest showed multiple pleural disseminated nodules with a pleural effusion in the right thorax. The patient was treated with carboplatin on day 1 plus nab-paclitaxel on day 1 and 8 in cycles repeated every 4 weeks. Objective tumor shrinkage was observed after 4 cycles of this regimen. In addition, the elevated serum cytokeratin 19 fragment level decreased, and the patient's back pain was relieved without any analgesics. Although he experienced grade 4 neutropenia and granulocyte colony-stimulating factor (G-CSF injection, the severity of thrombocytopenia and nonhematological toxicities such as reversible neuropathy did not exceed grade 1 during the treatment. To our knowledge, this is the first report to demonstrate the efficacy of combination chemotherapy consisting of carboplatin and nab-paclitaxel against thymic carcinoma. This case report suggests that nab-paclitaxel in combination with carboplatin can be a favorable chemotherapy regimen for advanced thymic carcinoma.

  2. Intraperitoneal carboplatin: favorable results in women with minimal residual ovarian cancer after cisplatin therapy.

    Science.gov (United States)

    Speyer, J L; Beller, U; Colombo, N; Sorich, J; Wernz, J C; Hochster, H; Green, M; Porges, R; Muggia, F M; Canetta, R

    1990-08-01

    From August 1985 to November 1989 we conducted a trial of intraperitoneal (IP) carboplatin including a dose-escalation design in 25 women with advanced gynecologic malignancies. All had extensive prior therapy with cisplatin (median cumulative dose, 525 mg/m2). Carboplatin was administered IP in 2 L of 1.5% dextrose with a 4-hour dwell time every 4 weeks for six cycles at a starting dose of 200 mg/m2. Patients with reduced creatinine clearance (30 to 60 cc/min) were escalated more slowly than those with high (greater than 60 cc/min) clearance. Thrombocytopenia was dose-limiting and often more severe in patients with compromised renal function; there was no local drug toxicity. The median time of follow-up is 25 months. Complete responses (CRs) were documented in six of 23 assessable patients (26%) by repeat laparotomy, and an additional 11 patients (48%) had no disease evident by noninvasive restaging. Five of the CRs and six of the patients with no clinically evident disease have relapsed from 3 to 40 months after therapy. Six patients (26%) are alive and free of disease 8 to 47 (median, 20) months after therapy. IP carboplatin is effective against relapsed ovarian cancer, even after prior cisplatin therapy.

  3. Intraperitoneal chemotherapy in the management of ovarian cancer: focus on carboplatin

    Directory of Open Access Journals (Sweden)

    Maurie Markman

    2009-02-01

    Full Text Available Maurie MarkmanUniversity of Texas MD Anderson Cancer Center, Houston, Texas, USAAbstract: Both pre-clinical studies and phase 1–2 clinical trials have provided strong support for the potential role of regional drug delivery in the management of epithelial ovarian cancer, a disease process whose major manifestations remain largely localized to the peritoneal cavity in the majority of individuals with this malignancy. The results of 3 phase 3 randomized trials have revealed the favorable impact of primary cisplatin-based intraperitoneal chemotherapy in women who initiate drug treatment with small-volume residual ovarian cancer following an attempt at optimal surgical cytoreduction. Concerns have been raised regarding the toxicity of regional treatment, particularly the side-effect profile associated with cisplatin. One rational approach to improving the tolerability of intraperitoneal chemotherapy is to substitute carboplatin for cisplatin. This review discusses the rationale for and data supporting regional treatment of epithelial ovarian cancer, and highlights the potential role for intraperitoneal carboplatin in this clinical setting.Keywords: ovarian cancer, intraperitoneal chemotherapy, cisplatin, carboplatin

  4. Absolute lymphocyte count predicts response to rituximab-containing salvage treatment for relapsed/refractory B-cell non-Hodgkin's lymphoma with prior rituximab exposure

    Directory of Open Access Journals (Sweden)

    Man-Hsin Hung

    2013-04-01

    Conclusion: Our study results show that for patients with relapsed/refractory B-cell NHL, rituximab-containing salvage treatment is feasible and generally tolerable. A high ALC-R value was significantly associated with a better response to this treatment.

  5. Clinical study on bevacizumab combined with carboplatin therapy for malignant pleural effusion of non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Li-Ping Yang1

    2017-06-01

    Full Text Available Objective: To investigate the effect of bevacizumab combined with carboplatin therapy for malignant pleural effusion of non-small cell lung cancer on tumor markers, angiogenesis molecules and invasive growth molecules. Methods: A total of 68 patients who were diagnosed with non-small cell lung cancer complicated by pleural effusion in the Affiliated T.C.M Hospital of Southwest Medical University between June 2013 and August 2016 were selected and randomly divided into two groups, the combined group received bevacizumab combined with carboplatin chemotherapy, and the carboplatin group received carboplatin chemotherapy. Before treatment as well as 3 cycles and 6 cycles after treatment, the contents of tumor markers, angiogenesis molecules and invasive growth molecules in pleural effusion were examined. Results: 3 cycles and 6 cycles after treatment, CEA, SCCAg, CYFRA21-1, sHLA-G, VEGF, VEGFR, PTN, MMP7 and MMP10 contents in pleural effusion of both groups of patients were significantly lower than those before treatment while TIMP1 and TIMP2 contents were significantly higher than those before treatment, and CEA, SCCAg, CYFRA21-1, sHLA-G, VEGF, VEGFR, PTN, MMP7 and MMP10 contents in pleural effusion of combined group were significantly lower than those of carboplatin group while TIMP1 and TIMP2 contents were significantly higher than those of carboplatin group. Conclusion: Bevacizumab combined with carboplatin therapy for malignant pleural effusion of non-small cell lung cancer can effectively kill cancer cells, and inhibit angiogenesis and cell invasion.

  6. Novel use of rituximab in a case of Riedel's thyroiditis refractory to glucocorticoids and tamoxifen.

    Science.gov (United States)

    Soh, Shui-Boon; Pham, Alan; O'Hehir, Robyn E; Cherk, Martin; Topliss, Duncan J

    2013-09-01

    A 42-year-old woman presented with a rapidly enlarging right-sided thyroid mass and underwent hemithyroidectomy. Riedel's thyroiditis was only diagnosed upon surgical decompression of the right carotid artery 2 years later. She became more symptomatic as Riedel's thyroiditis progressed, and mediastinal fibrosclerosis developed over the next 12 months. Oral prednisolone failed to improve her condition, and she was commenced on tamoxifen. Despite initial improvement, her symptoms recurred 2 years later, mainly arising from compression of the trachea and esophagus at the thoracic inlet. Fluorodeoxyglucose positron emission tomographic scan showed locally advanced active invasive fibrosclerosis in the neck and mediastinum. An elevated activin-A level of 218 pg/mL was consistent with active inflammation. IgG subtypes (including IgG4) were normal. Two courses of iv methylprednisolone were given but only produced transient improvement. Subsequently, the patient received 3 doses of i.v. rituximab at monthly intervals and had prompt sustained symptomatic improvement. Activin-A level decreased to 122 pg/mL 10 months after rituximab therapy. Fluorodeoxyglucose positron emission tomographic scan 6 weeks after therapy showed reduction in inflammation. A further scan at 10 months demonstrated ongoing response to rituximab. This is a case of refractory Riedel's thyroiditis with symptomatic, biochemical, and radiological improvement that has persisted 14 months after rituximab. The likelihood and duration of response to rituximab in Riedel's thyroiditis requires further study.

  7. Rituximab treatment for relapsed opsoclonus-myoclonus syndrome.

    Science.gov (United States)

    Toyoshima, Daisaku; Morisada, Naoya; Takami, Yuichi; Kidokoro, Hiroyuki; Nishiyama, Masahiro; Nakagawa, Taku; Ninchoji, Takeshi; Nozu, Kandai; Takeshima, Yasuhiro; Takada, Satoshi; Nishio, Hisahide; Iijima, Kazumoto

    2016-03-01

    Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disorder that is associated with paraneoplastic diseases. Because OMS can frequently relapse, patients may be inflicted with neurological problems for a long time. Recently, rituximab (RTX) was introduced as a drug to treat OMS. To assess RTX treatment, we studied a patient who experienced recurrence of OMS. A 2-year-old Japanese boy, who had left adrenal neuroblastoma, suddenly showed OMS symptoms, including ataxia and opsoclonus. Surgical resection of the tumor and subsequent steroid therapy ameliorated his symptoms. When OMS relapsed during the time when prednisolone was reduced, he was treated with full-dose RTX therapy (375 mg/m2/week) for 4 consecutive weeks. However, 1year later, he presented again with OMS symptoms. This time, we only administered an additional single dose of RTX treatment (375 mg/m2), allowing remission of OMS symptoms. During 2 years after the additional RTX treatment, OMS symptoms did not appear, even when prednisolone was reduced. He had no adverse events associated with RTX during the whole treatment period. An additional single-dose RTX therapy might be effective for relapsed OMS patients who were previously treated with full-dose RTX therapy. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  8. Remission Achieved in Refractory Advanced Takayasu Arteritis Using Rituximab

    Directory of Open Access Journals (Sweden)

    D. Ernst

    2012-01-01

    Full Text Available A 25-year-old patient was referred due to subclavian stenosis, identified on echocardiography. She presented with exertional dizziness and dyspnoea. Questioning revealed bilateral arm claudication. Examination demonstrated an absent right ulnar pulse and asymmetrical brachial blood pressure. Bruits were evident over both common carotid arteries. Doppler ultrasound and MRI angiograms revealed occlusion or stenosis in multiple large arteries. Takayasu arteritis (TA was diagnosed and induction therapy commenced: 1 mg/kg oral prednisolone and 500 mg/m2 intravenous cyclophosphamide (CYC. Attempts to reduce prednisolone below 15 mg/d proved impossible due to recurring disease activity. Adjuvant azathioprine 100 mg/d was subsequently added. Several weeks later, the patient was admitted with a left homonymous hemianopia. The culprit lesion in the right carotid artery was surgically managed and the patient discharged on azathioprine 150 mg/d and prednisolone 30 mg/d. Despite this, deteriorating exertional dyspnoea and angina pectoris were reported. Reimaging confirmed new stenosis in the right pulmonary artery. Surgical treatment proved infeasible. Given evidence of refractory disease activity on maximal standard therapy, we initiated rituximab, based on recently reported B-cell activity in TA.

  9. Effect of baseline rheumatoid factor and anticitrullinated peptide antibody serotype on rituximab clinical response: a meta-analysis

    NARCIS (Netherlands)

    Isaacs, John D.; Cohen, Stanley B.; Emery, Paul; Tak, Paul P.; Wang, Jianmei; Lei, Guiyuan; Williams, Sarah; Lal, Preeti; Read, Simon J.

    2013-01-01

    Studies examining the relationship between serological status (rheumatoid factor and/or anticitrullinated antibody) and rituximab treatment outcome in rheumatoid arthritis (RA) have been hampered by limited numbers of seronegative patients. To carry out a meta-analysis of trials from the rituximab

  10. B cells and immunoglobulin in ABO-incompatible renal transplant patients receiving rituximab and double filtration plasmapheresis

    Directory of Open Access Journals (Sweden)

    Meng-Kun Tsai

    2015-04-01

    Conclusion: With the aid of tacrolimus and mycophenolate mofetil, rituximab resulted in sustained suppression of B cell count and total IgG and IgM. Among the IgG subclasses, IgG3 was less sensitive to rituximab.

  11. Neoadjuvant Interdigitated Chemoradiotherapy Using Mesna, Doxorubicin, and Ifosfamide for Large, High-grade, Soft Tissue Sarcomas of the Extremity: Improved Efficacy and Reduced Toxicity.

    Science.gov (United States)

    Chowdhary, Mudit; Sen, Neilayan; Jeans, Elizabeth B; Miller, Luke; Batus, Marta; Gitelis, Steven; Wang, Dian; Abrams, Ross A

    2018-05-18

    Patients with large, high-grade extremity soft tissue sarcoma (STS) are at high risk for both local and distant recurrence. RTOG 95-14, using a regimen of neoadjuvant interdigitated chemoradiotherapy with mesna, doxorubicin, ifosfamide, and dacarbazine followed by surgery and 3 cycles of adjuvant mesna, doxorubicin, ifosfamide, and dacarbazine, demonstrated high rates of disease control at the cost of significant toxicity (83% grade 4, 5% grade 5). As such, this regimen has not been widely adopted. Herein, we report our institutional outcomes utilizing a modified interdigitated chemoradiotherapy regimen, without dacarbazine, and current radiotherapy planning and delivery techniques for high-risk STS. Adults with large (≥5 cm; median, 12.9 cm), grade 3 extremity STS who were prospectively treated as part of our institutional standard of care from 2008 to 2016 are included. Neoadjuvant chemoradiotherapy consisted of 3 cycles of mesna, doxorubicin, and ifosfamide (MAI) and 44 Gy (22 Gy in 11 fractions between cycles of MAI) after which patients underwent surgical resection and received 3 additional cycles of MAI. Twenty-six patients received the MAI treatment protocol. At a median follow-up of 47.3 months, 23 (88.5%) patients are still alive. Three year locoregional recurrence-free survival, disease-free survival, and overall survival are 95.0%, 64.0%, and 95.0%, respectively. There have been no therapy-related deaths or secondary malignancies. The nonhematologic grade 4 toxicity rate was 7.7%. Neoadjuvant interdigitated MAI radiotherapy followed by resection and 3 cycles of adjuvant MAI has resulted in acceptable and manageable toxicity and highly favorable survival in patients at greatest risk for treatment failure.

  12. A phase II study of VP-16-ifosfamide-cisplatin combination chemotherapy plus early concurrent thoracic irradiation for previously untreated limited small cell lung cancer

    International Nuclear Information System (INIS)

    Woo, In Sook; Park, Young Suk; Kwon, Sung Hee

    2000-01-01

    At present the addition of thoracic irradiation to combination chemotherapy is a standard treatment for limited staged small cell ling cancer. However, there is still controversy about the optimum timing of chest irradiation. We conducted a phase II study of etoposide (VP-16)-ifosfamide-cisplatin (VIP) combination chemotherapy plus early concurrent thoracic irradiation for the patients with previously untreated limited small cell lung cancer in order to assess if the treatment modality could improve the response rate and the toxicity. Forty-four patients with limited small cell lung cancer were treated with etoposide-ifosfamide-cisplatin and concurrent thoracic irradiation. Combination chemotherapy consisted of etoposide 100 mg/m 2 (on day 1-3), ifosfamide 1000 mg/m 2 (on days 1 and 2) and cisplatin 100 mg/m 2 (on day 1). Concurrent thoracic irradiation consisted of a total of 4000 cGy over 4 weeks starting on the first day of the first chemotherapy. All patients who showed a complete response were given prophylactic cranial irradiation for 2.5 weeks. Forty-four of the 49 patients who entered the study from May 1994 to August 1998 were evaluable. The median age was 59 years and 40 patients had a performance status of 0 or 1. The median survival time was 22.5 months. Twenty-eight patients (62%) showed a complete response and 16 (38%) a partial response. Twenty-four patients (54%) developed grade 3 or 4 neutropenia; there was a 9% RTOG score 3 or 4 esophagitis. VIP combination chemotherapy and early concurrent thoracic irradiation for patients with limited stage small cell lung cancer revealed excellent antitumor response with tolerable toxicity. (author)

  13. Pneumocystis jiroveci Pneumonia in Patients with Non-Hodgkin's Lymphoma Receiving Chemotherapy Containing Rituximab

    Directory of Open Access Journals (Sweden)

    Hung Chang

    2008-11-01

    Full Text Available Rituximab enhances treatment efficacy of B-lineage lymphoma by targeting CD20+ B-cells. Such target therapies may compromise the immune system and render patients susceptible to opportunistic infections. We report 2 cases of lymphoma complicated with Pneumocystis jiroveci (previously known as P. carinii pneumonia (PCP while being treated with rituximab-containing chemotherapy regimens. In both cases, PCP developed during the neutropenic period. With timely diagnosis and proper management, both were treated successfully. We searched the literature and found that such opportunistic infection occurred only infrequently in lymphoma patients, and it has not been reported in the large-scale clinical trials of rituximab. Such cases demonstrate the importance of taking PCP into diagnostic consideration in lymphoma patients receiving similar therapies.

  14. Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON)

    DEFF Research Database (Denmark)

    Jerkeman, Mats; Eskelund, Christian Winther; Hutchings, Martin

    2018-01-01

    BACKGROUND: Regimens based on ibrutinib alone and lenalidomide and rituximab in combination show high activity in patients with relapsed or refractory mantle cell lymphoma. We hypothesised that the combination of all three drugs would improve efficacy compared with previously published data...... performance status score of 0-3, and at least one site of measurable disease, and who met criteria for several laboratory-assessed parameters. Treatment was divided into an induction phase of 12 cycles of 28 days with all three drugs and a maintenance phase with ibrutinib and rituximab only (cycle duration 56...... days), given until disease progression or unacceptable toxicity. In the induction phase, patients received intravenous (375 mg/m2) or subcutaneous (1400 mg) rituximab once a week during cycle 1 and then once every 8 weeks. Oral ibrutinib (560 mg once a day) was given to patients every day in the cycle...

  15. Rituximab in the treatment of primary cutaneous B-cell lymphoma: a review.

    Science.gov (United States)

    Fernández-Guarino, M; Ortiz-Romero, P L; Fernández-Misa, R; Montalbán, C

    2014-06-01

    Rituximab is a chimeric mouse-human antibody that targets the CD20 antigen, which is found in both normal and neoplastic B cells. In recent years, it has been increasingly used to treat cutaneous B-cell lymphoma and is now considered an alternative to classic treatment (radiotherapy and surgery) of 2 types of indolent lymphoma, namely, primary cutaneous follicle center lymphoma and primary cutaneous marginal zone B-cell lymphoma. Rituximab is also administered as an alternative to polychemotherapy in the treatment of primary cutaneous large B-cell lymphoma, leg type. Its use as an alternative drug led to it being administered intralesionally, with beneficial effects. In the present article, we review the literature published on the use of rituximab to treat primary cutaneous B-cell lymphoma. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

  16. A Case of Rituximab-Induced Necrotizing Fasciitis and a Review of the Literature

    Directory of Open Access Journals (Sweden)

    Abdullateef Abdulkareem

    2017-01-01

    Full Text Available Necrotizing fasciitis is a fulminant soft tissue infection characterized by rapid progression and high mortality. Rituximab is a generally well-tolerated immunosuppresive medication used for B-cell malignancies and some rheumatological disorders. We report a case of a 69-year-old male with chronic lymphocytic leukemia who suffered necrotizing fasciitis of his left lower extremity secondary to Clostridium septicum 7 weeks after treatment with rituximab. Despite immediate intravenous antimicrobial therapy and emergent fasciotomy with extensive debridement, his hospital course was complicated by septic shock and he required an above-the-knee amputation. Physicians need to be aware of the possibility of necrotizing fasciitis in patients presenting with skin infections after rituximab therapy.

  17. A Case of Rituximab-Induced Necrotizing Fasciitis and a Review of the Literature.

    Science.gov (United States)

    Abdulkareem, Abdullateef; D'Souza, Ryan S; Shogbesan, Oluwaseun; Donato, Anthony

    2017-01-01

    Necrotizing fasciitis is a fulminant soft tissue infection characterized by rapid progression and high mortality. Rituximab is a generally well-tolerated immunosuppresive medication used for B-cell malignancies and some rheumatological disorders. We report a case of a 69-year-old male with chronic lymphocytic leukemia who suffered necrotizing fasciitis of his left lower extremity secondary to Clostridium septicum 7 weeks after treatment with rituximab. Despite immediate intravenous antimicrobial therapy and emergent fasciotomy with extensive debridement, his hospital course was complicated by septic shock and he required an above-the-knee amputation. Physicians need to be aware of the possibility of necrotizing fasciitis in patients presenting with skin infections after rituximab therapy.

  18. Remission Time after Rituximab Treatment for Autoimmune Bullous Disease: A Proposed Update Definition.

    Science.gov (United States)

    Iranzo, Pilar; Pigem, Ramon; Giavedoni, Priscila; Alsina-Gibert, Mercè

    2015-01-01

    A therapeutic endpoint is a very important tool to evaluate response in clinical trials. In 2005, a consensus statement identified two late endpoints of disease activity in pemphigus: complete remission off therapy and complete remission on therapy, both definitions applying to patients without lesions for at least 2 months. The same period of time was considered for partial remission off/on therapy. These definitions were later applied to bullous pemphigoid and are considered in most studies on autoimmune bullous disease. These endpoints were established for different adjuvant agents, but at that moment, rituximab was not considered. Rituximab is known for the long duration of its effect, and in most studies relapses have been reported later than 6 months after treatment. In our opinion, time to remission after rituximab treatment should be redefined. © 2015 S. Karger AG, Basel.

  19. Experiencia con rituximab en miopatía inflamatoria idiopática refractaria

    Directory of Open Access Journals (Sweden)

    Elmer R. García-Salazar

    2013-10-01

    Full Text Available Se describe las características clínicas y de laboratorio de dos pacientes que recibieron rituximab por miopatía inflamatoria idiopática (MII. Ellas eran refractarias a tratamiento convencional con DARMES, por lo que recibieron rituximab 1 gramo cada 14 días, en dos infusiones en ciclo semestral. En las historias clínicas se obtuvo los datos clínicos de fuerza muscular proximal, lesiones cutáneas patognomónicas, elevación de CPK, TGO, DHL y VSG, resultados de electromiografía, biopsia muscular y de piel. Ninguno de los dos casos presentó reacción medicamentosa ni infecciones durante y posterior a las infusiones. Rituximab mostró efectividad en la respuesta clínica y enzimática en estas pacientes con dermatomiositis refractarias a corticoides y DARMES tradicionales.

  20. Rituximab as maintenance therapy for ANCA associated vasculitis: how, when and why?

    Science.gov (United States)

    Alba, Marco A; Flores-Suárez, Luis Felipe

    2016-01-01

    ANCA-associated vasculitides (AAV) are chronic autoimmune diseases characterized by inflammation and destruction of small vessels. Rituximab is now licensed for use as a remission-induction agent in the treatment of these disorders. During recent years, several non-controlled studies have suggested that rituximab may be of value in maintaining disease remission in AAV. In these series, 3 techniques have been tried: "watch-and-wait", repeated cycles in fixed intervals, or administration based on proposed biomarkers. More importantly, the results of the MAINRITSAN trial showed that this anti-CD20 agent is superior to azathioprine for preventing major relapses in AAV. This review summarizes current information regarding the effectiveness, timing, dosing, duration and safety of rituximab as a valid option for remission maintenance. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  1. Rituximab as a first-line agent for the treatment of dermatomyositis.

    LENUS (Irish Health Repository)

    2012-02-01

    B cells may play a pivotal role in the pathophysiology of DM, and reports have claimed that targeting B cells is a viable treatment option in patients with dermatomyositis. A 20-year-old girl presented in October 2007, with few weeks\\' history of proximal muscle weakness. Gottron\\'s papules were noted on her knuckles. She had normal inflammatory markers and negative autoantibody screen. Her CPK was 7,000 U\\/L (normal range 0-170) with an LDH of 1,300 U\\/L (normal range 266-500). EMG and muscle biopsy was consistent with active myositis. She had normal pulmonary function tests. HRCT showed no interstitial lung disease. She was started with 60 mg glucocorticoids (1 mg\\/kg), with a good clinical response. However, any attempt to taper down the steroid dose led to recurrence of her symptoms. The options of available immunosuppressive therapies, including the experimental usage of rituximab, were discussed with her; averse to long-term systemic treatments, she opted to try a course of rituximab. She had rituximab 1,000 mg on days 0 and 14, and her glucocorticoids were tapered in next few weeks. Now, 24 months since her rituximab infusions, she remains in complete clinical and biochemical remission and is naive to other immunosuppressive agents apart from glucocorticoids and rituximab. Depleting peripheral B cells with rituximab (one course) in our patient has led not only to complete resolution of muscle and skin disease (induction) but also remains off all immunosuppressives including glucocorticoids.

  2. Prophylaxis of hepatitis B reactivation using lamivudine in a patient receiving rituximab.

    Science.gov (United States)

    Hamaki, T; Kami, M; Kusumi, E; Ueyama, J; Miyakoshi, S; Morinaga, S; Mutou, Y

    2001-12-01

    A 53-year-old man who had a history of fluminant hepatitis caused by precore mutant hepatitis B virus (HBV) was admitted to our hospital for the treatment of relapsed non-Hodgkin's lymphoma in July 2000. At admission, serum levels of aspartate aminotransferase and alanine aminotransferase were normal, but he tested positive for HBs antigen. The titer was 64-fold by radioimmunoassay. We initiated lamivudine at a daily dose of 75 mg to prevent HBV proliferation during chemotherapy. By September 2000, he had received six courses of rituximab at 375 mg/m(2) and four courses of fludarabine and mitoxantrone. No hepatic damage was observed from the initiation of treatment until March 2001. At present, four months after the completion of chemotherapy, he continues lamivudine, and the titer of HBs antigen is low at 4-fold. Rituximab is usually associated with mild toxicity, usually limited to infusion periods. The drug is not generally associated with increased incidence of opportunistic infections. However, some case reports have been recently published on severe viral infections following administration of rituximab. These include fluminant hepatitis caused by HBV, pure red cell aplasia due to parvovirus B19 and fatal varicella-zoster infection. While it remains unknown whether rituximab can be safely administered in patients with chronic HBV infection, this case report suggested that prophylactic administration of lamivudine is beneficial for suppressing reactivation of HBV during chemotherapy including rituximab. Rituximab should be used cautiously for patients with HBV infection, but prophylactic administration of lamivudine may be beneficial for preventing reactivation of HBV. Copyright 2001 Wiley-Liss, Inc.

  3. Randomized phase II trial of carboplatin versus paclitaxel and carboplatin in platinum-sensitive recurrent advanced ovarian carcinoma: a GEICO (Grupo Espanol de Investigacion en Cancer de Ovario) study.

    Science.gov (United States)

    González-Martín, A J; Calvo, E; Bover, I; Rubio, M J; Arcusa, A; Casado, A; Ojeda, B; Balañá, C; Martínez, E; Herrero, A; Pardo, B; Adrover, E; Rifá, J; Godes, M J; Moyano, A; Cervantes, A

    2005-05-01

    The aim of this study was to determine whether the response rate for the paclitaxel-carboplatin combination is superior to carboplatin alone in the treatment of patients with platinum-sensitive recurrent ovarian carcinoma. Patients with recurrent ovarian carcinoma, 6 months after treatment with a platinum-based regimen and with no more than two previous chemotherapy lines, were randomized to receive carboplatin area under the curve (AUC) 5 (arm A) or paclitaxel 175 mg/m(2) + carboplatin AUC 5 (arm B). The primary end point was objective response, following a 'pick up the winner' design. Secondary end points included time to progression (TTP), overall survival, tolerability and quality of life (QoL). Eighty-one patients were randomized and included in the intention-to-treat analysis. The response rate in arm B was 75.6% [26.8% complete response (CR) + 48.8% partial response (PR)] [95% confidence interval (CI) 59.7% to 87.6%] and 50% in arm A (20% CR + 30% PR) (95% CI 33.8% to 66.2%). No significant differences were observed in grade 3-4 hematological toxicity. Conversely, mucositis, myalgia/arthralgia and peripheral neurophaty were more frequent in arm B. Median TTP was 49.1 weeks in arm B (95% CI 36.9-61.3) and 33.7 weeks in arm A (95% CI 25.8-41.5). No significant differences were found in the QoL analysis. Paclitaxel-carboplatin combination is a tolerable regimen with a higher response rate than carboplatin monotherapy in platinum-sensitive recurrent ovarian carcinoma.

  4. Crohn's disease complicated by Epstein-Barr virus-driven haemophagocytic lymphohistiocytosis successfully treated with rituximab.

    Science.gov (United States)

    Thompson, Grace; Pepperell, Dominic; Lawrence, Ian; McGettigan, Benjamin David

    2017-02-22

    We report a case of Epstein-Barr virus (EBV)-driven haemophagocytic lymphohistiocytosis (HLH) in a man with Crohn's disease treated with 6-mercaptopurine and adalimumab therapy who was successfully treated with rituximab therapy alone. This is the first published case in an adult patient with EBV-driven HLH in the setting of thiopurine use and inflammatory bowel disease to be successfully treated with rituximab therapy alone. Here, we will discuss putative immunological mechanisms which may contribute to this potentially life-threatening complication. 2017 BMJ Publishing Group Ltd.

  5. Lenalidomide-bendamustine-rituximab in untreated mantle cell lymphoma > 65 years with untreated mantle cell lymphoma

    DEFF Research Database (Denmark)

    Albertsson-Lindblad, Alexandra; Kolstad, Arne; Laurell, Anna

    2016-01-01

    For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter open-label phase I/II trial we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment to elderly MCL patients. Patients >65 years with untr......For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter open-label phase I/II trial we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment to elderly MCL patients. Patients >65 years...

  6. A case of "refractory" lupus erythematosus profundus responsive to rituximab [case report].

    LENUS (Irish Health Repository)

    McArdle, Adrian

    2012-02-01

    Lupus erythematosus profundus is a rare complication of systemic lupus erythematosus characterized by the presence of deep, tender subcutaneous nodules. A 22-year-old African-American female with extensive lupus profundus resistant to conventional therapies was treated with two infusions of the anti-CD20 monoclonal antibody, rituximab, at a dosage of 1,000 mg each. The patient demonstrated a remarkable clinical response as indicated by the disappearance of the nodules. B-cell depletion therapy with rituximab used alone or in combination with other therapies may be a viable option in patients with lupus profundus refractory to current therapies.

  7. A multicenter phase II study of carboplatin in advanced ovarian carcinoma: final report.

    Science.gov (United States)

    Kjorstad, K; Harris, A; Bertelsen, K; Slevin, M; Schultz, H; Hellman, K; Janssens, N; Martin, A; Canetta, R

    1992-03-01

    A phase II trial of single-agent carboplatin in advanced ovarian cancer was performed by 19 institutions from 10 European countries. A total of 260 patients were treated, with a median age of 55 (range: 20-79) years. Karnofsky performance status was 80-100 in about two-thirds of the patients. Prior therapy consisted of surgery only in 31 patients, irradiation in 9, chemotherapy without cisplatin in 45, and with cisplatin in 175. Carboplatin was administered as second-line therapy in about one-half and as third-line or more in one additional third of the study population. Initial dose was 400 mg/m2 in 90, 360 mg/m2 in 152, and 320 mg/m2 or less in 18 patients. A total of 971 courses (mean 3.7, median 2, range: 1-13) of therapy were administered. A total of 16 complete and 46 partial responses were observed in 226 evaluable patients, for an objective response rate of 27%. Efficacy was greater in chemotherapy-untreated patients (51% vs. 23%, p = 0.002). In cisplatin-pretreated patients activity was significantly higher in non-refractory patients (26% vs. 4%, p = 0.015). Myelosuppression was the most significant side effect. However, low hematologic counts seldom translated into clinically significant complications. Patients with impaired baseline creatinine clearance and poor performance status were at higher risk of developing severe myelosuppression during the initial course of treatment. Non hematologic side effects were rare and mild, except for emesis. Carboplatin has a definite role in the treatment of ovarian cancer, but almost complete cross-resistance with the parent compound was observed clinically.

  8. Gemcitabine and carboplatin in advanced transitional cell carcinoma of the urinary tract: an alternative therapy.

    Science.gov (United States)

    Nogué-Aliguer, Miquel; Carles, Joan; Arrivi, Antonio; Juan, Oscar; Alonso, Lorenzo; Font, Albert; Mellado, Begoña; Garrido, Pilar; Sáenz, Alberto

    2003-05-01

    Cisplatin-based combinations are considered to be the standard treatment for advanced transitional cell carcinoma (TCC) of the urothelium. Many of the patients are elderly with concomitant diseases or impaired renal function. We studied the tolerance and activity of the gemcitabine/carboplatin combination as a therapeutic alternative. Patients with locally advanced or metastatic TCC of the urothelium were treated with gemcitabine 1000 mg/m(2) on Days 1 and 8 and carboplatin area under the concentration-time curve 5 on Day 1 every 21 days. Patients with creatinine clearance of 30 mL/min or above and Karnofsky performance status (KPS) scores 60 or above were enrolled. A total of 227 cycles were administered to 41 patients, with an average of 5.5 cycles per patient (range, 1-8 cycles). Creatinine clearance was below 60 mL/min in 54% of patients, KPS was 70 or below in 37% of patients, and 37% of patients were 70 years old or older. Hematologic toxicity was mainly Grade 3/4 neutropenia in 63%, Grade 3/4 thrombocytopenia in 32%, and Grade 3/4 anemia in 54% of patients. There were only three episodes of febrile neutropenia and one death from neutropenic sepsis. Nonhematologic toxicity was mild, with asthenia as the most frequently reported event. We obtained 6 complete and 17 partial responses, for an overall response rate of 56.1% (95% confidence interval [CI], 40.6-71.6%). Progression-free survival was 7.2 months (95% CI, 5.7-8.5) and median survival was 10.1 months (95% CI, 8.8-12.2). The combination of gemcitabine plus carboplatin achieves a similar result to doublets using cisplatin. It has an acceptable toxicity profile and enables patients with impaired renal function and/or poor performance status and elderly patients to be treated. Copyright 2003 American Cancer Society.DOI 10.1002/cncr.10990

  9. A multicenter phase II trial of carboplatin and cetuximab for treatment of advanced nonsmall cell lung cancer.

    Science.gov (United States)

    Stinchcombe, Thomas E; Bradford, Daniel S; Hensing, Thomas A; LaRocca, Renato V; Saleh, Mansoor; Evans, Tracey; Bakri, Kamal; Socinski, Mark A

    2010-02-01

    To investigate the activity of carboplatin and cetuximab in NSCLC. This was a single arm, multicenter phase II trial, and the primary objective was response rate. The overall response rate observed was 9% (95% confidence interval [CI], 3-19), the progression-free survival was 2.9 months (95% CI, 1.9-3.6), the median overall survival was 8.2 months (95% CI, 4.9-10.5), and 1-year survival rate was 33% (95% CI, 21-45). The combination of carboplatin and cetuximab demonstrated lower activity than double agent platinum-based therapy and does not warrant further development.

  10. Malignant melanoma in 63 dogs (2001-2011): the effect of carboplatin chemotherapy on survival.

    Science.gov (United States)

    Brockley, L K; Cooper, M A; Bennett, P F

    2013-01-01

    The aim of the study was to compare the effect of carboplatin chemotherapy on the survival of canine patients diagnosed with malignant melanoma after loco-regional control or as a sole therapy. A retrospective study of 63 dogs with oral, digital or cutaneous malignant melanoma treated with surgery and/or chemotherapy was undertaken. Dogs were grouped based on the anatomical site of melanoma development. For oral melanoma, dogs were subclassified into two groups: loco-regional control and gross disease. All patients in the digital and cutaneous groups had achieved loco-regional control with surgery. Comparisons between survival data for each group at each anatomical site were then made. Within the loco-regional control groups survival time was compared between those treated with and without chemotherapy post surgery. For the oral melanoma patients with gross disease survival was compared between those treated with chemotherapy and palliative therapy. The toxicity of carboplatin chemotherapy was evaluated overall. The overall median survival times for patients with oral, digital and cutaneous melanoma were 389, 1,350 days and not reached (with a median follow-up of 776 days) respectively. Median survival time was defined as "not reached" when less than 50% of the subjects died of the disease at the end of the follow-up period, or at the time they were lost to follow-up. The addition of chemotherapy to surgery did not confer a survival benefit in the loco-regional control setting when assessing survival for each anatomical site. For oral melanoma patients with gross disease there was no difference between survival of patients treated with chemotherapy and palliative intent therapy. There was however an improvement in survival in the three dogs that responded to chemotherapy (978 days; p=0.039) compared to the eight non-responders (147 days). On univariate and multivariate analysis, anatomic location was the only variable that was significantly related to survival (p=0

  11. Treatment of malignant pleural mesothelioma with carboplatin, liposomized doxorubicin, and gemcitabine: a phase II study

    DEFF Research Database (Denmark)

    Hillerdal, G.; Sundstrom, S.; Riska, H.

    2008-01-01

    BACKGROUND: Malignant pleural mesothelioma has a poor prognosis and there is limited effect of treatment. The Nordic Mesothelioma groups decided in the year 2000 to investigate a combination of liposomized doxorubicin, carboplatin, and gemcitabine for this disease in a phase II study. METHODS: From...... January 2001, to December 2003, 173 evaluable patients with biopsy-verified malignant mesothelioma were included. Two patients were lost to follow-up, but all the others were followed for at least 4 years or until death. RESULTS: Toxicity was fairly low. There were 56 responses (32.4%), of which 2 were...

  12. A pioneer experience in Malaysia on In-house Radio-labelling of (131)I-rituximab in the treatment of Non-Hodgkin's Lymphoma and a case report of high dose (131)I-rituximab-BEAM conditioning autologous transplant.

    Science.gov (United States)

    Kuan, Jew Win; Law, Chiong Soon; Wong, Xiang Qi; Ko, Ching Tiong; Awang, Zool Hilmi; Chew, Lee Ping; Chang, Kian Meng

    2016-10-01

    Radioimmunotherapy is an established treatment modality in Non-Hodgkin's lymphoma. The only two commercially available radioimmunotherapies - (90)Y-ibritumomab tiuxetan is expensive and (131)I-tositumomab has been discontinued from commercial production. In resource limited environment, self-labelling (131)I-rituximab might be the only viable practical option. We reported our pioneer experience in Malaysia on self-labelling (131)I-rituximab, substituting autologous haematopoietic stem cell transplantation (HSCT) and a patient, the first reported case, received high dose (131)I-rituximab (6000MBq/163mCi) combined with BEAM conditioning for autologous HSCT. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Phase III trial of two investigational schedules of ifosfamide compared with standard-dose doxorubicin in advanced or metastatic soft tissue sarcoma: a European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study

    NARCIS (Netherlands)

    Lorigan, Paul; Verweij, Jaap; Papai, Zsuzsa; Rodenhuis, Sjoerd; Le Cesne, Axel; Leahy, Michael G.; Radford, John A.; van Glabbeke, Martine M.; Kirkpatrick, Anne; Hogendoorn, Pancras C. W.; Blay, Jean-Yves

    2007-01-01

    PURPOSE: Single-agent doxorubicin remains the standard treatment for advanced soft tissue sarcomas. Combining doxorubicin with standard-dose ifosfamide has not been shown to improve survival and is associated with a significantly increased toxicity; it is not known whether higher dose single-agent

  14. Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma

    DEFF Research Database (Denmark)

    van Imhoff, Gustaaf W; McMillan, Andrew; Matasar, Matthew J

    2017-01-01

    Purpose We compared the efficacy of ofatumumab (O) versus rituximab (R) in combination with cisplatin, cytarabine, and dexamethasone (DHAP) salvage treatment, followed by autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Pat...

  15. Rituximab and Dexamethasone vs Dexamethasone Monotherapy in Newly Diagnosed Patients with Primary Immune Thrombocytopenia

    DEFF Research Database (Denmark)

    Gudbrandsdottir, Sif; Birgens, Henrik Sverre; Frederiksen, Henrik

    2013-01-01

    In this study, we report the results from the largest cohort to date of newly diagnosed adult immune thrombocytopenia patients randomized to treatment with dexamethasone alone or in combination with rituximab. Eligible were patients with platelet counts ≤25×10(9)/L or ≤50×10(9)/L with bleeding sy...

  16. Early plasmapheresis and rituximab for acute humoral rejection after ABO-compatible liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Nassim Kamar; Laurence Lavayssière; Fabrice Muscari; Janick Selves; Céline Guilbeau-Frugier; Isabelle Cardeau; Laure Esposito; Olivier Cointault; Marie Béatrice Nogier; Jean Marie Peron; Philippe Otal; Marylise Fort; Lionel Rostaing

    2009-01-01

    Acute humoral rejection (AHR) is uncommon after ABOcompatible liver transplantation. Herein, we report two cases of AHR treated with plasmapheresis and rituximab in two ABO-compatible liver-transplant patients with preformed anti-human leukocyte antigen donor-specific antibodies. Patient 1 experienced a biopsy-proven AHR at day 10 post-transplant. She was treated by steroid pulses, and OKT3. Because of persisting signs of biopsy-proven AHR at day 26, she was treated by plasmapheresis and rituximab. Liver enzyme levels did not improve, and she died on day 41. Patient 2 experienced a biopsy-proven AHR on day 10 post-transplant. She was treated by steroid pulses, plasmapheresis, and rituximab.Liver enzymes returned to within normal range 18 dafter diagnosis. Liver biopsies, at 3 and 9 mo post-transplant,showed complete resolution of AHR. We conclude that plasmapheresis should be started as soon as AHR is diagnosed, and be associated with a B-cell depleting agent. Rituximab may be considered as a first-line therapy.

  17. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adult refractory idiopathic thrombocytopenic purpura

    DEFF Research Database (Denmark)

    Braendstrup, Peter; Bjerrum, Ole W; Nielsen, Ove J

    2005-01-01

    . Recent studies have shown that rituximab, a chimeric anti-CD20 monoclonal antibody, is useful in the treatment of these patients, with overall response rates of about 50%. Most published reports have included a small number patients including case reports. The present study reports the results...

  18. The identification of irreversible rituximab-resistant lymphoma caused by CD20 gene mutations

    Energy Technology Data Exchange (ETDEWEB)

    Mishima, Y [Department of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Olympas Bio-Imaging Lab, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Terui, Y [Department of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Takeuchi, K [Division of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo (Japan); Matsumoto-Mishima, Y; Matsusaka, S [Department of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Utsubo-Kuniyoshi, R [Department of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Olympas Bio-Imaging Lab, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Hatake, K [Department of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan)

    2011-04-01

    C-terminal mutations of CD20 constitute part of the mechanisms that resist rituximab therapy. Most CD20 having a C-terminal mutation was not recognized by L26 antibody. As the exact epitope of L26 has not been determined, expression and localization of mutated CD20 have not been completely elucidated. In this study, we revealed that the binding site of L26 monoclonal antibody is located in the C-terminal cytoplasmic region of CD20 molecule, which was often lost in mutated CD20 molecules. This indicates that it is difficult to distinguish the mutation of CD20 from under expression of the CD20 protein. To detect comprehensive CD20 molecules including the resistant mutants, we developed a novel monoclonal antibody that recognizes the N-terminal cytoplasm region of CD20 molecule. We screened L26-negative cases with our antibody and found several mutations. A rituximab-binding analysis using the cryopreserved specimen that mutation was identified in CD20 molecules indicated that the C-terminal region of CD20 undertakes a critical role in presentation of the large loop in which the rituximab-binding site locates. Thus, combination of antibodies of two kinds of epitope permits the identification of C-terminal CD20 mutations associated with irreversible resistance to rituximab and may help the decision of the treatment strategy.

  19. The value of rituximab treatment in primary Sjögren's syndrome

    NARCIS (Netherlands)

    Verstappen, Gwenny M.; van Nimwegen, Jolien F.; Vissink, Arjan; Kroese, Frans G. M.; Bootsma, Hendrika

    The rationale for B cell depletion therapy with rituximab in primary Sjogren's syndrome relies upon the well-established role of B cell hyperactivity in immunopathogenesis. In line with this notion, several biomarkers of B cell activity are significantly affected by treatment, both in the target

  20. B lymphocyte depletion with the monoclonal antibody rituximab in Graves' disease: a controlled pilot study

    DEFF Research Database (Denmark)

    El Fassi, Daniel; Nielsen, Claus H; Bonnema, Steen J

    2007-01-01

    Graves' disease (GD) is a common TSH receptor autoantibody (TRAb)-mediated disorder. Because B lymphocytes are important self-antigen presenting cells and precursors for antibody-secreting plasma cells, temporary B-lymphocyte depletion with the monoclonal antibody rituximab (RTX) might...

  1. Autoantibody levels in myositis patients correlate with clinical response during B cell depletion with rituximab.

    Science.gov (United States)

    Aggarwal, Rohit; Oddis, Chester V; Goudeau, Danielle; Koontz, Diane; Qi, Zengbiao; Reed, Ann M; Ascherman, Dana P; Levesque, Marc C

    2016-06-01

    To determine the longitudinal trends in serum levels of four myositis-associated autoantibodies: anti-Jo-1, -transcription intermediary factor 1 γ (TIF1-γ), -signal recognition particle (SRP) and -Mi-2, after B cell depletion with rituximab, and to determine the longitudinal association of these autoantibody levels with disease activity as measured by myositis core-set measures (CSMs). Treatment-resistant adult and pediatric myositis subjects (n = 200) received rituximab in the 44-week Rituximab in Myositis Trial. CSMs [muscle enzymes, manual muscle testing (MMT), physician and patient global disease activity, HAQ, and extramuscular disease activity] were evaluated monthly and anti-Jo-1 (n = 28), -TIF1-γ (n = 23), -SRP (n = 25) and -Mi-2 (n = 26) serum levels were measured using validated quantitative ELISAs. Temporal trends and the longitudinal relationship between myositis-associated autoantibodies levels and CSM were estimated using linear mixed models. Following rituximab, anti-Jo-1 levels decreased over time (P myositis subjects decreased after B cell depletion and were correlated with changes in disease activity, whereas anti-SRP levels were only associated with longitudinal muscle enzyme levels. The strong association of anti-Jo-1 levels with clinical outcomes suggests that anti-Jo-1 autoantibodies may be a good biomarker for disease activity. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Individualized rituximab treatment for relapsing neuromyelitis optica: a pediatric case report.

    Science.gov (United States)

    He, Dian; Yu, YunLi; Yan, WeiBo; Dai, QingQing; Xu, Zhu; Chu, Lan

    2014-08-01

    Neuromyelitis optica is an autoimmune inflammatory disorder of the central nervous system. Current therapeutic approaches are based on small uncontrolled trials, case series, or case reports. There are only a few case reports describing rituximab for pediatric neuromyelitis optica. A 7-year-old girl with neuromyelitis optica had high disease activity with recurrent myelitis and steroid dependence. A remarkable increase of CD19(+) B-cell count in the peripheral blood mononuclear cells and seropositivity for anti-aquaporin 4 antibody were detected at each attack. After induction therapy with rituximab, the CD19(+) B-cell number was significantly reduced and sustained at low levels. The level of serum anti-aquaporin 4 antibody normalized. She was relapse-free over 1-year follow-up period. An individualized maintenance therapy scheme is underway. Treatment with rituximab for relapsing neuromyelitis optica requires an individualized regimen to optimize the frequency and dosage of administration to maximize efficacy yet minimize overtreatment and cost. Personal levels of CD19(+) B cells in peripheral blood mononuclear cells at previous attacks and responsiveness to rituximab in induction therapy may be two useful indicators in establishing individualized maintenance therapy schemes for relapsing neuromyelitis optica. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Neuromyelitis optica spectrum disorders: long-term safety and efficacy of rituximab in Caucasian patients.

    Science.gov (United States)

    Radaelli, M; Moiola, L; Sangalli, F; Esposito, F; Barcella, V; Ferrè, L; Rodegher, M; Colombo, B; Fazio, R; Martinelli, V; Comi, G

    2016-04-01

    To assess the long-term benefit-risk profile of repeated courses of rituximab in Caucasian patients affected by neuromyelitis optica (NMO) and related disorders, in everyday clinical practice. This is a prospective observational study performed at San Raffaele Hospital, Milan, Italy. From February 2006, we recruited 21 patients affected by NMO and NMO spectrum of disorders (NMOSD) whom underwent at least one cycle of intravenous (i.v.) rituximab and then were followed for at least 2 years. At a mean follow-up time of 48 months, we observed a significant reduction of the annualized relapse rate (ARR), from 2.0 to 0.16 (p < 0.01); and of the median Expanded Disability Status Scale (EDSS), from 5.5 to 4.0 (p < 0.013). There were 12 patients (57%) who remained disease free during the follow-up period. Five patients (24%) reported mild hematological adverse events. Serious infectious adverse events were reported by another four patients: These were all wheelchair bound at the beginning of their rituximab treatment. A fixed treatment scheme of rituximab, with re-treatment every 6 months, was efficacious for NMO and NMOSD, with a good safety profile; however, to obtain an even better benefit-risk ratio, close monitoring of CD19(+) B cells should be performed before the re-treatment of patients with high-level disability, concomitant leukopenia and hypogammaglobulinemia. © The Author(s), 2015.

  4. Correction to: Progressive multifocal leukoencephalopathy in rituximab-treated rheumatic diseases: a rare event.

    Science.gov (United States)

    Berger, Joseph R; Malik, Vineeta; Lacey, Stuart; Brunetta, Paul; Lehane, Patricia B

    2018-04-10

    The article "Progressive multifocal leukoencephalopathy in rituximab-treated rheumatic diseases: a rare event," written by Joseph R. Berger, Vineeta Malik, Stuart Lacey, Paul Brunetta, and Patricia B. Lehane 3 , was originally published electronically on the publisher's internet portal (currently SpringerLink).

  5. Rituximab therapy in steroid-resistant severe hypothyroid Grave′s ophthalmopathy

    Directory of Open Access Journals (Sweden)

    Aditi Pandit

    2013-01-01

    Full Text Available Association of Grave′s ophthalmopathy with hyperthyroidism is well known, and it has also been reported in euthyroid or hypothyroid autoimmune thyroiditis, which rarely requires treatment. Here, we report a case of bilaterally symmetrical severe corticosteroid-resistant hypothyroid Grave′s ophthalmopathy successfully treated with rituximab.

  6. Preclinical safety, pharmacokinetics, pharmacodynamics, and biodistribution studies with Ad35K++ protein: a novel rituximab cotherapeutic

    Directory of Open Access Journals (Sweden)

    Maximilian Richter

    2016-01-01

    Full Text Available Rituximab is a mouse/human chimeric monoclonal antibody targeted toward CD20. It is efficient as first-line therapy of CD20-positive B-cell malignancies. However, a large fraction of treated patients relapse with rituximab-resistant disease. So far, only modest progress has been made in treatment options for rituximab refractory patients. One of the mechanisms for rituximab resistance involves the upregulation of CD46, which is a key cell surface protein that blocks the activation of complement. We have recently developed a technology that depletes CD46 from the cell surface and thereby sensitizes tumor cells to complement-dependent cytotoxicity. This technology is based on a small recombinant protein, Ad35K++ that binds with high affinity to CD46. In preliminary studies using a 6 × histidinyl tagged protein, we had demonstrated that intravenous Ad35K++ injection in combination with rituximab was safe and increased rituximab-mediated killing of CD20-positive target cells in mice and nonhuman primates (NHPs. The presence of the tag, while allowing for easy purification by Ni-NTA chromatography, has the potential to increase the immunogenicity of the recombinant protein. For clinical application, we therefore developed an Ad35K++ protein without His-tag. In the present study, we performed preclinical studies in two animal species (mice and NHPs with this protein demonstrating its safety and efficacy. These studies estimated the Ad35K++ dose range and treatment regimen to be used in patients. Furthermore, we showed that intravenous Ad35K++ injection triggers the shedding of the CD46 extracellular domain in xenograft mouse tumor models and in macaques. Shed serum CD46 can be measured in the serum and can potentially be used as a pharmacodynamic marker for monitoring Ad35K++ activity in patient undergoing treatment with this agent. These studies create the basis for an investigational new drug application for the use of Ad35K++ in combination with

  7. Analytical similarity assessment of rituximab biosimilar CT-P10 to reference medicinal product.

    Science.gov (United States)

    Lee, Kyoung Hoon; Lee, Jihun; Bae, Jin Soo; Kim, Yeon Jung; Kang, Hyun Ah; Kim, Sung Hwan; Lee, So Jung; Lim, Ki Jung; Lee, Jung Woo; Jung, Soon Kwan; Chang, Shin Jae

    2018-04-01

    CT-P10 (Truxima™) was recently approved as the world's first rituximab biosimilar product in the European Union (EU) and South Korea. To demonstrate biosimilarity of CT-P10 with the reference medicinal product (RMP), extensive 3-way similarity assessment has been conducted between CT-P10, EU-Rituximab and US-Rituximab, focusing on the physicochemical and biological quality attributes. A multitude of state-of-the-art analyses revealed that CT-P10 has identical primary and higher order structures compared to the original product. Purity/impurity profiles of CT-P10 measured by the levels of aggregates, fragments, non-glycosylated form and process-related impurities were also found to be comparable with those of RMPs. In terms of the post-translational modification, CT-P10 contains slightly less N-terminal pyro-glutamate variant, which has been known not to affect product efficacy or safety. Oligosaccharide profiling has revealed that, although CT-P10 contains the same conserved glycan species and relative proportion with the RMPs, the content of total afucosylated glycan in CT-P10 was slightly higher than in EU- or US-Rituximab. Nevertheless, the effect of the observed level of afucosylation in CT-P10 drug product on Fc receptor binding affinity or antibody-dependent cell-mediated cytotoxicity was found to be negligible based on the spiking study with highly afucosylated sample. Arrays of biological assays representative of known and putative mechanisms of action for rituximab have shown that biological activities of CT-P10 are within the quality range of RMPs. Recent results of clinical studies have further confirmed that the CT-P10 exhibits equivalent clinical efficacy and safety profiles compared to EU- and US-Rituximab. The current 3-way similarity assessment together with clinical study results confidently demonstrate that CT-P10 is highly similar with EU- and US-Rituximab in terms of physicochemical properties, biological activities, efficacy, and safety for

  8. Safety of Neoadjuvant Bevacizumab plus Pemetrexed and Carboplatin 
in Patients with IIIa Lung Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Songliang ZHANG

    2015-06-01

    Full Text Available Background and objective Bevacizumab has showed its efficacy in advanced non-squamous lung cancer. The aim of this study is to assess the safety of bevacizumab plus pemetrexed and carboplatin neoadjuvant chemotherapy in patients with lung adenocarcinoma. Methods 25 patients with IIIa lung adenocarcinoma undergoing lobectemy or pneumonectomy with mediastinal lymphadenectomy after induction bevacizumab (Bev plus pemetrexed/carboplatin (PC were selected. Toxicity of chemotherapy and postoperative complications were analyzed. Results Grade 3 or 4 neoadjuvant-related adverse events included fatigue (3 patients, neutropenia (3 patients, hypertension (1 patient. The adverse events thought to be related to bevacizumab included epistaxis in 2 patients (grade 1: 1; grade 2: 1 and hypertension in 3 patients (grade 1: 2; grade 3: 1. Postoperative complications included pneumonia in 2 patients, bronchial stump insufficiency in 1 case, atelectasis in 2 cases, and arrhythmia in 1 case. Hemorrhage events, thromboembolic events and wound-healing problems were not observed in the perioperative period. Conclusion The treatment modality of neoadjuvant Bev-PC appears to be safe and tolerant in patients with stage IIIa lung adenocarcinoma.

  9. Targeted intra-arterial carboplatin chemoradiotherapy and tegafur/uracil for oral and oropharyngeal cancer

    International Nuclear Information System (INIS)

    Oya, Ryoichi; Takagi, Shinji; Inenaga, Ryuichiro; Nakamura, Shoichi; Ikemura, Kunio; Onari, Nobuhiro; Imada, Hajime; Korogi, Yukunori

    2006-01-01

    The aim of this study was to evaluate the usefulness of targeted intra-arterial carboplatin chemoradiotherapy in allowing less invasive surgery for patients with oral and oropharyngeal squamous cell carcinoma. Twenty patients with previously untreated squamous cell carcinoma of the oral cavity and oropharynx (T4; 8, T2; 12 patients) were treated with targeted transfemoral intra-arterial carboplatin infusion with concurrent hyperfractionated radiotherapy and the administration of tegafur/uracil (UFT). Of 20 patients, 15 underwent surgery after completion of one course of targeted chemoradiotherapy, and five were given another course or radiotherapy only. Eighteen (90%) of 20 patients had a clinically complete response at the primary site and two (10%) had a partial response. Of the 15 patients who underwent tumor resection, 11 (73%) showed histopathological disappearance of cancer cells at the primary site. Sixteen (80%) of 20 tumors were controlled at the primary site within a mean follow-up of 30 months. Adverse effects were relatively mild. Targeted intra-arterial chemoradiotherapy caused a down-staging of tumors and facilitated the use of less invasive surgery in patients with squamous cell carcinoma of the oral cavity and oropharynx as a result of its favorable anti-tumor effect. (author)

  10. Efficacy and Safety of Prolonged Rituximab Treatment in Patients with Systemic Juvenile Idiopathic Arthritis

    Directory of Open Access Journals (Sweden)

    E. I. Alexeeva

    2013-01-01

    Full Text Available Aim: to assess efficacy and safety of rituximab treatment in children with systemic juvenile idiopathic arthritis under prolonged follow-up. Patients and methods: results of treatment of 60 children (33 girls and 27 boys with systemic variant of juvenile idiopathic arthritis being followed-up in rheumatology department of the Federal State Institution «Scientific Centre of Children Health» of RAMS (FSI «SCCH» RAMS were analyzed. The mean age of children was 8,7 years. The mean duration of disease course at the moment of first rituximab administration was 5,3 years. At the beginning of rituximab therapy all children had active articular syndrome, severe systemic manifestations and significantly increased laboratory markers of activity. As the signs of improvement the authors used pediatric criteria of the American College of Rheumatology. The treatment was approved by the local ethic committee of the FSI «SCCH» RAMS; the patients’ representatives and patients older than 14 years old had signed informed agreement. Results: remission was induced in 26 of 60 (43% patients: in 9 of them after the 1st course of treatment, in 8 — after the 2nd, in 6 — after the 3d and in 3 — after the 4th. The maximal duration of remission was 5 years 4 months, minimal — 6 months. Other genetically engineered drugs were administered to 34 (57% of the patients: due to the primary inefficiency in 15, secondary inefficiency — in 10; due to partial inefficiency — in 9 children. The drug was well-tolerated in most of the patients. Undesirable effects were represented by transfusional reactions to the rituximab infusion, infections with different severity and granulocytopenia. Conclusions: rituximab has high efficiency in patients with severe systemic variant of juvenile idiopathic arthritis. The drug induced remission in patients who had been considered almost incurable, with low status of physical and social adaptation.

  11. Metronomic chemotherapy using orally active carboplatin/deoxycholate complex to maintain drug concentration within a tolerable range for effective cancer management.

    Science.gov (United States)

    Mahmud, Foyez; Chung, Seung Woo; Alam, Farzana; Choi, Jeong Uk; Kim, Seong Who; Kim, In-San; Kim, Sang Yoon; Lee, Dong Soo; Byun, Youngro

    2017-03-10

    Metronomic chemotherapy has translated into favorable toxicity profile and capable of delaying tumor progression. Despite its promise, conventional injectable chemotherapeutics are not meaningful to use as metronomic due to the necessity of frequent administration for personalized therapy in long-term cancer treatments. This study aims to exploit the benefits of the oral application of carboplatin as metronomic therapy for non-small cell lung cancer (NSCLC). We developed an orally active carboplatin by physical complexation with a deoxycholic acid (DOCA). The X-ray diffraction (XRD) patterns showed the disappearance of crystalline peaks from carboplatin by forming the complex with DOCA. In vivo pharmacokinetic (PK) study confirmed the oral absorption of carboplatin/DOCA complex. The oral bioavailability of carboplatin/DOCA complex and native carboplatin were calculated as 24.33% and 1.16%, respectively, when a single 50mg/kg oral dose was administered. Further findings of oral bioavailability during a low-dose daily administration of the complex (10mg/kg) for 3weeks were showed 19.17% at day-0, 30.27% at day-7, 26.77% at day-14, and 22.48% at day-21, demonstrating its potential for metronomic chemotherapy. The dose dependent antitumor effects of oral carboplatin were evaluated in SCC7 and A549 tumor xenograft mice. It was found that the oral carboplatin complex exhibited potent anti-tumor activity at 10mg/kg (74.09% vs. control, Peffective and safe oral formulation of carboplatin as a metronomic chemotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Phase II activity of belinostat (PXD-101), carboplatin, and paclitaxel in women with previously treated ovarian cancer

    DEFF Research Database (Denmark)

    Dizon, Don S; Damstrup, Lars; Finkler, Neil J

    2012-01-01

    specifically for women with recurrent epithelial ovarian cancer (EOC). METHODS: Thirty-five women were treated on the phase 2 expansion cohort. BelCap was given as follows: belinostat, 1000 mg/m² daily for 5 days with carboplatin, AUC 5; and paclitaxel, 175 mg/m² given on day 3 of a 21-day cycle. The primary...

  13. The incidence of ototoxicity in child malignancy cases that received carboplatin therapy with otoacoustic emission (OAE) examination

    Science.gov (United States)

    Wibowo, J. K.; Zizlavsky, S.; Suwento, R.; Sjakti, H. A.; Prihartono, J.

    2017-08-01

    Malignancy is a significant public health problem, both globally and in Indonesia. Chemotherapy is one of the modality in malignancy cases. Carboplatin (cis-diammine-cyclobutanedi-carboxylato platinum) is a second-generation platinum compound that has often been used in the management of cases of malignancies. On the other hand, side effects of cytotoxic drugs need to be considered, especially ototoxic effects. Ototoxicity is dysfunction and damage to the structure of the inner ear that has been caused by drugs or other certain chemicals. The aim of this study is to assess ototoxic effects due to the influence of carboplatin in the cases of children with malignancy. This study uses a serial cross-sectional design to evaluate otoacoustic emission (OAE) signal-to-noise ratio (SNR) change as a result of ototoxic effects and risk factors due to the use of ototoxic carboplatin in the Division of Hematology-Oncology of the Department of Pediatrics at Cipto Mangunkusumo General Hospital in Jakarta, where two of 52 studies’ subjects experienced ototoxicity. In the group were receiving chemotherapy, two (5%) of the 40 subjects has experienced ototoxic events characterized by SNR values less than six, whereas SNR values were not less than six in the group that had not received chemotherapy. Risk factors such as gender, age, carboplatin dose, and cycles of chemotherapy did not have a statistically significant relationship to ototoxity.

  14. Concurrent radiotherapy and carboplatin in non small-cell lung cancer: a pilot study using conventional and accelerated fractionation

    International Nuclear Information System (INIS)

    Ball, D.; Bishop, J.; Crennan, E.; Olver, I.

    1991-01-01

    Thirteen patients with unresectable non small cell lung cancer were treated with radical radiotherapy and carboplatin administered in order to ascertain the toxicity of concurent carboplatin/radiotherapy. The first 6 patients were treated to a total dose of 60 Gy in 30 fractions in 6 weeks, with carboplatin 70 mg/m 2 /day on days 1 to 5 during weeks 1 and 5 of radiotherapy. The remaining 7 patients were given 60 Gy in 30 fractions in 3 weeks, treating twice a day (accelerated fractionation). Carboplatin was given as above but only during week 1 of radiotherapy. Twelve patients completed radiotherapy without interruption but 2 patients developed grade 3 neutropenia. Major toxicity was oesophagitis, one patient requiring nasogastric feeding. Average duration of dysphagia (any grade) in the accelerated fractionation group was 21 weeks. Four patients achieved good partial responses even though initial tumour volume was large. It is concluded that this treatment is associated with increased but acceptable early mucosal toxicity. 6 refs., 1 tab., 1 fig

  15. Carboplatin- and cisplatin-induced potentiation of moderate-dose radiation cytotoxicity in human lung cancer cell lines

    NARCIS (Netherlands)

    Groen, H. J.; Sleijfer, S.; Meijer, C.; Kampinga, H. H.; Konings, A. W. T.; de Vries, E. G. E.; Mulder, N. H.

    1995-01-01

    The interaction between moderate-dose radiation and cisplatin or carboplatin was studied in a cisplatin-sensitive (GLC(4)) and -resistant (GLC(4)-CDDP) human small-cell lung cancer cell line. Cellular toxicity was analysed under oxic conditions with the microculture tetrazolium assay. For the

  16. Re-refinement of 4xan: hen egg-white lysozyme with carboplatin in sodium bromide solution

    NARCIS (Netherlands)

    Tanley, Simon W. M.; Schreurs, Antoine M. M.; Kroon - Batenburg, Louise; Helliwell, John R.

    2016-01-01

    A re-refinement of 4xan, hen egg white lysozyme (HEWL) with carboplatin crystallised in NaBr solution, has been made (Tanley et al 2016). This follows our Response article (Tanley et al 2015) to the Critique article of Shabalin et al 2015, suggesting the need for corrections to some solute molecule

  17. Radiation with cisplatin or carboplatin for locally advanced cervix cancer: the experience of a tertiary cancer centre

    International Nuclear Information System (INIS)

    Au-Yeung, George; Mileshkin, Linda; Rischin, Danny; Bernshaw, David M.; Kondalsamy-Chennakesavan, Srinivas; Narayan, Kailash

    2013-01-01

    Definitive treatment with concurrent cisplatin and radiation is the standard of care for locally advanced cervix cancer. The optimal management of patients with a contraindication to cisplatin has not been established. We conducted a retrospective audit of concurrent chemotherapy in a cohort of patients with locally advanced cervix cancer. All patients with locally advanced cervix cancer treated with definitive radiation were entered into a prospective database. Information regarding their demographics, stage, histology, recurrence and survival were recorded. Pharmacy records were reviewed to determine concurrent chemotherapy use. A total of 442 patients were included in the audit. Two hundred sixty-nine patients received cisplatin, 59 received carboplatin and 114 received no concurrent chemotherapy. Overall survival was significantly improved with the use of concurrent cisplatin compared with radiation alone (adjusted hazard ratio 0.53, P=0.001), as was disease-free survival and rate of distant failure. The use of carboplatin was not associated with any significant benefit in terms of overall survival or disease-free survival. The results of this audit are consistent with the known significant survival benefit with concurrent cisplatin chemotherapy. However, there did not appear to be any significant benefit with carboplatin although there were potential confounding factors. The available evidence in the literature would favour the use of non-platinum chemotherapy rather than carboplatin in patients with contraindications to cisplatin.

  18. Estimation of glomerular filtration rate in cancer patients with abnormal body composition and relation with carboplatin toxicity.

    Science.gov (United States)

    Bretagne, M; Jouinot, A; Durand, J P; Huillard, O; Boudou Rouquette, P; Tlemsani, C; Arrondeau, J; Sarfati, G; Goldwasser, F; Alexandre, J

    2017-07-01

    Carboplatin clearance is correlated with glomerular filtration rate (GFR) and usually estimated with creatinine clearance using Cockcroft-Gault (CG) formula. Because plasma creatinine level is highly correlated with muscle mass, we hypothesized that an abnormal body composition with a low lean body mass (LBM) percentage [(LBM/weight) × 100] may result in inadequate carboplatin dosing. Serum cystatin C is an alternative marker of GFR, not affected by muscle mass. We aimed to investigate the influence of total LBM and LBM percentage on GFR calculation, using creatinine (CrCl) or cystatin C (GFR cysC-creat ) in cancer patients. Pretreatment serum creatinine and cystatin C were prospectively measured in consecutive patients. CrCl (CG formula), GFR cysC-creat (CKD-EPI creatinine-cystatin equation), and LBM (CT scan) were calculated. Severe thrombocytopenia post-carboplatin were analyzed. In 131 patients without renal insufficiency, LBM was correlated with creatinine (r = 0.30, p LBM percentage, the CrCl was significantly higher than GFR cysC-creat indicating an overestimation of GFR with creatinine (p = 0.0004). In 24 patients treated with carboplatin AUC 5 (mg/ml min) ± paclitaxel, the risk of severe thrombocytopenia was associated with lower LBM percentage (p = 0.0002) and higher CrCl/GFR cysC-creat ratio (p = 0.006). By ROC analysis, the CrCl/GFR cysC-creat ratio threshold predicting severe thrombocytopenia was 1.23. A low LBM percentage increases the risk of inadequate GFR calculation by CG formula, and carboplatin overdosage with severe thrombocytopenia. High CrCl/GFR cysC-creat ratio allows the identification of these patients.

  19. A Phase I study of capecitabine, carboplatin, and paclitaxel with external beam radiation therapy for esophageal carcinoma

    International Nuclear Information System (INIS)

    Czito, Brian G.; Kelsey, Chris R.; Hurwitz, Herbert I.; Willett, Chris G.; Morse, Michael A.; Blobe, Gerard C.; Fernando, Nishan H.; D'Amico, Thomas A.; Harpole, David H.; Honeycutt, Wanda R.N.; Yu Daohai; Bendell, Johanna C.

    2007-01-01

    Purpose: Concurrent chemotherapy and radiation therapy (RT) are used to treat patients with esophageal cancer. The optimal combination of chemotherapeutic agents with RT is undefined. We evaluated a combination of capecitabine, carboplatin, and paclitaxel with RT in a phase I study. Methods and Materials: Patients with squamous cell carcinoma or adenocarcinoma of the esophagus initially received capecitabine, carboplatin, and paclitaxel with RT (1.8 Gy daily to 50.4 Gy). After completion, patients were restaged and evaluated for surgery. Primary endpoints included determination of dose-limiting toxicities (DLT) and a recommended phase II dose, non-DLT, and preliminary radiographic and pathologic response rates. Results: Thirteen patients were enrolled (10 men, 3 women). All were evaluable for toxicity and efficacy. Two of 3 patients at dose level 1 (capecitabine 825 mg/m 2 twice daily on RT days, carboplatin area under the curve (AUC) 2 weekly, paclitaxel 60 mg/m 2 weekly) had DLT (both Grade 4 esophagitis). Of these 3, 2 underwent esophagectomy and had pathologic complete response (pCR). Ten patients were then enrolled at dose level -1 (capecitabine 600 mg/m 2 twice daily, carboplatin AUC 1.5, paclitaxel 45 mg/m 2 ). Overall, 3 of 10 patients at dose level -1 developed DLT (2 Grade 3 esophagitis, 1 Grade 3 hypotension). Esophagectomy was performed in 6 of 10 patients. All patients had pathologic downstaging and 2 of 6 had pCR. Conclusions: The maximally tolerated/recommended phase II doses were capecitabine 600 mg/m 2 twice daily, carboplatin AUC 1.5 weekly, and paclitaxel 45 mg/m 2 weekly with RT to 50.4 Gy. In our small study, this regimen appears active but is accompanied by significant toxicities, primarily esophagitis

  20. Cisplatin superior to carboplatin in adjuvant radiochemotherapy for locally advanced cancers of the oropharynx and oral cavity

    Energy Technology Data Exchange (ETDEWEB)

    Rades, D. [Univ. of Luebeck (Germany). Dept. of Radiation Oncology; Ulbricht, T.; Hakim, S.G. [Univ. of Luebeck (Germany). Dept. of Maxillofacial Surgery; Schild, S.E. [Mayo Clinic, Scottsdale, AZ (United States). Dept. of Radiation Oncology

    2012-01-15

    The optimal radiochemotherapy regimen for squamous cell carcinoma of the head and neck (SCCHN) is controversial. In most cases, platin-based chemotherapy regimens are used. However, uncertainty exists whether cisplatin or carboplatin is the better choice. This retrospective study compared radiochemotherapy with either cisplatin or carboplatin in patients with locally advanced SCC of the oropharynx and oral cavity. Patients and methods Concurrent chemotherapy consisted of two courses of cisplatin (20 mg/m{sup 2} on days 1-5 and days 29 - 33; n = 65) or two courses of carboplatin (AUC 1.5 on days 1-5 and days 29 - 33; n = 41). Both regimens were retrospectively compared for locoregional control (LRC), overall survival (OS), and toxicity. Thirteen additional potential prognostic factors were evaluated including age, gender, ECOG performance status, tumor site, histologic grade, T/N category, AJCC stage, year of treatment, extent of resection, interval between surgery and RT, completion of chemotherapy, and radiotherapy breaks. Results The 3-year LRC rates were 85% in the cisplatin group and 62% in the carboplatin group, respectively (p = 0.004). The 3-year OS rates were 78% and 51%, respectively (p = 0.001). Acute toxicity (mucositis, skin toxicity, nausea/vomiting, renal toxicity, hematologic toxicity) and late toxicity (xerostomia, neck fibrosis, skin toxicity, lymph edema) rates were not significantly different between the two groups. On multivariate analysis, better LRC was significantly associated with cisplatin (p < 0.001), an ECOG performance status of 0-1 (p = 0.001), and an interval between surgery and RT of {<=} 6 weeks (p = 0.001). Improved OS was significantly associated with cisplatin (p < 0.001) and completion of chemotherapy (p = 0.002). Conclusion For adjuvant radiochemotherapy of patients with locally advanced cancer of the oropharynx and oral cavity, cisplatin appears preferable to carboplatin as it resulted in better outcomes without increased

  1. Development and biological studies of ¹⁷⁷Lu-DOTA-rituximab for the treatment of Non-Hodgkin's lymphoma.

    Science.gov (United States)

    Massicano, Adriana V F; Pujatti, Priscilla B; Alcarde, Lais F; Suzuki, Miriam F; Spencer, Patrick J; Araújo, Elaine B

    2016-01-01

    The optimization of DOTA-NHS-ester conjugation to Rituximab using different Ab:DOTA molar ratios (1:10, 1:20, 1:50 and 1:100) was studied. High radiochemical yield, in vitro stability and immunoreactive fraction were obtained for the Rituximab conjugated at 1:50 molar ratio, resulting in the incorporation of an average number of 4.9 ± 1.1 DOTA per Rituximab molecule. Labeling with 177Lu was performed in high specific activity with great in vitro stability. Biodistribution in healthy and xenographed mice showed tumor uptake and high in vivo stability as evidenced by low uptake in bone. The properties of 177Lu-DOTA-Rituximab prepared from DOTA-NHS-ester suggest the potential for the application of the 177Lu-labeled antibody in preliminary clinical studies.

  2. Prognostic and predictive factors for outcome to first-line ifosfamide-containing chemotherapy for adult patients with advanced soft tissue sarcomas An exploratory, retrospective analysis on large series from the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone

    DEFF Research Database (Denmark)

    Sleiffer, S.; Ouali, M.; van Glabbeke, M.

    2010-01-01

    prognostic and predictive factors for outcome to ifosfamide-based therapy. Methods: A retrospective, exploratory analysis was performed on data from 1337 advanced STS patients who received first-time ifosfamide-containing chemotherapy. For predictive factor analysis, 660 patients treated with doxorubicin...... patients having the highest chance to respond. Predictive factor analysis showed that compared to doxorubicin monotherapy, patients who benefited less from ifosfamide-based therapies were leiomyosarcoma patients in terms of OS, and patients with liposarcoma for response. No predictive factors were found...... for PFS. Conclusion: In this study, we established an independent set of prognostic and predictive factors for outcome to ifosfamide-based chemotherapy in advanced STS patients. This study provides important information for the interpretation and design of clinical trials for specific STS entities and may...

  3. Efficacy and Safety of Rituximab in the Treatment of Vasculitic Leg Ulcers Associated with Hepatitis C Virus Infection

    Directory of Open Access Journals (Sweden)

    Fabio Bonilla-Abadía

    2012-01-01

    Full Text Available Vasculitic leg ulcers are a cutaneous manifestation of hepatitis C virus (HCV infection often associated with cryoglobulinemia. Their treatment is difficult and is based on steroids and immunosuppressive drugs with an erratic response and a high probability of adverse reaction. We report three patients with vasculitic leg ulcers associated with hepatitis C virus infection who were treated successfully with rituximab. The pain control and healing were achieved quickly. No adverse effects with rituximab in these patients were presented.

  4. 99mTc-rituximab radiolabelled by photo-activation: a new non-Hodgkin's lymphoma imaging agent

    International Nuclear Information System (INIS)

    Gmeiner Stopar, T.; Fettich, J.; Hojker, S.; Mlinaric-Rascan, I.; Mather, S.J.

    2006-01-01

    Rituximab was the first chimeric monoclonal antibody to be approved for treatment of indolent B-cell non-Hodgkin's lymphoma (NHL). It is directed against the CD20 antigen, which is expressed by 95% of B-cell NHLs. The aim of this study was to explore the possibility of radiolabelling rituximab with 99m Tc for use as an imaging agent in NHL for early detection, staging, remission assessment, monitoring for metastatic spread and tumour recurrence, and assessment of CD20 expression prior to (radio)immunotherapy. Rituximab was purified from Mabthera solution (Roche), photo-activated at 302 nm by UV irradiation and radiolabelled with 99m Tc. The effectiveness of the labelling method was evaluated by determination of the number of free thiol groups per photoreduced antibody, radiochemical purity and in vitro stability of 99m Tc-rituximab. On average, 4.4 free thiol groups per photoreduced antibody were determined. Radiolabelling yields greater than 95% were routinely observed after storage of the photo-activated antibody at -80 C for 195 days. The direct binding assay showed preserved ability of 99m Tc-rituximab to bind to CD20, with an average immunoreactive fraction of 93.3%. The internalisation rate was proven to be low, with only 5.3% of bound 99m Tc-rituximab being internalised over 4 h at 37 C. Our results demonstrate that 99m Tc-rituximab of high radiochemical purity and with preserved binding affinity for the antigen can be prepared by photoreduction and that the method shows good reproducibility. 99m Tc-rituximab will be further explored as an imaging agent applicable in NHL for the purposes mentioned above. (orig.)

  5. Off-label use of rituximab in autoimmune disease in the Top End of the Northern Territory, 2008-2016.

    Science.gov (United States)

    Wongseelashote, Sarah; Tayal, Vipin; Bourke, Peter Francis

    2018-02-01

    Rituximab, an anti-CD20 B-cell depleting monoclonal antibody, is increasingly prescribed off-label for a range of autoimmune diseases. There has not previously been an audit of off-label rituximab use in the Northern Territory, where the majority of patients are Aboriginal. To evaluate retrospectively off-label rituximab use in autoimmune diseases in the Top End of the Northern Territory. We performed a retrospective audit of 8 years of off-label rituximab use at the Royal Darwin Hospital, the sole tertiary referral centre for the Darwin, Katherine and East Arnhem regions. Electronic and paper records were reviewed for demographic information, diagnosis/indication for rituximab, doses, previous/concomitant immunosuppression, clinical outcomes and specific adverse events. Rituximab was prescribed off-label to 66 patients for 24 autoimmune diseases. The majority of patients (62.1%) were Aboriginal and 60.6% female. The most common indications were refractory/relapsing disease despite standard therapies (68.7%) or severe disease with rituximab incorporated into an induction immunosuppressive regimen (19.4%). Systemic lupus erythematosus was the underlying diagnosis in 28.8% of cases. A clinically significant response was demonstrated in 74.2% of cases overall. There were 18 clinically significant infections; however, 13 were in patients receiving concurrent immunosuppressive therapy. There was a total of nine deaths from any cause. Rituximab has been used off-label for a range of autoimmune diseases in this population with a high proportion of Aboriginal patients successfully and safely in the majority of cases. © 2017 Royal Australasian College of Physicians.

  6. Evaluation of serum iohexol clearance for use in predicting carboplatin clearance in cats.

    Science.gov (United States)

    Bailey, Dennis B; Rassnick, Kenneth M; Prey, Joshua D; Dykes, Nathan L

    2009-09-01

    To determine whether a glomerular filtration rate (GFR) assay based on serum iohexol clearance can be used to predict carboplatin clearance in cats. 10 cats with tumors. GFR was measured concurrently by use of plasma clearance of technetium Tc 99m-labeled diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) to yield GFR(99mTc-DTPA) and serum clearance of iohexol to yield GFR(Iohexol). A single dose of carboplatin was administered IV as a bolus. Dose was calculated by use of a target value for the area under the plasma platinum concentration-versus-time curve (AUC(Target)) and estimation of platinum clearance (CL(PT)) derived from GFR(99mTc-DTPA) as follows: dose = AUC(Target) x 2.6 x GFR(99mTc-DTPA) x body weight, where AUC(Target) is 2.75 min.mg.mL(-1). Plasma platinum concentrations were measured via atomic absorption spectrophotometry. Values for GFR(99mTc-DTPA) and GFR(Iohexol) were compared by use of least-squares regression and Bland-Altman analysis. Least-squares regression was used to determine whether CL(PT) could be predicted from GFR(99mTc-DTPA) or GFR(Iohexol) (or both). GFR(99mTc-DTPA) and GFR(Iohexol) were strongly correlated (r = 0.90), but GFR(Iohexol) values were significantly larger by a factor of approximately 1.4. Platinum clearance had a significant linear relationship to GFR(99mTc-DTPA) (CL(PT) = 2.5 x GFR(99mTc-DTPA)) and to GFR(Iohexol) (CL(PT) = [1.3 x GFR(Iohexol)] + 1.4). In cats, serum iohexol clearance was an accurate predictor of CL(PT) and can be used to calculate the carboplatin dose as follows: dose = AUC(Target) x ([1.3 x GFR(Iohexol)] + 1.4) x body weight.

  7. Impact of rituximab on patient-reported outcomes in patients with rheumatoid arthritis from the US Corrona Registry.

    Science.gov (United States)

    Harrold, Leslie R; John, Ani; Best, Jennie; Zlotnick, Steve; Karki, Chitra; Li, YouFu; Greenberg, Jeffrey D; Kremer, Joel M

    2017-09-01

    To evaluate the impact of rituximab on patient-reported outcomes (PROs) in a US-based observational cohort of patients with rheumatoid arthritis (RA). Patients with active RA, prior exposure to ≥1 tumor necrosis factor inhibitor (TNFi) and who newly initiated rituximab were identified. Changes in PROs were assessed 1 year after rituximab initiation. PRO measures included Clinical Disease Activity Index (CDAI); patient global disease activity, pain and fatigue (visual analog score; 0-100); morning stiffness (hours); modified Health Assessment Questionnaire (mHAQ; 0-3); and EuroQoL EQ-5D. Of the 667 patients who newly initiated rituximab, baseline PRO and clinical measures indicated that patients were substantially impacted by their RA disease and quality of life; 54% of patients had high disease activity. One year after rituximab initiation, 49.0, 47.1, 49.8, and 23.2% of patients reported clinically meaningful improvements in patient global, pain, fatigue, and mHAQ, respectively. Morning stiffness and EuroQol EQ-5D domains improved in 48 and 19-32% of patients, respectively. These real-world registry data demonstrated that patients with long-standing, refractory RA experienced improvements in PROs 1 year after initiating rituximab.

  8. Immunological profile in cerebrospinal fluid of patients with multiple sclerosis after treatment switch to rituximab and compared with healthy controls.

    Directory of Open Access Journals (Sweden)

    Pierre de Flon

    Full Text Available To investigate changes in the cerebrospinal fluid (CSF immunological profile after treatment switch from first-line injectables to rituximab in patients with relapsing-remitting MS (RRMS, and to compare the profile in MS patients with healthy controls (HC.Cerebrospinal fluid from 70 patients with clinically stable RRMS and 55 HC was analysed by a multiplex electrochemiluminescence method for a broad panel of cytokines and immunoactive substances before, and over a two-year period after, treatment switch to rituximab. After quality assessment of data, using a predefined algorithm, 14 analytes were included in the final analysis.Ten of the 14 analytes differed significantly in MS patients compared with HC at baseline. Levels of IP-10 (CXCL10, IL-12/23p40, IL-6, sVCAM1, IL-15, sICAM1 and IL-8 (CXCL8 decreased significantly after treatment switch to rituximab. The cytokines IP-10 and IL-12/IL-23p40 displayed the largest difference versus HC at baseline and also the largest relative reduction after therapy switch to rituximab.We found significant changes in the immunological profile after therapy switch to rituximab in RRMS in the direction towards the values of HC. IP-10 and IL12/IL-23p40 deserve further studies as part of the immunopathogenesis of MS as well as for the mode of action of rituximab in MS.

  9. Imaging and measuring the rituximab-induced changes of mechanical properties in B-lymphoma cells using atomic force microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Li, Mi [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); Liu, Lianqing, E-mail: lqliu@sia.cn [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Xi, Ning, E-mail: xin@egr.msu.edu [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Department of Electrical and Computer Engineering, Michigan State University, East Lansing, MI 48824 (United States); Wang, Yuechao; Dong, Zaili [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Tabata, Osamu [Department of Micro Engineering, Kyoto University, Kyoto 606-8501 (Japan); Xiao, Xiubin [Department of Lymphoma, Affiliated Hospital of Military Medical Academy of Sciences, Beijing 100071 (China); Zhang, Weijing, E-mail: zhangwj3072@163.com [Department of Lymphoma, Affiliated Hospital of Military Medical Academy of Sciences, Beijing 100071 (China)

    2011-01-14

    Research highlights: {yields} Single B-lymphoma living cells were imaged by AFM with the assistance of microfabricated pillars. {yields} The apoptosis of B-lymphoma cells triggered by rituximab without cross-linking was observed by AO/EB double fluorescent staining. {yields} The B-lymphoma cells became dramatically softer after adding rituximab. -- Abstract: The topography and mechanical properties of single B-lymphoma cells have been investigated by atomic force microscopy (AFM). With the assistance of microfabricated patterned pillars, the surface topography and ultrastructure of single living B-lymphoma cell were visualized by AFM. The apoptosis of B-lymphoma cells induced by rituximab alone was observed by acridine orange/ethidium bromide (AO/EB) double fluorescent staining. The rituximab-induced changes of mechanical properties in B-lymphoma cells were measured dynamically and the results showed that B-lymphoma cells became dramatically softer after incubation with rituximab. These results can improve our understanding of rituximab'effect and will facilitate the further investigation of the underlying mechanisms.

  10. Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab's Efficacy in MTX iNadequate rEsponders (SERENE)).

    Science.gov (United States)

    Emery, P; Deodhar, A; Rigby, W F; Isaacs, J D; Combe, B; Racewicz, A J; Latinis, K; Abud-Mendoza, C; Szczepanski, L J; Roschmann, R A; Chen, A; Armstrong, G K; Douglass, W; Tyrrell, H

    2010-09-01

    This phase III study evaluated the efficacy and safety of rituximab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an inadequate response to MTX and who were naïve to prior biological treatment. Patients with active disease on stable MTX (10-25 mg/week) were randomised to rituximab 2 x 500 mg (n=168), rituximab 2 x 1000 mg (n=172), or placebo (n=172). From week 24, patients not in remission (Disease Activity Score (28 joints) > or =2.6) received a second course of rituximab; patients initially assigned to placebo switched to rituximab 2 x 500 mg. The primary end point was American College of Rheumatology 20 (ACR20) response at week 24. All patients were followed until week 48. At week 24, both doses of rituximab showed statistically superior efficacy (p<0.0001) to placebo (ACR20: 54%, 51% and 23%; rituximab (2 x 500 mg) + MTX, rituximab (2 x 1000 mg) + MTX and placebo + MTX, respectively). Secondary end points were also significantly improved for both rituximab groups compared with placebo. Further improvements in both rituximab arms were observed from week 24 to week 48. Rituximab + MTX was well tolerated, demonstrating comparable safety to placebo + MTX through to week 24, and between rituximab doses through to week 48. Rituximab (at 2 x 500 mg and 2 x 1000 mg) plus MTX significantly improved clinical outcomes at week 24, which were further improved by week 48. No significant differences in either clinical or safety outcomes were apparent between the rituximab doses.

  11. Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naïve with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab's Efficacy in MTX iNadequate rEsponders (SERENE))

    Science.gov (United States)

    Emery, P; Deodhar, A; Rigby, W F; Isaacs, J D; Combe, B; Racewicz, A J; Latinis, K; Abud-Mendoza, C; Szczepański, L J; Roschmann, R A; Chen, A; Armstrong, G K; Douglass, W; Tyrrell, H

    2010-01-01

    Objectives This phase III study evaluated the efficacy and safety of rituximab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an inadequate response to MTX and who were naïve to prior biological treatment. Methods Patients with active disease on stable MTX (10–25 mg/week) were randomised to rituximab 2×500 mg (n=168), rituximab 2×1000 mg (n=172), or placebo (n=172). From week 24, patients not in remission (Disease Activity Score (28 joints) ≥2.6) received a second course of rituximab; patients initially assigned to placebo switched to rituximab 2×500 mg. The primary end point was American College of Rheumatology 20 (ACR20) response at week 24. All patients were followed until week 48. Results At week 24, both doses of rituximab showed statistically superior efficacy (p<0.0001) to placebo (ACR20: 54%, 51% and 23%; rituximab (2×500 mg) + MTX, rituximab (2×1000 mg) + MTX and placebo + MTX, respectively). Secondary end points were also significantly improved for both rituximab groups compared with placebo. Further improvements in both rituximab arms were observed from week 24 to week 48. Rituximab + MTX was well tolerated, demonstrating comparable safety to placebo + MTX through to week 24, and between rituximab doses through to week 48. Conclusions Rituximab (at 2×500 mg and 2×1000 mg) plus MTX significantly improved clinical outcomes at week 24, which were further improved by week 48. No significant differences in either clinical or safety outcomes were apparent between the rituximab doses. PMID:20488885

  12. Internalisation of uncross-linked rituximab is not essential for the induction of caspase-independent killing in Burkitt lymphoma cell lines.

    Science.gov (United States)

    Turzanski, Julie; Daniels, Ian; Haynes, Andrew P

    2008-08-01

    Characterising the mechanisms underpinning caspase-independent programmed cell death (CI-PCD) induction by uncross-linked rituximab in B-cells may positively impact upon the treatment of disease states in which the classical apoptotic pathway is disabled. The necessity of rituximab internalisation for CI-PCD induction was investigated by flow cytometry and confocal microscopy in human BL cell lines with (e.g. Mutu I) and without (Mutu III) susceptibility to rituximab-induced killing. Flow cytometry demonstrated small, significant and similar amounts of rituximab internalisation by Mutu I cells after 1, 2, 4 and 24 h (p internalisation (p = 0.02, n = 5 and p = 0.0002, n = 6, respectively) in Mutu I cells, but confocal microscopy showed no correlation between internalised rituximab and phosphatidylserine exposure. We conclude that rituximab internalisation is not essential for CI-PCD induction in BL cell lines.

  13. Synthesis of novel monomeric graphene quantum dots and corresponding nanocomposite with molecularly imprinted polymer for electrochemical detection of an anticancerous ifosfamide drug.

    Science.gov (United States)

    Bali Prasad, Bhim; Kumar, Anil; Singh, Ragini

    2017-08-15

    This paper reports a typical synthesis of a nanocomposite of functionalized graphene quantum dots and imprinted polymer at the surface of screen-printed carbon electrode using N-acryloyl-4-aminobenzamide, as a functional monomer, and an anticancerous drug, ifosfamide, as a print molecule (test analyte). Herein, graphene quantum dots in nanocomposite practically induced the electrocatalytic activity by lowering the oxidation overpotential of test analyte and thereby amplifying electronic transmission, without any interfacial barrier in between the film and the electrode surface. The differential pulse anodic stripping signal at functionalized graphene quantum dots based imprinted sensor was realized to be about 3- and 7-fold higher as compared to the traditionally made imprinted polymers prepared in the presence and the absence of graphene quantum dots (un-functionalized), respectively. This may be attributed to a pertinent synergism in between the positively charged functionalized graphene quantum dots in the film and the target analyte toward the enhancement of electro-conductivity of the film and thereby the electrode kinetics. In fact, the covalent attachment of graphene quantum dots with N-acryloyl-4-aminobenzamide molecules might exert an extended conjugation at their interface facilitating electro conducting to render the channelized pathways for the electron transport. The proposed sensor is practically applicable to the ultratrace evaluation of ifosfamide in real (biological/pharmaceutical) samples with detection limit as low as 0.11ngmL -1 (S/N=3), without any matrix effect, cross-reactivity, and false-positives. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Paclitaxel/carboplatin with or without belinostat as empiric first-line treatment for patients with carcinoma of unknown primary site

    DEFF Research Database (Denmark)

    Hainsworth, John D; Daugaard, Gedske; Lesimple, Thierry

    2015-01-01

    : The addition of belinostat to paclitaxel/carboplatin did not improve the PFS of patients with CUP who were receiving first-line therapy, although the patients who received belinostat had a higher investigator-assessed response rate. Future trials in CUP should focus on specific subsets, defined either......BACKGROUND: The objective of this study was to evaluate the efficacy of belinostat, a histone deacetylase inhibitor, when added to paclitaxel/carboplatin in the empiric first-line treatment of patients with carcinoma of unknown primary site (CUP). METHODS: In this randomized phase 2 trial......, previously untreated patients with CUP were randomized to receive belinostat plus paclitaxel/carboplatin (group A) or paclitaxel/carboplatin alone (group B) repeated every 21 days. Patients were re-evaluated every 2 cycles, and those without disease progression continued treatment for 6 cycles. Patients...

  15. First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10)

    DEFF Research Database (Denmark)

    Eichhorst, Barbara; Fink, Anna-Maria; Bahlo, Jasmin

    2016-01-01

    BACKGROUND: Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab is the standard therapy for physically fit patients with advanced chronic lymphocytic leukaemia. This international phase 3 study compared the efficacy and tolerance of the standard therapy with a potentially less....... The final analysis was done by intention to treat. The study is registered with ClinicalTrials.gov, number NCT%2000769522. FINDINGS: 688 patients were recruited between Oct 2, 2008, and July 11, 2011, of which 564 patients who met inclusion criteria were randomly assigned. 561 patients were included...

  16. nab-Paclitaxel/carboplatin in elderly patients with advanced squamous non-small cell lung cancer: a retrospective analysis of a Phase III trial

    Directory of Open Access Journals (Sweden)

    Gridelli C

    2018-05-01

    Full Text Available Cesare Gridelli,1 Tianlei Chen,2 Amy Ko,2 Mary E O’Brien,3 Teng Jin Ong,4 Mark A Socinski,5 Pieter E Postmus6 1Division of Medical Oncology, S. G. Moscati Hospital, Avellino, Italy; 2Biostatistics, Celgene Corporation, Summit, NJ, USA; 3Medical Oncology, Royal Marsden Hospital, London, UK; 4Medical Affairs, Celgene Corporation, Summit, NJ, USA; 5Lung Cancer & Esophageal Cancer, Florida Hospital Cancer Institute, Orlando, FL, USA; 6Pulmonary Diseases, Clatterbridge Cancer Center, Liverpool, UK Background: Limited data on elderly patients with squamous advanced non-small cell lung cancer (NSCLC preclude optimal treatment. Here, we report the outcomes of a retrospective analysis of a subset of patients ≥70 years with squamous histology from the Phase III trial that evaluated nab-paclitaxel/carboplatin vs paclitaxel/carboplatin. Patients and methods: Patients with stage IIIB/IV NSCLC received (1:1 nab-paclitaxel 100 mg/m2 on days 1, 8, and 15 or paclitaxel 200 mg/m2 on day 1, both with carboplatin area under the curve 6 mg×min/mL on day 1 every 3 weeks. The primary endpoint was independently assessed overall response rate as per the Response Evaluation Criteria in Solid Tumors v1.0. Secondary endpoints included progression-free survival, overall survival, and safety. Results: Sixty-five patients ≥70 years with squamous histology were included (nab-paclitaxel/carboplatin, n=35; paclitaxel/carboplatin, n=30. nab-Paclitaxel/carboplatin vs paclitaxel/carboplatin, respectively, resulted in an overall response rate of 46% vs 20% (response rate ratio, 2.29, P=0.029 and a median overall survival of 16.9 vs 8.6 months (hazard ratio, 0.50, P=0.018. No difference was observed in median progression-free survival (5.7 months for both. Incidences of grade 3/4 neutropenia (50% vs 63%, leukopenia (29% vs 37%, fatigue (3% vs 13%, and peripheral neuropathy (3% vs 13% were lower, but those of thrombocytopenia (21% vs 10% and anemia (21% vs 7% were higher with

  17. Recurrent Pseudomembranous Colitis in an Ovarian Cancer Patient Undergoing Carboplatin Chemotherapy

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    Valerie A. Allen

    2016-01-01

    Full Text Available Background. Diarrhea is a common problem in ovarian cancer patients undergoing chemotherapy and Clostridium difficile infection has been identified as a cause. The proper diagnosis and treatment of diarrhea are critical to patient care, especially to prevent the serious complications from a severe Clostridium difficile infection (CDI. Case. We present a heavily pretreated ovarian cancer patient who developed recurrent pseudomembranous colitis while receiving carboplatin chemotherapy. Despite treatment with oral metronidazole for fourteen days, the patient’s diarrhea relapsed and colonoscopy revealed extensive pseudomembranous colitis. The infection eventually resolved with the combination of oral vancomycin and metronidazole. Conclusions. Diarrhea is a common problem in patients undergoing chemotherapy for ovarian cancer. Management requires obtaining the proper diagnosis. Clostridium difficile associated pseudomembranous colitis must be part of the differential diagnosis. Treatment must be sufficient to prevent relapses of the Clostridium difficile infection to prevent serious consequences in an already vulnerable patient population.

  18. Randomized phase III trial of piroxicam in combination with mitoxantrone or carboplatin for first-line treatment of urogenital tract transitional cell carcinoma in dogs.

    Science.gov (United States)

    Allstadt, S D; Rodriguez, C O; Boostrom, B; Rebhun, R B; Skorupski, K A

    2015-01-01

    Reported response rates of transitional cell carcinoma (TCC) in dogs to piroxicam in combination with either mitoxantrone or carboplatin are similar; however, it is unknown whether either drug might provide superior duration of response. To determine if the progression-free interval (PFI) of dogs with TCC treated with mitoxantrone and piroxicam was different than that of dogs receiving carboplatin and piroxicam. The hypothesis was that the efficacy of mitoxantrone is no different from carboplatin. Fifty dogs with TCC without azotemia. Prospective open-label phase III randomized study. Either mitoxantrone or carboplatin was administered every 3 weeks concurrently with piroxicam with restaging at 6-week intervals. Twenty-four dogs received carboplatin and 26 received mitoxantrone. Response was not different between groups (P = .56). None of the dogs showed complete response. In the mitoxantrone group, there were 2 (8%) partial responses (PR) and 18 (69%) dogs with stable disease (SD). In the carboplatin group, there were 3 PR (13%) and 13 (54%) dogs with SD. The PFI was not significantly different between groups (mitoxantrone = 106 days; carboplatin = 73.5 days; P = .62; hazard ratio 0.86; 95% confidence interval 0.47-1.56). Dogs with prostatic involvement experienced a shorter survival (median, 109 days) compared to dogs with urethral, trigonal, or apically located tumors; this difference was significant (median 300, 190, and 645 days, respectively; P = .005). This study did not detect a different in outcome in dogs with TCC treated with either mitoxantrone or carboplatin in combination with piroxicam. Copyright © 2015 by the American College of Veterinary Internal Medicine.

  19. Dose-dense paclitaxel with carboplatin for advanced ovarian cancer: a feasible treatment alternative.

    Science.gov (United States)

    Glaze, Sarah; Teitelbaum, Lisa; Chu, Pamela; Ghatage, Prafull; Nation, Jill; Nelson, Gregg

    2013-01-01

    Epithelial ovarian cancer is the leading cause of death from gynaecologic cancers in the Western world. If possible, initial cytoreductive surgery is the treatment of choice, followed by adjuvant chemotherapy, usually with a platinum/taxane combination. Increased survival has been recently reported in women who were given adjuvant chemotherapy weekly rather than at three-week intervals, which has been the standard. At our centre, we have been treating patients with advanced ovarian cancer with a dose-dense protocol since March 2010. Treatment is given in an outpatient setting on days 1, 8, and 15 of a 21-day cycle for six cycles. Carboplatin for an AUC of 5 mg/mL/min and paclitaxel 80mg/m² are given on day 1, followed by paclitaxel 80mg/m² on days 8 and 15. Our objective was to determine whether this protocol is a feasible alternative treatment in our population and whether or not the toxicity profile is acceptable. We performed a chart review of 46 patients undergoing treatment with dose-dense chemotherapy for advanced ovarian cancer. Demographic information, patient characteristics, adverse events, and treatment endpoints were recorded. Sixty-one percent of women completed the six-cycle protocol as planned with minimal interruption, which is comparable to the only previously reported trial using this regimen. The most common side effects of treatment were fatigue, neuropathy, and neutropenia. Supplementation with regular magnesium and granulocyte colony-stimulating factor reduced delays. Dose-dense paclitaxel with carboplatin chemotherapy for the treatment of advanced ovarian cancer shows promise in terms of progression-free and overall survival. We have shown this protocol to be practical and feasible in our population.

  20. Weekly dose-dense paclitaxel and carboplatin in recurrent ovarian carcinoma: A phase II trial

    International Nuclear Information System (INIS)

    Shawky, H.; Tawfik, H.; Hewidy, M.

    2014-01-01

    Purpose: The aim of this study was to investigate efficacy and toxicity of the dose-dense weekly paclitaxel (T) and carboplatin (C) in the management of platinum-resistant/sensitive recurrent epithelial ovarian cancer (EOC) previously treated with 3 weekly paclitaxel/carboplatin. Methods: Thirty two patients with recurrent EOC who had received 3 weekly TC before were enrolled. Nine patients relapsed within 6 months (platinum-resistant), 13 patients relapsed after 12 months (platinum-sensitive) and in 10 patients recurrence occurred between 6 and 12 months (intermediate platinum-sensitive). Weekly (T) at a dose of 80 mg/m2, followed by weekly (C) AUC 2 on day 1, 8, and 15 of a 28-day cycle for 6 planned cycles were administrated. End-points were overall response rate (ORR), progression free survival (PFS), overall survival (OS) and toxicity. Results: The ORR was 62.5%. For the platinum-resistant, intermediate platinum-sensitive and platinum-sensitive patients the ORR was 44.4% (4/9), 60% (6/10) and 76.9% (10/13), respectively, and 1 (11.1%), 2 (20%) and 5 (38.46%) patients, respectively had CR. PFS was 9.1 months (6.13, 9.1 and 12.17 months, for the 3 groups, respectively) (P < 0.001). OS was 14 months (9.17, 15.2, and 19.23 months, for the 3 groups, respectively) (P < 0.001). Treatment-related adverse events were manageable with only 1 patient (3.1%) suffering from grade 4 neutropenia. Grade 3 hematological and non-hematological toxicities were neutropenia in 8 (25%), and peripheral neuropathy in 4 (12.5%) patients, respectively. Conclusion: Weekly TC is active and well-tolerated in platinum-resistant and platinum-sensitive patients with recurrent EOC previously treated with TC given every 3 weeks

  1. Leuconostoc sp. Meningitis in a Patient Treated with Rituximab for Mantle Cell Lymphoma

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    Hrvoje Holik

    2015-09-01

    Full Text Available We present a 64-year-old man who was treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone chemoimmunotherapy for mantle cell lymphoma and developed purulent meningitis, probably caused by Leuconostoc sp. The patient had severe hypogammaglobulinemia, which is a possible complication of rituximab therapy. To our knowledge and after reviewing the available medical literature, this is the first described case of purulent meningitis caused by Leuconostoc sp. in a patient with mantle cell lymphoma that appeared after treatment with the R-CHOP protocol. The diagnosis of purulent meningitis was based on clinical, laboratory and cytological cerebrospinal fluid findings, in addition to blood culture results in which we isolated Leuconostoc sp. The patient was treated with meropenem with full recovery.

  2. Posterior reversible encephalopathy syndrome masquerading as progressive multifocal leukoencephalopathy in rituximab treated neuromyelitis optica.

    Science.gov (United States)

    Berger, Joseph R; Neltner, Janna; Smith, Charles; Cambi, Franca

    2014-11-01

    Both progressive multifocal leukoencephalopathy (PML) and posterior reversible encephalopathy syndrome (PRES) have been reported as complications of rituximab therapy. These disorders may appear indistinguishable on magnetic resonance imaging (MRI). We report on a 42 year old woman with neuromyelitis optica (NMO) of 10 years duration who developed extensive white matter disease affecting chiefly both parietal lobes 6 months after her first and only dose of rituximab. The MRI findings suggested the diagnosis of PML, but her history was more consistent with PRES. Ultimately, a brain biopsy was performed which was consistent with the diagnosis of PRES. PRES and PML may have overlapping symptomatology and be indistinguishable on MRI. An approach to distinguishing between these two disorders is addressed. Copyright © 2014. Published by Elsevier B.V.

  3. Response to rituximab in a refractory case of thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus

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    Niaz Faraz

    2010-01-01

    Full Text Available Thrombotic thrombocytopenic purpura (TTP is a serious disorder with a significant morbidity and mortality. Majority of cases of TTP are idiopathic, but some cases may be secon-dary to connective tissue diseases. TTP has been rarely associated with systemic lupus erythe-matosus (SLE and may be refractory to treatment with plasma exchange, requiring immuno-suppressive therapy. We describe a patient with TTP and SLE who was refractory to plasma exchange and corticosteroids but responded to anti-CD20 antibody rituximab with continued re-mission after eight months of follow-up. Rituximab appears to be an effective treatment in re-fractory cases of TTP associated with SLE.

  4. Assessment of Physicochemical Properties of Rituximab Related to Its Immunomodulatory Activity

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    Mariana P. Miranda-Hernández

    2015-01-01

    Full Text Available Rituximab is a chimeric monoclonal antibody employed for the treatment of CD20-positive B-cell non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis and microscopic polyangiitis. It binds specifically to the CD20 antigen expressed on pre-B and consequently on mature B-lymphocytes of both normal and malignant cells, inhibiting their proliferation through apoptosis, CDC, and ADCC mechanisms. The immunomodulatory activity of rituximab is closely related to critical quality attributes that characterize its chemical composition and spatial configuration, which determine the recognition of CD20 and the binding to receptors or factors involved in its effector functions, while regulating the potential immunogenic response. Herein, we present a physicochemical and biological characterization followed by a pharmacodynamics and immunogenicity study to demonstrate comparability between two products containing rituximab. The physicochemical and biological characterization revealed that both products fit within the same response intervals exhibiting the same degree of variability. With regard to clinical response, both products depleted CD20+ B-cells until posttreatment recovery and no meaningful differences were found in their pharmacodynamic profiles. The evaluation of anti-chimeric antibodies did not show differential immunogenicity among products. Overall, these data confirm that similarity of critical quality attributes results in a comparable immunomodulatory activity.

  5. Rituximab Therapy for Severe Cutaneous Leukocytoclastic Angiitis Refractory to Corticosteroids, Cellcept and Cyclophosphamide

    Directory of Open Access Journals (Sweden)

    Kamel El-Reshaid

    2013-04-01

    Full Text Available We report our clinical experience with rituximab in the treatment of 2 patients with idiopathic cutaneous angiitis who relapsed after treatment with high-dose corticosteroids and cyclophosphamide. A 39-year-old woman and a 51-year-old man presented with ulcerating maculopapular rash in both lower limbs which relapsed 6 months after treatment with a combination of high-dose corticosteroids and cyclophosphamide. After treatment with 2 g of rituximab, the first patient has still been in clinical remission for 32 months while the second has finished 28 months. Interestingly, CD19 which had dropped to 0.5% 8 months later in both patients. Despite that, our patients are still in clinical remission. No significant side effects were noted during infusions and up to the period of follow-up. In conclusion, rituximab is a useful and safe agent in the treatment of idiopathic cutaneous angiitis refractory to conventional therapy. Clinical remission persists years after improvement of B-cell suppression.

  6. EFFICACY OF RECURRENT RITUXIMAB TREATMENT IN PATIENT WITH SEVERE REFRACTORY SYSTEMIC JUVENILE RHEUMATOID ARTHRITIS

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    E.I. Alexeeva

    2011-01-01

    Full Text Available The article contains clinical case description of a severe systemic juvenile rheumatoid arthritis, that was refractory to classic immunosuppressant therapy. The disease was characterized by such extraarticular manifestations as fever, lymphadenopathy,  hepatosplenomegaly, polyserositis, generalized joint involvement and high activity in lab tests. As a result of severe clinical course of the disease, patients develop bilateral aseptic bone necrosis in coxofemoral joints and coxarthrosis. Against the background of glucocorticosteroid treatment the patient has developed hormone-dependency and hormone resistance. Inclusion into the treatment of anti-CD20 monoclonal antibodies (rituximab has stopped systemic manifestations of the disease, inflammation in the joints, normalized lab activity rates. The positive therapeutic effect allowed to perform surgery due to bilateral coxarthrosis. These results show that rituximab is highly effective in children with systemic juvenile rheumatoid arthritis, that is resistant to classic immunosupressants and glucocorticoides. Key words: children, systemic juvenile rheumatoid arthritis, rituximab, recurrent treatment, prosthetics, hip joint. (Voprosy sovremennoi pediatrii — Current Pediatrics. — 2011; 10 (5: 157–163.

  7. Malignant lymphoma of the vagina successfully treated with rituximab, adryamicin, cyclophosphamide, vincristine sulfate, and prednisolone.

    Science.gov (United States)

    Nasu, K; Okamoto, M; Nishida, M; Takai, N; Narahara, H

    2012-01-01

    Primary malignant lymphoma of the vagina is extremely rare. The most common histologic subtype is diffuse large B-cell lymphoma (DLBCL). We report a case of vaginal DLBCL successfully treated with chemotherapy consisting of rituximab, adryamicin, cyclophosphamide, vincristine sulfate, and prednisolone (R-CHOP), followed by pelvic irradiation. A 44-year-old Japanese woman was admitted complaining of atypical genital bleeding and puruloid vaginal discharge. Gynecological examination showed an ulceration of the vaginal wall and a hard mass the size of a goose egg beneath the left vaginal wall, which had infiltrated to the left pelvic wall. The pathological diagnosis based on a punch biopsy taken from the vaginal tumor was non-Hodgkin's lymphoma. Based on immunohistochemical study, the tumor was subclassified as activated B-cell type DLBCL. The patient was diagnosed with Ann Arbor Stage IEA DLBCL and Stage III vaginal cancer, according to the International Federation of Gynecologists and Obstetricians (FIGO) classification system. She was successfully treated by six courses of R-CHOP, followed by radiation therapy. The patient is well without evidence of disease 13 months following the initial treatment. Little attention has been paid to the use of rituximab in addition to conventional chemotherapy and the importance of clinical and morphological subgrouping of DLBCL arising in the vagina. The present case indicates that the effects of rituximab on the prognosis of vaginal DLBCL must be evaluated, and that clinical use of immunophenotypic subgrouping should be considered for vaginal DLBCL.

  8. Rituximab and new regimens for indolent lymphoma: a brief update from 2012 ASCO Annual Meeting

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    Zhao Jiangning

    2012-08-01

    Full Text Available Abstract Indolent lymphoma (IL, the second most common lymphoma, remains incurable with chemotherapy alone. While R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone remains the standard frontline regimen for diffuse Large B –cell lymphoma, the optimal chemotherapy regimen for frontline therapy of advanced IL remains uncertain. FCR (fludarabine, cyclophosphamide, rituximab has been shown to be better than fludarabine alone and fludarabine plus cyclophosphamide for IL. In FOLL05 trial, R-CHOP was compared with R-CVP (cyclophosphamide, vincristine, prednisone and R-FM (fludarabine, mitoxantrone. The study showed that R-CHOP appears to have the best risk-benefit ratio for IL. The StiL NHL1 trial showed that BR (bendamustine, rituximab has longer progression free survival and is better tolerated than R-CHOP. Long-term complications with secondary malignancies between the two regimens appear to be comparable. In this review, new combination regimens reported at 2012 ASCO annual meeting were evaluated for frontline and salvage therapy of indolent lymphoma.

  9. Effects of hypertonic buffer composition on lymph node uptake and bioavailability of rituximab, after subcutaneous administration.

    Science.gov (United States)

    Fathallah, Anas M; Turner, Michael R; Mager, Donald E; Balu-Iyer, Sathy V

    2015-03-01

    The subcutaneous administration of biologics is highly desirable; however, incomplete bioavailability after s.c. administration remains a major challenge. In this work we investigated the effects of excipient dependent hyperosmolarity on lymphatic uptake and plasma exposure of rituximab as a model protein. Using Swiss Webster (SW) mice as the animal model, we compared the effects of NaCl, mannitol and O-phospho-L-serine (OPLS) on the plasma concentration of rituximab over 5 days after s.c. administration. An increase was observed in plasma concentrations in animals administered rituximab in hypertonic buffer solutions, compared with isotonic buffer. Bioavailability, as estimated by our pharmacokinetic model, increased from 29% in isotonic buffer to 54% in hypertonic buffer containing NaCl, to almost complete bioavailability in hypertonic buffers containing high dose OPLS or mannitol. This improvement in plasma exposure is due to the improved lymphatic trafficking as evident from the increase in the fraction of dose trafficked through the lymph nodes in the presence of hypertonic buffers. The fraction of the dose trafficked through the lymphatics, as estimated by the model, increased from 0.05% in isotonic buffer to 13% in hypertonic buffer containing NaCl to about 30% for hypertonic buffers containing high dose OPLS and mannitol. The data suggest that hypertonic solutions may be a viable option for improving s.c. bioavailability. Copyright © 2014 John Wiley & Sons, Ltd.

  10. Induction therapy with carboplatin/paclitaxel followed by concurrent carboplatin/paclitaxel and dose-escalating conformal radiotherapy in the treatment of locally advanced, unresectable non-small cell lung cancer: preliminary report of a phase I trial.

    Science.gov (United States)

    Socinski, M A; Clark, J A; Halle, J; Steagall, A; Kaluzny, B; Rosenman, J G

    1997-08-01

    Locally advanced non-small cell lung cancer is optimally managed with chemotherapy and thoracic irradiation, although the most appropriate strategy is not yet defined. In this phase I trial, we use two 21-day cycles of induction chemotherapy with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (225 mg/m2 over 3 hours) and carboplatin (area under the concentration-time curve = 6) followed by concurrent weekly paclitaxel (45 mg/m2/wk x 6) and carboplatin (area under the concentration-time curve = 2/wk x 6) and thoracic irradiation. Patients undergo three-dimensional treatment planning (conformal radiotherapy) to define the cancer target volume precisely. The phase I question being addressed in this study is the maximum tolerated radiation dose given concurrently with low-dose paclitaxel and carboplatin. The initial radiation dose is 60 Gy, with dose escalations to 66 Gy, 70 Gy, and 74 Gy being planned. Ten patients have been entered thus far (eight men and two women). Their median age is 67 years (range, 59 to 78 years), and none of the patients has had greater than 5% pretreatment weight loss. Seven of 10 are evaluable for response to induction carboplatin and paclitaxel, with a response rate of 57% (three partial responses and one minor response). Three patients had stable disease and none of the patients had evidence of progressive disease during induction chemotherapy. Three patients have completed all treatment at 60 Gy and one has completed all treatment at 66 Gy. Three of the four patients have had partial responses (75%), with the remaining patient having stable disease. Toxicity in the concurrent chemoradiotherapy portion of the trial thus far has consisted of grade 3 neutropenia in one patient and grade 4 lymphocytopenia in all four patients. No grade 3 or 4 nonhematologic toxicity has been seen. The trial data are not yet mature enough to report on survival. Accrual and treatment is continuing at the 66 Gy radiation dose level.

  11. Testing of mechanisms of action of rituximab and clinical results in high-risk patients with aggressive CD20+ lymphoma

    International Nuclear Information System (INIS)

    Jezersek Novakovic, B.; Juznic Setina, T.; Vovk, M.; Kotnik, V.; Novakovic, S.

    2007-01-01

    Rituximab has been applied successfully in the treatment of indolent and aggressive CD20 positive B cell lymphomas, yet the exact in vivo mechanisms of its action have not been unambiguously explained. This study was therefore aimed to confirm the presumed major mechanisms of action of rituximab and concomitantly to assess the effectiveness of first-line chemo immunotherapy in high-risk patients with aggressive CD20 lymphomas. The activity of rituximab was tested in vitro on Raji and SU-DHL-4 cells using the cell proliferation assay and flow cytometry. In the clinical part of the study, 20 high-risk patients with aggressive CD 20 lymphomas were treated with R-CHOP. Only complement-mediated cytotoxicity was observed under the in vitro applied experimental conditions. Neither the direct apoptotic effect nor the antibody-dependent cell-mediated cytotoxicity was detected probably due to a too low concentration of rituximab and a too low ratio of cytotoxic lymphocytes to tumor cells. The treatment outcome in patients was excellent since complete remissions were achieved in 90% of poor-risk patients at the end of primary treatment and 80% of patients were disease-free at 18.5 months median observation period. According to our results, the complement-dependent cytotoxicity is an important mechanism of rituximab action in vitro. To achieve direct apoptosis, higher concentrations than 20 μg/ml of rituximab should be used, while for an effective antibody-dependent cell-mediated cytotoxicity, the ratio of cytotoxic lymphocytes to tumor cells should be higher than 1:1. In the high-risk patients with aggressive CD20 lymphomas, the addition of rituximab to CHOP substantially improves the therapeutic results. (author)

  12. Anti-Ma2 paraneoplastic encephalitis associated with testicular germ cell tumor treated by carboplatin, etoposide and bleomycin.

    Science.gov (United States)

    Kimura, Masaki; Onozawa, Mizuki; Fujisaki, Akira; Arakawa, Takashi; Takeda, Katsuhiko; Dalmau, Joseph; Hattori, Kazunori

    2008-10-01

    Anti-Ma2-associated encephalitis is a paraneoplastic disorder that predominantly affects the limbic system, diencephalon and brainstem, and is usually associated with tumors of the testis. We report a 35-year-old man with a right testicular mass who presented with multiple neurological complains, and clinical, serological and radiological features compatible with anti-Ma2-associated encephalitis. After three courses of carboplatin, etoposide and bleomycin for metastatic testicular germ-cell tumor, all elevated tumor markers normalized and the retroperitoneal metastases disappeared, but the neurological disorder deteriorated. To our knowledge, this is the first case in which orchiectomy followed by carboplatin, etoposide and bleomycin for a testicular tumor with anti-Ma2 encephalitis was performed.

  13. Identification of Fc Gamma Receptor Glycoforms That Produce Differential Binding Kinetics for Rituximab.

    Science.gov (United States)

    Hayes, Jerrard M; Frostell, Asa; Karlsson, Robert; Müller, Steffen; Martín, Silvia Míllan; Pauers, Martin; Reuss, Franziska; Cosgrave, Eoin F; Anneren, Cecilia; Davey, Gavin P; Rudd, Pauline M

    2017-10-01

    Fc gamma receptors (FcγR) bind the Fc region of antibodies and therefore play a prominent role in antibody-dependent cell-based immune responses such as ADCC, CDC and ADCP. The immune effector cell activity is directly linked to a productive molecular engagement of FcγRs where both the protein and glycan moiety of antibody and receptor can affect the interaction and in the present study we focus on the role of the FcγR glycans in this interaction. We provide a complete description of the glycan composition of Chinese hamster ovary (CHO) expressed human Fcγ receptors RI (CD64), RIIa Arg131/His131 (CD32a), RIIb (CD32b) and RIIIa Phe158/Val158 (CD16a) and analyze the role of the glycans in the binding mechanism with IgG. The interactions of the monoclonal antibody rituximab with each FcγR were characterized and we discuss the CHO-FcγRIIIa Phe158/Val158 and CHO-FcγRI interactions and compare them to the equivalent interactions with human (HEK293) and murine (NS0) produced receptors. Our results reveal clear differences in the binding profiles of rituximab, which we attribute in each case to the differences in host cell-dependent FcγR glycosylation. The glycan profiles of CHO expressed FcγRI and FcγRIIIa Phe158/Val158 were compared with the glycan profiles of the receptors expressed in NS0 and HEK293 cells and we show that the glycan type and abundance differs significantly between the receptors and that these glycan differences lead to the observed differences in the respective FcγR binding patterns with rituximab. Oligomannose structures are prevalent on FcγRI from each source and likely contribute to the high affinity rituximab interaction through a stabilization effect. On FcγRI and FcγRIIIa large and sialylated glycans have a negative impact on rituximab binding, likely through destabilization of the interaction. In conclusion, the data show that the IgG1-FcγR binding kinetics differ depending on the glycosylation of the FcγR and further support a

  14. Squalene Selectively Protects Mouse Bone Marrow Progenitors Against Cisplatin and Carboplatin-Induced Cytotoxicity In Vivo Without Protecting Tumor Growth

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    Bikul Das

    2008-10-01

    Full Text Available Squalene, an isoprenoid antioxidant is a potential cytoprotective agent against chemotherapy-induced toxicity. We have previously published that squalene protects light-density bone marrow cells against cis-diamminedichloroplatinum( II (cisplatin-induced toxicity without protecting tumor cells in vitro. Here, we developed an in vivo mouse model of cisplatin and cis-diammine (cyclobutane-1,1-dicarboxylato platinum(II (carboplatin-induced toxicity to further investigate squalene-mediated LD-BM cytoprotection including the molecular mechanism behind selective cytoprotection. We found that squalene significantly reduced the body weight loss of cisplatin and carboplatin-treated mice. Light-density bone marrow cells from squalene-treated mice exhibited improved formation of hematopoietic colonies (colony-forming unit-granulocyte macrophage. Furthermore, squalene also protected mesenchymal stem cell colonies (colony-forming unit-fibroblast from cisplatin and carboplatin-induced toxicity. Squalene-induced protection was associated with decreased reactive oxygen species and increased levels of glutathione and glutathione peroxidase/glutathione-S-transferase. Importantly, squalene did not protect neuroblastoma, small cell carcinoma, or medulloblastoma xenografts against cisplatin-induced toxicity. These results suggest that squalene is a potential candidate for future development as a cytoprotective agent against chemotherapeutic toxicity.

  15. Successful Treatment of a Bullous Pemphigoid Patient with Rituximab Who Was Refractory to Corticosteroid and Omalizumab Treatments

    Directory of Open Access Journals (Sweden)

    Aslı Bilgiç Temel

    2017-02-01

    Full Text Available Omalizumab is a humanized monoclonal antibody which is an FDA-approved treatment of severe allergic asthma and inhibits IgE binding to FcεRI. According to increasing evidence of IgE inhibition, omalizumab was suggested as a therapeutic approach for bullous pemphigoid (BP. Rituximab has been reported to be effective in various autoimmune diseases, including autoimmune bullous dermatoses. A specific protocol for the use of rituximab to treat BP patients is not yet available. There are only small case series and case reports about the efficacy and safety of rituximab in BP. Here we present a young BP patient who responded well to rituximab therapy and was refractory to conventional and omalizumab therapies although he had elevated IgE levels and eosinophilia. Our case supports the knowledge about the effectiveness and safety of rituximab not only in pemphigus but also in BP. On the other hand, although it did not work in our case, omalizumab may be a potentially effective agent in some carefully selected patients with certain subtypes of BP.

  16. Efficacy of rituximab and plasmapharesis in an adult patient with antifactor H autoantibody-associated hemolytic uremic syndrome

    Science.gov (United States)

    Deville, Clemence; Garrouste, Cyril; Coppo, Paul; Evrard, Bertrand; Lautrette, Alexandre; Heng, Anne Elisabeth

    2016-01-01

    Abstract Antifactor H antibody (anti-CFHAb) is found in 6% to 25% cases of atypical hemolytic uremic syndrome (aHUS) in children, but has been only exceptionally reported in adults. There is no consensus about the best treatment for this type of aHUS. We report the case of an adult patient treated successfully with plasma exchange (PE), steroids, and rituximab. A 27-year-old Caucasian male presented to hospital with anemia, thrombocytopenia, and acute renal failure. One week earlier, he had digestive problems with diarrhea. The diagnosis of anti-CFHAb-associated aHUS (82,000 AU/mL) without CFHR gene mutations was established. He received Rituximab 375 mg/m2 (4 pulses) with PE and steroids. This treatment achieved renal and hematological remission at day (D) 31 and negative anti-CFHAb at D45 (<100 AU/mL). At D76, a fifth rituximab pulse was performed while CD19 was higher than 10/mm3. Steroids were stopped at month (M) 9. The patient has not relapsed during long-term follow-up (M39). Rituximab therapy can be considered for anti-CFHAb-associated aHUS. Monitoring of anti-CFHAb titer may help to guide maintenance therapeutic strategies including Rituximab infusion. PMID:27684863

  17. A multi-centre retrospective study of rituximab use in the treatment of relapsed or resistant warm autoimmune haemolytic anaemia.

    LENUS (Irish Health Repository)

    Maung, Su W

    2013-10-01

    This retrospective analysis assessed the response, safety and duration of response to standard dose rituximab 375 mg\\/m(2) weekly for four weeks as therapy for patients with primary or secondary warm autoimmune haemolytic anaemia (WAIHA), who had failed initial treatment. Thirty-four patients received rituximab for WAIHA in seven centres in the Republic of Ireland. The overall response rate was 70·6% (24\\/34) with 26·5% (9\\/34) achieving a complete response (CR). The time to response was 1 month post-initiation of rituximab in 87·5% (21\\/24) and 3 months in 12·5% (3\\/24) of patients. The median duration of follow-up was 36 months (range 6-90 months). Of the patients who responded, 50% (12\\/24) relapsed during follow up with a median time to next treatment of 16·5 months (range 6-60 months). Three patients were re-treated with rituximab 375 mg\\/m2 weekly for four weeks at relapse and responded. There was a single episode of neutropenic sepsis. Rituximab is an effective and safe treatment for WAIHA but a significant number of patients will relapse in the first two years post treatment. Re-treatment was effective in a small number of patients, suggesting that intermittent pulse treatment or maintenance treatment may improve long-term response.

  18. Cisplatin vs. carboplatin-based chemoradiotherapy in patients >65 years of age with stage III non-small cell lung cancer

    International Nuclear Information System (INIS)

    Ezer, Nicole; Smith, Cardinale B.; Galsky, Matthew D.; Mhango, Grace; Gu, Fei; Gomez, Jorge; Strauss, Gary M.; Wisnivesky, Juan

    2014-01-01

    Background and purpose: Combined chemoradiotherapy (CRT) is considered the standard care for unresectable stage III non-small cell lung cancer (NSCLC). There have been limited data comparing outcomes of carboplatin vs. cisplatin-based CRT, particularly in elderly. Material and methods: From the Surveillance, Epidemiology and End Results-Medicare registry, we identified 1878 patients >65 years of age with unresected stage III NSCLC that received concurrent CRT between 2002 and 2009. We fitted a propensity score model predicting use of cisplatin-based therapy and compared adjusted overall and lung-cancer specific survival of carboplatin- vs. cisplatin-treated patients. Rates of severe toxicity requiring hospital admission were compared in propensity score adjusted analyses. Results: Overall 1552 (83%) received carboplatin (77% in combination with paclitaxel) and 17% cisplatin (67% in combination with etoposide). Adjusted cox models showed similar overall (hazard ratio [HR]: 0.98; 95% confidence interval [CI]: 0.86–1.12) and lung cancer-specific (HR: 0.99; 95% CI: 0.84–1.17) survival among patients treated with carboplatin vs. cisplatin. Adjusted rates of neutropenia (odds ratio [OR]: 0.35; 95% CI: 0.21–0.61), anemia (OR: 0.67; 95% CI: 0.51–0.89), and thrombocytopenia (OR: 0.51; 95% CI: 0.31–0.85) were lower among carboplatin-treated patients; other toxicities were not different between groups. Conclusion: Carboplatin-based CRT is associated with similar long-term survival but lower rates of toxicity. These findings suggest carboplatin may be the most appropriate chemotherapeutic agent for elderly stage III patients

  19. Safety and Feasibility of Carboplatin and Paclitaxel followed by Fluoropyrimidine Analogs and Radiation as Adjuvant Therapy for Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Mohammad Mobayed

    2009-11-01

    Full Text Available Background: Adjuvant 5-fluorouracil (5FU-based chemo-radiotherapy is currently considered a standard of care for the treatment of gastric cancer. The impact of 5FU-based adjuvant therapy on the rate of distant recurrence has been modest. In order to improve the systemic effects of adjuvant therapy, we have been treating patients with resected gastric cancer with carboplatin and paclitaxel followed by fluoropyrimidine analogue and radiation. Methods: We report on the outcomes of 21 consecutive gastric cancer patients treated off protocol with adjuvant carboplatin (area under the curve 5 mg/ml × min and paclitaxel (175–200 mg/m2 every 3 weeks, followed by concurrent pyrimidine analogs (either capecitabine 1,600–2,000 mg/m2/day in 17 patients, or 5FU 200 mg/m2/day in 4 patients and radiation (45–50.4 Gy. Patients received a total of 4–6 cycles of carboplatin and paclitaxel. Results: The median age at diagnosis was 60 years. Sixteen patients had stage 3 disease and 7 of them had positive surgical margins (6 with R1 and 1 with R2 resection, 3 patients were stage 2, and 2 patients were stage 1 (all had R0 resection. All patients had D1/D2 (4 had D2 and 17 had D1 lymph node dissection. The incidence of grade 3 or higher overall, hematologic, or gastrointestinal toxicity in the patients receiving carboplatin and paclitaxel was 57, 48 and 10%, respectively. No treatment-related deaths were observed. After adjuvant treatment 15 patients developed recurrent disease, 10 of whom had distant metastases. The median recurrence-free survival (RFS was 12.3 months. The median overall survival (OS was 16.0 months. Patients with R0 resection had significantly longer OS than did those with positive surgical margins (log-rank p = 0.0060. Median OS for the R0 resection group was 28.8 months. Conclusions: Carboplatin and paclitaxel added to radiation plus fluoropyrimidine analogs is a well-tolerated regimen in the adjuvant setting. The activity of this regimen

  20. Investigating the heterogeneity of alkylating agents' efficacy and toxicity between sexes: A systematic review and meta-analysis of randomized trials comparing cyclophosphamide and ifosfamide (MAIAGE study).

    Science.gov (United States)

    Fresneau, Brice; Hackshaw, A; Hawkins, D S; Paulussen, M; Anderson, J R; Judson, I; Litière, S; Dirksen, U; Lewis, I; van den Berg, H; Gaspar, N; Gelderblom, H; Whelan, J; Boddy, A V; Wheatley, K; Pignon, J P; De Vathaire, F; Le Deley, M C; Le Teuff, G

    2017-08-01

    A marginal interaction between sex and the type of alkylating agent was observed for event-free survival in the Euro-EWING99-R1 randomized controlled trial (RCT) comparing cyclophosphamide and ifosfamide in Ewing sarcoma. To further evaluate this interaction, we performed an individual patient data meta-analysis of RCTs assessing cyclophosphamide versus ifosfamide in any type of cancer. A literature search produced two more eligible RCTs (EICESS92 and IRS-IV). The endpoints were progression-free survival (PFS, main endpoint) and overall survival (OS). The hazard ratios (HRs) of the treatment-by-sex interaction and their 95% confidence interval (95% CI) were assessed using stratified multivariable Cox models. Heterogeneity of the interaction across age categories and trials was explored. We also assessed this interaction for severe acute toxicity using logistic models. The meta-analysis comprised 1,528 pediatric and young adult sarcoma patients from three RCTs: Euro-EWING99-R1 (n = 856), EICESS92 (n = 155), and IRS-IV (n = 517). There were 224 PFS events in Euro-EWING99-R1 and 200 in the validation set (EICESS92 + IRS-IV), and 171 and 154 deaths in each dataset, respectively. The estimated treatment-by-sex interaction for PFS in Euro-EWING99-R1 (HR = 1.73, 95% CI = 1.00-3.00) was not replicated in the validation set (HR = 0.97, 95% CI = 0.55-1.72), without heterogeneity across trials (P = 0.62). In the pooled analysis, the treatment-by-sex interaction was not significant (HR = 1.31, 95% CI = 0.89-1.95, P = 0.17), without heterogeneity across age categories (P = 0.88) and trials (P = 0.36). Similar results were observed for OS. No significant treatment-by-sex interaction was observed for leucopenia/neutropenia (P = 0.45), infection (P = 0.64), or renal toxicity (P = 0.20). Our meta-analysis did not confirm the hypothesis of a treatment-by-sex interaction on efficacy or toxicity outcomes. © 2017 Wiley Periodicals, Inc.

  1. Cetuximab plus carboplatin and paclitaxel with or without bevacizumab versus carboplatin and paclitaxel with or without bevacizumab in advanced NSCLC (SWOG S0819): a randomised, phase 3 study.

    Science.gov (United States)

    Herbst, Roy S; Redman, Mary W; Kim, Edward S; Semrad, Thomas J; Bazhenova, Lyudmila; Masters, Gregory; Oettel, Kurt; Guaglianone, Perry; Reynolds, Christopher; Karnad, Anand; Arnold, Susanne M; Varella-Garcia, Marileila; Moon, James; Mack, Philip C; Blanke, Charles D; Hirsch, Fred R; Kelly, Karen; Gandara, David R

    2018-01-01

    EGFR antibodies have shown promise in patients with advanced non-small-cell lung cancer (NSCLC), particularly with squamous cell histology. We hypothesised that EGFR copy number by fluorescence in-situ hybridisation (FISH) can identify patients most likely to benefit from these drugs combined with chemotherapy and we aimed to explore the activity of cetuximab with chemotherapy in patients with advanced NSCLC who are EGFR FISH-positive. We did this open-label, phase 3 study (SWOG S0819) at 277 sites in the USA and Mexico. We randomly assigned (1:1) eligible patients with treatment-naive stage IV NSCLC to receive paclitaxel (200 mg/m 2 ; every 21 days) plus carboplatin (area under the curve of 6 by modified Calvert formula; every 21 days) or carboplatin plus paclitaxel and bevacizumab (15 mg/kg; every 21 days), either with cetuximab (250 mg/m 2 weekly after loading dose; cetuximab group) or without (control group), stratified by bevacizumab treatment, smoking status, and M-substage using a dynamic-balancing algorithm. Co-primary endpoints were progression-free survival in patients with EGFR FISH-positive cancer and overall survival in the entire study population. We analysed clinical outcomes with the intention-to-treat principle and analysis of safety outcomes included patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov (number NCT00946712). Between Aug 13, 2009, and May 30, 2014, we randomly assigned 1313 patients to the control group (n=657; 277 with bevacizumab and 380 without bevacizumab in the intention-to-treat population) or the cetuximab group (n=656; 283 with bevacizumab and 373 without bevacizumab in the intention-to-treat population). EGFR FISH was assessable in 976 patients and 400 patients (41%) were EGFR FISH-positive. The median follow-up for patients last known to be alive was 35·2 months (IQR 22·9-39·9). After 194 progression-free survival events in the cetuximab group and 198 in the control

  2. Cyclooxygenase Inhibitor Associated with Carboplatin in Treatment of Metastatic Nasal Carcinoma in Dog

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Fonseca-Alves

    2014-01-01

    Full Text Available A 10-year-old, intact male, pinscher was presented with unilateral bloodstained nasal discharge, sneezing, dyspnea, zygomatic arch deformity, submandibular lymph node increase, blindness in right eye, and exophthalmia. After clinical examination, it was found that the animal presented with upper respiratory tract dyspnea origin, possibly caused by an obstructive process. Complete blood count (CBC, ocular ultrasonography, thoracic radiographs, mandibular lymph node, and nasal sinus fine needle aspiration were performed. The right mandibular lymph node excisional biopsy was conducted and a tumor sample was obtained through the nasal fistula at hard palate. The material was processed, paraffin embedded, sectioned, and stained with hematoxylin and eosin. Immunohistochemical staining for cytokeratin (AE1/AE3, vimentin, and COX-2 was performed. After histopathological evaluation nasal carcinoma diagnosis was obtained. Chemotherapy was established with carboplatin 300 mg/m2 intravenously—four cycles with intervals of 21 days—and firocoxib 5 mg/kg orally every 24 hours for 7 months. After 7 months the treatment started, the animal presented with ataxia, vocalization, hyperesthesia, and anorexia. Due the clinical condition presented, the animal owner opted for performing euthanasia. The chemotherapy protocol was effective causing the disease stagnation, minimizing the clinical signs, and extending patient survival and quality of life.

  3. Refractory myasthenia gravis – clinical profile, comorbidities and response to rituximab

    Science.gov (United States)

    Sudulagunta, Sreenivasa Rao; Sepehrar, Mona; Sodalagunta, Mahesh Babu; Settikere Nataraju, Aravinda; Bangalore Raja, Shiva Kumar; Sathyanarayana, Deepak; Gummadi, Siddharth; Burra, Hemanth Kumar

    2016-01-01

    Introduction: Myasthenia gravis (MG) is an antibody mediated autoimmune neuromuscular disorder characterized by fatigable muscle weakness. A proportion of myasthenia gravis patients are classified as refractory due to non responsiveness to conventional treatment. This retrospective study was done to evaluate clinical profile, epidemiological, laboratory, and features of patients with MG and mode of management using rituximab and complications. Methods: Data of myasthenia gravis patients admitted or presented to outpatient department (previous medical records) with MG between January 2008 and January 2016 were included. A total of 512 patients fulfilled the clinical and diagnostic criteria of myasthenia gravis of which 76 patients met the diagnostic certainty for refractory myasthenia gravis and were evaluated. Results: Out of 76 refractory MG patients, 53 (69.73%) patients fulfilled all the three defined criteria. The median age of onset of the refractory MG group was 36 years with a range of 27–53 years. In our study 25 patients (32.89%) belonged to the age group of 21–30 years. Anti-MuSK antibodies were positive in 8 non-refractory MG patients (2.06%) and 36 refractory MG patients (47.36%). Mean HbA1C was found to be 8.6±2.33. The dose of administered prednisone decreased by a mean of 59.7% (p=3.3x10–8) to 94.6% (p=2.2x10–14) after the third cycle of rituximab treatment. Conclusion: The refractory MG patients are most commonly female with an early age of onset, anti-MuSK antibodies, and thymomas. Refractory MG patients have higher prevalence and poor control (HbA1C >8%) of diabetes mellitus and dyslipidemia probably due to increased steroid usage. Rituximab is very efficient in treatment of refractory MG with adverse effects being low. PMID:27790079

  4. Efficacy, outcomes, and cost-effectiveness of desensitization using IVIG and rituximab.

    Science.gov (United States)

    Vo, Ashley A; Petrozzino, Jeffrey; Yeung, Kai; Sinha, Aditi; Kahwaji, Joseph; Peng, Alice; Villicana, Rafael; Mackowiak, John; Jordan, Stanley C

    2013-03-27

    Transplantation rates are very low for the broadly sensitized patient (panel reactive antibody [PRA]>80%; HS). Here, we examine the efficacy, outcomes, and cost-effectiveness of desensitization using high-dose intravenous immunoglobulin (IVIG) and rituximab to improve transplantation rates in HS patients. From July 2006 to December 2011, 207 HS (56 living donors/151 deceased donors) patients (donor-specific antibody positive, PRA>80%) were desensitized using IVIG and rituximab. After desensitization, responsive patients proceeded to transplantation with an acceptable crossmatch. Cost and outcomes of desensitization were compared with dialysis. Of the 207 treated patients, 146 (71%) were transplanted. At 48 months, patient and graft survival by Kaplan-Meier were 95% and 87.5%, respectively. The total 3-year cost for patients treated in the desensitization arm was $219,914 per patient compared with $238,667 per patient treated in the dialysis arm. Thus, each patient treated with desensitization is estimated to save the U.S. healthcare system $18,753 in 2011 USD. Overall, estimated patient survival at the end of 3 years was 96.6% for patients in the desensitization arm of the model (based on Cedars-Sinai survival rate) compared with 79.0% for an age, end-stage renal disease etiology, and PRA matched group of patients remaining on dialysis during the study period. We conclude that desensitization with IVIG+rituximab is clinically and cost-effective, with both financial savings and an estimated 17.6% greater probability of 3-year survival associated with desensitization versus dialysis alone. However, the benefits of desensitization and transplantation are limited by organ availability and allocation policies.

  5. In Vitro Cytotoxicity of Low-Dose-Rate Radioimmunotherapy by the Alpha-Emitting Radioimmunoconjugate Thorium-227-DOTA-Rituximab

    International Nuclear Information System (INIS)

    Dahle, Jostein; Krogh, Cecilie; Melhus, Katrine B.; Borrebaek, Jorgen; Larsen, Roy H.; Kvinnsland, Yngve

    2009-01-01

    Purpose: To determine whether the low-dose-rate α-particle-emitting radioimmunoconjugate 227 Th-1,4,7,10-p-isothiocyanato-benzyl-tetraazacyclododecane-1,4,7, 10-tetraacetic acid (DOTA)-rituximab can be used to inactivate lymphoma cells growing as single cells and small colonies. Methods and Materials: CD20-positive lymphoma cell lines were treated with 227 Th-DOTA-rituximab for 1-5 weeks. To simulate the in vivo situation with continuous but decreasing supply of radioimmunoconjugates from the blood pool, the cells were not washed after incubation with 227 Th-DOTA-rituximab, but half of the medium was replaced with fresh medium, and cell concentration and cell-bound activity were determined every other day after start of incubation. A microdosimetric model was established to estimate the average number of hits in the nucleus for different localizations of activity. Results: There was a specific targeted effect on cell growth of the 227 Th-DOTA-rituximab treatment. Although the cells were not washed after incubation with 227 Th-DOTA-rituximab, the average contribution of activity in the medium to the mean dose was only 6%, whereas the average contribution from activity on the cells' own surface was 78%. The mean dose rates after incubation with 800 Bq/mL 227 Th-DOTA-rituximab varied from 0.01 to 0.03 cGy/min. The average delay in growing from 10 5 to 10 7 cells/mL was 15 days when the cells were treated with a mean absorbed radiation dose of 2 Gy α-particle radiation from 227 Th-DOTA-rituximab, whereas it was 11 days when the cells were irradiated with 6 Gy of X-radiation. The relative biologic effect of the treatment was estimated to be 2.9-3.4. Conclusions: The low-dose-rate radioimmunoconjugate 227 Th-DOTA-rituximab is suitable for inactivation of single lymphoma cells and small colonies of lymphoma cells.

  6. Interferon-regulated chemokine score associated with improvement in disease activity in refractory myositis patients treated with rituximab.

    Science.gov (United States)

    López De Padilla, Consuelo M; Crowson, Cynthia S; Hein, Molly S; Strausbauch, Michael A; Aggarwal, Rohit; Levesque, Marc C; Ascherman, Dana P; Oddis, Chester V; Reed, Ann M

    2015-01-01

    The purpose of this study was to investigate whether serum interferon (IFN)-regulated chemokine and distinct cytokine response profiles are associated with clinical improvement in patients with refractory inflammatory myopathy treated with rituximab. In a randomised, placebo-phase trial Rituximab in Myositis Trial (RIM), 200 refractory adult and paediatric myositis subjects received rituximab. Following rituximab, clinical response and disease activity were assessed. Serum samples and clinical data were collected at baseline and several time-points after rituximab treatment. Multiplexed sandwich immunoassays quantified serum levels of IFN-regulated chemokines and other pro-inflammatory cytokines. Composite IFN-regulated chemokine and Th1, Th2, Th17 and regulatory cytokine scores were computed. Baseline IFN-regulated chemokine, Th1, Th2, Th17 and regulatory cytokine scores correlated with baseline physician global VAS, whereas the baseline Th1, Th2 and Th17 cytokine scores correlated with baseline muscle VAS. We also found baseline IFN-regulated chemokine scores correlated with specific non-muscular targets such as baseline cutaneous (r=0.29; p=0.002) and pulmonary (r=0.18; p=0.02) VAS scores. Among all cytokine/chemokines examined, the baseline score of IFN-regulated chemokines demonstrated the best correlation with changes in muscle VAS at 8 (r=-0.19; p=0.01) and 16 weeks (r=-0.17; p=0.03) following rituximab and physician global VAS at 16 weeks (r=-0.16; p=0.04). In vitro experiments showed increased levels of IL-8 (p=0.04), MCP-1 (p=0.04), IL-6 (p=0.03), IL-1β (p=0.04), IL-13 (p=0.04), IL-10 (p=0.02), IL-2 (p=0.04) and IFN-γ (p=0.02) in supernatants of TLR-3 stimulated PBMCs from non-responder compared to patients responders to rituximab. IFN-regulated chemokines before treatment is associated with improvement in disease activity measures in refractory myositis patients treated with rituximab.

  7. B-lymphocyte reconstitution after repeated rituximab treatment in a child with steroid-dependent autoimmune hemolytic anemia

    Directory of Open Access Journals (Sweden)

    Annelieke A.A. van der Linde

    2011-12-01

    Full Text Available We report the detailed long-term reconstitution of B-lymphocyte subpopulations, immunoglobulins, and specific antibody production after two courses of rituximab in a young, previously healthy girl with steroid-dependent autoimmune hemolytic anemia. B-lymphocyte subpopulations were surprisingly normal directly after reconstitution. However, there was a slower reconstitution after the second rituximab course, especially of non-switched and switched memory B-lymphocytes, and a temporary decline in IgM below age-matched reference values.

  8. Radiolabeling of rituximab with 188Re and 99mTc using the tricarbonyl technology

    International Nuclear Information System (INIS)

    Dias, Carla Roberta; Jeger, Simone; Osso, Joao Alberto; Mueller, Cristina; De Pasquale, Christine; Hohn, Alexander; Waibel, Robert; Schibli, Roger

    2011-01-01

    Introduction: The most successful clinical studies of immunotherapy in patients with non-Hodgkin's lymphoma (NHL) use the antibody rituximab (RTX) targeting CD20 + B-cell tumors. Rituximab radiolabeled with β - emitters could potentiate the therapeutic efficacy of the antibody by virtue of the particle radiation. Here, we report on a direct radiolabeling approach of rituximab with the 99m Tc- and 188 Re-tricarbonyl core (IsoLink technology). Methods: The native format of the antibody (RTX wt ) as well as a reduced form (RTX red ) was labeled with 99m Tc/ 188 Re(CO) 3 . The partial reduction of the disulfide bonds to produce free sulfhydryl groups (-SH) was achieved with 2-mercaptoethanol. Radiolabeling efficiency, in vitro human plasma stability as well as transchelation toward cysteine and histidine was investigated. The immunoreactivity and binding affinity were determined on Ramos and/or Raji cells expressing CD20. Biodistribution was performed in mice bearing subcutaneous Ramos lymphoma xenografts. Results: The radiolabeling efficiency and kinetics of RTX red were superior to that of RTX wt ( 99m Tc: 98% after 3 h for RTX red vs. 70% after 24 h for RTX wt ). 99m Tc(CO) 3 -RTX red was used without purification for in vitro and in vivo studies whereas 188 Re(CO) 3 -RTX red was purified to eliminate free 188 Re-precursor. Both radioimmunoconjugates were stable in human plasma for 24 h at 37 o C. In contrast, displacement experiments with excess cysteine/histidine showed significant transchelation in the case of 99m Tc(CO) 3 -RTX red but not with pre-purified 188 Re(CO) 3 -RTX red . Both conjugates revealed high binding affinity to the CD20 antigen (K d =5-6 nM). Tumor uptake of 188 Re(CO) 3 -RTX red was 2.5 %ID/g and 0.8 %ID/g for 99m Tc(CO) 3 -RTX red 48 h after injection. The values for other organs and tissues were similar for both compounds, for example the tumor-to-blood and tumor-to-liver ratios were 0.4 and 0.3 for 99m Tc(CO) 3 -RTX red and for 188 Re

  9. THE ECSTACY OF GOLD Patent Expirations for Trastuzumab, Bevacizumab, Rituximab, and Cetuximab.

    Science.gov (United States)

    Serna-Gallegos, Tasha R; LaFargue, Christopher J; Tewari, Krishnansu S

    2017-11-22

    Fully humanized monoclonal antibodies have revolutionized the treatment of many solid tumors, including breast, lung, colorectal, and ovarian cancer. Among the most widely used monoclonal antibodies in clinical oncology are cetuximab, trastuzumab, rituximab, and bevacizumab. This article will review these four notable monoclonal antibodies, their role in clinical oncology, and the drug patents that are nearing expiration. They are used in both first and second line treatment regimens for multiple common malignancies. With recent patent expirations, pharmaceutical companies involved in biosimilar manufacture are looking to establish ownership over these financial monopolies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Comparison of the efficacy of azathioprine and rituximab in neuromyelitis optica spectrum disorder

    DEFF Research Database (Denmark)

    Nikoo, Zahra; Badihian, Shervin; Shaygannejad, Vahid

    2017-01-01

    Neuromyelitis optica spectrum disorder (NMOSD) often follows a relapsing course. As disability in NMOSD is attack-related, effective treatments are needed. We aimed to compare the efficacy of azathioprine (AZA) and rituximab (RIT) as maintenance therapy in NMOSD patients. An open, randomized...... = 0–7). Patients were randomized into two groups, which did not differ according to age, gender distribution, and disease duration. In the AZA group, 35 patients [20 aquaporin-4 (AQP4)-IgG positive] were started on 50 mg/day oral AZA and increased to 2–3 mg/kg/day (with oral prednisolone as adjunctive...

  11. Off-label use of rituximab for systemic lupus erythematosus in Europe

    DEFF Research Database (Denmark)

    Ryden-Aulin, Monica; Boumpas, Dimitrios T; Bultink, Irene

    2016-01-01

    Objectives: Rituximab (RTX) is a biological treatment used off-label in patients with systemic lupus erythematosus (SLE). This survey aimed to investigate the off-label use of RTX in Europe and compare the characteristics of patients receiving RTX with those receiving conventional therapy. Methods...... organ manifestations for which either RTX or conventional therapy was initiated were lupus nephritis followed by musculoskeletal and haematological. The reason for treatment was, besides disease control, corticosteroid-sparing for patients treated with conventional therapy. Conclusions: RTX use for SLE...

  12. First-line treatment of advanced ovarian cancer with paclitaxel/carboplatin with or without epirubicin (TEC versus TC)-a gynecologic cancer intergroup study of the NSGO, EORTC GCG and NCIC CTG

    DEFF Research Database (Denmark)

    Lindemann, K.; Christensen, R. D.; Vergote, I.

    2012-01-01

    Background: The addition of anthracyclines to platinum-based chemotherapy may provide benefit in survival in ovarian cancer patients. We evaluated the effect on survival of adding epirubicin to standard carboplatin and paclitaxel. Patients and methods: We carried out a prospectively randomized...... of epirubicin to standard carboplatin and paclitaxel treatment did not improve survival in patients with advanced ovarian, tubal or peritoneal cancer....

  13. A retrospective study of treatment and prophylaxis of ifosfamide-induced hemorrhagic cystitis in pediatric and adolescent and young adult (AYA) patients with solid tumors.

    Science.gov (United States)

    Saito, Yoshimasa; Kumamoto, Tadashi; Makino, Yoshinori; Tamai, Ikumi; Ogawa, Chitose; Terakado, Hiroyuki

    2016-09-01

    Ifosfamide (IFO) is considered an essential drug for the treatment of pediatric, adolescent and young adult patients with solid tumors. Hemorrhagic cystitis (HC) is one of the dose-limiting toxicity of IFO. However, there are insufficient evidence for risk factor and supportive care of IFO-induced HC. In this retrospective study, patients (daily IFO dosage was 1.2-3.0 g/m(2). HC occurred in 14/425 IFO-based chemotherapy cycles (3.3%). The daily IFO dosages (mean ± SD) in patients with or without HC were 2.23 ± 0.58 g/m(2) and 1.85 ± 0.50 g/m(2), respectively (P = 0.006). Only one of the nine patients who developed IFO-induced HC had experienced this complication in a subsequent cycle of treatment. The incidence of IFO-induced HC may be associated with the dosage of IFO. When administering IFO higher than 2.0 g/m(2)/day, the volume of hydration, dosage of mesna and duration of mesna infusion should be increased to prevent HC. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Pilot study of alternating radiotherapy and three-drug combined chemotherapy consisting of ifosfamide, cisplatin and vindesine in localized inoperable non-small cell lung cancer

    International Nuclear Information System (INIS)

    Rikimaru, Toru; Tanaka, Yasuyuki; Ichikawa, Yoichiro; Oizumi, Kotaro; Fukurono, Kazuyoshi; Hayabuchi, Naofumi

    1993-01-01

    During the period from February 1991 through October 1992, we conducted a pilot phase II trial of an 'Alternating Radiotherapy and Chemotherapy' for 15 patients with localized inoperable non-small cell lung cancer. The combined regimen, consisting of ifosfamide 1.5 g/m 2 on days 1 through 3, cisplatin 80 mg/m 2 and vindesine 3 mg/m 2 on day 1, was given repeatedly every 4 weeks. Patients were treated in a split course fashion with combination chemotherapy sandwiched between radiation therapy (total dose 60 Gy). Of 15 evaluable patients, complete remission, partial remission and no change were obtained in 1, 13 and 1 patients, respectively, with an overall response rate of 93.3%. The median survival for all patients was 62 weeks. Hematologic toxicity was severe and was judged to be dose limiting. It was, however, clinically manageable with colony stimulating factor. These results indicate that this alternating radiotherapy and chemotherapy is feasible for localized non-small cell lung cancer and warrants further clinical trials. (author)

  15. [Combination of etoposide, cisplatin and ifosfamide (VPH) in the salvage chemotherapy of relapsing or refractory aggressive malignant lymphoma. Study of 51 patients].

    Science.gov (United States)

    Eghbali, H; Catry-Thomas, I; Soubeyran, P; Bonnel, C; Hoerni, B

    1994-09-01

    Fifty-one patients with non-Hodgkin's lymphoma refractory or relapsing after CHOP-like regimen, underwent a salvage chemotherapy by VPH: etoposide 100 mg/m2/d, D1 to D3, cisplatin 20 mg/m2/d, D1 to D5, ifosfamide 1 g/m2/d D1 to D5, mesna 1.2 g/m2/d D1 to D5, every 4 weeks. Among 46 evaluable patients for efficacy, 21 (45.6%) achieved complete or partial response according to WHO criteria and 25 (54.3%) failed, while five cases (9.8% of all patients) were not evaluable (two initial complete remission before VPH, two early toxic deaths and one confusional syndrome). Thirty-five patients (68.6%) died of lymphoma, three (5.8%) of acute toxicity and 13 (25.5%) are alive: five in complete remission. The toxicity is mainly myelo-suppression, digestive and renal but could be managed as usually. Although the follow-up is short, this regimen appears effective in these circumstances after CHOP failure but it should be used early, before overt chemoresistance. It does not hinder a bone marrow transplantation programme.

  16. MDM2 phenotypic and genotypic profiling, respective to TP53 genetic status, in diffuse large B-cell lymphoma patients treated with rituximab-CHOP immunochemotherapy: a report from the International DLBCL Rituximab-CHOP Consortium Program

    NARCIS (Netherlands)

    Xu-Monette, Z.Y.; Moller, M.B.; Tzankov, A.; Montes-Moreno, S.; Hu, W.; Manyam, G.C.; Kristensen, L.; Fan, L.; Visco, C.; Dybkaer, K.; Chiu, A.; Tam, W.; Zu, Y.; Bhagat, G.; Richards, K.L.; Hsi, E.D.; Choi, W.W.; Krieken, J.H.J.M. van; Huang, Q.; Huh, J.; Ai, W.; Ponzoni, M.; Ferreri, A.J.; Wu, L.; Zhao, X.; Bueso-Ramos, C.E.; Wang, S.A.; Go, R.S.; Li, Y.; Winter, J.N.; Piris, M.A.; Medeiros, L.J.; Young, K.H.

    2013-01-01

    MDM2 is a key negative regulator of the tumor suppressor p53, however, the prognostic significance of MDM2 overexpression in diffuse large B-cell lymphoma (DLBCL) has not been defined convincingly. In a p53 genetically-defined large cohort of de novo DLBCL patients treated with rituximab,

  17. Clinical and economic aspects of the use of rituximab in non-Hodgkin's lymphoma

    Directory of Open Access Journals (Sweden)

    Camila Bezerra Melo Figueirêdo

    2014-09-01

    Full Text Available Non-Hodgkin's lymphoma (NHL consists of a group of neoplasias involving mainly B cells and represents 90% of all lymphomas. The current available therapy is based on chemotherapy associated with the monoclonal antibody rituximab (Mab Thera(r, which targets the CD20 protein, present in over 80% of NHL mature B cells. Recent clinical reports show a preference for combining the benefits of immunotherapy and adjuvant chemotherapy, thus generating safe and effective alternative treatments. The current review aimed at evaluating various aspects related to the use of rituximab for NHL, highlighting the possible inhibitory mechanisms of cell proliferation, the achieved clinical results, and the expected clinical and economic outcomes of treatments. The results from clinical tests indicate the need for a better understanding of the critical mechanisms of action of this antibody, which may maximize its therapeutic efficacy. This therapy not only represents a viable option to treat most types of NHLs, especially when associated with conventional chemotherapy, but also offers cost-utility and cost-effectiveness advantages.

  18. [Bendamustine-rituximab therapy is effective for transformed follicular lymphoma with significant expression of p53].

    Science.gov (United States)

    Kuroda, Hiroyuki; Jomen, Wataru; Miura, Shogo; Arihara, Yohei; Yamada, Michiko; Hirako, Tasuku; Abe, Tomoyuki; Sakurai, Tamaki; Fujii, Shigeyuki; Maeda, Masahiro; Fujita, Miri; Nagashima, Kazuo; Okagawa, Yutaka; Hoki, Toshifumi; Kato, Junji

    2013-08-01

    We describe a patient with transformed follicular lymphoma(FL), expressing p53 but remaining in complete remission(CR) due to bendamustine-rituximab(BR)therapy. She was a 64-year-old female diagnosed with stage IV FL(grade 3A)in July 2007 when she was admitted with right lower abdominal pain and body weight loss. Colonoscopy revealed Bauhin' valve lymphoma of the terminal ileum, and computed tomography(CT)scan showed lymphadenopathy, involving the cervical, mediastinal para-aortic lymph nodes and right tonsil. She received chemotherapy with eight courses of CHOP therapy with rituximab and achieved CR. Two and a half years later, mediastinal lymph node swelling relapsed, and ibritumomab tiuxetan therapy induced the second CR. After ten months, however, a third relapse occurred as a submucosal tumor(SMT)of the stomach. Gastric SMT biopsy showed diffuse large B cell lymphoma(DLBCL)transformation with immunohistochemical expression of p53. Although gastric SMT disappeared after radiotherapy, which achieved the third CR, lymph node swelling was detected again in the para-aortic and-iliac artery lymph nodes in September 2011. Subsequently, she was treated with five courses of BR therapy, because bendamustine had been reported to be effective for p53 gene-deficient B cell neoplasms. The therapy was successful and achieved the fourth CR, demonstrating that BR therapy was effective for p53-expressing DLBCL.

  19. Rituximab Treatment Prevents Lymphoma Onset in Gastric Cancer Patient-Derived Xenografts

    Directory of Open Access Journals (Sweden)

    Simona Corso

    2018-05-01

    Full Text Available Patient-Derived Xenografts (PDXs, entailing implantation of cancer specimens in immunocompromised mice, are emerging as a valuable translational model that could help validate biologically relevant targets and assist the clinical development of novel therapeutic strategies for gastric cancer.More than 30% of PDXs generated from gastric carcinoma samples developed human B-cell lymphomas instead of gastric cancer. These lymphomas were monoclonal, Epstein Barr Virus (EBV positive, originated tumorigenic cell cultures and displayed a mutational burden and an expression profile distinct from gastric adenocarcinomas. The ability of grafted samples to develop lymphomas did not correlate with patient outcome, nor with the histotype, the lymphocyte infiltration level, or the EBV status of the original gastric tumor, impeding from foreseeing lymphoma onset. Interestingly, lymphoma development was significantly more frequent when primary rather than metastatic samples were grafted.Notably, the development of such lympho-proliferative disease could be prevented by a short rituximab treatment upon mice implant, without negatively affecting gastric carcinoma engraftment.Due to the high frequency of human lymphoma onset, our data show that a careful histologic analysis is mandatory when generating gastric cancer PDXs. Such care would avoid misleading results that could occur if testing of putative gastric cancer therapies is performed in lymphoma PDXs. We propose rituximab treatment of mice to prevent lymphoma development in PDX models, averting the loss of human-derived samples.

  20. Rapid infusion with rituximab: short term safety in systemic autoimmune diseases

    DEFF Research Database (Denmark)

    Larsen, Janni Lisander; Jacobsen, Soren

    2013-01-01

    To describe the incidence, types and severity of adverse events, related to an accelerated regime of rituximab infusion in patients with various autoimmune diseases. Fifty-four patients with systemic autoimmune disease, to be treated with 1,000 mg of rituximab twice 2 weeks apart, participated. Pre......-medication (oral prednisolone, anti-histamine and paracetamol) was administered 1-4 h before infusion start. The first infusion was administered over a period of 195 min. The second infusion over a period of 90 min. Any adverse events were classified using the Clinical Trials Classification of Adverse Events...... (CTCAE) v. 3.0. Ten patients (18.5%) experienced at least one infusion-related reaction (IRR) ever. The first infusion was associated with reactions in 4 CTCAE categories of which rhinitis were the most frequent. The CTCAE severity grading showed six patients (11.1%) had a grade 1 reaction. One patient...

  1. Launching biosimilar rituximab: an industry opinion on biosimilar uptake in Europe.

    Science.gov (United States)

    Trollope, Richard; Johnson, Sue; Ireland, Henry

    2017-06-01

    Richard Trollope and Sue Johnson talk with Henry Ireland, Senior Editor about the recent approval of biosimilar rituximab (Truxima ® ) & the current state of biosimilar uptake across Europe Richard Trollope, Head of Biosimilars, Mundipharma International Limited, qualified as a biochemist before joining Wyeth's commercial operations, prior to its acquisition by Pfizer. Richard later joined Yamanouchi Pharmaceuticals (now Astellas Pharma). His fascination with oncology led him to join Mundipharma in Europe and after joining the company's UK arm (Napp Pharmaceuticals Limited), Richard began his journey in biosimilars. He now heads up the biosimilar franchise at Mundipharma International as it launches biosimilar rituximab (Truxima ® ) - the first biosimilar monoclonal antibody for the treatment of cancer, which will be distributed by Napp Pharmaceuticals in the UK. Sue Johnson, PhD, Medical Insights at Mundipharma International Limited, is a scientist by background and completed her postdoc fellowship at Harvard Medical School. On returning to the UK, she began her career in the pharmaceutical industry, working in UK Medical Affairs before transitioning to a European role with Mundipharma 2 years ago, where she leads on Medical Insights for the biosimilars franchise.

  2. Comparison of carboplatin and doxorubicin-based chemotherapy protocols in 470 dogs after amputation for treatment of appendicular osteosarcoma.

    Science.gov (United States)

    Selmic, L E; Burton, J H; Thamm, D H; Withrow, S J; Lana, S E

    2014-01-01

    Many chemotherapy protocols have been reported for treatment of canine appendicular osteosarcoma (OSA), but outcome comparisons in a single population are lacking. To evaluate the effects of protocol and dose intensity (DI) on treatment outcomes for carboplatin and doxorubicin-based chemotherapy protocols. Four hundred and seventy dogs with appendicular OSA. A retrospective cohort study was performed comprising consecutive dogs treated (1997-2012) with amputation followed by 1 of 5 chemotherapy protocols: carboplatin 300 mg/m(2) IV q21d for 4 or 6 cycles (CARBO6), doxorubicin 30 mg/m(2) IV q14d or q21d for 5 cycles, and alternating carboplatin 300 mg/m(2) IV and doxorubicin 30 mg/m(2) IV q21d for 3 cycles. Adverse events (AE) and DI were evaluated. Kaplan-Meier survival curves and Cox proportional hazards regression were used to compare disease-free interval (DFI) and survival time (ST) among protocols. The overall median DFI and ST were 291 days and 284 days, respectively. A lower proportion of dogs prescribed CARBO6 experienced AEs compared to other protocols (48.4% versus 60.8-75.8%; P = .001). DI was not associated with development of metastases or death. After adjustment for baseline characteristics and prognostic factors, none of the protocols provided a significant reduction in risk of development of metastases or death. Although choice of protocol did not result in significant differences in DFI or ST, the CARBO6 protocol resulted in a lower proportion of dogs experiencing AEs, which could be advantageous in maintaining high quality of life during treatment. DI was not a prognostic indicator in this study. Copyright © 2014 by the American College of Veterinary Internal Medicine.

  3. Cost-effectiveness analysis of paclitaxel + carboplatin vs. alternative combinations in the treatment of non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Mario Eandi

    2006-06-01

    Full Text Available Non-small cell lung cancer (NSCLC is the most common type of lung cancer and its medical and economical burden represents a serious matter in Europe and Usa, due to its high mortality rates and drug costs. Lung cancer is responsible for about 30% of cancer death in men and women; in Europe only about 8 per cent of people with lung cancer survive for 5 years. At present combination chemotherapy based on cisplatin or carboplatin associated with paclitaxel, vinorelbine or gemcitabine is the state of the art for the treatment in patients with stage IIIb or IV NSCLC. Aim of this study was to compare the cost-effectiveness of paclitaxel/carboplatin (PCb, gemcitabine/cisplatin (GC and vinorelbine/cisplatin (VC in the perspective of the Italian National Health Service. Therefore we perfomed a semi-Markov decision model mainly based on clinical results from the Italian Lung Cancer Project. The model included differential direct medical costs registered for two years from starting chemotherapy, using tariffs valid for 2005. Benefits was measured by years of life saved (YOLs. The model also allowed to estimate only costs accrued over the period of time, performing a cost-minimisation analysis. According to cost-effectiveness analysis, VC is dominated because it’s more costly and less effective than GC. On the contrary, combination chemotherapy with GC is more inexpensive but less effective than paclitaxel/carboplatin (PCb: in this case we compared the incremental cost-effectiveness ratio (ICER with a maximum acceptable willingness-to-pay (WTP value. In the base scenario the ICER of PCb over GC treatment is 52,326 euro/ YOLs, which is definitely lower than the maximum acceptable WTP value. Sensitivity analyses confirmed the robustness of the results from cost-effectiveness analysis in the base scenario.

  4. A phase I trial of sorafenib combined with cisplatin/etoposide or carboplatin/pemetrexed in refractory solid tumor patients.

    Science.gov (United States)

    Davies, Janine M; Dhruva, Nirav S; Walko, Christine M; Socinski, Mark A; Bernard, Stephen; Hayes, D Neil; Kim, William Y; Ivanova, Anastasia; Keller, Kimberly; Hilbun, Layla R; Chiu, Michael; Dees, E Claire; Stinchcombe, Thomas E

    2011-02-01

    Sorafenib has demonstrated single agent activity in non-small cell (NSCLC) and small cell lung cancer (SCLC). Carboplatin/pemetrexed (CbP) and cisplatin/etoposide (PE) are commonly used in the treatment of these diseases. A phase I trial escalating doses of sorafenib in combination with fixed doses of PE (Arm A) or CbP (Arm B) was performed using a 3-patient cohort design to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT); DLT were assessed in the first cycle. The trial was subsequently amended with closure of Arm B and to include Arm C with a reduced dose of carboplatin. Between 9/2007 and 9/2008, 20 pts were treated on the trial; median age 62 (range 42-73), male/female ratio 12/8, PS 0/1 ratio 6/14, and median number of prior therapies 2 (range 1-4). The most common tumor types were NSCLC and SCLC. On Arm A at dose level 0 (sorafenib 200 mg BID), 2 of 4 patients experienced DLT; 2 patients were enrolled at dose level -1 (sorafenib 200 mg QD) without DLT, but this arm was closed due to slow accrual. On Arm B, 2 of 3 patients experienced DLT at dose level 0 (sorafenib 200 mg BID). On Arm C at dose level 0 (sorafenib 200 mg BID), 1 of 6 patients experienced DLT, and at dose level +1 (sorafenib 400 mg BID) 2 of 5 patients experienced a DLT. The MTD of sorafenib was 200 mg BID continuously in combination with carboplatin (AUC of 5) and pemetrexed 500 mg/m² every 3 weeks. However, only 6 patients were treated at this dose level, and the results should be interpreted cautiously. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  5. Efficacy of tropisetron in patients with advanced non-small-cell lung cancer receiving adjuvant chemotherapy with carboplatin and taxanes.

    Science.gov (United States)

    Tsavaris, N; Kosmas, C; Kopterides, P; Vadiaka, M; Kosmas, N; Skopelitis, H; Karadima, D; Kolliokosta, G; Tzima, E; Loukeris, D; Pagouni, E; Batziou, E; Xyla, V; Koufos, C

    2008-03-01

    Even though significant progress has been made, chemotherapy-induced emesis remains a challenging problem. Few studies focus on emesis in patients treated with carboplatin and the observation period is limited to the initial 24 h following chemotherapy. Thus, we investigated if tropisetron (T) monotherapy can adequately prevent acute and delayed emesis in non-small-cell lung cancer (NSCLC) patients receiving a moderately emetogenic chemotherapy (MEC) (carboplatin-containing) regimen. Furthermore, we explored the merits of adding dexamethasone (D) or alprazolam (A) to T, especially in the setting of a pre-existing high level of stress. We studied 60 patients with advanced NSCLC receiving carboplatin and taxanes in three consecutive cycles. During the first cycle, patients received 5 mg of T intravenously before chemotherapy and the same dose per os on each of the following 3 days. In the second cycle, T was co-administered with 8 mg of D once a day, while, during the third cycle, T was combined with per os A 0.25 mg every 12 h and continued over the following 3 days. Finally, we evaluated the impact of stress on the anti-emetic response achieved with the previously described regimens. The combination of T + A was superior to T monotherapy and the combination of T + D, regarding the prevention of acute and delayed emesis. Both T + A and T + D combinations led to appetite improvement, while patients receiving T + A experienced sedation more frequently. Interestingly, subgroup analysis revealed that patients without underlying stress obtained no further benefit by the addition of A or D, while both T + A and T + D combinations led to a better anti-emetic response in patients with stress. In conclusion, T monotherapy provides a satisfactory result in controlling nausea and emesis caused by a MEC regimen in patients without stress. However, the addition of D and, mainly, A improves its anti-emetic effect in patients with obvious stress.

  6. Standardization of Procedures for the Preparation of (177)Lu- and (90)Y-labeled DOTA-Rituximab Based on the Freeze-dried Kit Formulation.

    Science.gov (United States)

    Wojdowska, Wioletta; Karczmarczyk, Urszula; Maurin, Michal; Garnuszek, Piotr; Mikołajczak, Renata

    2015-01-01

    Rituximab when radiolabelled with (177)Lu or (90)Y has been investigated for the treatment of patients with Non-Hodgkin's Lymphoma. In this study, we optimized the preparation of antibody conjugates with chelating agent in the freeze-dried kit. It shortens procedures needed for the successful radiolabeling with lutetium-177 and yttrium-90 and assures reproducible labelling yields. Various molar ratios of Rituximab:DOTA (from 1:5 to 1:100) were used at the conjugation step and different purification method to remove unbound DOTA were investigated (size-exclusion chromatography, dialysis, ultrafiltration). The final monoclonal antibody concentration was quantified by Bradford method, and the number of DOTA molecules was determined by radiolabeling assay using (64)Cu. The specific activity of (177)Lu-DOTA-Rituximab and (90)Y-DOTA-Rituximab were optimized using various amounts of radiometal. Quality control (SE-HPLC, ITLC) and stability study were performed. An average of 4.2 ± 0.8 p-SCN-Bz-DOTA molecules could be randomly conjugated to a single molecule of Rituximab. The ultrafiltration system was the most efficient for purification and resulted in the highest recovery efficiency (77.2%). At optimized conditions the (177)Lu-DOTARituximab and (90)Y-DOTA-Rituximab were obtained with radiochemical purity >99% and specific activity ca. 600 MBq/mg. The radioimmunoconjugates were stable in human serum and 0.9% NaCl. After 72 h of incubation the radiochemical purity of (177)Lu-DOTA-Rituximab decreased to 94% but it was still more than 88% for (90)Y-DOTA-Rituximab. The radioimmunoconjugate showed stability after six months storage at 2 - 8(0)C, as a lyophilized formulation. Our study shows that Rituximab-DOTA can be efficiently radiolabeled with (177)Lu and (90)Y via p-SCN-Bn-DOTA using a freezedried kit.

  7. Combination studies of platinum(II)-based metallointercalators with buthionine-S,R-sulfoximine, 3-bromopyruvate, cisplatin or carboplatin.

    Science.gov (United States)

    Garbutcheon-Singh, K Benjamin; Harper, Benjamin W J; Myers, Simon; Aldrich-Wright, Janice R

    2014-01-01

    With current chemotherapeutic treatment regimes often limited by adverse side effects, the synergistic combination of complexes with anticancer activity appears to offer a promising strategy for effective cancer treatment. This work investigates the anti-proliferative activity using a combination therapy approach where metallointercalators of the type [Pt(IL)(AL)](2+) (where IL is the intercalating ligand and AL is the ancillary ligand) are used in combination with currently approved anticancer drugs cisplatin and carboplatin and organic molecules buthionine-S,R-sulfoximine and 3-bromopyruvate. Synergistic relationships were observed, indicating a potential to decrease dose-dependent toxicity and improve therapeutic efficacy.

  8. Nye behandlinger af Graves' sygdom med fokus på det B-lymfocyt-depleterende antistof rituximab

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; El Fassi, Daniel; Hegedüs, Laszlo

    2008-01-01

    Graves' disease (GD) is caused by autoantibodies to the thyrotropin receptor (TRAb). In a controlled study using the B-lymphocyte depleting agent rituximab (RTX), an RTX-specific effect was found on long-term remission following methimazole (MMI) therapy. However, benefits were limited to patients...

  9. HDL protein composition alters from proatherogenic into less atherogenic and proinflammatory in rheumatoid arthritis patients responding to rituximab

    NARCIS (Netherlands)

    Raterman, Hennie G.; Levels, Han; Voskuyl, Alexandre E.; Lems, Willem F.; Dijkmans, Ben A.; Nurmohamed, Michael T.

    2013-01-01

    An atherogenic lipid profile is an established risk factor for cardiovascular (CV) diseases. Interestingly, high inflammatory states as present in rheumatoid arthritis (RA) are associated with unfavourable lipid profile. Data about effects of novel immunomodulating agents as rituximab (RTX) on lipid

  10. A phase III randomized trial comparing glucocorticoid monotherapy versus glucocorticoid and rituximab in patients with autoimmune haemolytic anaemia

    DEFF Research Database (Denmark)

    Birgens, Henrik Sverre; Frederiksen, Henrik; Hasselbalch, Hans C

    2013-01-01

    The impact of first-line treatment with the anti-CD 20 chimeric monoclonal antibody rituximab in patients with warm-antibody reactive autoimmune haemolytic anaemia (WAIHA) is unknown. We report the first randomized study of 64 patients with newly diagnosed WAIHA who received prednisolone and ritu...

  11. Pre-emptive treatment with rituximab of molecular relapse after autologous stem cell transplantation in mantle cell lymphoma

    DEFF Research Database (Denmark)

    Andersen, Niels S; Pedersen, Lone B; Laurell, Anna

    2009-01-01

    PURPOSE: Minimal residual disease (MRD) is predictive of clinical progression in mantle-cell lymphoma (MCL). According to the Nordic MCL-2 protocol we prospectively analyzed the efficacy of pre-emptive treatment using rituximab to MCL patients in molecular relapse after autologous stem cell...

  12. Chemokine/cytokine profiling after rituximab: reciprocal expression of BCA-1/CXCL13 and BAFF in childhood OMS.

    Science.gov (United States)

    Pranzatelli, Michael R; Tate, Elizabeth D; Travelstead, Anna L; Verhulst, Steven J

    2011-03-01

    The aim of the study was to test the hypothesis that B-cell repopulation following rituximab (anti-CD20) therapy is orchestrated by chemokines and non-chemokine cytokines. Twenty-five children with opsoclonus-myoclonus syndrome (OMS) received rituximab with or without conventional agents. A comprehensive panel of 40 chemokines and other cytokines were measured in serum by ELISA and multiplexed fluorescent bead-based immunoassay. Serum BAFF concentration changed dramatically (even after first infusion) and inversely with B-cell depletion/repopulation and CXCL13 concentration at 1, 3, and 6 months. Negative correlations were found for BAFF concentration vs blood B cell percentage and serum CXCL13 concentration; positive correlations with serum rituximab concentrations. Six months after initiation of therapy, no significant difference in the levels of APRIL, CXCL10, IL-6, or 17 other cytokines/chemokines were detected. These data reveal a major role for BAFF in peripheral B cell repopulation following rituximab-induced B-cell depletion, and novel changes in CXCL13. ClinicalTrials.gov NCT0024436. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. Time-Dependent Structural Alteration of Rituximab Analyzed by LC/TOF-MS after a Systemic Administration to Rats.

    Directory of Open Access Journals (Sweden)

    Yuki Otani

    Full Text Available Therapeutic monoclonal antibodies (mAbs have heterogeneities in their structures. Multiple studies have reported that the variety of post-translational modifications could affect the pharmacokinetic profiles or pharmacological potencies of therapeutic mAbs. Taking into the account that the structural modification of mAbs would affect the efficacy, it is worth investigating the structural alteration of therapeutic mAbs in the blood and the relationship between their structures and pharmacological effects. Herein, we have developed the method to isolate rituximab from plasma in which endogenous IgGs interfere the detection of rituximab, and successfully developed the analytical method with a liquid chromatograph time-of-flight mass spectrometer to detect the structure of rituximab in plasma with errors less than 30 parts per millions. Eight types of carbohydrate chains in rituximab were detected by this method. Interestingly, time-dependent changes in carbohydrate chains such as AAF (G2F and GnGn (G0 were observed in rats, although the amino acids were stable. Additionally, these structural changes were observed via incubation in plasma as in the rat experiment, suggesting that a certain type of enzyme in plasma caused the alterations of the carbohydrate chains. The present analytical methods could clarify the actual pharmacokinetics of therapeutic mAbs, and help to evaluate the interindividual variations in pharmacokinetics and efficacy.

  14. A Multicenter Randomized Controlled Trial of Rituximab versus Cyclosporine in the Treatment of Idiopathic Membranous Nephropathy (MENTOR).

    Science.gov (United States)

    Fervenza, Fernando C; Canetta, Pietro A; Barbour, Sean J; Lafayette, Richard A; Rovin, Brad H; Aslam, Nabeel; Hladunewich, Michelle A; Irazabal, Maria V; Sethi, Sanjeev; Gipson, Debbie S; Reich, Heather N; Brenchley, Paul; Kretzler, Matthias; Radhakrishnan, Jai; Hebert, Lee A; Gipson, Patrick E; Thomas, Leslie F; McCarthy, Ellen T; Appel, Gerald B; Jefferson, J Ashley; Eirin, Alfonso; Lieske, John C; Hogan, Marie C; Greene, Eddie L; Dillon, John J; Leung, Nelson; Sedor, John R; Rizk, Dana V; Blumenthal, Samuel S; Lasic, Lada B; Juncos, Luis A; Green, Dollie F; Simon, James; Sussman, Amy N; Philibert, David; Cattran, Daniel C

    2015-01-01

    Idiopathic membranous nephropathy remains the leading cause of nephrotic syndrome in Caucasian adults. Immunosuppressive therapy with cyclosporine (CSA) is often successful in reducing proteinuria, but its use is associated with a high relapse rate. Rituximab, a monoclonal antibody that specifically targets CD20 on the surface of B-cells, is effective in achieving a complete remission of proteinuria in patients with idiopathic membranous nephropathy. However, whether rituximab is as effective as CSA in inducing and maintaining complete or partial remission of proteinuria in these patients is unknown. The membranous nephropathy trial of rituximab (MENTOR) hypothesizes that B-cell targeting with rituximab is non-inferior to CSA in inducing long-term remission of proteinuria. Patients with idiopathic membranous nephropathy, proteinuria ≥5 g/24 h, and a minimum of 3 months of Angiotensin-II blockade will be randomized into a 12-month treatment period with i.v. rituximab, 1,000 mg (2 infusions, 14 days apart; repeated at 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months) or oral CSA 3.5-5 mg/kg/day for 6 months (continued for another 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months). The efficacy of treatment will be assessed by the remission status (based on changes in proteinuria) at 24 months from randomization. Patient safety will be assessed via collection of adverse event data and evaluation of pre- and posttreatment laboratory data. At the 6-month post-randomization visit, patients who have been randomized to either CSA or rituximab but who do not have a reduction in proteinuria ≥25% (confirmed on repeat measurements within 2 weeks) will be considered treatment failures and exit the study. This study will test for the first time whether treatment with rituximab is non-inferior to CSA in inducing long-term remission (complete or partial) of proteinuria in patients with idiopathic

  15. Medical resource utilization in dermatomyositis/polymyositis patients treated with repository corticotropin injection, intravenous immunoglobulin, and/or rituximab

    Directory of Open Access Journals (Sweden)

    Knight T

    2017-05-01

    Full Text Available Tyler Knight,1 T Christopher Bond,1 Breanna Popelar,2 Li Wang,3 John W Niewoehner,4 Kathryn Anastassopoulos,1 Michael Philbin4 1Covance Market Access Services Inc., Gaithersburg, MD, 2Xcenda, LLC, Palm Harbor, FL, 3STATinMED Research, Ann Arbor, MI, 4Mallinckrodt, LLC, Hazelwood, MO, USA Background: Dermatomyositis and polymyositis (DM/PM are rare, incurable inflammatory diseases that cause progressive muscle weakness and can be associated with increased medical resource use (MRU. When corticosteroid treatment is unsuccessful, patients may receive intravenous immunoglobulin (IVIg, rituximab, or repository corticotropin injection (RCI. This study compared real-world, non-medication MRU between patients treated with RCI and those treated with IVIg and/or rituximab for DM/PM.Methods: Claims of DM/PM patients were analyzed from the combination of three commercial health insurance databases in the United States from July 2009 to June 2014. Patients treated with RCI were propensity score matched to those treated with IVIg, rituximab, and both (IVIg+rituximab based on demographics, prior clinical characteristics, and prior MRU. Per-patient per-month (PPPM MRU and costs were compared using Poisson regression and generalized linear modeling, respectively.Results: One-hundred thirty-two RCI, 1,150 IVIg, and 562 rituximab patients had an average age of 52.6, 46.6, and 51.7 years, respectively, and roughly two-thirds were female. After matching, there were no significant differences in demographics or prior clinical characteristics. RCI patients had fewer PPPM hospitalizations (0.09 vs 0.17; P=0.049, shorter length of stay (LOS; 3.24 days vs 4.55 days; P=0.004, PPPM hospital outpatient department (HOPD visits (0.60 vs 1.39; P<0.001, and PPPM physician office visits (2.01 vs 2.33; P=0.035 than IVIg. RCI had fewer PPPM HOPD visits (0.56 vs 0.92; P<0.001 than rituximab. Patients treated with RCI had shorter LOS (2.18 days vs 5.15; P<0.001 and less PPPM HOPD

  16. Long-Term Maintenance Therapy Using Rituximab-Induced Continuous B-Cell Depletion in Patients with ANCA Vasculitis

    Science.gov (United States)

    Pendergraft, William F.; Cortazar, Frank B.; Wenger, Julia; Murphy, Andrew P.; Rhee, Eugene P.; Laliberte, Karen A.; Niles, John L.

    2014-01-01

    Background and objectives Remission in the majority of ANCA vasculitis patients is not sustained after a single course of rituximab, and risk of relapse warrants development of a successful strategy to ensure durable remission. Design, setting, participants, & measurements A retrospective analysis of ANCA vasculitis patients who underwent maintenance therapy using rituximab-induced continuous B-cell depletion for up to 7 years was performed. Maintenance therapy with rituximab was initiated after achieving remission or converting from other prior maintenance therapy. Continuous B-cell depletion was achieved in all patients by scheduled rituximab administration every 4 months. Disease activity, serologic parameters, adverse events, and survival were examined. Results In the study, 172 patients (mean age=60 years, 55% women, 57% myeloperoxidase–ANCA) treated from April of 2006 to March of 2013 underwent continuous B-cell depletion with rituximab. Median remission maintenance follow-up time was 2.1 years. Complete remission (Birmingham Vasculitis Activity Score [BVAS]=0) was achieved in all patients. Major relapse (BVAS≥3) occurred in 5% of patients and was associated with weaning of other immunosuppression drugs. Remission was reinduced in all patients. Survival mirrored survival of a general age-, sex-, and ethnicity-matched United States population. Conclusion This analysis provides evidence for long-term disease control using continuous B-cell depletion. This treatment strategy in ANCA vasculitis patients also seems to result in survival rates comparable with rates in a matched reference population. These findings suggest that prospective remission maintenance treatment trials using continuous B-cell depletion are warranted. PMID:24626432

  17. Radioimmunotherapy using 131I-rituximab in patients with advanced stage B-cell non-Hodgkin's lymphoma: initial experience

    International Nuclear Information System (INIS)

    Bienert, Maren; Reisinger, Ingrid; Humplik, Beatrice I.; Reim, Christel; Kroessin, Thomas; Avril, Norbert; Munz, Dieter L.; Srock, Stefanie; Pezzutto, Antonio

    2005-01-01

    The aim of this study was to evaluate the safety, toxicity and therapeutic response of non-myeloablative radioimmunotherapy using 131 I-rituximab in previously heavily treated patients with B-cell non-Hodgkin's lymphoma (B-NHL). Nine patients with relapsed, refractory or transformed B-NHL received ten radioimmunotherapies. Patients had a median of 5 (range 2-7) prior standard therapies. Four patients had received prior high-dose chemotherapy followed by autologous stem cell transplantation, and eight had received prior rituximab therapy. Histopathology consisted of four mantle cell, one follicular and four diffuse large B-cell lymphomas. Rituximab, a monoclonal chimeric anti-CD20 antibody (IDEC-C2B8), was labelled with 131 I using the Iodogen method. The administered activity (2,200±600 MBq) was based on a dosimetrically calculated 45 cGy total-body radiation dose. All patients received an infusion of 2.5 mg/kg of rituximab prior to administration of the radiopharmaceutical. No acute adverse effects were observed after the administration of 131 I-rituximab. Radioimmunotherapy was safe in our patient group and achieved one complete response ongoing at 14 months and two partial responses progressing at 12 and 13 months after treatment. One partial responder was re-treated with radioimmunotherapy and achieved an additional progression-free interval of 7 months. Four non-responders with bulky disease died 4.8±2.0 months after therapy. Three patients had an elevated serum lactate dehydrogenase (LDH) level prior to radioimmunotherapy and none of the patients responded. Of two patients who received radioimmunotherapy as an additional treatment after salvage chemotherapy, one continues to be disease-free at 9 months and one relapsed at 5 months' follow-up. Reversible grade 3 or 4 haematological toxicity occurred in seven of nine patients. Median nadirs were 35 days for platelets, 44 days for leucocytes and 57 days for erythrocytes. (orig.)

  18. Results of a phase I dose escalation study of eltrombopag in patients with advanced soft tissue sarcoma receiving doxorubicin and ifosfamide

    International Nuclear Information System (INIS)

    Chawla, Sant P; Staddon, Arthur; Hendifar, Andrew; Messam, Conrad A; Patwardhan, Rita; Kamel, Yasser Mostafa

    2013-01-01

    The objective of this Phase I dose escalation study was to explore the safety and tolerability of eltrombopag, an oral, nonpeptide, thrombopoietin receptor agonist, in patients with advanced soft tissue sarcoma (STS) and thrombocytopenia due to treatment with doxorubicin and ifosfamide (AI) combination chemotherapy. Patients aged 18 or older with histologically confirmed, locally advanced or metastatic STS were treated with 1 cycle of AI followed by AI with eltrombopag starting at Cycle 2, using 2 different dosing schedules. The study design included an eltrombopag dose escalation phase starting at 75 mg daily to determine the optimal biological dose (OBD). Eighteen patients were enrolled and 15 received at least 1 dose of chemotherapy; 3 patients withdrew prior to receiving eltrombopag. Seven, 4, and 1 patients received 75 mg, 100 mg, and 150 mg eltrombopag daily, respectively. No dose-limiting toxicities were reported. Due to slow recruitment, the study was closed prior to identifying an OBD. The most common hematologic adverse events (AEs) were thrombocytopenia (80%), neutropenia (73%), and anemia (67%). The most common nonhematologic AEs were fatigue (53%), alanine aminotransferase increased, constipation, and nausea (47% each). Eleven of 12 patients who received eltrombopag completed at least 2 chemotherapy cycles; all had increased platelet counts on Day 1 of Cycle 2 (cycle with eltrombopag) compared to Day 1 of Cycle 1 (cycle without eltrombopag). Although data are limited, safety data were consistent with the known toxicities of AI combination chemotherapy or the side effect profile of eltrombopag seen in other studies. Available data suggest a potential pre- and post-chemotherapy dosing scheme for eltrombopag when administered with AI chemotherapy, and support further investigation of eltrombopag treatment in patients with chemotherapy-induced thrombocytopenia

  19. Role of CYP2B6 and CYP3A4 in the in vitro N-dechloroethylation of (R)- and (S)-ifosfamide in human liver microsomes.

    Science.gov (United States)

    Granvil, C P; Madan, A; Sharkawi, M; Parkinson, A; Wainer, I W

    1999-04-01

    The central nervous system toxicity of ifosfamide (IFF), a chiral antineoplastic agent, is thought to be dependent on its N-dechloroethylation by hepatic cytochrome P-450 (CYP) enzymes. The purpose of this study was to identify the human CYPs responsible for IFF-N-dechloroethylation and their corresponding regio- and enantioselectivities. IFF exists in two enantiomeric forms, (R) - and (S)-IFF, which can be dechloroethylated at either the N2 or N3 positions, producing the corresponding (R,S)-2-dechloroethyl-IFF [(R, S)-2-DCE-IFF] and (R,S)-3-dechloroethyl-IFF [(R,S)-3-DCE-IFF]. The results of the present study suggest that the production of (R)-2-DCE-IFF and (S)-3-DCE-IFF from (R)-IFF is catalyzed by different CYPs as is the production of (S)-2-DCE-IFF and (R)-3-DCE-IFF from (S)-IFF. In vitro studies with a bank of human liver microsomes revealed that the sample-to-sample variation in the production of (S)-3-DCE-IFF from (R)-IFF and (S)-2-DCE-IFF from (S)-IFF was highly correlated with the levels of (S)-mephenytoin N-demethylation (CYP2B6), whereas (R)-2-DCE-IFF production from (R)-IFF and (R)-3-DCE-IFF production from (S)-IFF were both correlated with the activity of testosterone 6beta-hydroxylation (CYP3A4/5). Experiments with cDNA-expressed P-450 and antibody and chemical inhibition studies supported the conclusion that the formation of (S)-3-DCE-IFF and (S)-2-DCE-IFF is catalyzed primarily by CYP2B6, whereas (R)-2-DCE-IFF and (R)-3-DCE-IFF are primarily the result of CYP3A4/5 activity.

  20. Nonmetastatic osteosarcoma of the extremity. Neoadjuvant chemotherapy with methotrexate, cisplatin, doxorubicin and ifosfamide. An Italian Sarcoma Group study (ISG/OS-Oss).

    Science.gov (United States)

    Ferrari, Stefano; Meazza, Cristina; Palmerini, Emanuela; Tamburini, Angela; Fagioli, Franca; Cozza, Raffaele; Ferraresi, Virginia; Bisogno, Gianni; Mascarin, Maurizio; Cefalo, Graziella; Manfrini, Marco; Capanna, Rodolfo; Biagini, Roberto; Donati, Davide; Picci, Piero

    2014-01-01

    Based on the results of the ISG/OS-1 study, the MAP regimen (methotrexate [MTX], doxorubicin [ADM] and cisplatin [CDP] with the addition of ifosfamide [IFO] in poor-responder patients) was investigated in patients with nonmetastatic osteosarcoma of the extremity (ISG/OS-Oss study). Compared with the ISG/OS-1 study (cumulative doses: ADM 420 mg/m(2), MTX 120 g/m(2), CDP 600 mg/m(2), IFO 30 g/m(2)), the ISG/OS-Oss study reduced the number of MTX cycles from 10 to 5 (cumulative MTX dose: 60 g/m(2)) in order to diminish treatment duration and toxicity. From January 2007 to June 2011, 171 patients (median age 16 years, 60% males) were registered. The limb salvage rate was 94% and the good pathologic response rate 51% (these figures were 92% and 48%, respectively, in the ISG/OS-1 study). At a median follow-up of 39 months (range, 4-80), the 5-year overall survival rate was 80% (95% CI, 73%-87%) and the event-free survival was 50% (95% CI, 39%-59%). For comparison, the 5-year overall and event-free survival rates in ISG/OS-1 were 73% (95% CI, 65%-81%) and 64% (95% CI, 56%-73%), respectively. This study confirms that in nonmetastatic osteosarcoma of the extremity, conservative surgery in more than 90% and a good pathologic response rate of 50% can be expected with primary chemotherapy based on the MAP regimen. The response and resection rates in the ISG/OS-Oss study are in the same range as those of the previous study, whereas the event-free survival is lower than that previously achieved. Since the only difference between the two studies was the cumulative dose of postoperatively given MTX, our data support the importance of the cumulative dose of MTX in the MAP regimen.

  1. Study of conjugation and radiolabeling of monoclonal antibody rituximab for use in radionuclide therapy

    International Nuclear Information System (INIS)

    Massicano, Adriana Vidal Fernandes

    2011-01-01

    Lymphomas are tumors originated from the transformation of a lymphocyte in the lymphatic system. The most common lymphoma is the Non-Hodgkin Lymphoma (NHL). Advances in immunology and molecular biology have been improving NHL's detection and treatment strategies development, such as Radioimmunotherapy (RIT). Rituximab is an anti-CD20 monoclonal antibody used as immunotherapeutic to treat refractory or relapsed NHL. The goal of the present work was to conjugate this antibody to DOTA-NHS-ester bifunctional chelator and to radiolabel it with 177 Lu radioisotope in order to develop a radio immunotherapeutic agent for NHL's treatment. Different rituximab to DOTA molar ratios (1:5, 1:10, 1:20, 1:50, 1:250, 1:500 and 1:1000) were evaluated in order to determine the best condition for obtaining the highest radiochemical purity of radio immunotherapeutic. The stability of the unlabeled immuno conjugated was evaluated by high performance liquid chromatography (HPLC) for up to 240 days in different storage conditions. The stability of the labeled preparations was evaluated either after storing at 2-8 degree C or incubation in human serum at 37 degree C. The binding to serum proteins was also determined. In vivo studies were performed in healthy Swiss mice, in order to characterize the biological properties of labeled conjugate. Finally, preliminary studies of radio immuno conjugated competitive binding to CD20 positive Raji cells were carried out in order to analyze if the process of conjugation and radiolabeling compromises the immunoreactivity of the antibody. The conjugation applying lower antibody to chelator molar ratios (1:5, 1:10 and 1:20) showed high stability when stored for up to 240 days in different conditions. The HPLC analysis showed that the monoclonal antibody conjugated in molar ratio 1:50 was labeled with higher radiochemical purity (> 95%) when purified in PD-10 column. This conjugate showed reasonable stability at 2-8 degree C. The analysis of the

  2. B-cell depletion with rituximab in the treatment of autoimmune diseases. Graves' ophthalmopathy the latest addition to an expanding family

    DEFF Research Database (Denmark)

    Nielsen, Claus H; El Fassi, Daniel; Hasselbalch, Hans K

    2007-01-01

    In this review, the authors summarise the clinical results obtained after therapy with rituximab in autoimmune diseases, including Graves' disease and Graves' ophthalmopathy. On the basis of qualitative and quantitative analyses of B- and T-cell subsets, and autoantibody levels obtained in other...... diseases before and after rituximab therapy, the authors interpret the results of the only two clinical investigations of the efficacy of rituximab in the treatment of Graves' disease and Graves' opthalmopathy reported so far. No significant effect on autoantibody levels was observed. Nonetheless, 4 out...... of 10 Graves' disease patients remained in remission 400 days after rituximab treatment versus none in the control group, and remarkable improvements in the eye symptoms of patients with Graves' ophthalmopathy were observed. This supports a role for B cells in the pathogenesis of Graves' ophthalmopathy...

  3. Differences in RRM1 protein expression between diagnostic biopsies and resection specimens, and changes during carboplatin and paclitaxel treatment, in non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Jakobsen, Jan N; Santoni-Rugiu, Eric; Sørensen, Jens B

    2014-01-01

    was performed on tumour samples from a total of 118 NSCLC patients with stage T1-4N0-2M0 disease. Samples were included from 65 patients treated with paclitaxel and carboplatin before surgery [neoadjuvant chemotherapy (NAC) group], and 53 patients who had undergone surgery but not chemotherapy [operation (OP...

  4. Effect of Chemotherapy Bleomycin, Vincristin, Mitomycin and Carboplatin by Tumor Mass and Infiltration Parametrial for Cervical Cancer Patients: Case Study in Sanglah General Hospital, Denpasar

    Directory of Open Access Journals (Sweden)

    Rini Noviyani

    2017-09-01

    Full Text Available BOM-cisplatin regimen for chemotherapy for cervical cancer patients has not resulted high efficacy, hence a replacement of cisplatin with carboplatin is proposed. BOM-carboplatin chemotherapy is at present a treatment for cervical cancer patients in Sanglah Hospital in Denpasar. Information about the efficacy of using the BOM-carboplatin for cervical cancer chemotherapy is not provided, therefore this research performed by observing tumor mass and parametrial infiltration. This research was carried out using case study method on 9 patients with squamous cell cervical cancer stage IIB–IIIB before and after BOM-carboplatin chemotherapy at Sanglah Hospital from February until August 2015. Examination of tumor mass and parametrial infiltration (%CFS conducted prior to chemotherapy series I and after chemotherapy series III. Sampling was done consecutively. The research data were analyzed using the normal distribution Shapiro-Wilk test continued by paired t-test with 95% confidence level, while data that is classified otherwise is transformed to logarithmic function and were analyzed using the Wilcoxon test. Based on statistical analysis there is significant reduction in tumor mass and left parametrial infiltration after the third chemotherapy with (p0.05 that is p>0,083.

  5. Phase I and pharmacologic study of the combination paclitaxel and carboplatin as first-line chemotherapy in stage III and IV ovarian cancer

    NARCIS (Netherlands)

    Huizing, M. T.; van Warmerdam, L. J.; Rosing, H.; Schaefers, M. C.; Lai, A.; Helmerhorst, T. J.; Veenhof, C. H.; Birkhofer, M. J.; Rodenhuis, S.; Beijnen, J. H.; ten Bokkel Huinink, W. W.

    1997-01-01

    To determine the maximum-tolerated dose for the combination paclitaxel and carboplatin administered every 4 weeks and to gain more insight into the pharmacokinetics and pharmacodynamics of this combination in previously untreated ovarian cancer patients. Thirty-five chemotherapy-naive patients with

  6. Room-temperature X-ray diffraction studies of cisplatin and carboplatin binding to His15 of HEWL after prolonged chemical exposure

    NARCIS (Netherlands)

    Tanley, S.W.M.; Schreurs, A.M.M.; Kroon-Batenburg, L.M.J.; Helliwell, J.R.

    2012-01-01

    The anticancer complexes cisplatin and carboplatin are known to bind to both the N and the N" atoms of His15 of hen egg-white lysozyme (HEWL) in the presence of dimethyl sulfoxide (DMSO). However, neither binds in aqueous media after 4 d of crystallization and crystal growth, suggesting that DMSO

  7. Systemic adverse events following rituximab therapy in patients with Graves' disease

    DEFF Research Database (Denmark)

    El Fassi, D; Nielsen, C H; Junker, P

    2010-01-01

    had the third highest increase in immunoglobulin deposition on monocytes by day 14. The arthralgias persisted in two of the patients, despite glucocorticoid rescue therapy. Conclusions: We report articular adverse events in three and gastrointestinal symptoms in two out of ten GD patients who received...... methimazole only. Adverse events were recorded, and the presence of circulating immune complexes (CICs) was measured as IgG, IgM and complement component 3 (C3) depositing on normal monocytes following incubation with patient plasma. Results: Five patients had benign infusion-related adverse events at first......Background and aim: Rituximab (RTX) therapy has shown promising results in Graves´ disease (GD), with or without ophthalmopathy. We examined the occurrence of adverse events in GD patients treated with RTX. Subjects and methods: Ten patients received RTX and methimazole, while ten patients received...

  8. Phase I and pharmacokinetic trial of carboplatin and albumin-bound paclitaxel, ABI-007 (Abraxane®) on three treatment schedules in patients with solid tumors

    Science.gov (United States)

    Stinchcombe, Thomas E.; Socinski, Mark A.; Walko, Christine M.; O’Neil, Bert H.; Collichio, Frances A.; Ivanova, Anastasia; Mu, Hua; Hawkins, Michael J.; Goldberg, Richard M.; Lindley, Celeste; Dees, E Claire

    2010-01-01

    Purpose Albumin-bound paclitaxel, ABI-007 (Abraxane ®), has a different toxicity profile than solvent-based paclitaxel, including a lower rate of severe neutropenia. The combination of ABI-007 and carboplatin may have significant activity in a variety of tumor types including non-small and small cell lung cancer, ovarian cancer, and breast cancer. The purpose of this study was to determine the maximum tolerated dose (MTD) of ABI-007, on three different schedules in combination with carboplatin. Methods Forty-one patients with solid tumors were enrolled, and received ABI-007 in combination with carboplatin AUC of 6 on day 1. Group A received ABI-007 at doses ranging from 220 to 340 mg/m2 on day 1 every 21 days; group B received ABI-007 at 100 or 125 mg/m2 on days 1, 8, and 15 every 28 days; and group C received ABI-007 125 or 150 mg/m2 on days 1 and 8 every 21 days. Dose-limiting toxicities were assessed after the first cycle. Doses were escalated in cohorts of three to six patients. Fifteen patients participated in a pharmacokinetic study investigating the effects of the sequence of infusion. ABI-007 was infused first followed by carboplatin in cycle 1, and vice versa in cycle 2. Results The MTD of ABI-007 in combination with carboplatin was 300, 100, and 125 mg/m2 in groups A, B, and C, respectively. Myelosuppression was the primary dose limiting toxicity. No unexpected or new toxicities were reported. Sequence of infusion did not affect either the pharmacokinetics of ABI-007 or the degree of neutropenia. Responses were seen in melanoma, lung, bladder, esophageal, pancreatic, breast cancer, and cancer of unknown primary. Conclusions The recommended dose for phase II studies of ABI-007 in combination with carboplatin (AUC of 6) is 300, 100, 125 mg/m2 for the schedules A, B, and C, respectively. The combination of ABI-007 and carboplatin is well tolerated and active in this heavily pretreated patient population. PMID:17285317

  9. {sup 99m}Tc-rituximab radiolabelled by photo-activation: a new non-Hodgkin's lymphoma imaging agent

    Energy Technology Data Exchange (ETDEWEB)

    Gmeiner Stopar, T.; Fettich, J.; Hojker, S. [University Medical Centre Ljubljana, Department for Nuclear Medicine, Ljubljana (Slovenia); Mlinaric-Rascan, I. [University of Ljubljana, Faculty of Pharmacy, Ljubljana (Slovenia); Mather, S.J. [St Bartholomew' s Hospital, Cancer Research UK, Department Nuclear Medicine, London (United Kingdom)

    2006-01-01

    Rituximab was the first chimeric monoclonal antibody to be approved for treatment of indolent B-cell non-Hodgkin's lymphoma (NHL). It is directed against the CD20 antigen, which is expressed by 95% of B-cell NHLs. The aim of this study was to explore the possibility of radiolabelling rituximab with {sup 99m}Tc for use as an imaging agent in NHL for early detection, staging, remission assessment, monitoring for metastatic spread and tumour recurrence, and assessment of CD20 expression prior to (radio)immunotherapy. Rituximab was purified from Mabthera solution (Roche), photo-activated at 302 nm by UV irradiation and radiolabelled with {sup 99m}Tc. The effectiveness of the labelling method was evaluated by determination of the number of free thiol groups per photoreduced antibody, radiochemical purity and in vitro stability of {sup 99m}Tc-rituximab. On average, 4.4 free thiol groups per photoreduced antibody were determined. Radiolabelling yields greater than 95% were routinely observed after storage of the photo-activated antibody at -80 C for 195 days. The direct binding assay showed preserved ability of {sup 99m}Tc-rituximab to bind to CD20, with an average immunoreactive fraction of 93.3%. The internalisation rate was proven to be low, with only 5.3% of bound {sup 99m}Tc-rituximab being internalised over 4 h at 37 C. Our results demonstrate that {sup 99m}Tc-rituximab of high radiochemical purity and with preserved binding affinity for the antigen can be prepared by photoreduction and that the method shows good reproducibility. {sup 99m}Tc-rituximab will be further explored as an imaging agent applicable in NHL for the purposes mentioned above. (orig.)

  10. Preclinical activity of the type II CD20 antibody GA101 (obinutuzumab) compared with rituximab and ofatumumab in vitro and in xenograft models.

    Science.gov (United States)

    Herter, Sylvia; Herting, Frank; Mundigl, Olaf; Waldhauer, Inja; Weinzierl, Tina; Fauti, Tanja; Muth, Gunter; Ziegler-Landesberger, Doris; Van Puijenbroek, Erwin; Lang, Sabine; Duong, Minh Ngoc; Reslan, Lina; Gerdes, Christian A; Friess, Thomas; Baer, Ute; Burtscher, Helmut; Weidner, Michael; Dumontet, Charles; Umana, Pablo; Niederfellner, Gerhard; Bacac, Marina; Klein, Christian

    2013-10-01

    We report the first preclinical in vitro and in vivo comparison of GA101 (obinutuzumab), a novel glycoengineered type II CD20 monoclonal antibody, with rituximab and ofatumumab, the two currently approved type I CD20 antibodies. The three antibodies were compared in assays measuring direct cell death (AnnexinV/PI staining and time-lapse microscopy), complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), and internalization. The models used for the comparison of their activity in vivo were SU-DHL4 and RL xenografts. GA101 was found to be superior to rituximab and ofatumumab in the induction of direct cell death (independent of mechanical manipulation required for cell aggregate disruption formed by antibody treatment), whereas it was 10 to 1,000 times less potent in mediating CDC. GA101 showed superior activity to rituximab and ofatumumab in ADCC and whole-blood B-cell depletion assays, and was comparable with these two in ADCP. GA101 also showed slower internalization rate upon binding to CD20 than rituximab and ofatumumab. In vivo, GA101 induced a strong antitumor effect, including complete tumor remission in the SU-DHL4 model and overall superior efficacy compared with both rituximab and ofatumumab. When rituximab-pretreated animals were used, second-line treatment with GA101 was still able to control tumor progression, whereas tumors escaped rituximab treatment. Taken together, the preclinical data show that the glyoengineered type II CD20 antibody GA101 is differentiated from the two approved type I CD20 antibodies rituximab and ofatumumab by its overall preclinical activity, further supporting its clinical investigation. ©2013 AACR.

  11. Severe neuropsychiatric systemic lupus erythematosus successfully treated with rituximab: an alternative to standard of care

    Directory of Open Access Journals (Sweden)

    Chessa E

    2017-09-01

    Full Text Available Elisabetta Chessa, Matteo Piga, Alberto Floris, Alessandro Mathieu, Alberto Cauli Rheumatology Unit, University Clinic AOU of Cagliari, Cagliari, Italy Abstract: Demyelinating syndrome secondary to systemic lupus erythematosus (DS-SLE is a rare encephalomyelitis burden with a high risk of disability and death. We report on a 49-year-old Caucasian woman with systemic lupus erythematosus (SLE complicated by severe cognitive dysfunction, brainstem disease, cranial nerve palsies, weakness and numbness in limbs and multiple discrete magnetic resonance imaging (MRI areas of damage within the white matter of semioval centers, temporal lobe, external capsule, claustrum, subinsular regions and midbrain. She also had multiple mononeuritis diagnosed through sensory and motor nerve conduction study. She was diagnosed with severe DS-SLE prominently involving the brain and was treated with 500 mg methylprednisolone (PRE pulses for 3 consecutive days, followed by one single pulse of 500 mg cyclophosphamide, and 1 g rituximab, which was then repeated 14 days later. PRE 25 mg/day, rapidly tapered to 7.5 mg/day in 6 months, and mycophenolate mofetil 1 g/day were prescribed as maintenance therapy. She had progressive and sustained improvement in neurological symptoms with almost complete resolution of brain MRI lesions after 1 year. B-cell depleting therapy could be considered as a possible alternative to standard of care in the management of severe inflammatory neuropsychiatric SLE but it should be associated with a conventional immunosuppressant as maintenance treatment to reduce the risk of flare and reduce corticosteroids dose. Keywords: systemic lupus erythematosus, neuropsychiatric lupus, rituximab, demyelinating syndrome, brain MRI

  12. [Efficacy and safety of rituximab in the treatment of primary antiphospholipid syndrome: analysis of 24 cases from the bibliography review].

    Science.gov (United States)

    Pons, Isaac; Espinosa, Gerard; Cervera, Ricard

    2015-02-02

    Antiphospholipid syndrome (APS) is characterized by the presence of antiphospholipid antibodies (aPL) and thrombotic and/or obstetric manifestations. Patients without another associated autoimmune disease are considered to have primary APS. Some patients develop thrombosis recurrence despite anticoagulant treatment and some clinical features do not respond to standard therapy. Rituximab may be an alternative in these cases. We review the published scientific evidence on the use of rituximab in the treatment of primary APS. Description of a case and review of the literature with descriptive analysis of the demographic, clinical, and immunologic features, treatment and outcome of patients. We identified 24 patients (15 women [62.5%]), with a mean age of 37.0 ± 13.4 years. The reasons for the use of rituximab were thrombocytopenia (41.7%), skin involvement (33.3%), neurologic and heart valve involvement (12.5%), hemolytic anemia (8.3%) and pulmonary and renal involvement (4.2%). Lupus anticoagulant was present in 72.7% of the cases, the IgG and IgM isotypes of anticardiolipin antibodies in 75 and 50%, respectively, and the anti-β2GPI (IgG e IgM) antibodies in 80% of patients. Thirteen (54.1%) patients received 2 doses of 1,000 mg of rituximab fortnightly, 10 (41.7%) 4 doses of 375 mg/m(2) weekly and one (4.2%) 8 doses of 375 mg/m(2) weekly. Eleven (45.8%) patients presented a complete clinical response, 7 (29.2%) a partial response and 6 (25%) did not respond to rituximab. Four patients with clinical improvement presented with aPL titer decrease and in one patient, aPL levels did not change. In one patient without clinical response, aPL remained positive. A clinical-immunologic dissociation existed in 2 additional cases. The results obtained suggest a possible potential benefit of rituximab in the treatment of some clinical manifestations of primary APS such as thrombocytopenia, skin and heart valve involvement. Copyright © 2013 Elsevier España, S.L.U. All rights

  13. Reduction of fatigue in Sjögren syndrome with rituximab: results of a randomised, double-blind, placebo-controlled pilot study.

    Science.gov (United States)

    Dass, S; Bowman, S J; Vital, E M; Ikeda, K; Pease, C T; Hamburger, J; Richards, A; Rauz, S; Emery, P

    2008-11-01

    Primary Sjögren syndrome (pSS) causes significant systemic symptoms including fatigue as well as glandular dysfunction. There are currently no effective systemic therapies; however, open label series have suggested that rituximab may be beneficial for systemic and glandular manifestations. Therefore, we performed a double blind, placebo-controlled, randomised pilot study of the efficacy of rituximab in reducing fatigue in pSS. A total of 17 patients with pSS and a score on fatigue visual analogue scale (VAS) >50 were randomised to receive either 2 infusions of rituximab 1 g or placebo; patients also received oral and intravenous steroids. Outcome measures included: the proportion of patients with >20% reduction in fatigue VAS, changes in pSS related symptoms, health related quality of life and immunological parameters of pSS. These were measured 6 months after therapy. There was significant improvement from baseline in fatigue VAS in the rituximab group (p<0.001) in contrast to the placebo group (p = 0.147). There was a significant difference between the groups at 6 months in the social functioning score of SF-36 (p = 0.01) and a trend to significant difference in the mental health domain score of SF-36 (p = 0.06). There was one episode of serum sickness in the rituximab treated group. This is the first double blind study of rituximab in pSS to show benefit; further studies are justified.

  14. Enhanced CDC of B cell chronic lymphocytic leukemia cells mediated by rituximab combined with a novel anti-complement factor H antibody.

    Directory of Open Access Journals (Sweden)

    Mark T Winkler

    Full Text Available Rituximab therapy for B cell chronic lymphocytic leukemia (B-CLL has met with mixed success. Among several factors to which resistance can be attributed is failure to activate complement dependent cytotoxicity (CDC due to protective complement regulatory proteins, including the soluble regulator complement factor H (CFH. We hypothesized that rituximab killing of non-responsive B-CLL cells could be augmented by a novel human monoclonal antibody against CFH. The B cells from 11 patients with B-CLL were tested ex vivo in CDC assays with combinations of CFH monoclonal antibody, rituximab, and a negative control antibody. CDC of rituximab non-responsive malignant B cells from CLL patients could in some cases be augmented by the CFH monoclonal antibody. Antibody-mediated cytotoxicity of cells was dependent upon functional complement. In one case where B-CLL cells were refractory to CDC by the combination of rituximab plus CFH monoclonal antibody, additionally neutralizing the membrane complement regulatory protein CD59 allowed CDC to occur. Inhibiting CDC regulatory proteins such as CFH holds promise for overcoming resistance to rituximab therapy in B-CLL.

  15. Outcome of Children With Metastatic Medulloblastoma Treated With Carboplatin During Craniospinal Radiotherapy: A Children's Oncology Group Phase I/II Study

    Science.gov (United States)

    Jakacki, Regina I.; Burger, Peter C.; Zhou, Tianni; Holmes, Emiko J.; Kocak, Mehmet; Onar, Arzu; Goldwein, Joel; Mehta, Minesh; Packer, Roger J.; Tarbell, Nancy; Fitz, Charles; Vezina, Gilbert; Hilden, Joanne; Pollack, Ian F.

    2012-01-01

    Purpose We evaluated the feasibility of administering carboplatin as a radiosensitizer during craniospinal radiation therapy (CSRT) to patients with high-risk medulloblastomas (MBs) and supratentorial primitive neuroectodermal tumors, and we report the outcome in the subset with metastatic (M+) MB. Patients and Methods After surgery, patients received 36 Gy CSRT with boosts to sites of disease. During radiation, patients received 15 to 30 doses of carboplatin (30-45 mg/m2/dose), along with vincristine (VCR) once per week for 6 weeks. Patients on regimen A received 6 months of maintenance chemotherapy (MC) with cyclophosphamide and VCR. Once the recommended phase II dose (RP2D) of carboplatin was determined, cisplatin was added to the MC (regimen B). Results In all, 161 eligible patients (median age, 8.7 years; range, 3.1 to 21.6 years) were enrolled. Myelosuppression was dose limiting and 35 mg/m2/dose × 30 was determined to be the RP2D of carboplatin. Twenty-nine (36%) of 81 patients with M+ MB had diffuse anaplasia. Four patients were taken off study within 11 months of completing radiotherapy for presumed metastatic progression and are long-term survivors following palliative chemotherapy. Excluding these four patients, 5-year overall survival ± SE and progression-free survival ± SE for M+ patients treated at the RP2D on regimen A was 82% ± 9% and 71% ± 11% versus 68% ± 10% and 59% ± 10% on regimen B (P = .36). There was no difference in survival by M stage. Anaplasia was a negative predictor of outcome. Conclusion The use of carboplatin as a radiosensitizer is a promising strategy for patients with M+ MB. Early progression should be confirmed by biopsy. PMID:22665539

  16. Impact of Toceranib/Piroxicam/Cyclophosphamide Maintenance Therapy on Outcome of Dogs with Appendicular Osteosarcoma following Amputation and Carboplatin Chemotherapy: A Multi-Institutional Study.

    Directory of Open Access Journals (Sweden)

    Cheryl A London

    Full Text Available We hypothesized that the addition of toceranib to metronomic cyclophosphamide/piroxicam therapy would significantly improve disease-free interval (DFI and overall survival (OS in dogs with appendicular osteosarcoma (OSA following amputation and carboplatin chemotherapy.This was a randomized, prospective clinical trial in which dogs with OSA free of gross metastatic disease (n = 126 received carboplatin chemotherapy (4 doses following amputation. On study entry, dogs were randomized to receive piroxicam/cyclophosphamide with or without toceranib (n = 63 each after completing chemotherapy. Patient demographics were not significantly different between both groups. During or immediately following carboplatin chemotherapy, 32 dogs (n = 13 toceranib; n = 19 control developed metastatic disease, and 13 dogs left the study due to other medical conditions or owner preference. Following carboplatin chemotherapy, 81 dogs (n = 46 toceranib; n = 35 control received the metronomic treatment; 35 dogs (n = 20 toceranib; n = 15 control developed metastatic disease during the maintenance therapy, and 26 dogs left the study due to other medical conditions or owner preference. Nine toceranib-treated and 11 control dogs completed the study without evidence of metastatic disease 1-year following amputation. Toceranib-treated dogs experienced more episodes of diarrhea, neutropenia and weight loss than control dogs, although these toxicities were low-grade and typically resolved with supportive care. More toceranib-treated dogs (n = 8 were removed from the study for therapy-associated adverse events compared to control dogs (n = 1. The median DFI for control and toceranib treated dogs was 215 and 233 days, respectively (p = 0.274; the median OS for control and toceranib treated dogs was 242 and 318 days, respectively (p = 0.08. The one year survival rate for control dogs was 35% compared to 38% for dogs receiving toceranib.The addition of toceranib to metronomic

  17. Impact of Toceranib/Piroxicam/Cyclophosphamide Maintenance Therapy on Outcome of Dogs with Appendicular Osteosarcoma following Amputation and Carboplatin Chemotherapy: A Multi-Institutional Study.

    Science.gov (United States)

    London, Cheryl A; Gardner, Heather L; Mathie, Tamra; Stingle, Nicole; Portela, Roberta; Pennell, Michael L; Clifford, Craig A; Rosenberg, Mona P; Vail, David M; Williams, Laurel E; Cronin, Kim L; Wilson-Robles, Heather; Borgatti, Antonella; Henry, Carolyn J; Bailey, Dennis B; Locke, Jennifer; Northrup, Nicole C; Crawford-Jakubiak, Martin; Gill, Virginia L; Klein, Mary K; Ruslander, David M; Thamm, Doug H; Phillips, Brenda; Post, Gerald

    2015-01-01

    We hypothesized that the addition of toceranib to metronomic cyclophosphamide/piroxicam therapy would significantly improve disease-free interval (DFI) and overall survival (OS) in dogs with appendicular osteosarcoma (OSA) following amputation and carboplatin chemotherapy. This was a randomized, prospective clinical trial in which dogs with OSA free of gross metastatic disease (n = 126) received carboplatin chemotherapy (4 doses) following amputation. On study entry, dogs were randomized to receive piroxicam/cyclophosphamide with or without toceranib (n = 63 each) after completing chemotherapy. Patient demographics were not significantly different between both groups. During or immediately following carboplatin chemotherapy, 32 dogs (n = 13 toceranib; n = 19 control) developed metastatic disease, and 13 dogs left the study due to other medical conditions or owner preference. Following carboplatin chemotherapy, 81 dogs (n = 46 toceranib; n = 35 control) received the metronomic treatment; 35 dogs (n = 20 toceranib; n = 15 control) developed metastatic disease during the maintenance therapy, and 26 dogs left the study due to other medical conditions or owner preference. Nine toceranib-treated and 11 control dogs completed the study without evidence of metastatic disease 1-year following amputation. Toceranib-treated dogs experienced more episodes of diarrhea, neutropenia and weight loss than control dogs, although these toxicities were low-grade and typically resolved with supportive care. More toceranib-treated dogs (n = 8) were removed from the study for therapy-associated adverse events compared to control dogs (n = 1). The median DFI for control and toceranib treated dogs was 215 and 233 days, respectively (p = 0.274); the median OS for control and toceranib treated dogs was 242 and 318 days, respectively (p = 0.08). The one year survival rate for control dogs was 35% compared to 38% for dogs receiving toceranib. The addition of toceranib to metronomic piroxicam

  18. A phase 1 study of KOS-862 (Epothilone D) co-administered with carboplatin (Paraplatin®) in patients with advanced solid tumors.

    Science.gov (United States)

    Monk, J Paul; Villalona-Calero, Miguel; Larkin, Joe; Otterson, Greg; Spriggs, David S; Hannah, Alison L; Cropp, Gillian F; Johnson, Robert G; Hensley, Martee L

    2012-08-01

    To determine the maximally tolerated dose (MTD) and pharmacokinetics of carboplatin plus KOS-862 (Epothilone D) a novel cytotoxic macrolide capable of causing mitotic arrest, in patients with advanced solid malignancies. Patients who have progressed on standard regimens were treated at four different levels of KOS-862(mg/m(2))/Carboplatin(AUC): 50/5,75/5, 75/6 and 100/6 in a "3 + 3" phase I study study design to determine MTD. Patients received KOS-862 on Days 1 and 8, and carboplatin on day 1, of 3-week cycles. Pharmacokinetics of KOS-862 and Carboplatin were studied. Twenty-seven patients enrolled in the study. At the top dose level, 2 out of the 9 patients experienced Dose Limiting Toxicity. (grade 3 peripheral motor neuropathy in both patients) Twenty-seven patients had sufficient plasma data points for pharmacokinetic analysis Both the parent drug, KOS-862, and the major inactive metabolite Seco-D KOS-862 (KOS-1965) were quantified in plasma. Kinetics of KOS-862 were the same as seen in monotherapy studies using the same route and time of administration. Two patients had tumor response after study treatment. Ten of 20 evaluable patients had stable disease after 2 cycles of study treatment. The MTD in the present study was KOS-862 100 mg/m(2) + carboplatin AUC = 6. The pharmacokinetics of KOS-862 were similar in this combination study to those seen in previous monotherapy studies using the same route and time of administration. We have described the MTD of this schedule. The neurotoxicity seen with this regimen should be considered prior to its administration in unselected populations.

  19. Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): a randomised, double-blind, phase 3 study.

    Science.gov (United States)

    Chanan-Khan, Asher; Cramer, Paula; Demirkan, Fatih; Fraser, Graeme; Silva, Rodrigo Santucci; Grosicki, Sebastian; Pristupa, Aleksander; Janssens, Ann; Mayer, Jiri; Bartlett, Nancy L; Dilhuydy, Marie-Sarah; Pylypenko, Halyna; Loscertales, Javier; Avigdor, Abraham; Rule, Simon; Villa, Diego; Samoilova, Olga; Panagiotidis, Panagiots; Goy, Andre; Mato, Anthony; Pavlovsky, Miguel A; Karlsson, Claes; Mahler, Michelle; Salman, Mariya; Sun, Steven; Phelps, Charles; Balasubramanian, Sriram; Howes, Angela; Hallek, Michael

    2016-02-01

    Most patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma relapse after initial therapy. Bendamustine plus rituximab is often used in the relapsed or refractory setting. We assessed the efficacy and safety of adding ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase (BTK), to bendamustine plus rituximab in patients with previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma. The HELIOS trial was an international, double-blind, placebo-controlled, phase 3 study in adult patients (≥18 years of age) who had active chronic lymphocytic leukaemia or small lymphocytic lymphoma with measurable lymph node disease (>1·5 cm) by CT scan, and had relapsed or refractory disease following one or more previous lines of systemic therapy consisting of at least two cycles of a chemotherapy-containing regimen, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and adequate bone marrow, liver, and kidney function. Patients with del(17p) were excluded because of known poor response to bendamustine plus rituximab. Patients who had received previous treatment with ibrutinib or other BTK inhibitors, refractory disease or relapse within 24 months with a previous bendamustine-containing regimen, or haemopoietic stem-cell transplant were also excluded. Patients were randomly assigned (1:1) by a web-based system to receive bendamustine plus rituximab given in cycles of 4 weeks' duration (bendamustine: 70 mg/m(2) intravenously on days 2-3 in cycle 1, and days 1-2 in cycles 2-6; rituximab: 375 mg/m(2) on day 1 of cycle 1, and 500 mg/m(2) on day 1 of cycles 2-6 for a maximum of six cycles) with either ibrutinib (420 mg daily orally) or placebo until disease progression or unacceptable toxicity. Patients were stratified according to whether they were refractory to purine analogues and by number of previous lines of therapy. The primary endpoint was independent review committee (IRC)-assessed progression

  20. A randomized phase III study comparing standard dose BEP with sequential high-dose cisplatin, etoposide, and ifosfamide (VIP) plus stem-cell support in males with poor-prognosis germ-cell cancer. An intergroup study of EORTC, GTCSG, and Grupo Germinal (EORTC 30974)

    DEFF Research Database (Denmark)

    Daugaard, G; Skoneczna, I; Aass, N

    2011-01-01

    To compare the efficacy of one cycle of standard dose cisplatin, etoposide, and ifosfamide (VIP) plus three cycles of high-dose VIP followed by stem-cell infusion [high-dose chemotherapy (HD-CT arm)] to four cycles of standard cisplatin, etoposide, and bleomycin (BEP) in patients with poor-progno...

  1. IMPACT OF BEP OR CARBOPLATIN CHEMOTHERAPY ON TESTICULAR FUNCTION AND SPERM NUCLEUS OF SUBJECTS WITH TESTICULAR GERM CELL TUMOR

    Directory of Open Access Journals (Sweden)

    Marco eGhezzi

    2016-05-01

    Full Text Available Young males have testicular germ cells tumours (TGCT as the most common malignancy and its incidence is increasing in several countries. Besides unilateral orchiectomy (UO, the treatment of TGCT may include surveillance, radiotherapy or chemotherapy (CT, basing on tumour histology and stage of disease. It is well known that both radio and CT may have negative effects on testicular function, affecting spermatogenesis and sex hormones. Many reports investigated these aspects in patients treated with bleomycin, etoposide and cisplatin (BEP, after UO. In contrast no data are available on the side effects of carboplatin treatment in these patients. We included in this study 212 consecutive subjects who undergone to sperm banking at our Andrology and Human Reproduction Unit after UO for TGCT. Hundred subjects were further treated with one or more BEP cycles (BEP-group, 54 with carboplatin (Carb group and 58 were just surveilled (S-group. All patients were evaluated for seminal parameters, sperm aneuploidy, sperm DNA, sex hormones, volume of the residual testis at baseline (T0 and after 12 (T1 and 24 months (T2 from UO or end of CT. Seminal parameters, sperm aneuploidies, DNA status, gonadic hormones and testicular volume at baseline were not different between groups. At T1 we observed a significant reduction of sperm concentration and sperm count in the BEP group versus baseline and versus both Carb and S- group. A significant increase of sperm aneuploidies was present at T1 in the BEP group. Similarly, the same group at 1 had altered sperm DNA integrity and fragmentation compared with baseline, S group and Carb group. These alterations were persistent after two years from the end of BEP treatment. Despite a slight improvement at T2, the BEP group had still higher percentages of sperm aneuploidies than other groups. No impairment of sperm aneuploidies and DNA status were observed in the Carb group both after one and two years from the end of treatment

  2. Induction chemotherapy with carboplatin, irinotecan, and paclitaxel followed by high dose three-dimension conformal thoracic radiotherapy (74 Gy) with concurrent carboplatin, paclitaxel, and gefitinib in unresectable stage IIIA and stage IIIB non-small cell lung cancer.

    Science.gov (United States)

    Stinchcombe, Thomas E; Morris, David E; Lee, Carrie B; Moore, Dominic T; Hayes, D Neil; Halle, Jan S; Rivera, M Patricia; Rosenman, Julian G; Socinski, Mark A

    2008-03-01

    Combined modality therapy is a standard therapy for patients with unresectable stage III non-small cell lung cancer (NSCLC). Gefitinib is active in advanced NSCLC, and in preclinical models, it potentiates the activity of radiation therapy. We investigate the tolerability of gefitinib in combined modality therapy in combination with three-dimensional thoracic conformal radiation therapy (3-dimensional TCRT). Stage III patients with a good performance status were treated with induction chemotherapy (carboplatin area under the curve [AUC] of 5, irinotecan 100 mg/m(2), and paclitaxel 175 mg/m(2) days 1 and 22) with pegfilgrastim support followed by concurrent chemotherapy (carboplatin AUC 2, and paclitaxel 45 mg/m(2) weekly) and gefitinib 250 mg daily beginning on day 43 with 3-dimensional TCRT to 74 Gy. Between March 2004 and January 2006, 23 patients received treatment on the trial: median age 62 years (range 44-82), 52% female, 61% stage IIIA, 61% performance status 0, 17% > or =5% weight loss, and 91% underwent positron emission tomography staging. Induction chemotherapy with pegfilgrastim support was well tolerated and active (partial response rate, 24%; stable disease, 76%; and early progression, 0%). Twenty-one patients initiated the concurrent chemoradiation, and 20 patients completed therapy to 74 Gy. The primary toxicities of concurrent chemoradiation were grade 3 esophagitis (19.5%) and cardiac arrhythmia (atrial fibrillation) (9.5%). The median progression-free survival and overall survival were 9 months (95% confidence intervals [CI]: 7-13 months) and 16 months (95% CI: 10-20 months), respectively. Treatment with induction chemotherapy and gefitinib concurrent with 3-dimensional TCRT has an acceptable toxicity and tolerability, but the survival results were disappointing.

  3. An update on the evidence for the efficacy and safety of rituximab in the management of neuromyelitis optica

    Science.gov (United States)

    Collongues, Nicolas; de Seze, Jérôme

    2016-01-01

    Neuromyelitis optica spectrum disorders (NMOSDs) is a new concept which includes classical neuromyelitis optica (NMO) and partial forms of NMO such as recurrent optic neuritis with positive aquaporin-4 antibodies (AQP4) or brainstem symptoms (intractable hiccups or vomiting). This disease is clearly distinguished from multiple sclerosis (MS) and the therapeutic approach is clearly different. Rituximab is actually considered to be one of the most efficient treatments of NMOSD, even if class I studies are clearly lacking. In the present review, we describe the state of the art about rituximab treatment in NMOSD, including adults and children, plus its efficacy and tolerance and we also underline the questions that should be addressed in the near future. PMID:27134673

  4. An update on the evidence for the efficacy and safety of rituximab in the management of neuromyelitis optica.

    Science.gov (United States)

    Collongues, Nicolas; de Seze, Jérôme

    2016-05-01

    Neuromyelitis optica spectrum disorders (NMOSDs) is a new concept which includes classical neuromyelitis optica (NMO) and partial forms of NMO such as recurrent optic neuritis with positive aquaporin-4 antibodies (AQP4) or brainstem symptoms (intractable hiccups or vomiting). This disease is clearly distinguished from multiple sclerosis (MS) and the therapeutic approach is clearly different. Rituximab is actually considered to be one of the most efficient treatments of NMOSD, even if class I studies are clearly lacking. In the present review, we describe the state of the art about rituximab treatment in NMOSD, including adults and children, plus its efficacy and tolerance and we also underline the questions that should be addressed in the near future.

  5. Pre-emptive rituximab for Epstein-Barr virus reactivation after haplo-hematopoietic stem cell transplantation.

    Science.gov (United States)

    Kobayashi, Shogo; Sano, Hideki; Mochizuki, Kazuhiro; Ohara, Yoshihiro; Takahashi, Nobuhisa; Ohto, Hitoshi; Kikuta, Atsushi

    2017-09-01

    Epstein-Barr virus-related post-transplantation lymphoproliferative disease (EBV-PTLD) is a serious complication in hematopoietic stem cell transplantation (HSCT) recipients. We conducted a retrospective study to investigate the incidence and potential risk factors for EBV reactivation and to assess the efficacy of the management of EBV reactivation with pre-emptive rituximab in children who had T-cell-replete haploidentical HSCT (TCR-haplo-SCT) with low-dose anti-thymocyte globulin (ATG). EBV-DNA level in peripheral blood (PB) was measured when suspected EBV reactivation were observed. When the EBV-DNA level in PB increased to >1,000 copies/10 6 peripheral blood mononuclear cells (PBMC), patients were pre-emptively treated with rituximab (375 mg/m 2 /dose). A total of 19 (50%) of 38 patients received rituximab infusion at a median time of 56 days after HSCT (range, 17-270 days). The median viral load at initiation of therapy was 2,900 copies/10 6 PBMC (range, 1,000-650 000). Pre-emptive therapy was started after a median of 2 days (range, 0-7 days). The median number of weekly treatment cycles was 2 (range, 1-3). None of the patients developed PTLD or other EBV-associated diseases. Pre-emptive rituximab therapy could be a useful strategy for EBV-PTLD in TCR-haplo-SCT recipients with low-dose ATG. © 2017 Japan Pediatric Society.

  6. Rituximab is associated with improved survival in Burkitt lymphoma: a retrospective analysis from two US academic medical centers.

    Science.gov (United States)

    Wildes, Tanya M; Farrington, Laura; Yeung, Cecilia; Harrington, Alexandra M; Foyil, Kelley V; Liu, Jingxia; Kreisel, Friederike; Bartlett, Nancy L; Fenske, Timothy S

    2014-02-01

    Burkitt lymphoma (BL) is a rare, highly aggressive B-cell malignancy treated most successfully with brief-duration, high-intensity chemotherapeutic regimens. The benefit of the addition of rituximab to these regimens remains uncertain. We sought to examine the effectiveness of chemotherapy with and without rituximab in patients with BL. This study is a retrospective cohort study of all adult patients with BL diagnosed and treated with modern, dose-intense chemotherapeutic regimens from 1998-2008 at two tertiary care institutions. All cases were confirmed by application of WHO 2008 criteria by hematopathologists. Medical records were reviewed for patient-, disease-, and treatment- related factors as well as treatment response and survival. Factors associated with survival were analyzed using Cox proportional hazards modeling. A total of 35 patients were analyzed: 18 patients received rituximab with chemotherapy (R-chemo) and 17 received chemotherapy (chemo) alone. The median age was 42 (range 20-74 years); 57% were male; 71% had Ann Arbor Stage IV disease; 33% had central nervous system involvement; 78% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. R-chemo was associated with significantly longer overall survival (OS) than chemo alone (5-year OS 70% and 29%, respectively, p = 0.040). On multivariate regression analysis, poor performance status and central nervous system involvement were associated with poorer survival. The addition of rituximab to chemotherapy was associated with improved OS in patients with Burkitt lymphoma. Poor performance status and central nervous system involvement were prognostically significant on multivariate analysis.

  7. Mitomycin-C-Induced TTP/HUS Treated Successfully with Rituximab: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Gunjan Shah

    2013-01-01

    Full Text Available Microangiopathic hemolytic anemia (MAHA, thrombocytopenia, fever, renal failure, and neurologic symptoms comprise the cardinal features of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Etiologies can include medications, infections, cancers, or transplantation. We present a patient with a history of rectal cancer treated with mitomycin-C who developed MAHA, acute kidney injury, and thrombocytopenia 6 months after completing therapy and to did not respond the plasmapheresis or steroids. She was treated with four weekly doses of rituximab with full recovery.

  8. Severe infection in patients with rheumatoid arthritis taking anakinra, rituximab, or abatacept: a systematic review of observational studies.

    Science.gov (United States)

    Cabral, Vanderlea Poeys; Andrade, Carlos Augusto Ferreira de; Passos, Sonia Regina Lambert; Martins, Maria de Fátima Moreira; Hökerberg, Yara Hahr Marques

    A question is raised about an increased risk of severe infection from the use of biological drugs in patients with rheumatoid arthritis. This systematic review of observational studies aimed at assessing the risk of severe infection associated with the use of anakinra, rituximab, and abatacept in patients with rheumatoid arthritis. The following databases were searched: PubMed, Science Direct, Scopus, Web of Knowledge, Scirus, Cochrane, Exerpta Medica Database, Scielo, and Lilacs up to July 2010. Severe infections were defined as those life-threatening ones in need of the use of parenteral antibiotics or of hospitalization. Longitudinal observational studies were selected without language restriction, involving adult patients diagnosed with rheumatoid arthritis and who used anakinra, rituximab, or abatacept. In four studies related to anakinra, 129 (5.1%) severe infections were related in 2896 patients, of which three died. With respect to rituximab, two studies reported 72 (5.9%) severe infections in 1224 patients, of which two died. Abatacept was evaluated in only one study in which 25 (2.4%) severe infections were reported in 1046 patients. The main site of infection for these three drugs was the respiratory tract. One possible explanation for the high frequency of severe infections associated with anakinra may be the longer follow-up time in the selected studies. The high frequency of severe infections associated with rituximab could be credited to the less strict inclusion criteria for the patients studied. Therefore, infection monitoring should be cautious in patients with rheumatoid arthritis in use of these three drugs. Copyright © 2016. Published by Elsevier Editora Ltda.

  9. Treatment of post-transplantation lymphoproliferative disorders after kidney transplant with rituximab and conversion to m-TOR inhibitor.

    Science.gov (United States)

    Nieto-Rios, John Fredy; Gómez de Los Ríos, Sandra Milena; Serna-Higuita, Lina María; Ocampo-Kohn, Catalina; Aristizabal-Alzate, Arbey; Gálvez-Cárdenas, Kenny Mauricio; Zuluaga-Valencia, Gustavo Adolfo

    2016-12-30

    Post-transplantation lymphoproliferative disorders are serious complications of organ transplantation which treatment is not yet standardized. To describe the clinical response, overall and graft survival of patients in our center with this complication after kidney transplantation, which received rituximab as part of their treatment as well as conversion to m-TOR. Retrospective study, which included patients, diagnosed with post-transplant lymphoproliferative disorders after kidney transplantation from January 2011 to July 2014. Eight cases were found with a wide spectrum of clinical presentations. Most had monomorphic histology, 85% were associated with Epstein-Barr virus, 25% of patients had tumor involvement of the renal graft, and 12.5% ​​had primary central nervous system lymphoma. All patients were managed with reduction of immunosuppression, conversion to m-TOR (except one who lost the graft at diagnosis) and rituximab-based therapy. The overall response rate was 87.5% (62.5% complete response, 25% partial response). Survival was 87.5% with a median follow-up of 34 months. An additional patient lost the graft, with chronic nephropathy already known. All the remaining patients had stable renal function. There are no standardized treatment regimens for lymphoproliferative disorders after kidney transplantation, but these patients can be managed successfully with reduction of immunosuppression, conversion to m-TOR and rituximab-based schemes.

  10. Splenectomy vs. rituximab as a second-line therapy in immune thrombocytopenic purpura: a single center experience.

    Science.gov (United States)

    Al Askar, Ahmed S; Shaheen, Naila A; Al Zahrani, Mohsen; Al Otaibi, Mohammed G; Al Qahtani, Bader S; Ahmed, Faris; Al Zughaibi, Mohand; Kamran, Ismat; Mendoza, May Anne; Khan, Altaf

    2018-01-01

    Immune thrombocytopenic purpura (ITP) is a common hematological disease treated primarily by corticosteroids. The aim of the present study was to compare response rate between patients, underwent splenectomy vs. rituximab as second-line therapy. Adult patients diagnosed with ITP who did not respond to corticosteroids or relapsed during the period 1990-2014 were included in a quasi-experimental study. Categorical variables were compared using Fisher exact test. Response to treatment was compared using logistic regression. Data were analyzed using SAS V9.2. One-hundred and forty-three patients with ITP were identified through medical records. Of 62 patients treated, 30 (48.38%) required second-line therapy. 19 (63%) patients received rituximab, and 11 (37%) underwent splenectomy. Platelets at diagnosis were not different between study groups (p = 0.062). Splenectomy group patients were younger (p = 0.011). Response to second-line therapy showed no significant difference between two groups (OR 2.03, 95% CI (0.21-22.09), p = 0.549). Results did not show a statistically significant difference in platelet counts over time between treatment groups (p = 0.101). When used exclusively as a second-line therapy for steroid-refractory ITP, the response rate was not statistically different between rituximab and splenectomy. However, further large studies are needed to assess the response rates for these treatment modalities as a second-line therapy.

  11. The effects of taurolidine alone and in combination with doxorubicin or carboplatin in canine osteosarcoma in vitro

    Directory of Open Access Journals (Sweden)

    Marley Kevin

    2013-01-01

    Full Text Available Abstract Background Osteosarcoma (OS affects over 8000 dogs/year in the United States. The disease usually arises in the appendicular skeleton and metastasizes to the lung. Dogs with localized appendicular disease benefit from limb amputation and chemotherapy but most die within 6–12 months despite these treatments. Taurolidine, a derivative of taurine, has anti-tumor and anti-angiogenic effects against a variety of cancers. The following in vitro studies tested taurolidine as a candidate for adjuvant therapy for canine OS. Tests for p53 protein status and caspase activity were used to elucidate mechanisms of taurolidine-induced cell death. Results Taurolidine was cytotoxic to osteosarcoma cells and increased the toxicity of doxorubicin and carboplatin in vitro. Apoptosis was greatly induced in cells exposed to 125 μM taurolidine and less so in cells exposed to 250 μM taurolidine. Taurolidine cytotoxicity appeared caspase-dependent in one cell line; with apparent mutant p53 protein. This cell line was the most sensitive to single agent taurolidine treatment and had a taurolidine-dependent reduction in accumulated p53 protein suggesting taurolidine’s effects may depend on the functional status of p53 in canine OS. Conclusion Taurolidine’s cytotoxic effect appears dependent on cell specific factors which may be explained, in part, by the functional status of p53. Taurolidine initiates apoptosis in canine OS cells and this occurs to a greater extent at lower concentrations. Mechanisms of cell death induced by higher concentrations were not elucidated here. Taurolidine combined with doxorubicin or carboplatin can increase the toxicity of these chemotherapy drugs and warrants further investigation in dogs with osteosarcoma.

  12. The effects of taurolidine alone and in combination with doxorubicin or carboplatin in canine osteosarcoma in vitro.

    Science.gov (United States)

    Marley, Kevin; Helfand, Stuart C; Edris, Wade A; Mata, John E; Gitelman, Alix I; Medlock, Jan; Séguin, Bernard

    2013-01-18

    Osteosarcoma (OS) affects over 8000 dogs/year in the United States. The disease usually arises in the appendicular skeleton and metastasizes to the lung. Dogs with localized appendicular disease benefit from limb amputation and chemotherapy but most die within 6-12 months despite these treatments. Taurolidine, a derivative of taurine, has anti-tumor and anti-angiogenic effects against a variety of cancers. The following in vitro studies tested taurolidine as a candidate for adjuvant therapy for canine OS. Tests for p53 protein status and caspase activity were used to elucidate mechanisms of taurolidine-induced cell death. Taurolidine was cytotoxic to osteosarcoma cells and increased the toxicity of doxorubicin and carboplatin in vitro. Apoptosis was greatly induced in cells exposed to 125 μM taurolidine and less so in cells exposed to 250 μM taurolidine. Taurolidine cytotoxicity appeared caspase-dependent in one cell line; with apparent mutant p53 protein. This cell line was the most sensitive to single agent taurolidine treatment and had a taurolidine-dependent reduction in accumulated p53 protein suggesting taurolidine's effects may depend on the functional status of p53 in canine OS. Taurolidine's cytotoxic effect appears dependent on cell specific factors which may be explained, in part, by the functional status of p53. Taurolidine initiates apoptosis in canine OS cells and this occurs to a greater extent at lower concentrations. Mechanisms of cell death induced by higher concentrations were not elucidated here. Taurolidine combined with doxorubicin or carboplatin can increase the toxicity of these chemotherapy drugs and warrants further investigation in dogs with osteosarcoma.

  13. Effectiveness of carboplatin and paclitaxel as first- and second-line treatment in 61 patients with metastatic melanoma.

    Directory of Open Access Journals (Sweden)

    Annette Pflugfelder

    Full Text Available BACKGROUND: Patients with metastatic melanoma have a very unfavorable prognosis with few therapeutic options. Based on previous promising experiences within a clinical trial involving carboplatin and paclitaxel a series of advanced metastatic melanoma patients were treated with this combination. METHODS: Data of all patients with cutaneous metastatic melanoma treated with carboplatin and paclitaxel (CP at our institution between October 2005 and December 2007 were retrospectively evaluated. For all patients a once-every-3-weeks dose-intensified regimen was used. Overall and progression free survival were calculated using the method of Kaplan and Meier. Tumour response was evaluated according to RECIST criteria. RESULTS: 61 patients with cutaneous metastatic melanoma were treated with CP. 20 patients (85% M1c received CP as first-line treatment, 41 patients (90.2% M1c had received at least one prior systemic therapy for metastatic disease. Main toxicities were myelosuppression, fatigue and peripheral neuropathy. Partial responses were noted in 4.9% of patients, stable disease in 23% of patients. No complete response was observed. Median progression free survival was 10 weeks. Median overall survival was 31 weeks. Response, progression-free and overall survival were equivalent in first- and second-line patients. 60 patients of 61 died after a median follow up of 7 months. Median overall survival differed for patients with controlled disease (PR+SD (49 weeks compared to patients with progressive disease (18 weeks. CONCLUSIONS: Among patients with metastatic melanoma a subgroup achieved disease control under CP therapy which may be associated with a survival benefit. This potential advantage has to be weighed against considerable toxicity. Since response rates and survival were not improved in previously untreated patients compared to pretreated patients, CP should thus not be applied as first-line treatment.

  14. Multimodality Molecular Imaging of [18F]-Fluorinated Carboplatin Derivative Encapsulated in [111In]-Labeled Liposomes

    Science.gov (United States)

    Lamichhane, Narottam

    Platinum based chemotherapy is amongst the mainstream DNA-damaging agents used in clinical cancer therapy today. Agents such as cisplatin, carboplatin are clinically prescribed for the treatment of solid tumors either as single agents, in combination, or as part of multi-modality treatment strategy. Despite the potent anti-tumor activity of these drugs, overall effectiveness is still hampered by inadequate delivery and retention of drug in tumor and unwanted normal tissue toxicity, induced by non-selective accumulation of drug in normal cells and tissues. Utilizing molecular imaging and nanoparticle technologies, this thesis aims to contribute to better understanding of how to improve the profile of platinum based therapy. By developing a novel fluorinated derivative of carboplatin, incorporating a Flourine-18 (18F) moiety as an inherent part of the molecule, quantitative measures of drug concentration in tumors and normal tissues can be directly determined in vivo and within the intact individual environment. A potential impact of this knowledge will be helpful in predicting the overall response of individual patients to the treatment. Specifically, the aim of this project, therefore, is the development of a fluorinated carboplatin drug derivative with an inherent positron emission tomography (PET) imaging capability, so that the accumulation of the drug in the tumor and normal organs can be studied during the course of therapy . A secondary objective of this research is to develop a proof of concept for simultaneous imaging of a PET radiolabeled drug with a SPECT radiolabeled liposomal formulation, enabling thereby bi-modal imaging of drug and delivery vehicle in vivo. The approach is challenging because it involves development in PET radiochemistry, PET and SPECT imaging, drug liposomal encapsulation, and a dual-modal imaging of radiolabeled drug and radiolabeled vehicle. The principal development is the synthesis of fluorinated carboplatin 19F-FCP using 2

  15. Paraneoplastic Seronegative Pauci-Immune Glomerulonephritis Associated with Lung Adenocarcinoma Responds to Rituximab: A Case Report

    Directory of Open Access Journals (Sweden)

    Pragnan Kancharla

    2018-06-01

    Full Text Available Anti-neutrophil cytoplasmic antibodies (ANCA play an important role in the pathogenesis of pauci-immune renal vasculitis. However, in 10% of the cases, ANCA are absent. We present a case of a 64-year-old man with a chronic untreated hepatitis C virus infection and Middle Eastern thalassemia who was ANCA-negative when he was hospitalized due to acute kidney injury and accounts for an uncommon presentation of renal vasculitis. The patient had earlier reported to have undergone local lobectomy and adjuvant chemotherapy (carboplatin/pemetrexed for lung adenocarcinoma a month prior. IL-6 has been reported to be involved in the pathophysiological cascade causing pauci-immune glomerulonephritis amongst non-small cell lung cancer patients. Previous studies with subgroup analysis have demonstrated that ANCA negativity has been associated with more chronic glomerular lesions and less crescent formation, which tends to have a critical outcome in the renal system. However, our patient underwent kidney biopsy exhibiting active crescentic glomerulonephritis, pauci-immune type with 5 cellular crescents amongst 15 glomeruli. To our knowledge, this is the third reported case of ANCA-negative vasculitis with typical presentation on biopsy in non-small cell lung cancer patients.

  16. Room-temperature X-ray diffraction studies of cisplatin and carboplatin binding to His15 of HEWL after prolonged chemical exposure

    International Nuclear Information System (INIS)

    Tanley, Simon W. M.; Schreurs, Antoine M. M.; Kroon-Batenburg, Loes M. J.; Helliwell, John R.

    2012-01-01

    Binding of cisplatin to His15 in hen egg-white lysozyme in aqueous media is observed after prolonged chemical exposure for 15 months, in contrast to the lack of binding that was observed after 4 d in a previous study. Binding of carboplatin is seen in greater detail in the case of room-temperature data collection compared with cryo data collection. The anticancer complexes cisplatin and carboplatin are known to bind to both the N δ and the N ∊ atoms of His15 of hen egg-white lysozyme (HEWL) in the presence of dimethyl sulfoxide (DMSO). However, neither binds in aqueous media after 4 d of crystallization and crystal growth, suggesting that DMSO facilitates cisplatin/carboplatin binding to the N atoms of His15 by an unknown mechanism. Crystals of HEWL cocrystallized with cisplatin in both aqueous and DMSO media, of HEWL cocrystallized with carboplatin in DMSO medium and of HEWL cocrystallized with cisplatin and N-acetylglucosamine (NAG) in DMSO medium were stored for between seven and 15 months. X-ray diffraction studies of these crystals were carried out on a Bruker APEX II home-source diffractometer at room temperature. Room-temperature X-ray diffraction data collection removed the need for cryoprotectants to be used, ruling out any effect that the cryoprotectants might have had on binding to the protein. Both cisplatin and carboplatin still bind to both the N δ and N ∊ atoms of His15 in DMSO media as expected, but more detail for the cyclobutanedicarboxylate (CBDC) moiety of carboplatin was observed at the N ∊ binding site. However, two molecules of cisplatin were now observed to be bound to His15 in aqueous conditions. The platinum peak positions were identified using anomalous difference electron-density maps as a cross-check with F o − F c OMIT electron-density maps. The occupancies of each binding site were calculated using SHELXTL. These results show that over time cisplatin binds to both N atoms of His15 of HEWL in aqueous media, whereas this

  17. Spotlight on rituximab in the treatment of antineutrophil cytoplasmic antibody-associated vasculitis: current perspectives

    Directory of Open Access Journals (Sweden)

    Moog P

    2015-11-01

    Full Text Available Philipp Moog, Klaus Thuermel Abteilung für Nephrologie, Klinikum rechts der Isar, Technische Universität München, Munich, Germany Abstract: A 54-year-old patient presented to his general practitioner because of strong muscle pain in both thighs. Inflammatory parameters (CRP 16.3 mg/dL and white blood cells (15 g/L were elevated. The patient reported a weight loss of 10 kg in 4 weeks. There was no fever or any other specific symptoms. Urine dipstick examination and computed tomography of the chest were unremarkable. Because of increasing symptoms, the patient was referred to our department. Magnetic resonance tomography showed diffuse inflammatory changes of the muscles of both thighs. Neurological examination and electrophysiology revealed axonal sensorimotor neuropathy and ground-glass opacities of both lungs had occurred. Serum creatinine increased to 229 µmol/L within a few days, with proteinuria of 3.3 g/g creatinine. Kidney biopsy showed diffuse pauci-immune proliferative glomerulonephritis. Proteinase 3-specific antineutrophil cytoplasmic antibodies were markedly increased. Birmingham Vasculitis Activity Score was 35. Within 2 days, serum creatinine further increased to 495 µmol/L. Plasma exchange, high-dose glucocorticosteroids, and hemodialysis were started. The patient received cyclophosphamide 1 g twice and rituximab 375 mg/m2 four times according to the RITUXVAS protocol. Despite ongoing therapy, hemodialysis could not be withdrawn and had to be continued over 3 weeks until diuresis normalized. Glucocorticosteroids were tapered to 20 mg after 2 months, and serum creatinine was 133 µmol/L. However, nephritic urinary sediment reappeared. Another dose of 1 g cyclophosphamide was given, and glucocorticosteroids were raised for another 4 weeks. After 6 months, the daily prednisolone dose was able to be tapered to 5 mg. Serum creatinine was 124 µmol/L, proteinuria further decreased to 382 mg/g creatinine, and the Birmingham

  18. Bendamustine mitoxantrone and rituximab (BMR): a new effective regimen for refractory or relapsed indolent lymphomas.

    Science.gov (United States)

    Weide, Rudolf; Heymanns, Jochen; Gores, Annette; Köppler, Hubert

    2002-02-01

    Bendamustine (B) and mitoxantrone (M) have been shown to be potent cytotoxic drugs for the treatment of relapsed or refractory indolent lymphomas. The anti-CD20 monoclonal antibody rituximab (R) has produced an overall response rate (ORR) of 50% as a single agent in relapsed or refractory indolent lymphomas. We posed the question whether a combination of the above agents (BMR) could improve these results. This study was an open label, single center pilot study for patients with relapsed or refractory, CD20-positive (indolent) lymphoma or chronic lymphocytic leukaemia. The therapy consisted of bendamustine (80 mg/m2, day 1-3), mitoxantrone (10 mg/m2, day 1), rituximab (375 mg/m2, week 2-5). BM was repeated on day 36 or when the haematological parameters had recovered. The maximum therapy consisted of one BMR-cycle, followed by five BM courses. Treatment was stopped when the disease responded with PR/CR. During March 1999 and December 2000, 20 patients received the BMR-regimen (four secondary high grade lymphoma, 12 indolent lymphoma, four B-CLL). The median age of the patients was 67 years (range 36-82) and their performance status ranged from 0 to 3. Median number of previous treatment regimens was two (1-6). Of the lymphoma patients, 14 had stage IV disease, 1 stage III and 1 stage II. B-CLL patients were all Rai stage IV (Binet C). Overall response rate was 95% (19/20) with seven patients achieving a CR (35%) and 12 patients achieving a PR (60%). Median time to progression is 7 months (1-21) with a median observation time of 7 months (1-21). Response is still durable in 15/20 patients (75%) (1+ to 21+ months after therapy). Symptomatic, reversible grade three or four haematotoxicity occurred in 4/20 patients (20%). Non-symptomatic grade three or four haematotoxicity was seen in 9/20 patients (45%). No major non-haematological toxicity was observed. In conclusion, BMR is a well tolerated, very effective outpatient regimen of treatment for relapsed and refractory

  19. Rituximab in the treatment of refractory or relapsing eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome).

    Science.gov (United States)

    Thiel, Jens; Hässler, Fabian; Salzer, Ulrich; Voll, Reinhard E; Venhoff, Nils

    2013-09-24

    Eosinophilic granulomatosis with polyangiitis (EGPA) is part of antineutrophil cytoplasmic antibodies (ANCAs)-associated vasculitides. In EGPA small-vessel vasculitis is associated with eosinophilia and asthma. About 40% of EGPA patients are ANCA-positive, suggesting a role for B cells in the pathogenesis of EGPA. B cell-depleting therapy with rituximab (RTX) can be effective in ANCA-positive EGPA, but very few patients have been published to date. The role of RTX in the treatment of ANCA-negative EGPA is unclear. We report a single-center cohort of patients with eosinophilic granulomatosis with polyangiitis. Of these patients, nine (six ANCA-positive, three ANCA-negative) had been treated with RTX for relapsing or refractory disease on standard immunosuppressive treatment. In a retrospective analysis, data on treatment response, frequency of relapses, adverse events, and peripheral B-cell reconstitution were evaluated. Furthermore, serum immunoglobulin concentrations, ANCA status, and peripheral B cell subpopulations were assessed after RTX treatment. All patients had high disease activity before RTX treatment. At presentation 3 months after RTX therapy, all ANCA-positive and ANCA-negative patients had responded to RTX, with one patient being in complete remission, and eight patients being in partial remission. After a mean follow-up of 9 months, C-reactive protein concentrations had normalized, eosinophils had significantly decreased, and prednisone had been tapered in all patients. In all patients, RTX therapy was combined with a standard immunosuppressive therapy. Within the 9-month observation period, no relapse was recorded. Three patients were preemptively retreated with RTX, and during the median follow-up time of 3 years, no relapse occurred in these patients. During the follow-up of 13 patient-years, five minor but no major infections were recorded. In our analysis on nine patients with EGPA resistant to standard therapy, rituximab proved to be an

  20. Internalization of rituximab and the efficiency of B Cell depletion in rheumatoid arthritis and systemic lupus erythematosus.

    Science.gov (United States)

    Reddy, Venkat; Cambridge, Geraldine; Isenberg, David A; Glennie, Martin J; Cragg, Mark S; Leandro, Maria

    2015-05-01

    Rituximab, a type I anti-CD20 monoclonal antibody (mAb), induces incomplete B cell depletion in some patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), thus contributing to a poor clinical response. The mechanisms of this resistance remain elusive. The purpose of this study was to determine whether type II mAb are more efficient than type I mAb at depleting B cells from RA and SLE patients, whether internalization influences the efficiency of depletion, and whether Fcγ receptor type IIb (FcγRIIb) and the B cell receptor regulate this internalization process. We used an in vitro whole blood B cell-depletion assay to assess the efficiency of depletion, flow cytometry to study cell surface protein expression, and surface fluorescence-quenching assays to assess rituximab internalization, in samples from patients with RA and patients with SLE. Paired t-test or Mann-Whitney U test was used to compare groups, and Spearman's rank correlation test was used to assess correlation. We found that type II mAb internalized significantly less rituximab than type I mAb and depleted B cells from patients with RA and SLE at least 2-fold more efficiently than type I mAb. Internalization of rituximab was highly variable between patients, was regulated by FcγRIIb, and inversely correlated with cytotoxicity in whole blood B cell-depletion assays. The lowest levels of internalization were seen in IgD- B cells, including postswitched (IgD-CD27+) memory cells. Internalization of type I anti-CD20 mAb was also partially inhibited by anti-IgM stimulation. Variability in internalization of rituximab was observed and was correlated with impaired B cell depletion. Therefore, slower-internalizing type II mAb should be considered as alternative B cell-depleting agents for the treatment of RA and SLE. © 2015 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

  1. Cost-effectiveness of adding rituximab to fludarabine and cyclophosphamide for treatment of chronic lymphocytic leukemia in Ukraine

    Directory of Open Access Journals (Sweden)

    Mandrik O

    2015-08-01

    Full Text Available Olena Mandrik,1 Isaac Corro Ramos,2 Saskia Knies,1,3 Maiwenn Al,1,2 Johan L Severens1,2 1Institute of Health Policy and Management, Erasmus University Rotterdam, Rotterdam, the Netherlands; 2Institute of Medical Technology Assessment (iMTA, Erasmus University Rotterdam, Rotterdam, the Netherlands; 3National Health Care Institute, Diemen, the Netherlands Abstract: The aim of this study was to assess the cost-effectiveness, from a health care perspective, of adding rituximab to fludarabine and cyclophosphamide scheme (FCR versus FC for treatment-naïve and refractory/relapsed Ukrainian patients with chronic lymphocytic leukemia. A decision-analytic Markov cohort model with three health states and 1-month cycle time was developed and run within a life time horizon. Data from two multinational, prospective, open-label Phase 3 studies were used to assess patients' survival. While utilities were generalized from UK data, local resource utilization and disease-associated treatment, hospitalization, and side effect costs were applied. The alternative scenario was performed to assess the impact of lower life expectancy of the general population in Ukraine on the incremental cost-effectiveness ratio (ICER for treatment-naïve patients. One-way, two-way, and probabilistic sensitivity analyses were conducted to assess the robustness of the results. The ICER (in US dollars of treating chronic lymphocytic leukemia patients with FCR versus FC is US$8,704 per quality-adjusted life year gained for treatment-naïve patients and US$11,056 for refractory/relapsed patients. When survival data were modified to the lower life expectancy of the general population in Ukraine, the ICER for treatment-naïve patients was higher than US$13,000. This value is higher than three times the current gross domestic product per capita in Ukraine. Sensitivity analyses have shown a high impact of rituximab costs and a moderate impact of differences in utilities on the ICER

  2. Dosimetric analysis of 177Lu-DOTA-rituximab in patients with relapsed/refractory non-Hodgkin's lymphoma.

    Science.gov (United States)

    Yadav, Madhav P; Singla, Suhas; Thakral, Parul; Ballal, Sanjana; Bal, Chandrasekhar

    2016-07-01

    Radioimmunotherapy targeting CD20 receptors in lymphoma using radiolabeled chimeric antibodies may lead to better therapeutic responses than cold anti-CD20 antibodies. This study aimed to assess the biodistribution and present reasonable estimates of normal organ doses, including red marrow using Lu-DOTA-rituximab. Patients with relapsed/refractory CD20+ B-cell non-Hodgkin's lymphoma were recruited into this prospective study. In-house labeling of Lu-DOTA-rituximab was performed and administered after quality assurance. Rituximab (375 mg/m), followed by 50 mCi (1850 MBq) of Lu-DOTA-rituximab was administered as a slow intravenous infusion and emission images were acquired. Regions of interest were drawn for kidney, liver, heart, bladder, spleen, and tumor lesions on both anterior and posterior images. Internal dose estimation was performed using OLINDA v1.0 software. The mean age of the 10 patients (eight men and two women) was 52±13 years. The uptake of radiolabeled antibody was visualized within 30 min of administration in the liver, kidneys, heart, spleen, and bladder. The coefficient of determination (R) was greater than 0.95 for organs and the whole body in all patients. The effective half-life of radioimmunoconjugate was 100±28 h (42-126 h). The critical organ in our study was the red marrow. The average total body dose, effective dose, and effective dose equivalent calculated in all 10 patients were 0.13±0.02, 0.15±0.03, and 0.22±0.04 mGy/MBq, respectively. There may be considerable interindividual differences in absorbed doses of organs and generalization or extrapolation of doses in the clinical setting at present is not feasible with Lu-DOTA-rituximab in non-Hodgkin's lymphoma patients. Patient-specific dosimetry is thus recommended to eliminate the variations and reduce the possibility of dose-limiting toxicity.

  3. A pioneer experience in Malaysia on In-house Radio-labelling of "1"3"1I-rituximab in the treatment of Non-Hodgkin's Lymphoma and a case report of high dose "1"3"1I-rituximab-BEAM conditioning autologous transplant

    International Nuclear Information System (INIS)

    Kuan, Jew Win; Law, Chiong Soon; Wong, Xiang Qi; Ko, Ching Tiong; Awang, Zool Hilmi; Chew, Lee Ping; Chang, Kian Meng

    2016-01-01

    Radioimmunotherapy is an established treatment modality in Non-Hodgkin's lymphoma. The only two commercially available radioimmunotherapies – "9"0Y-ibritumomab tiuxetan is expensive and "1"3"1I-tositumomab has been discontinued from commercial production. In resource limited environment, self-labelling "1"3"1I-rituximab might be the only viable practical option. We reported our pioneer experience in Malaysia on self-labelling "1"3"1I-rituximab, substituting autologous haematopoietic stem cell transplantation (HSCT) and a patient, the first reported case, received high dose "1"3"1I-rituximab (6000 MBq/163 mCi) combined with BEAM conditioning for autologous HSCT. - Highlights: • Usual dose: Day 0 (dosimetry) – 5 mCi, Day 7 (therapeutic) 0.75 Gy to whole body. • High dose: 6000 MBq (163 mCi) on Day − 18, BEAM conditioning starts on Day − 8. • Self-labelled "1"3"1I-rituximab is a viable treatment in resource limited environment. • "1"3"1I-rituximab may substitute autologous transplant. • High dose "1"3"1I-rituximab-BEAM is a feasible conditioning regime.

  4. International standards for monoclonal antibodies to support pre- and post-marketing product consistency: Evaluation of a candidate international standard for the bioactivities of rituximab.

    Science.gov (United States)

    Prior, Sandra; Hufton, Simon E; Fox, Bernard; Dougall, Thomas; Rigsby, Peter; Bristow, Adrian

    2018-01-01

    The intrinsic complexity and heterogeneity of therapeutic monoclonal antibodies is built into the biosimilarity paradigm where critical quality attributes are controlled in exhaustive comparability studies with the reference medicinal product. The long-term success of biosimilars will depend on reassuring healthcare professionals and patients of consistent product quality, safety and efficacy. With this aim, the World Health Organization has endorsed the need for public bioactivity standards for therapeutic monoclonal antibodies in support of current controls. We have developed a candidate international potency standard for rituximab that was evaluated in a multi-center collaborative study using participants' own qualified Fc-effector function and cell-based binding bioassays. Dose-response curve model parameters were shown to reflect similar behavior amongst rituximab preparations, albeit with some differences in potency. In the absence of a common reference standard, potency estimates were in poor agreement amongst laboratories, but the use of the candidate preparation significantly reduced this variability. Our results suggest that the candidate rituximab standard can support bioassay performance and improve data harmonization, which when implemented will promote consistency of rituximab products over their life-cycles. This data provides the first scientific evidence that a classical standardization exercise allowing traceability of bioassay data to an international standard is also applicable to rituximab. However, we submit that this new type of international standard needs to be used appropriately and its role not to be mistaken with that of the reference medicinal product.

  5. IMPACT OF PRE-TRANSPLANT RITUXIMAB ON SURVIVAL AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR DIFFUSE LARGE B-CELL LYMPHOMA

    Science.gov (United States)

    Fenske, Timothy S.; Hari, Parameswaran N.; Carreras, Jeanette; Zhang, Mei-Jie; Kamble, Rammurti T.; Bolwell, Brian J.; Cairo, Mitchell S.; Champlin, Richard E.; Chen, Yi-Bin; Freytes, César O.; Gale, Robert Peter; Hale, Gregory A.; Ilhan, Osman; Khoury, H. Jean; Lister, John; Maharaj, Dipnarine; Marks, David I.; Munker, Reinhold; Pecora, Andrew L.; Rowlings, Philip A.; Shea, Thomas C.; Stiff, Patrick; Wiernik, Peter H.; Winter, Jane N.; Rizzo, J. Douglas; van Besien, Koen; Lazarus, Hillard M.; Vose, Julie M.

    2010-01-01

    Incorporation of the anti-CD20 monoclonal antibody rituximab into front-line regimens for diffuse large B-cell lymphoma (DLBCL) has resulted in improved survival. Despite this progress, many patients develop refractory or recurrent DLBCL and then receive autologous hematopoietic stem cell transplantation (AuHCT). It is unclear to what extent pre-transplant exposure to rituximab affects outcomes following AuHCT. Outcomes of 994 patients receiving AuHCT for DLBCL between 1996 and 2003 were analyzed according to whether rituximab was (n=176, “+R” group) or was not (n=818, “ −R” group) administered with front-line or salvage therapy prior to AuHCT. The +R group had superior progression-free survival (50% versus 38%, p=0.008) and overall survival (57% versus 45%, p=0.006) at 3 years. Platelet and neutrophil engraftment were not affected by exposure to rituximab. Non-relapse mortality (NRM) did not differ significantly between the +R and −R groups. In multivariate analysis, the +R group had improved progression-free survival (relative risk of relapse/progression or death 0.64, p<0.001) and improved overall survival (relative risk of death of 0.74, p=0.039). We conclude that pre-transplant rituximab is associated with a lower rate of progression and improved survival following AuHCT for DLBCL, with no evidence of impaired engraftment or increased NRM. PMID:19822306

  6. Efficacy of rituximab and plasmapharesis in an adult patient with antifactor H autoantibody-associated hemolytic uremic syndrome: A case report and literature review.

    Science.gov (United States)

    Deville, Clemence; Garrouste, Cyril; Coppo, Paul; Evrard, Bertrand; Lautrette, Alexandre; Heng, Anne Elisabeth

    2016-09-01

    Antifactor H antibody (anti-CFHAb) is found in 6% to 25% cases of atypical hemolytic uremic syndrome (aHUS) in children, but has been only exceptionally reported in adults. There is no consensus about the best treatment for this type of aHUS. We report the case of an adult patient treated successfully with plasma exchange (PE), steroids, and rituximab.A 27-year-old Caucasian male presented to hospital with anemia, thrombocytopenia, and acute renal failure. One week earlier, he had digestive problems with diarrhea. The diagnosis of anti-CFHAb-associated aHUS (82,000 AU/mL) without CFHR gene mutations was established.He received Rituximab 375 mg/m (4 pulses) with PE and steroids. This treatment achieved renal and hematological remission at day (D) 31 and negative anti-CFHAb at D45 (<100 AU/mL). At D76, a fifth rituximab pulse was performed while CD19 was higher than 10/mm. Steroids were stopped at month (M) 9. The patient has not relapsed during long-term follow-up (M39).Rituximab therapy can be considered for anti-CFHAb-associated aHUS. Monitoring of anti-CFHAb titer may help to guide maintenance therapeutic strategies including Rituximab infusion.

  7. Results of a multicenter prospective clinical study in Japan for evaluating efficacy and safety of desensitization protocol based on rituximab in ABO-incompatible kidney transplantation.

    Science.gov (United States)

    Takahashi, Kota; Saito, Kazuhide; Takahara, Shiro; Fuchinoue, Shohei; Yagisawa, Takashi; Aikawa, Atsushi; Watarai, Yoshihiko; Yoshimura, Norio; Tanabe, Kazunari; Morozumi, Kunio; Shimazu, Motohide

    2017-08-01

    Deceased organ donations are rare in Japan, with most kidney transplants performed from a limited number of living donors. Researchers have thus developed highly successful ABO-incompatible transplantation procedures, emphasizing preoperative desensitization and postoperative immunosuppression. A recent open-label, single-arm, multicenter clinical study prospectively examined the efficacy and safety of rituximab/mycophenolate mofetil desensitization in ABO-incompatible kidney transplantation without splenectomy. Mycophenolate mofetil and low dose steroid were started 28 days pretransplant, followed by two doses of rituximab 375 mg/m 2 at day -14 and day -1, and postoperative immunosuppression with tacrolimus or ciclosporin and basiliximab. The primary endpoint was the non-occurrence rate of acute antibody-mediated rejection. Patient survival and graft survival were monitored for 1 year posttransplant. Eighteen patients received rituximab and underwent ABO-incompatible kidney transplantation. CD19-positive peripheral B cell count decreased rapidly after the first rituximab infusion and recovered gradually after week 36. The desensitization protocol was tolerable, and most rituximab-related infusion reactions were mild. No anti-A/B antibody-mediated rejection occurred with this series. One patient developed anti-HLA antibody-mediated rejection (Banff 07 type II) on day 2, which was successfully managed. Patient and graft survival were both 100 % after 1 year. Our desensitization protocol was confirmed to be clinically effective and with acceptable toxicities for ABO-I-KTx (University Hospital Medical Information Network Registration Number: UMIN000006635).

  8. Cleavage of the interchain disulfide bonds in rituximab increases its affinity for FcγRIIIA.

    Science.gov (United States)

    Suzuki, Mami; Yamanoi, Ayaka; Machino, Yusuke; Kobayashi, Eiji; Fukuchi, Kaori; Tsukimoto, Mitsutoshi; Kojima, Shuji; Kohroki, Junya; Akimoto, Kazunori; Masuho, Yasuhiko

    2013-07-05

    The Fc region of human IgG1 mediates effector function via binding to Fcγ receptors and complement activation. The H and L chains of IgG1 antibodies are joined by four interchain disulfide bonds. In this study, these bonds within the therapeutic IgG1 rituximab (RTX) were cleaved either by mild reduction followed by alkylation or by mild S-sulfonation; consequently, two modified RTXs - A-RTX (alkylated) and S-RTX (S-sulfonated) - were formed, and both were almost as potent as unmodified RTX when binding CD20 antigen. Unexpectedly, each modified RTX had a higher binding affinity for FcγRIIIA (CD16A) than did unmodified RTX. However, S-RTX and A-RTX were each less potent than RTX in an assay of antibody-dependent cellular cytotoxicity (ADCC). In this ADCC assay, each modified RTX showed decreased secretion of granzyme B, but no change in perforin secretion, from effector cells. These results provide significant information on the structures within IgG1 that are involved in binding FcγRIIIA, and they may be useful in the development of therapeutic antagonists for FcγRIIIA. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Splenic marginal zone lymphoma: excellent outcomes in 64 patients treated in the rituximab era.

    Science.gov (United States)

    Starr, Adam G; Caimi, Paolo F; Fu, PingFu; Massoud, Mira R; Meyerson, Howard; Hsi, Eric D; Mansur, David B; Cherian, Sheen; Cooper, Brenda W; De Lima, Marcos J G; Lazarus, Hillard M; Gerson, Stanton L; Jagadeesh, Deepa; Smith, Mitchell R; Dean, Robert M; Pohlman, Brad L; Hill, Brian T; William, Basem M

    2017-08-01

    Splenic marginal zone lymphoma (SMZL) is a rare non-Hodgkin lymphoma. We sought to identify prognostic factors and define outcomes in a cohort of 64 patients with SMZL who were treated at two large academic medical centers in North America in the rituximab era. Over a median follow-up of 37.8 (range 6-167.1) months, Kaplan-Meier estimate of median OS was 156.3 months and median PFS was 52.9 months. On univariate analysis, baseline hemoglobin marginally significant with regard to OS (p = 0.056). Splenectomy was not predictive of OS or PFS (p = 0.563 and 0.937, respectively). Transformation to diffuse large B-cell lymphoma occurred in four (6.3%) patients during the observation period. OS was comparable to contemporaneous cohorts of patients with extranodal and nodal marginal lymphomas and FLIPI score was highly predictive for inferior PFS and OS when all three cohorts were analyzed together. Outcomes of SMZL, in our series, were excellent, with a median OS of >13 years. Low hemoglobin and high-risk FLIPI were associated with inferior outcomes.

  10. Characterization of CD4 T Cell Epitopes of Infliximab and Rituximab Identified from Healthy Donors

    Directory of Open Access Journals (Sweden)

    Moustafa Hamze

    2017-05-01

    Full Text Available The chimeric antibodies anti-CD20 rituximab (Rtx and anti-TNFα infliximab (Ifx induce antidrug antibodies (ADAs in many patients with inflammatory diseases. Because of the key role of CD4 T lymphocytes in the initiation of antibody responses, we localized the CD4 T cell epitopes of Rtx and Ifx. With the perspective to anticipate immunogenicity of therapeutic antibodies, identification of the CD4 T cell epitopes was performed using cells collected in healthy donors. Nine T cell epitopes were identified in the variable chains of both antibodies by deriving CD4 T cell lines raised against either Rtx or Ifx. The T cell epitopes often exhibited a good affinity for human leukocyte antigen (HLA-DR molecules and were part of the peptides identified by MHC-associated peptide proteomics assay from HLA-DR molecules of dendritic cells (DCs loaded with the antibodies. Two-third of the T cell epitopes identified from the healthy donors stimulated peripheral blood mononuclear cells from patients having developed ADAs against Rtx or Ifx and promoted the secretion of a diversity of cytokines. These data emphasize the predictive value of evaluating the T cell repertoire of healthy donors and the composition of peptides bound to HLA-DR of DCs to anticipate and prevent immunogenicity of therapeutic antibodies.

  11. Mortality in patients with interstitial lung disease treated with rituximab or TNFi as a first biologic.

    Science.gov (United States)

    Druce, Katie L; Iqbal, Kundan; Watson, Kath D; Symmons, Deborah P M; Hyrich, Kimme L; Kelly, Clive

    2017-01-01

    Guidelines cautioned prescribing of tumour necrosis factor inhibitors (TNFi) to patients with rheumatoid arthritis and interstitial lung disease (RA-ILD) after reports of new or worsening of ILD. Less is known about outcomes among patients with RA-ILD who receive rituximab (RTX). This study compares mortality in patients with RA-ILD who received RTX or TNFi as their first biologic. Participants with RA-ILD recruited to the British Society for Rheumatology Biologics Register for RA were included. Death rates were calculated and risk comparisons were made using Cox regression. Causes of death, including the frequency in which ILD was recorded on death certificates were examined. 43 patients on RTX and 309 on TNFi were included. RTX recipients had shorter disease duration and less disability. Death rates were 94.8 (95%CI: 74.4 to 118.7) and 53.0 (22.9 to 104.6) per 1000 person years, respectively. The adjusted mortality risk was halved in the RTX cohort, but the difference was not statistically significant (HR 0.53, 95% CI: 0.26 to 1.10). ILD was the underlying cause of death in 1 of 7 RTX deaths (14%) and 12 of 76 TNFi deaths (16%). Patients with RA-ILD who received RTX had lower mortality rates compared to TNFi. The absence of information on ILD severity or subtype prevents conclusions of which drug represents the best choice in patients with RA-ILD and active arthritis.

  12. Efficiency of using rituximab in a patient with generalized granulomatosis with polyangiitis: A case report

    Directory of Open Access Journals (Sweden)

    Gulazyk Malikovna Koilubaeva

    2014-01-01

    Full Text Available Systemic vasculitides (SVs are characterized by inflammation of the blood vessels wall; the spectrum of their clinical manifestations depends on the type, extent, and location of affected vessels and the activity of systemic inflammation. The etiology of most primary SVs is unknown. Antineutrophil cytoplasmic antibodies (ANCAs are implicated in its pathogenesis. The presence of ANCAa in patients' serum and the correlation of their level with the severity of clinical manifestations served as a basis for identifying a subgroup of systemic necrotizing vasculitides associated with ANCA synthesis: granulomatosis with polyangiitis (GPA, microscopic polyangiitis, and Churg – Strauss syndrome. GPA is characterized by systemic granulomatous necrotizing vasculitis involving the small vessels of the upper respiratory tract, lung, and kidney.The paper describes a case of difficult diagnosis and successful rituximab (RTM treatment of generalized GPA in a 45-year-old female patients. The disease occurred with local damage to the upper respiratory tract, granulomatous inflammation of the pulmonary vessels to form multiple infiltrates with lung tissue destruction elements and necrotizing glomerulonephritis. Despite intensive immunosuppressive treatment, there was a rapid GPA progression with the further development of respiratory failure, which had been induced by stenotic laryngitis subglottica leading to tracheostoma. Damage to the organ of vision could lead to severe complications, including amaurosis. RMT was shown to be effective in treating generalized GPA with a poor prognosis.

  13. Rituximab for the therapy of systemic sclerosis: a series of 10 cases in a single center.

    Science.gov (United States)

    Vilela, Verônica Silva; Maretti, Giselle Baptista; Gama, Lívia Marques da Silva; Costa, Claudia Henrique da; Rufino, Rogério Lopes; Levy, Roger A

    Systemic sclerosis (SSc) is a chronic autoimmune disease with a high morbidity and mortality. Although cyclophosphamide is effective for severe and refractory cases, there is demand for new treatments. The biological treatment with B-cell depletion with rituximab (RTX) has demonstrated efficacy for this demand in open-label studies. This study was conducted with the aim to retrospectively evaluate all patients who used RTX for the treatment of SSc in our center. We retrospectively evaluated medical records of all patients with SSc who used RTX to treat this disease from January 2009 to January 2015. Systemic, cutaneous, and pulmonary involvement data and laboratory results before and six months after the first infusion of RTX were collected. Ten patients received treatment during the study period and were included in this series. All patients had a diffuse form of the disease. Five patients suffered from an early (duration of disease shorter or equal to four years), rapidly progressive disease, and another five received RTX at late stages of the disease. In both groups of patients, stabilization of the pulmonary picture was observed, with a fall in the skin score in those patients with early forms of the disease. Similar to findings in previous studies, RTX was effective in treating early and rapidly progressive forms of SSc. We also found that patients with long-term illness may benefit from the treatment. Copyright © 2016. Published by Elsevier Editora Ltda.

  14. Successful plasma exchange combined with rituximab therapy in aggressive APS-related cutaneous necrosis.

    Science.gov (United States)

    Costa, Rubens; Fazal, Salman; Kaplan, Robert B; Spero, Joel; Costa, Ricardo

    2013-03-01

    Antiphospholipid antibody syndrome (APS) is a systemic autoimmune disorder characterized by venous and/or arterial thrombosis or recurrent fetal loss associated with the presence of antiphospholipid antibodies and/or a lupus anticoagulant. The skin appears to be an important target organ and many cases of APS may present with skin manifestations. These lesions may be manifold and may take the form of livedo reticularis, livedo racemosa, ulcerations, digital gangrene, subungeal splinter hemorrhages, superficial venous thrombosis, thrombocytopenic purpura, pseudovasculitic manifestations, extensive cutaneous necrosis, or primary anetoderma. We report a case of fulminant APS-related cutaneous necrosis. A 38-year-old Caucasian male with a past history of APS, multiple deep vein thrombi/pulmonary emboli, presented with necrotic lesions on his right upper and right lower extremities. Initially, baseline anticoagulation was increased without improvement. Subsequently, plasma exchange was initiated on a daily schedule. Furthermore, rituximab 1,000 mg IV was administered on days 1 and 15. After six consecutive daily sessions of plasma exchange, there was significant regression of the necrotic lesions. After a 22-day hospital stay, the patient was discharged to home on fondaparinux. The patient presented approximately 2 months later after missing follow-up appointments. At the time, his initial lesions looked remarkably improved.

  15. Challenges in economic evaluation of new drugs: experience with rituximab in Hungary.

    Science.gov (United States)

    Brodszky, Valentin; Orlewska, Ewa; Pentek, Martha; Karpati, Krisztian; Skoupa, Jana; Gulacsi, Laszlo

    2010-01-01

    Implementation of a new therapy into clinical practice is a complex process. Various countries have different requirements for information but most often focus on economic evaluation, which often plays a stronger role in healthcare decision making than does clinical evidence. To identify all potential challenges in economic evaluation, the case of a new biological drug, rituximab, used to treat rheumatoid arthritis, has been taken as an example. We present methods and results of economic assessment, highlighting the specific issues that should be considered in countries with economic and health care conditions similar to those of Hungary. In principle, economic evaluation requires data on characteristics of target population, disease progression, treatment impact, preferences, resource utilization and unit prices. Treatment effect/relative risk reduction and clinical practice patterns (resource use) may be more generalizable, whereas prices and baseline risk need to be jurisdiction specific. In order to address issues of transferability, investments need to be made in the collection of epidemiological and demographic data, plus data on clinical practice patterns, resource use, costs and health state valuation. In Hungary this problem has been solved through conducting a well designed 255 patient cross-sectional study. The Hungarian example shows that there should be more investment in data collection for those parameters that are thought to differ most from place to place. Owing to the similarities between Central and Eastern Europe countries in health care systems, clinical practice patterns and economic indicators, they may be able to develop partnerships to develop relevant regional databases and registries.

  16. ABO-Incompatible Adult Living Donor Liver Transplantation Under the Desensitization Protocol With Rituximab.

    Science.gov (United States)

    Song, G-W; Lee, S-G; Hwang, S; Kim, K-H; Ahn, C-S; Moon, D-B; Ha, T-Y; Jung, D-H; Park, G-C; Kim, W-J; Sin, M-H; Yoon, Y-I; Kang, W-H; Kim, S-H; Tak, E-Y

    2016-01-01

    ABO incompatibility is no longer considered a contraindication for adult living donor liver transplantation (ALDLT) due to various strategies to overcome the ABO blood group barrier. We report the largest single-center experience of ABO-incompatible (ABOi) ALDLT in 235 adult patients. The desensitization protocol included a single dose of rituximab and total plasma exchange. In addition, local graft infusion therapy, cyclophosphamide, or splenectomy was used for a certain time period, but these treatments were eventually discontinued due to adverse events. There were three cases (1.3%) of in-hospital mortality. The cumulative 3-year graft and patient survival rates were 89.2% and 92.3%, respectively, and were comparable to those of the ABO-compatible group (n = 1301). Despite promising survival outcomes, 17 patients (7.2%) experienced antibody-mediated rejection that manifested as diffuse intrahepatic biliary stricture; six cases required retransplantation, and three patients died. ABOi ALDLT is a feasible method for expanding a living liver donor pool, but the efficacy of the desensitization protocol in targeting B cell immunity should be optimized. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  17. Controversies on Rituximab Therapy in Sjögren Syndrome-Associated Lymphoproliferation

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    Luca Quartuccio

    2009-01-01

    Full Text Available Sjögren's syndrome (SS is a systemic autoimmune disease characterized by chronic inflammation of salivary and lachrymal glands, and frequently accompanied by systemic symptoms. A subgroup of SS patients develops malignant B cell non-Hodgkin's lymphoma (NHL, usually of the mucosa-associated lymphoid tissue (MALT type and very often located in the major salivary glands. Currently, there is a lack of evidence-based intervention therapy which may influence SS-related chronic inflammation and lymphoproliferation. B cells are involved in the pathogenesis of SS, and B cell downregulation may lead to a decrease of disease activity. Rituximab (RTX, a chimeric monoclonal antibody targeting the CD20 antigen on the B cell surface, has been successfully investigated in other autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, ANCA-associated vasculitis, and mixed cryoglobulinemic syndrome. Preliminary experiences of RTX therapy in SS patients with or without a lymphoproliferative disorder suggest that SS patients with more residual exocrine gland function might better benefit from RTX. Efficacy of RTX in SS-associated B-cell lymphoma, mainly in low-grade salivary gland lymphomas, remains an open issue.

  18. Phase II Trial of Adjuvant Pelvic Radiation “Sandwiched” Between Combination Paclitaxel and Carboplatin in Women with Uterine Papillary Serous Carcinoma

    Science.gov (United States)

    Einstein, Mark H.; Frimer, Marina; Kuo, Dennis Y-S; Reimers, Laura L.; Mehta, Keyur; Mutyala, Subhakar; Huang, Gloria S.; Hou, June Y.; Goldberg, Gary L.

    2013-01-01

    Objective To evaluate the safety and survival in women treated with adjuvant pelvic radiation “sandwiched” between six cycles of paclitaxel and carboplatin chemotherapy with completely resected UPSC. Methods Surgically staged women with UPSC (FIGO stage 1-4) and no visible residual disease were enrolled. Treatment involved paclitaxel (175 mg/m2) and carboplatin (AUC=6.0-7.5) every 21 days for 3 doses, followed by radiation therapy (RT), followed by an additional 3 cycles of paclitaxel and carboplatin (AUC=5-6). Survival analysis, using Kaplan-Meier methods, was performed on patients who completed at least 3 cycles of chemotherapy and RT. Results A total of 81 patients were enrolled, of which 72 patients completed the first 3 cycles of chemotherapy followed by prescribed RT. Median age was 67 years (range: 43–82 years). 59/72 (82%) had disease confined to the uterus and 13/72 (18%) had completely resected extra-uterine disease (stage 3&4). 65 (83%) completed the protocol. Overall PFS and OS for combined stage 1&2 patients was 65.5±3.6 months and 76.5±4.3 months, respectively. PFS and OS for combined stage 3&4 patients was 25.8±3.0 and 35.9±5.3 months, respectively. Three-year % survival probability for stage 1&2 patients was 84% and for stage 3&4 patients was 50%. Of the 435 chemotherapy cycles administered, there were 11(2.5%) G3/G4 non-hematologic toxicities. 26(6.0%) cycles had dose reductions and 37(8.5%) had dose delays. Conclusions Compared to prior studies of single modality adjuvant therapy, RT “sandwiched” between paclitaxel and carboplatin chemotherapy is well-tolerated and highly efficacious in women with completely resected UPSC. PMID:22035806

  19. Phase i study of 'dose-dense' pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma

    International Nuclear Information System (INIS)

    Shen, Xinglei; DeNittis, Albert; Werner-Wasik, Maria; Axelrod, Rita; Gilman, Paul; Meyer, Thomas; Treat, Joseph; Curran, Walter J; Machtay, Mitchell

    2011-01-01

    This phase I study investigates the feasibility of carboplatin plus dose-dense (q2-week) pemetrexed given concurrently with radiotherapy (XRT) for locally advanced and oligometastatic non-small cell lung cancer (NSCLC). Eligible patients had Stage III or IV (oligometastatic) NSCLC. Patients received XRT to 63 Gy in standard fractionation. Patients received concurrent carboplatin (AUC = 6) during weeks 1 and 5 of XRT, and pemetrexed during weeks 1, 3, 5, and 7 of XRT. The starting dose level (level 1) of pemetrexed was 300 mg/m 2 . Following the finding of dose limiting toxicity (DLT) in dose level 1, an amended dose level (level 1A) continued pemetrexed at 300 mg/m 2 , but with involved field radiation instead of extended nodal irradiation. Consolidation consisted of carboplatin (AUC = 6) and pemetrexed (500 mg/m 2 ) q3 weeks × 2 -3 cycles. Eighteen patients were enrolled. Fourteen patients are evaluable for toxicity analysis. Of the initial 6 patients treated on dose level 1, two experienced DLTs (one grade 4 sepsis, one prolonged grade 3 esophagitis). There was one DLT (grade 5 pneumonitis) in the 8 patients treated on dose level 1A. In 16 patients evaluable for response (4 with oligometastatic stage IV disease and 12 with stage III disease), the median follow-up time is 17.8 months. Thirteen of 16 patients had in field local regional response. The actuarial median survival time was 28.6 months in all patients and 34.7 months (estimated) in stage III patients. Concurrent carboplatin with dose-dense (q2week) pemetrexed at 300 mg/m 2 with involved field XRT is feasible and encouraging in patients with locally advanced and oligometastatic NSCLC.

  20. Oxaliplatin-Based Doublets Versus Cisplatin or Carboplatin-Based Doublets in the First-Line Treatment of Advanced Nonsmall Cell Lung Cancer.

    Science.gov (United States)

    Yu, Jing; Xiao, Jing; Yang, Yifan; Cao, Bangwei

    2015-07-01

    The efficacy and toxicity of oxaliplatin-based versus carboplatin/cisplatin-based doublets in patients with previously untreated nonsmall cell lung cancer (NSCLC) have been compared.We searched published randomized controlled trials of oxaliplatin-based or carboplatin/cisplatin-based medications for NSCLC. A fixed effect model was used to analyze outcomes which were expressed as the hazard ratio for overall survival (OS) and time-to-progression (TTP), relative risk, overall response rate (ORR), disease control rate (DCR), 1-year survival, and the odds ratios for toxicity were pooled.Eight studies involving 1047 patients were included. ORR tended to favor carboplatin/cisplatin but the effect was not significantly different compared with oxaliplatin doublets (P = 0.05). The effects of OS, TTP, DCR, and 1-year survival between the 2 regimens were comparable. Oxaliplatin doublets caused less grade 3/4 leukocytopenia and neutropenia. Grades 3 to 4 nonhematological toxicities and grades 3 to 4 hematological toxicities showed little difference between oxaliplatin doublets and carboplatin/cisplatin doublets.Meta-analysis shows that the efficacy of oxaliplatin doublets is similar to that of other currently used platinum doublets. The lack of significant differences in the statistic analysis does not preclude genuine differences in clinical efficacy, because higher diversities between the studies covered differences between the 2 groups in each study. Oxaliplatin combined with a third-generation agent should be considered for use as alternative chemotherapy in patients who cannot tolerate conventional platinum-based regimens because the toxicity profile is much more favorable.

  1. Usefulness of antiemetic therapy with aprepitant, palonosetron, and dexamethasone for lung cancer patients on cisplatin-based or carboplatin-based chemotherapy.

    Science.gov (United States)

    Kitazaki, Takeshi; Fukuda, Yuichi; Fukahori, Susumu; Oyanagi, Kazuhiko; Soda, Hiroshi; Nakamura, Yoichi; Kohno, Shigeru

    2015-01-01

    The purpose of the study is to investigate the usefulness of the triplet regimen comprising aprepitant, palonosetron, and dexamethasone in patients treated with highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC). Patients with lung cancer (aged 65.8 ± 8.4 years) who received carboplatin-based MEC and those treated with cisplatin-based HEC were enrolled. The antiemetic regimen for both types of chemotherapy consisted of aprepitant, palonosetron, and dexamethasone based on the May 2010 guidelines prepared by the Japan Society of Clinical Oncology. The incidence of chemotherapy-induced nausea and vomiting (CINV) and the use of salvage treatment were assessed. The primary endpoints were the percentage of patients with a complete response (CR: no nausea and no salvage treatment) during the entire study period (5 days) after chemotherapy, during the acute phase (day 1), and during the delayed phase (days 2-5). CR rates for the entire period were 86 and 71% in patients receiving carboplatin-based and cisplatin-based chemotherapy, respectively. CR rates were respectively 98 and 100% in the acute phase versus 87 and 71% in the delayed phase. Most of the patients could ingest food throughout the entire period after chemotherapy. Assessment of various risk factors for acute and delayed CINV (gender, age, prior vomiting due to antineoplastic therapy, prior experience of motion sickness, and history of drinking) revealed no significant influence of these factors on the CR rate for the entire period in patients receiving either carboplatin-based or cisplatin-based chemotherapy. The present triple therapy can be recommended for supporting both carboplatin-based and cisplatin-based chemotherapy regimens.

  2. Phase i study of 'dose-dense' pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma

    Directory of Open Access Journals (Sweden)

    Treat Joseph

    2011-02-01

    Full Text Available Abstract Background This phase I study investigates the feasibility of carboplatin plus dose-dense (q2-week pemetrexed given concurrently with radiotherapy (XRT for locally advanced and oligometastatic non-small cell lung cancer (NSCLC. Methods Eligible patients had Stage III or IV (oligometastatic NSCLC. Patients received XRT to 63 Gy in standard fractionation. Patients received concurrent carboplatin (AUC = 6 during weeks 1 and 5 of XRT, and pemetrexed during weeks 1, 3, 5, and 7 of XRT. The starting dose level (level 1 of pemetrexed was 300 mg/m2. Following the finding of dose limiting toxicity (DLT in dose level 1, an amended dose level (level 1A continued pemetrexed at 300 mg/m2, but with involved field radiation instead of extended nodal irradiation. Consolidation consisted of carboplatin (AUC = 6 and pemetrexed (500 mg/m2 q3 weeks × 2 -3 cycles. Results Eighteen patients were enrolled. Fourteen patients are evaluable for toxicity analysis. Of the initial 6 patients treated on dose level 1, two experienced DLTs (one grade 4 sepsis, one prolonged grade 3 esophagitis. There was one DLT (grade 5 pneumonitis in the 8 patients treated on dose level 1A. In 16 patients evaluable for response (4 with oligometastatic stage IV disease and 12 with stage III disease, the median follow-up time is 17.8 months. Thirteen of 16 patients had in field local regional response. The actuarial median survival time was 28.6 months in all patients and 34.7 months (estimated in stage III patients. Conclusions Concurrent carboplatin with dose-dense (q2week pemetrexed at 300 mg/m2 with involved field XRT is feasible and encouraging in patients with locally advanced and oligometastatic NSCLC. Trial Registration ClinicalTrials.gov NCT00330044

  3. Outpatient rapid 4-step desensitization for gynecologic oncology patients with mild to low-risk, moderate hypersensitivity reactions to carboplatin/cisplatin.

    Science.gov (United States)

    Li, Quan; Cohn, David; Waller, Allyson; Backes, Floor; Copeland, Larry; Fowler, Jeffrey; Salani, Ritu; O'Malley, David

    2014-10-01

    The primary objective of this study is to assess the efficacy and safety of an outpatient, 4-step, one-solution desensitization protocol in gynecologic oncology patients with history of mild to low-risk, moderate hypersensitivity reactions (HSRs) to platinums (carboplatin and cisplatin). This was a single institutional retrospective review. Gynecologic oncology patients with a documented history of mild or low-risk, moderate immediate HSRs to carboplatin/cisplatin and continued treatment with 4-step, one-solution desensitization protocols in the outpatient infusion center were included. Patients with delayed HSRs or immediate high-risk, moderate or severe HSRs were excluded. The primary end point was the rate of successful administrations of each course of platinums. From January 2011 to June 2013, eighteen eligible patients were evaluated for outpatient 4-step, one-solution desensitization. Thirteen patients had a history of HSRs to carboplatin and 5 with HSRs to cisplatin. All of 18 patients successfully completed 94 (98.9%) of 95 desensitization courses in the outpatient infusion center. Eight of 8 (100%) patients with initial mild HSRs completed 29/29 (100%) desensitization courses, and 9 of 10 (90%) of patients with initial moderate HSRs completed 65/66 (94%) desensitization courses. In total, 65/95 (68%) desensitizations resulted in no breakthrough reactions, and mild, moderate and severe breakthrough reactions were seen in 19%, 12% and 1% desensitizations, respectively. No patients were hospitalized during desensitization. The outpatient rapid, 4-step, one-solution desensitization protocol was effective and appeared safe among gynecologic oncology patients who experienced mild to low-risk, moderate HSRs to carboplatin/cisplatin. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Phase I study of combination of vorinostat, carboplatin, and gemcitabine in women with recurrent, platinum-sensitive epithelial ovarian, fallopian tube, or peritoneal cancer.

    Science.gov (United States)

    Matulonis, Ursula; Berlin, Suzanne; Lee, Hang; Whalen, Christin; Obermayer, Elizabeth; Penson, Richard; Liu, Joyce; Campos, Susana; Krasner, Carolyn; Horowitz, Neil

    2015-08-01

    Combining histone deacetylase inhibitors and chemotherapy is synergistic. This phase I study combined escalating vorinostat doses with constant doses of carboplatin and gemcitabine for the treatment of recurrent platinum-sensitive ovarian cancer. The objectives of this study were to determine the maximally tolerated dose of this combination; secondary objectives included preliminary response rate of this regimen and toxicity profile. Fifteen patients with relapsed ovarian cancer were enrolled into this phase I study. Doses of carboplatin and gemcitabine were AUC 4 on day 1 and 1000 mg/m(2) on days 1 and 8, respectively; cycles were administered every 21 days. Vorinostat was tested using four different schedules. The first dose level (DL A) tested vorinostat as daily oral dosing from days 1 to 14. DL B tested twice daily (BID) vorinostat dosing on days 1-3 and 8-10. DL C tested BID vorinostat dosing on days 1, 2, 8, and 9, starting vorinostat 1 day prior to initiation of carboplatin and gemcitabine, and DL D tested vorinostat on days 1 and 2 with chemotherapy starting on day 2. All four DLs tested resulted in dose-limiting toxicities, and no MTD was determined. Toxicities were mostly hematologic. Seven patients were evaluable for RECIST assessment, and six of them had partial responses (PR) via RECIST. Combination of carboplatin, gemcitabine, and vorinostat has activity in relapsed platinum-sensitive ovarian cancer, but was difficult to combine because of hematologic toxicities in this phase I study. No maximally tolerated dose was found, and the study was terminated early.

  5. Simultaneous quantification of preactivated ifosfamide derivatives and of 4-hydroxyifosfamide by high performance liquid chromatography-tandem mass spectrometry in mouse plasma and its application to a pharmacokinetic study.

    Science.gov (United States)

    Deroussent, Alain; Skarbek, Charles; Maury, Adeline; Chapuis, Hubert; Daudigeos-Dubus, Estelle; Le Dret, Ludivine; Durand, Sylvère; Couvreur, Patrick; Desmaële, Didier; Paci, Angelo

    2015-06-15

    The antitumor drug, ifosfamide (IFO), requires activation by cytochrome P450 (CYP) to form the active metabolite, 4-hydroxyisfosfamide (4-OHIFO), leading to toxic by-products at high dose. In order to overcome these drawbacks, preactivated ifosfamide derivatives (RXIFO) were designed to release 4-OHIFO without CYP involvement. A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for the simultaneous quantification of 4-OHIFO, IFO and four derivatives RXIFO in mouse plasma using multiple reaction monitoring. Because of its instability in plasma, 4-OHIFO was immediately converted to the semi-carbazone derivative, 4-OHIFO-SCZ. For the six analytes, the calibration curves were linear from 20 to 5000ng/mL in 50μL plasma and the lower limit of quantitation was determined at 20ng/mL with accuracies within ±10% of nominal and precisions less than 12%. Their recoveries ranged from 62 to 96% by using liquid-liquid extraction. With an improved assay sensitivity compared to analogues, the derivative 4-OHIFO-SCZ was stable in plasma at 4°C for 24h and at -20°C for three months. For all compounds, the assay was validated with accuracies within ±13% and precisions less than 15%. This method was applied to a comparative pharmacokinetic study of 4-OHIFO from IFO and three derivatives RXIFO in mice. This active metabolite was produced by some of the novel conjugates with good pharmacokinetic properties. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Gemcitabina e ifosfamida no tratamento do linfoma de Hodgkin refratário ou recidivado após múltiplas terapias Gemcitabine and ifosfamide in the treatment of Hodgkin's lymphoma refractory to or relapsed after multiple therapies

    Directory of Open Access Journals (Sweden)

    Luís Fernando Pracchia

    2007-12-01

    Full Text Available Patients with Hodgkin's lymphoma relapsed after or refractory to multiple therapies (rHL have a dismal prognosis. Monotherapy with gemcitabine can promote an overall response rate of about 40% in these patients and its association with alkylating agents can provide better results. We retrospectively evaluated 17 rHL cases. All were treated with the combination of gemcitabine (1.0 g/m²; D1 and D8 and ifosfamide (1.0 g/m²; D1 to D5 in a 21-day cycle. Treatment response was evaluated according to the Cotswolds criteria. Toxicity was evaluated according to WHO criteria. The median age of all patients was 34 years (18-53. Nine of them (53% were men and eight (47% had Stage III/IV. The median number of previous treatments was 2 (2-3; two patients had already been treated with autologous stem cell transplant. Overall response rate to the combined regimen was 62.5% (95% CI = 38.8% - 86.2% and the median progression-free survival was 15 months (95% CI = 4 - 24 months. Fifty-six cycles were evaluated for toxicity. The most frequent toxicities observed by cycle were: hepatic Grade I/II in 48.2% of the cycles and Grade III/IV in 1.8%; anemia Grade I/II in 45%; neutropenia Grade I/II in 36% and Grade III/IV 16%. Grade III/IV renal toxicity on any degree of haematuria were not observed. Combined therapy with Gemcitabine and Ifosfamide promoted responses in more than half of the evaluated patients with an acceptable toxicity profile.

  7. The safety and efficacy of carboplatin plus nanoparticle albumin-bound paclitaxel in the treatment of non-small cell lung cancer patients with interstitial lung disease.

    Science.gov (United States)

    Yasuda, Yuichiro; Hattori, Yoshihiro; Tohnai, Rie; Ito, Shoichi; Kawa, Yoshitaka; Kono, Yuko; Urata, Yoshiko; Nogami, Munenobu; Takenaka, Daisuke; Negoro, Shunichi; Satouchi, Miyako

    2018-01-01

    The optimal chemotherapy regimen for non-small cell lung cancer patients with interstitial lung disease is unclear. We therefore investigated the safety and efficacy of carboplatin plus nab-paclitaxel as a first-line regimen for non-small cell lung cancer in patients with interstitial lung disease. We retrospectively reviewed advanced non-small cell lung cancer patients with interstitial lung disease who received carboplatin plus nab-paclitaxel as a first-line chemotherapy regimen at Hyogo Cancer Center between February 2013 and August 2016. interstitial lung disease was diagnosed according to the findings of pretreatment chest high-resolution computed tomography. Twelve patients were included (male, n = 11; female, n = 1). The overall response rate was 67% and the disease control rate was 100%. The median progression free survival was 5.1 months (95% CI: 2.9-8.3 months) and the median overall survival was 14.9 months (95% CI: 4.8-not reached). A chemotherapy-related acute exacerbation of interstitial lung disease was observed in one patient; the extent of this event was Grade 2. There were no treatment-related deaths. Carboplatin plus nab-paclitaxel, as a first-line chemotherapy regimen for non-small cell lung cancer, showed favorable efficacy and safety in patients with preexisting interstitial lung disease. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  8. Sustained platelet-sparing effect of weekly low dose paclitaxel allows effective, tolerable delivery of extended dose dense weekly carboplatin in platinum resistant/refractory epithelial ovarian cancer

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    Blagden Sarah

    2011-07-01

    Full Text Available Abstract Background Platinum agents have shown demonstrable activity in the treatment of patients with platinum resistant, recurrent ovarian cancer when delivered in a "dose-dense" fashion. However, the development of thrombocytopenia limits the weekly administration of carboplatin to no greater than AUC 2. Paclitaxel has a well-described platelet sparing effect however its use to explicitly provide thromboprotection in the context of dose dense carboplatin has not been explored. Methods We treated seven patients with platinum resistant ovarian cancer who had previously received paclitaxel or who had developed significant peripheral neuropathy precluding the use of further full dose weekly paclitaxel. Results We were able to deliver carboplatin AUC 3 and paclitaxel 20 mg/m2 with no thrombocytopenia or worsening of neuropathic side-effects, and with good activity. Conclusions We conclude that this regimen may be feasible and active, and could be formally developed as a "platinum-focussed dose-dense scaffold" into which targeted therapies that reverse platinum resistance can be incorporated, and merits further evaluation.

  9. Randomized clinical trial of post-operative radiotherapy versus concomitant carboplatin and radiotherapy for head and neck cancers with lymph node involvement

    International Nuclear Information System (INIS)

    Racadot, Severine; Mercier, Mariette; Dussart, Sophie; Dessard-Diana, Bernadette; Bensadoun, Rene-Jean; Martin, Michel; Malaurie, Emmanuelle; Favrel, Veronique; Housset, Martin; Durdux, Catherine; Journel, Catherine; Calais, Gilles; Huet, Jocelyne; Pillet, Gerard; Hennequin, Christophe; Haddad, Elias; Diana, Christian; Blaska-Jaulerry, Brigitte; Henry-Amar, Michel; Gehanno, Pierre

    2008-01-01

    Background and purpose: Post-operative radiotherapy is indicated for the treatment of head and neck cancers. In vitro, chemotherapy potentiates the cytotoxic effects of radiation. We report the results of a randomized trial testing post-operative radiotherapy alone versus concomitant carboplatin and radiotherapy for head and neck cancers with lymph node involvement. Materials and methods: The study involved patients undergoing curative-intent surgery for head and neck cancers with histological evidence of lymph node involvement. Patients were randomly assigned to receive radiotherapy alone (54-72 Gy, 30-40 fractions, 6-8 weeks) or identical treatment plus concomitant Carboplatin (50 mg/m 2 administered by IV infusion twice weekly). Results: Between February 1994 and June 2002, 144 patients were included. With a median follow-up of 106 months (95% confidence interval (CI) [92-119]), the 2-year rate of loco-regional control was 73% (95% CI: 0.61-0.84) in the combined treatment group and 68% (95% CI: 0.57-0.80) in the radiotherapy group (p = 0.26). Overall survival did not differ significantly between groups (hazard ratio for death, 1.05; 95% CI: 0.69-1.60; p = 0.81). Conclusions: Twice-weekly administration of carboplatin concomitant to post-operative radiotherapy did not improve local control or overall survival rates in this population of patients with node-positive head and neck cancers

  10. Randomized Phase II trial of paclitaxel and carboplatin followed by gemcitabine switch-maintenance therapy versus gemcitabine and carboplatin followed by gemcitabine continuation-maintenance therapy in previously untreated advanced non-small cell lung cancer

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    Minami Seigo

    2013-01-01

    Full Text Available Abstract Background In recent years, maintenance chemotherapy is increasingly being recognized as a new treatment strategy to improve the outcome of advanced non-small cell lung cancer (NSCLC. However, the optimal maintenance strategy is still controversial. Gemcitabine is a promising candidate for single-agent maintenance therapy because of little toxicity and good tolerability. We have conducted a randomized phase II study to evaluate the validity of single-agent maintenance chemotherapy of gemcitabine and to compare continuation- and switch-maintenance. Methods Chemonaïve patients with stage IIIB/IV NSCLC were randomly assigned 1:1 to either arm A or B. Patients received paclitaxel (200 mg/m2, day 1 plus carboplatin (AUC 6 mg/mL/min, day 1 every 3 weeks in arm A, or gemcitabine (1000 mg/m2, days 1 and 8 plus carboplatin (AUC 5 mg/mL/min, day1 every 3 weeks in arm B. Non-progressive patients following 3 cycles of induction chemotherapy received maintenance gemcitabine (1000 mg/m2, days 1 and 8 every 3 weeks. (Trial registration: UMIN000008252 Results The study was stopped because of delayed accrual at interim analysis. Of the randomly assigned 50 patients, 49 except for one in arm B were evaluable. Median progression-free survival (PFS was 4.6 months for arm A vs. 3.5 months for arm B (HR = 1.03; 95% CI, 0.45–2.27; p = 0.95 and median overall survival (OS was 15.0 months for arm A vs. 14.8 months for arm B (HR = 0.79; 95% CI, 0.40–1.51; p = 0.60, showing no difference between the two arms. The response rate, disease control rate, and the transit rate to maintenance phase were 36.0% (9/25, 64.0% (16/25, and 48% (12/25 for arm A vs. 16.7% (4/24, 50.0% (12/24, and 33% (8/24 for arm B, which were also statistically similar between the two arms (p = 0.13, p = 0.32, and p = 0.30, respectively. Both induction regimens were tolerable, except that more patients experienced peripheral neuropathy in arm A. Toxicities during

  11. Analysis of platinum content in biodegradable carboplatin-impregnated beads and retrospective assessment of tolerability for intralesional use of the beads in dogs following excision of subcutaneous sarcomas: 29 cases (2011-2014).

    Science.gov (United States)

    Hess, Theresa A; Drinkhouse, Macy E; Prey, Joshua D; Miller, Jonathan M; Fettig, Arthur A; Carberry, Carol A; Brenn, Stephen H; Bailey, Dennis B

    2018-02-15

    OBJECTIVE To evaluate platinum content in biodegradable carboplatin-impregnated beads and retrospectively assess tolerability and outcome data for dogs treated by intralesional placement of such beads following surgical excision of subcutaneous sarcomas. DESIGN Evaluation study and retrospective case series. SAMPLE 9 carboplatin-impregnated beads and 29 client-owned dogs. PROCEDURES Platinum content in 9 carboplatin-impregnated beads from 3 lots was measured by spectrophotometry, and calculated carboplatin content was compared with the labeled content. Medical records were searched to identify dogs with subcutaneous sarcomas for which treatment included placement of carboplatin-impregnated beads between 2011 and 2014. Signalment, tumor characteristics, surgical and histologic data, adverse events, and local recurrences were recorded. Associations between variables of interest and adverse events or local disease-free interval were analyzed. RESULTS In vitro analysis identified a mean ± SD platinum content of 5.38 ± 0.97 mg/bead. Calculated carboplatin content (10.24 ± 1.84 mg/bead) was significantly greater than the labeled amount (4.6 mg/bead). Bead weight and total platinum content differed significantly among lots, but platinum content per bead weight did not. Mild-to-moderate local adverse events were reported for 11 of 29 tumors; all resolved without additional surgery. No dogs had signs of systemic toxicosis. Overall local disease-free rates 1, 2, and 3 years after surgery were 70%, 70%, and 58%, respectively, as determined by Kaplan-Meier analysis. CONCLUSIONS AND CLINICAL RELEVANCE Carboplatin-impregnated beads were well tolerated; however, results of in vitro tests indicated that caution is needed because of manufacturing inconsistencies.

  12. Paclitaxel/carboplatin with or without sorafenib in the first-line treatment of patients with stage III/IV epithelial ovarian cancer: a randomized phase II study of the Sarah Cannon Research Institute

    International Nuclear Information System (INIS)

    Hainsworth, John D; Thompson, Dana S; Bismayer, John A; Gian, Victor G; Merritt, William M; Whorf, Robert C; Finney, Lindsey H; Dudley, B Stephens

    2015-01-01

    This trial compared the efficacy and toxicity of standard first-line treatment with paclitaxel/carboplatin versus paclitaxel/carboplatin plus sorafenib in patients with advanced ovarian carcinoma. Patients with stage 3 or 4 epithelial ovarian cancer with residual measurable disease or elevated CA-125 levels after maximal surgical cytoreduction were randomized (1:1) to receive treatment with paclitaxel (175 mg/m 2 , 3 h infusion, day 1) and carboplatin (AUC 6.0, IV, day 1) with or without sorafenib 400 mg orally twice daily (PO BID). Patients were reevaluated for response after completing 6 weeks of treatment (two cycles); responding or stable patients received six cycles of paclitaxel/carboplatin. Patients receiving the sorafenib-containing regimen continued sorafenib (400 PO BID) for a total of 52 weeks. Eighty-five patients were randomized and received treatment.Efficacy was similar for patients receiving paclitaxel/carboplatin/sorafenib versus paclitaxel/carboplatin: overall response rates 69% versus 74%; median progression-free survival 15.4 versus 16.3 months; 2 year survival 76% versus 81%. The addition of sorafenib added substantially to the toxicity of the regimen; rash, hand–foot syndrome, mucositis, and hypertension were significantly more common in patients treated with sorafenib. The addition of sorafenib to standard paclitaxel/carboplatin did not improve efficacy and substantially increased toxicity in the first-line treatment of advanced epithelial ovarian cancer. Based on evidence from this study and other completed trials, sorafenib is unlikely to have a role in the treatment of ovarian cancer

  13. Cyclophosphamide-refractory scleroderma-associated interstitial lung disease: remarkable clinical and radiological response to a single course of rituximab combined with high-dose corticosteroids.

    LENUS (Irish Health Repository)

    Haroon, Muhammad

    2011-10-01

    We would like to report our experience of using rituximab in cyclophosphamide refractory, rapidly progressive interstitial lung disease (ILD) in a patient with limited scleroderma. A 40-year-old man presented with 10-week history of inflammatory polyarthritis, which responded to a short course of oral corticosteroids. However, 3 weeks later, he developed new onset of exertional dyspnoea. High-resolution CT of the thorax was suggestive of early ILD. Surgical lung biopsy showed features of fibrotic non-specific interstitial pneumonia. He was diagnosed with scleroderma on the basis of: presence of anticentromere antibodies, Raynaud\\'s phenomenon, pulmonary fibrosis, digital oedema and hypomotility along with a dilated oesophagus. He was treated aggressively with pulse doses of corticosteroids and cyclophosphamide; however, his ILD continued to deteriorate. At this stage, he received rituximab (two pulses of 1 g each), which led to a gradual clinical improvement. Now, 12 months since his rituximab infusion, he walks 2 miles daily without any exertional dyspnoea.

  14. Randomized Study of Concurrent Carboplatin, Paclitaxel, and Radiotherapy with or Without Prior Induction Chemotherapy in Patients with Locally Advanced Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Gouda, Y.S.; Eldeeb, N.A.; Omar, A.M.; Kohail, H.M.; El-Geneidy, M.M.; Elkerm, Y.M.

    2006-01-01

    Background: Multiple concepts of combined modality therapy for locally advanced inoperable non-small cell lung cancer have been investigated. These include induction chemotherapy, concomitant chemo-radiotherapy, and radiation only. To date, combined modality therapy specially the use of concomitant chemo-radiotherapy has led to promising results and was shown to be superior to radiotherapy alone in phase II studies. However the optimum chemo-therapeutic regimen to be used as well as the benefit of induction chemotherapy before concomitant chemo-radiotherapy are yet to be determined. Based on these observations, we investigated the use of paclitaxel and carboplatin concomitantly with radiotherapy and the benefit of prior two cycles induction chemotherapy. Materials and Methods: In this trial 50 patients with locally advanced inoperable non small cell lung cancer, good performance status and minimal weight loss have been randomized into 3 groups each of 20 patients. Group A received induction 2 cycles paclitaxel (175 mg/m 2 ) and carboplatin (AUC 6) on day I and 28 th followed by concomitant paclitaxel (45 mg/m 2 ) and carboplatin (AUC 2) weekly with radiotherapy. Group B received concomitant carboplatin, paclitaxel (same doses as in group A) and radiotherapy with no prior induction chemotherapy. Group C received only radiotherapy to a total dose of 60 Gy in conventional fractionation. Results: A total of 60 patients were enrolled in this study between 1998 and 2000. Pretreatment characteristics, including age, gender, performance status, histological features and stage were comparable in each group. The incidence of oesophagi tis was significantly higher in group A and B than in group C (ρ=0.023). Hematological toxicities was also significantly higher in group A and B than in group C (ρ=0.003). The response rate was significantly higher in group A and B than in group C (75%,79%, and 40% respectively) (ρ =0.020). The time to in-field progresion was significantly

  15. Radioimmunotherapy in refractory b-cell nonhodgkins lymphoma with I-131-labeled chimeric anti cd-20 c2b8 (I-131 rituximab): preliminary result

    International Nuclear Information System (INIS)

    Kang, Hye Jin; Park, Yeon Hee; Kim, Sung Eun and others

    2005-01-01

    Recently, the native chimeric human-mouse anti CD-20 antibody IDEC-C2B8 (Rituximab) has been widely applied in NHL. This ongoing phase study was to evaluate whether radioimmunotherapy (RIT) with I-131 rituximab is effective in refractory B-cell NHL. Inclusion criteria were as follows: B-cell NHL with relapsed or refractory to primary standard therapy, measurable disease, adequate hematologic, renal, and hepatic function, informed consent. The rituximab (Mabthera, Roach) was radiolabeled with iodine-131(I-131) using a modified chloramine T method with high radiochemical purity (95%) and preservation of immuno-reactivity. All patients received loading doses of unlabeled rituximab (median, 40 mg: range, 20∼70 mg) immediately prior to administration of therapeutic dose (51.4∼152.2 MBq/kg), and then underwent gamma camera scan. 11 patients were enrolled (4 low-grade B-cell NHL, 7 DLBCL, median age 63 years). Patients had received a median of three prior chemotherapy regimens. The objective response rate was 36.4% (1 CR, 3 PRs). These all responses were observed in low-grade B-cell NHL, except one with DLBCL. Adverse events were primarily hematologic toxicities; the incidence of grade 3/4 neutropenia, thrombocytopenia, and anemia was 27.3%, 45.5%, and 18.2%, respectively. The treatment-related mortality was observed in one patient, who had been previously treated with high-dose chemotherapy plus TBI with autologous stem cell transplantation. RIT with I-131 rituximab seems to be effective tolerable in refractory low-grade B-cell NHL, although modest activity in refractory DLBCL. Further studies to define the efficacy of I-131 rituximab in DLBCL are warranted

  16. Rituximab Extended Schedule or Re-Treatment Trial for Low–Tumor Burden Follicular Lymphoma: Eastern Cooperative Oncology Group Protocol E4402

    Science.gov (United States)

    Kahl, Brad S.; Hong, Fangxin; Williams, Michael E.; Gascoyne, Randy D.; Wagner, Lynne I.; Krauss, John C.; Habermann, Thomas M.; Swinnen, Lode J.; Schuster, Stephen J.; Peterson, Christopher G.; Sborov, Mark D.; Martin, S. Eric; Weiss, Matthias; Ehmann, W. Christopher; Horning, Sandra J.

    2014-01-01

    Purpose In low–tumor burden follicular lymphoma (FL), maintenance rituximab (MR) has been shown to improve progression-free survival when compared with observation. It is not known whether MR provides superior long-term disease control compared with re-treatment rituximab (RR) administered on an as-needed basis. E4402 (RESORT) was a randomized clinical trial designed to compare MR against RR. Patients and Methods Eligible patients with previously untreated low–tumor burden FL received four doses of rituximab, and responding patients were randomly assigned to either RR or MR. Patients receiving RR were eligible for re-treatment at each disease progression until treatment failure. Patients assigned to MR received a single dose of rituximab every 3 months until treatment failure. The primary end point was time to treatment failure. Secondary end points included time to first cytotoxic therapy, toxicity, and health-related quality of life (HRQOL). Results A total of 289 patients were randomly assigned to RR or MR. With a median follow-up of 4.5 years, the estimated median time to treatment failure was 3.9 years for patients receiving RR and 4.3 years for those receiving MR (P = .54). Three-year freedom from cytotoxic therapy was 84% for those receiving RR and 95% for those receiving MR (P = .03). The median number of rituximab doses was four patients receiving RR and 18 for those receiving MR. There was no difference in HRQOL. Grade 3 to 4 toxicities were infrequent in both arms. Conclusion In low–tumor burden FL, a re-treatment strategy uses less rituximab while providing disease control comparable to that achieved with a maintenance strategy. PMID:25154829

  17. Radioimmunotherapy in refractory b-cell nonhodgkins lymphoma with I-131-labeled chimeric anti cd-20 c2b8 (I-131 rituximab): preliminary result

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Hye Jin; Park, Yeon Hee; Kim, Sung Eun and others [Korea University Medical School, Seoul (Korea, Republic of)

    2005-07-01

    Recently, the native chimeric human-mouse anti CD-20 antibody IDEC-C2B8 (Rituximab) has been widely applied in NHL. This ongoing phase study was to evaluate whether radioimmunotherapy (RIT) with I-131 rituximab is effective in refractory B-cell NHL. Inclusion criteria were as follows: B-cell NHL with relapsed or refractory to primary standard therapy, measurable disease, adequate hematologic, renal, and hepatic function, informed consent. The rituximab (Mabthera, Roach) was radiolabeled with iodine-131(I-131) using a modified chloramine T method with high radiochemical purity (95%) and preservation of immuno-reactivity. All patients received loading doses of unlabeled rituximab (median, 40 mg: range, 20{approx}70 mg) immediately prior to administration of therapeutic dose (51.4{approx}152.2 MBq/kg), and then underwent gamma camera scan. 11 patients were enrolled (4 low-grade B-cell NHL, 7 DLBCL, median age 63 years). Patients had received a median of three prior chemotherapy regimens. The objective response rate was 36.4% (1 CR, 3 PRs). These all responses were observed in low-grade B-cell NHL, except one with DLBCL. Adverse events were primarily hematologic toxicities; the incidence of grade 3/4 neutropenia, thrombocytopenia, and anemia was 27.3%, 45.5%, and 18.2%, respectively. The treatment-related mortality was observed in one patient, who had been previously treated with high-dose chemotherapy plus TBI with autologous stem cell transplantation. RIT with I-131 rituximab seems to be effective tolerable in refractory low-grade B-cell NHL, although modest activity in refractory DLBCL. Further studies to define the efficacy of I-131 rituximab in DLBCL are warranted.

  18. Addition of rituximab to chop does not increase the risk of cardiotoxicity in patients with non-Hodgkin's lymphoma.

    Science.gov (United States)

    Kilickap, Saadettin; Yavuz, Bunyamin; Aksoy, Sercan; Sahiner, Levent; Dincer, Murat; Harputluoglu, Hakan; Erman, Mustafa; Aytemir, Kudret; Tokgozoglu, Lale; Barista, Ibrahim

    2008-01-01

    The addition of rituximab to doxorubicin-containing standard chemotherapy significantly improves response to therapy and reduces the risk of death in B-cell non-Hodgkin's lymphoma (NHL) patients. However, the impact of this approach on doxorubicin-induced cardiotoxicity has not been elucidated. Patients who had been planned to receive CHOP or rituximab plus CHOP (R-CHOP) combination chemotherapy with a diagnosis of NHL were included in the study. In all patients, systolic and diastolic parameters were measured by using conventional and pulsed-wave tissue Doppler echocardiography, which is more sensitive than conventional lead-dependent techniques, both before and in the sixth month of therapy. There were 28 (M/F; 14/14) patients on CHOP and 33 (M/F; 16/17) patients on R-CHOP. Median age in CHOP and R-CHOP was 49 and 50 years (P = 0.44), respectively. Cumulative doxorubicin doses were 280 and 286 mg/m(2) on CHOP and R-CHOP (P = 0.65), respectively. None of the patients developed clinically evident congestive heart failure. Parameters of systolic function such as LVEF and FS did not significantly change in any patients. In both arms, tissue Doppler parameters of diastolic function such as lateral E and septal E velocity of mitral annulus decreased significantly after therapy (P 0.05). Conventional Doppler echocardiography yielded consistent findings. Both CHOP and R-CHOP cause diastolic dysfunction in the early period following their administration. The addition of rituximab to CHOP chemotherapy does not significantly increase the risk of doxorubicin-induced cardiotoxicity during this period.

  19. Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study.

    Directory of Open Access Journals (Sweden)

    Øystein Fluge

    Full Text Available Chronic fatigue syndrome (CFS is a disease of unknown aetiology. Major CFS symptom relief during cancer chemotherapy in a patient with synchronous CFS and lymphoma spurred a pilot study of B-lymphocyte depletion using the anti-CD20 antibody Rituximab, which demonstrated significant clinical response in three CFS patients.In this double-blind, placebo-controlled phase II study (NCT00848692, 30 CFS patients were randomised to either Rituximab 500 mg/m(2 or saline, given twice two weeks apart, with follow-up for 12 months. Xenotropic murine leukemia virus-related virus (XMRV was not detected in any of the patients. The responses generally affected all CFS symptoms. Major or moderate overall response, defined as lasting improvements in self-reported Fatigue score during follow-up, was seen in 10 out of 15 patients (67% in the Rituximab group and in two out of 15 patients (13% in the Placebo group (p = 0.003. Mean response duration within the follow-up period for the 10 responders to Rituximab was 25 weeks (range 8-44. Four Rituximab patients had clinical response durations past the study period. General linear models for repeated measures of Fatigue scores during follow-up showed a significant interaction between time and intervention group (p = 0.018 for self-reported, and p = 0.024 for physician-assessed, with differences between the Rituximab and Placebo groups between 6-10 months after intervention. The primary end-point, defined as effect on self-reported Fatigue score 3 months after intervention, was negative. There were no serious adverse events. Two patients in the Rituximab group with pre-existing psoriasis experienced moderate psoriasis worsening.The delayed responses starting from 2-7 months after Rituximab treatment, in spite of rapid B-cell depletion, suggests that CFS is an autoimmune disease and may be consistent with the gradual elimination of autoantibodies preceding clinical responses. The present findings will impact

  20. Cost-Effectiveness Analysis of Bendamustine Plus Rituximab as a First-Line Treatment for Patients with Follicular Lymphoma in Spain.

    Science.gov (United States)

    Sabater, Eliazar; López-Guillermo, Armando; Rueda, Antonio; Salar, Antonio; Oyagüez, Itziar; Collar, Juan Manuel

    2016-08-01

    Follicular lymphoma (FL) is the second most common type of lymphoid cancer in Western Europe. The aim of this study was to evaluate the cost utility of rituximab-bendamustine treatment compared with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) treatment as a first-line therapy for patients with advanced FL in Spain. A Markov model was developed to estimate the cost effectiveness of rituximab-bendamustine compared with R-CHOP as first-line treatment for patients with advanced FL in the Spanish National Health System (NHS). Transitions between health states (progression-free, including induction and maintenance; first relapse; second relapse; and death) were allowed for the patient cohort in 4-week-long cycles. Clinical data for the extrapolation of progression-free survival curves were obtained from randomized trials. Mortality rates and utilities were obtained from the literature. Outcomes were measured as quality-adjusted life-years (QALYs). The total costs (€, 2013) included drug costs (ex-factory prices with mandatory deductions), disease management costs and adverse event-associated costs. Costs and outcomes were discounted at a 3 % annual rate. Probabilistic sensitivity analysis was performed using 10,000 Monte Carlo simulations to assess the model robustness. Treatment and administration costs during the induction phase were higher for rituximab-bendamustine (€17,671) than for R-CHOP (€11,850). At the end of the 25-year period, the rituximab-bendamustine first-line strategy had a total cost of €68,357 compared with €69,528 for R-CHOP. Health benefits were higher for rituximab-bendamustine treatment (10.31 QALYs) than for R-CHOP treatment (9.82 QALYs). In the probabilistic analysis, rituximab-bendamustine was the dominant strategy over treatment with R-CHOP in 53.4 % of the simulations. First-line therapy with rituximab-bendamustine in FL patients was the dominant strategy over treatment with R-CHOP; it showed cost

  1. Ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study

    Science.gov (United States)

    Burger, Jan A.; Keating, Michael J.; Wierda, William G.; Hartmann, Elena; Hoellenriegel, Julia; Rosin, Nathalie Y.; de Weerdt, Iris; Jeyakumar, Ghayathri; Ferrajoli, Alessandra; Cardenas-Turanzas, Marylou; Lerner, Susan; Jorgensen, Jeffrey L; Nogueras-González, Graciela M.; Zacharian, Gracy; Huang, Xuelin; Kantarjian, Hagop; Garg, Naveen; Rosenwald, Andreas; O’Brien, Susan

    2014-01-01

    Summary Background Ibrutinib, an orally administered covalent inhibitor of Bruton tyrosine kinase (BTK), is an effective therapy for patients with relapsed chronic lymphocytic leukemia (CLL). We investigated the activity and safety of the combination of ibrutinib with the monoclonal antibody rituximab (iR) in patients with high-risk CLL. Methods In this single-arm, phase 2 studywe enrolled 40 patients with high-risk CLL at MD Anderson Cancer Center, Houston, Texas, USA. Patients with symptomatic CLL requiring therapy received 28 day cycles of once-daily ibrutinib 420 mg , together with rituximab (weekly during cycle 1, then once per cycle until cycle 6), followed by continuous single-agent ibrutinib. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01520519 and is no longer accruing patients. Findings Between February 28, 2012 and September 11, 2012, we enrolled 40 CLL patients with high-risk disease features. 20 patients had del17p or TP53 mutations (16 previously treated, 4 untreated), 13 had relapsed CLL with del11q, and 7 patients a PFS infections occurred in 4 patients (10%), no grade 4 or 5 infections occurred. At 18 months, the Kaplan Meier estimate of progression-free survival was 78% (95% CI 60.6–88.5) (del[17p] or TP53 mutation: 72%, 95% CI: 45.6–87.6) Interpretation Ibrutinib in combination with rituximab is a well-tolerated regimen for patients with high-risk CLL. It induces high rates of remissions and has positive impact on QOL in this difficult-to-treat patient population. These encouraging data merit further investigation of the added benefit of rituximab as combination partner for ibrutinib in an ongoing randomized trial, in which single-agent ibrutinib is compared to iR combination therapy (NCT02007044). Funding Pharmacyclics, Inc., Cancer Prevention and Research Institute of Texas (CPRIT), Leukemia & Lymphoma Society, NCI Grant P30 CA

  2. Infectious diseases and immunological markers associated with patients with non-Hodgkin lymphoma treated with rituximab.

    Science.gov (United States)

    de Souza, Kleber Jordão; Ferro, Rodrigo Sala; Prestes-Carneiro, Luiz Euribel; Carrilho, Paula Andreia Martins; Vasconcelos, Dewton de Moraes

    2018-02-01

    The use of rituximab (RTX) is increasing, even in developing countries. It has become the first-line therapy or adjuvant to chemotherapy (CHOP; cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone) for various diseases, including B cell lymphoma and autoimmune diseases. We describe the infectious diseases and immunological markers associated with RTX treatment of patients with non-Hodgkin lymphoma (NHL). Serum immunoglobulins were determined before and after intravenous immunoglobulin (IVIg) administration. Pneumo-23IgG-specific anti-pneumococcal antibodies were evaluated before and after vaccination. Immunophenotyping and lymphocyte proliferation were determined in the course of the treatment. Seven patients were followed and median age was 56.0 ± 5.0 years (range, 41.9-71.6 years). At baseline, the mean level of IgG was 333.7 ± 40.8 and IgM 40.9 ± 11.3 mg/dL, respectively; immunoglobulin A and E (IgA and IgE) were under the limit of detection. Two patients had reduced or absent B cells and T cell subsets were at normal levels in five patients. All patients failed to mount an efficient post-vaccination immune response against hepatitis B virus, tetanus, diphtheria and against the 23-valent pneumococcal polysaccharide vaccine. During RTX/CHOP treatment, human-IgG-immunoglobulin (IVIg) therapy was introduced in six patients after recurrent infections, including community-acquired pneumonia (85.7%), chronic sinusitis (85.7%) and gastroenteritis (42.9%). Poor response against pneumococcal vaccines increases the susceptibility of respiratory diseases in these patients. In patients with NHL treated with RTX, the benefits achieved with IVIg replacement for the control of recurrent infectious diseases is of paramount importance. Clinicians dealing with monoclonal antibodies against cancer therapy, especially RTX, should be aware of the increasing risks for symptomatic induced hypogammaglobulinemia and respiratory infections.

  3. A new prognostic score for AIDS-related lymphomas in the rituximab-era

    Science.gov (United States)

    Barta, Stefan K.; Xue, Xiaonan; Wang, Dan; Lee, Jeannette Y.; Kaplan, Lawrence D.; Ribera, Josep-Maria; Oriol, Albert; Spina, Michele; Tirelli, Umberto; Boue, Francois; Wilson, Wyndham H.; Wyen, Christoph; Dunleavy, Kieron; Noy, Ariela; Sparano, Joseph A.

    2014-01-01

    While the International Prognostic Index is commonly used to predict outcomes in immunocompetent patients with aggressive B-cell non-Hodgkin lymphomas, HIV-infection is an important competing risk for death in patients with AIDS-related lymphomas. We investigated whether a newly created prognostic score (AIDS-related lymphoma International Prognostic Index) could better assess risk of death in patients with AIDS-related lymphomas. We randomly divided a dataset of 487 patients newly diagnosed with AIDS-related lymphomas and treated with rituximab-containing chemoimmunotherapy into a training (n=244) and validation (n=243) set. We examined the association of HIV-related and other known risk factors with overall survival in both sets independently. We defined a new score (AIDS-related lymphoma International Prognostic Index) by assigning weights to each significant predictor [age-adjusted International Prognostic Index, extranodal sites, HIV-score (composed of CD4 count, viral load, and prior history of AIDS)] with three risk categories similar to the age-adjusted International Prognostic Index (low, intermediate and high risk). We compared the prognostic value for overall survival between AIDS-related lymphoma International Prognostic Index and age-adjusted International Prognostic Index in the validation set and found that the AIDS-related lymphoma International Prognostic Index performed significantly better in predicting risk of death than the age-adjusted International Prognostic Index (P=0.004) and better discriminated risk of death between each risk category (P=0.015 vs. P=0.13). Twenty-eight percent of patients were defined as low risk by the ARL-IPI and had an estimated 5-year overall survival (OS) of 78% (52% intermediate risk, 5-year OS 60%; 20% high risk, 5-year OS 50%). PMID:25150257

  4. Dexamethasone, Intravenous Immunoglobulin, and Rituximab Combination Immunotherapy for Pediatric Opsoclonus-Myoclonus Syndrome.

    Science.gov (United States)

    Pranzatelli, Michael R; Tate, Elizabeth D

    2017-08-01

    Although pulse-dose dexamethasone is increasingly favored for treating pediatric opsoclonus-myoclonus syndrome (OMS), and multimodal immunotherapy is associated with improved clinical response, there have been no neuroimmunologic studies of dexamethasone-based multimodal disease-modifying therapy. In this observational retrospective study, 19 children with OMS (with or without associated neuroblastoma) underwent multibiomarker evaluation for neuroinflammation. Nine children of varying OMS severity, duration, and treatment status were treated empirically with pulse dexamethasone, intravenous immunoglobulin (IVIg), and rituximab combination immunotherapy (DEXIR-CI). Another 10 children on dexamethasone alone or with IVIg at initial evaluation only provided a comparison group. Motor severity (total score) was scored rater-blinded via videotapes using the validated OMS Evaluation Scale. DEXIR-CI was associated with a 69% reduction in group total score (P = 0.004) and was clinically well tolerated. Patients given the dexamethasone combination exhibited significantly lowered B cell frequencies in cerebrospinal fluid (-94%) and blood (-76%), normalizing the cerebrospinal fluid B cell percentage. The number of patients with positive inflammatory markers dropped 87% (P = 0.002) as did the number of markers. Cerebrospinal fluid oligoclonal bands were positive in four of nine pretreatment patients but zero of six post-treatment patients. In the comparison group, partial response to dexamethasone alone or with IVIg was associated with multiple positive markers for neuroinflammation despite an average of seven months of treatment. Multimechanistic dexamethasone-based combination immunotherapy increases the therapeutic armamentarium for OMS, providing a viable option for less severely affected individuals. Partial response to dexamethasone with or without IVIg is indicative of ongoing neuroinflammation and should be treated promptly and accordingly. Copyright © 2017

  5. A randomized phase II study of carboplatin with weekly or every-3-week nanoparticle albumin-bound paclitaxel (abraxane) in patients with extensive-stage small cell lung cancer.

    Science.gov (United States)

    Grilley-Olson, Juneko E; Keedy, Vicki L; Sandler, Alan; Moore, Dominic T; Socinski, Mark A; Stinchcombe, Thomas E

    2015-02-01

    Platinum plus etoposide is the standard therapy for extensive-stage small cell lung cancer (ES-SCLC) and is associated with significant myelosuppression. We hypothesized that the combination of carboplatin and nanoparticle albumin-bound paclitaxel (nab-paclitaxel) would be better tolerated. We investigated carboplatin with nab-paclitaxel on every-3-week and weekly schedules. This noncomparative randomized phase II trial used a two-stage design. The primary objective was objective response rate, and secondary objectives were progression-free survival, overall survival, and toxicity. Patients with ES-SCLC and an Eastern Cooperative Oncology Group performance status ≤2 and no prior chemotherapy were randomized in a 1:1 ratio to arm A (carboplatin area under the curve [AUC] of 6 on day 1 and nab-paclitaxel of 300 mg/m(2) on day 1 every 3 weeks) or arm B (carboplatin AUC of 6 on day 1 and nab-paclitaxel 100 mg/m(2) on days 1, 8, and 15 every 21 days). Response was assessed after every two cycles. Patients required frequent dose reductions, treatment delays, and omission of the weekly therapy. The trial was closed because of slow accrual. Carboplatin and nab-paclitaxel demonstrated activity in ES-SCLC but required frequent dose adjustments. ©AlphaMed Press; the data published online to support this summary is the property of the authors.

  6. Pemetrexed-carboplatin with intercalated icotinib in the treatment of patient with advanced EGFR wild-type lung adenocarcinoma

    Science.gov (United States)

    Xu, Tongpeng; Wu, Hao; Jin, Shidai; Min, Huang; Zhang, Zhihong; Shu, Yongqian; Wen, Wei; Guo, Renhua

    2017-01-01

    Abstract Rationale: Tyrosine kinase inhibitors (TKIs) are known to have greater efficacy in epidermal growth factor receptor (EGFR) mutation nonsmall cell lung cancer (NSCLC). However, about 10% of EGFR wild-type (wt) patients respond to TKIs. Patient concerns: Several strategies to increase the efficacy of TKIs in wt NSCLC are the subjects of ongoing investigations. One of them is combining EGFR TKI with intercalated chemotherapy. Diagnoses: We describe a patient with EGFR wt NSCLC, who was found with ovarian and lung metastasis, was treated with pemetrexed and intercalated icotinib. Interventions: In this case, we reported the successful long-term maintenance treatment of a patient with EGFR wt NSCLC with pemetrexed and Icotinib. The patient (40-year-old female) was found with ovarian masses and lung masses. Pathological, immunohistochemical, and amplification refractory mutation system (ARMS) assay examinations of ovarian specimen suggested the expression of metastatic lung adenocarcinoma with wt EGFR. After failure treatment with paclitaxel-carboplatin, the patient received 4 cycles of pemetrexed plus platinum with intercalated icotinib and then remained on pemetrexed and icotinib. Outcomes: A partial response was achieved after the treatment. The patient's condition had remained stable on pemetrexed and icotinib for more than 20 months, with no evidence of progression. Lessons: To our knowledge, this is the first report using the long-term maintenance treatment with pemetrexed and intercalated icotinib in EGFR wt patient. The therapeutic strategies warrant further exploration in selected populations of NSCLC. PMID:28816950

  7. Lethal Clostridium difficile Colitis Associated with Paclitaxel and Carboplatin Chemotherapy in Ovarian Carcinoma: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    V. Masciullo

    2010-01-01

    Full Text Available Clostridium difficile colitis, although rare, could represent a serious complication following chemotherapy. Prior antibiotic use has been considered the single most important risk factor in the development of C. difficile infection. Recently, the association between antineoplastic therapy and C. difficile-associated diarrhea in the absence of a prior antibiotic therapy has become more apparent. A 75-year-old woman with serous adenocarcinoma of the ovary developed lethal pancolitis caused by C. difficile after five cycles of paclitaxel- and carboplatin-based chemotherapy. She presented with diarrhea, coffee-ground emesis, and oliguria and was hospitalized immediately for aggressive treatment. Despite all the medical efforts, her condition worsened and she died after twenty days. We describe the second case reported of a patient developing a severe C. difficile colitis following chemotherapy without any recent antibiotic use and review the data of the literature, emphasizing the need to a prompt diagnosis and management that can significantly decrease the morbidity and life-threatening complications associated with this infection.

  8. Targeted alpha therapy in vivo: direct evidence for single cancer cell kill using 149Tb-rituximab

    International Nuclear Information System (INIS)

    Beyer, G.J.; Soloviev, D.; Buchegger, F.; Miederer, M.; Vranjes-Duric, S.; Comor, J.J.; Kuenzi, G.; Hartley, O.; Senekowitsch-Schmidtke, R.

    2004-01-01

    This study demonstrates high-efficiency sterilisation of single cancer cells in a SCID mouse model of leukaemia using rituximab, a monoclonal antibody that targets CD20, labelled with terbium-149, an alpha-emitting radionuclide. Radio-immunotherapy with 5.5 MBq labelled antibody conjugate (1.11 GBq/mg) 2 days after an intravenous graft of 5.10 6 Daudi cells resulted in tumour-free survival for >120 days in 89% of treated animals. In contrast, all control mice (no treatment or treated with 5 or 300 μg unlabelled rituximab) developed lymphoma disease. At the end of the study period, 28.4%±4% of the long-lived daughter activity remained in the body, of which 91.1% was located in bone tissue and 6.3% in the liver. A relatively high daughter radioactivity concentration was found in the spleen (12%±2%/g), suggesting that the killed cancer cells are mainly eliminated through the spleen. This promising preliminary in vivo study suggests that targeted alpha therapy with 149 Tb is worthy of consideration as a new-generation radio-immunotherapeutic approach. (orig.)

  9. Clinical scale preparation and evaluation of {sup 131}I-Rituximab for Non-Hodgkin's lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Kameswaran, Mythili; Vimalnath, K. Viswanathan; Rajeswari, Ardhi; Joshi, Prahlad Vasudeo; Samuel, Grace [Bhabha Atomic Research Centre, Mumbai (India). Radiopharmaceuticals Div.; Sarma, H.D. [Bhabha Atomic Research Centre, Mumbai (India). Radiation Biology and Health Sciences Div.

    2014-09-01

    Radioimmunotherapy (RIT) with anti CD20 MoAb conjugated to a β{sup -} emitting radioisotope like {sup 131}I or {sup 90}Y has the added advantage of delivering radiation not only to tumor cells that bind the antibody but also due to a crossfire effect, to neighboring tumor cells inaccessible to the antibody. In order to make available an indigenous radioimmunotherapeutic agent for Non Hodgkin's Lymphoma (NHL), radioiodinated Rituximab has been prepared and evaluated at a clinical scale. Radioiodination of Rituximab was performed by the conventional Chloramine T method using 7.4 GBq Na{sup 131}I in a lead shielded plant. Six batches of radioiodination were prepared and characterized by electrophoresis and HPLC to evaluate the reproducibility of the product. The product remained stable retaining the radiochemical purity > 95% upto 5 days after radioiodination. In vitro cell binding studies and biodistribution studies in normal Swiss mice have indicated the potential of this molecule as a radioimmunotherapeutic agent for NHL. (orig.)

  10. Excision repair cross-complementation group 1 (ERCC1) in platinum-based treatment of non-small cell lung cancer with special emphasis on carboplatin: a review of current literature

    DEFF Research Database (Denmark)

    Vilmar, A.; Sorensen, J.B.

    2009-01-01

    on carboplatin based on the current literature. Research on the development of a reliable methodology is warranted followed by validation in large, prospective, randomized trials as ERCC1 may possibly play an important role as tumour marker in tailored chemotherapy for NSCLC Udgivelsesdato: 2009/5......-complementation group 1 (ERCC1) has shown potential as a predictive marker in patients with NSCLC treated with cisplatin-based chemotherapy. Carboplatin has gained widespread use in the treatment of advanced NSCLC and its mechanisms of action are likely similar to that of cisplatin. MATERIALS AND METHODS: A literature...... review on ERCC1 was conducted as predictor in NSCLC patients receiving platinum-based treatment with emphasis on carboplatin. English language publications from January 1996 to February 2008 were eligible and data on methodology and outcome were recorded. RESULTS: Eight preclinical articles, 25 clinical...

  11. B-cell depletion with rituximab in the treatment of autoimmune diseases. Graves' ophthalmopathy the latest addition to an expanding family

    DEFF Research Database (Denmark)

    Nielsen, Claus H; El Fassi, Daniel; Hasselbalch, Hans K

    2007-01-01

    of 10 Graves' disease patients remained in remission 400 days after rituximab treatment versus none in the control group, and remarkable improvements in the eye symptoms of patients with Graves' ophthalmopathy were observed. This supports a role for B cells in the pathogenesis of Graves' ophthalmopathy...

  12. Higher World Health Organization grades of follicular lymphoma correlate with better outcome in two Nordic Lymphoma Group trials of rituximab without chemotherapy

    DEFF Research Database (Denmark)

    Wahlin, Björn Engelbrekt; Sundström, Christer; Sander, Birgitta

    2014-01-01

    Abstract A common treatment for follicular lymphoma is rituximab monotherapy. To identify patients for whom this regimen is adequate as first-line therapy, we applied the World Health Organization (WHO) classification for grading follicular lymphoma in a prospective central pathology review...... increased with the malignant cell size (p useful tool for personalized therapy....

  13. MDM2 phenotypic and genotypic profiling, respective to TP53 genetic status, in diffuse large B-cell lymphoma patients treated with rituximab-CHOP immunochemotherapy

    DEFF Research Database (Denmark)

    Xu-Monette, Zijun Y; Møller, Michael B; Tzankov, Alexander

    2013-01-01

    MDM2 is a key negative regulator of the tumor suppressor p53, however, the prognostic significance of MDM2 overexpression in diffuse large B-cell lymphoma (DLBCL) has not been defined convincingly. In a p53 genetically-defined large cohort of de novo DLBCL patients treated with rituximab, cycloph...

  14. Addition of rituximab to chemotherapy overcomes the negative prognostic impact of cyclin E expression in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Frei, E; Visco, C; Xu-Monette, Z Y

    2013-01-01

    High levels of cyclin E (CCNE) are accompanied by shorter survival in cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone (CHOP)-treated diffuse large B-cell lymphomas (DLBCL), independent of the international prognostic index (IPI). Data on the prognostic role of CCNE in the 'rituximab...

  15. Rituximab Maintenance Treatment of Relapsed/Resistant Follicular Non-Hodgkin's Lymphoma: Long-Term Outcome of the EORTC 20981 Phase III Randomized Intergroup Study

    NARCIS (Netherlands)

    van Oers, Marinus H. J.; van Glabbeke, Martine; Giurgea, Livia; Klasa, Richard; Marcus, Robert E.; Wolf, Max; Kimby, Eva; van 't Veer, Mars; Vranovsky, Andrej; Holte, Harald; Hagenbeek, Anton

    2010-01-01

    Purpose In 2006, we published the results of the European Organisation for Research and Treatment of Cancer phase III trial EORTC 20981 on the role of rituximab in remission induction and maintenance treatment of relapsed/resistant follicular lymphoma (FL). At that time, the median follow-up for the

  16. [Safe and effective administration of carboplatin-based chemotherapy in a patient undergoing hemodialysis with cancer of unknown primary by monitoring observed AUC of carboplatin-a case report].

    Science.gov (United States)

    Kondo, Masahiro; Kuroda, Junko; Ikai, Yoshitomo; Hayashi, Rumiko; Uegaki, Shiori; Yoshida, Tatsuya; Yoshida, Atsuhiro; Komatsu, Hirokazu; Kimura, Kazunori

    2012-11-01

    Here we report a case of successful treatment with combination chemotherapy of carboplatin(CBDCA)and paclitaxel for a patient undergoing hemodialysis(HD)with cancer of unknown primary, conducted by monitoring the observed AUC of ultrafilterable CBDCA. CBDCA was administered at a dose of 125 mg on day 1 in each course, an amount which had been calculated by the Calvert formula(GFR: 0, target AUC: 5). HD was started at a point in time one hour after the completion of each CBDCA administration, and performed for 5 hours in each course. Blood samples were collected during the first 3 courses of chemotherapy to measure the plasma concentration of free-platinum. The observed AUCs(o-AUC)of CBDCA in the first, second and third courses were 3. 03, 3. 44 and 3. 50mg·min/mL, respectively. The o-AUC in the first course was lower than that in the second course. The o-AUC in the second course was nearly equal to that in the third course, while each o-AUC was below the target AUC(t-AUC). Partial response was achieved after two courses of the CBDCA and paclitaxel combination chemotherapy, with adverse events of Grade 3 neutropenia and Grade 3 peripheral neuropathy observed in each course after the second course of chemotherapy. o-AUC of CBDCA administered to HD patients can not only be below t-AUC, as in this case, but also oppositely above t-AUC in cases with different doses of CBDCA or HD settings. Our results suggest that the monitoring of o-AUC of CBDCA is useful when practicing CBDCA-based chemotherapy safely and effectively in cancer patients undergoing HD.

  17. Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial.

    Science.gov (United States)

    Iijima, Kazumoto; Sako, Mayumi; Nozu, Kandai; Mori, Rintaro; Tuchida, Nao; Kamei, Koichi; Miura, Kenichiro; Aya, Kunihiko; Nakanishi, Koichi; Ohtomo, Yoshiyuki; Takahashi, Shori; Tanaka, Ryojiro; Kaito, Hiroshi; Nakamura, Hidefumi; Ishikura, Kenji; Ito, Shuichi; Ohashi, Yasuo

    2014-10-04

    Rituximab could be an effective treatment for childhood-onset, complicated, frequently relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS). We investigated the efficacy and safety of rituximab in patients with high disease activity. We did a multicentre, double-blind, randomised, placebo-controlled trial at nine centres in Japan. We screened patients aged 2 years or older experiencing a relapse of FRNS or SDNS, which had originally been diagnosed as nephrotic syndrome when aged 1-18 years. Patients with complicated FRNS or SDNS who met all other criteria were eligible for inclusion after remission of the relapse at screening. We used a computer-generated sequence to randomly assign patients (1:1) to receive rituximab (375 mg/m(2)) or placebo once weekly for 4 weeks, with age, institution, treatment history, and the intervals between the previous three relapses as adjustment factors. Patients, guardians, caregivers, physicians, and individuals assessing outcomes were masked to assignments. All patients received standard steroid treatment for the relapse at screening and stopped taking immunosuppressive agents by 169 days after randomisation. Patients were followed up for 1 year. The primary endpoint was the relapse-free period. Safety endpoints were frequency and severity of adverse events. Patients who received their assigned intervention were included in analyses. This trial is registered with the University Hospital Medical Information Network clinical trials registry, number UMIN000001405. Patients were centrally registered between Nov 13, 2008, and May 19, 2010. Of 52 patients who underwent randomisation, 48 received the assigned intervention (24 were given rituximab and 24 placebo). The median relapse-free period was significantly longer in the rituximab group (267 days, 95% CI 223-374) than in the placebo group (101 days, 70-155; hazard ratio: 0·27, 0·14-0·53; p<0·0001). Ten patients (42%) in the rituximab group and six (25

  18. Real world costs and cost-effectiveness of Rituximab for diffuse large B-cell lymphoma patients: a population-based analysis.

    Science.gov (United States)

    Khor, Sara; Beca, Jaclyn; Krahn, Murray; Hodgson, David; Lee, Linda; Crump, Michael; Bremner, Karen E; Luo, Jin; Mamdani, Muhammad; Bell, Chaim M; Sawka, Carol; Gavura, Scott; Sullivan, Terrence; Trudeau, Maureen; Peacock, Stuart; Hoch, Jeffrey S

    2014-08-12

    Current treatment of diffuse-large-B-cell lymphoma (DLBCL) includes rituximab, an expensive drug, combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. Economic models have predicted rituximab plus CHOP (RCHOP) to be a cost-effective alternative to CHOP alone as first-line treatment of DLBCL, but it remains unclear what its real-world costs and cost-effectiveness are in routine clinical practice. We performed a population-based retrospective cohort study from 1997 to 2007, using linked administrative databases in Ontario, Canada, to evaluate the costs and cost-effectiveness of RCHOP compared to CHOP alone. A historical control cohort (n = 1,099) with DLBCL who received CHOP before rituximab approval was hard-matched on age and treatment intensity and then propensity-score matched on sex, comorbidity, and histology to 1,099 RCHOP patients. All costs and outcomes were adjusted for censoring using the inverse probability weighting method. The main outcome measure was incremental cost per life-year gained (LYG). Rituximab was associated with a life expectancy increase of 3.2 months over 5 years at an additional cost of $16,298, corresponding to an incremental cost-effectiveness ratio of $61,984 (95% CI $34,087-$135,890) per LYG. The probability of being cost-effective was 90% if the willingness-to-pay threshold was $100,000/LYG. The cost-effectiveness ratio was most favourable for patients less than 60 years old ($31,800/LYG) but increased to $80,600/LYG for patients 60-79 years old and $110,100/LYG for patients ≥ 80 years old. We found that post-market survival benefits of rituximab are similar to or lower than those reported in clinical trials, while the costs, incremental costs and cost-effectiveness ratios are higher than in published economic models and differ by age. Our results showed that the addition of rituximab to standard CHOP chemotherapy was associated with improvement in survival but at a higher cost, and was

  19. High treatment efficacy by dual targeting of Burkitt's lymphoma xenografted mice with a {sup 177}Lu-based CD22-specific radioimmunoconjugate and rituximab

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Tobias; Boetticher, Benedikt; Keller, Armin; Schlegelmilch, Anne; Jaeger, Dirk; Krauss, Juergen [Heidelberg University Hospital, Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg (Germany); Mier, Walter; Kraemer, Susanne; Leotta, Karin [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); Sauter, Max; Haberkorn, Uwe [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); German Cancer Research Center (DKFZ), Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); Grosse-Hovest, Ludger [University of Tuebingen, Department of Immunology, Tuebingen (Germany); Arndt, Michaela A.E. [Heidelberg University Hospital, Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg (Germany); German Cancer Research Center (DKFZ), Immunotherapy Program, National Center for Tumor Diseases, Heidelberg (Germany)

    2016-03-15

    Dual-targeted therapy has been shown to be a promising treatment option in recurrent and/or refractory B-cell non-Hodgkin's lymphoma (B-NHL). We generated radioimmunoconjugates (RICs) comprising either a novel humanized anti-CD22 monoclonal antibody, huRFB4, or rituximab, and the low-energy β-emitter {sup 177}Lu. Both RICs were evaluated as single agents in a human Burkitt's lymphoma xenograft mouse model. To increase the therapeutic efficacy of the anti-CD22 RIC, combination therapy with unlabelled anti-CD20 rituximab was explored. The binding activity of CHX-A''-DTPA-conjugated antibodies to target cells was analysed by flow cytometry. To assess tumour targeting of {sup 177}Lu-labelled antibodies, in vivo biodistribution experiments were performed. For radioimmunotherapy (RIT) studies, non-obese diabetic recombination activating gene-1 (NOD-Rag1{sup null}) interleukin-2 receptor common gamma chain (IL2r γ {sup null}) null mice (NRG mice) were xenografted subcutaneously with Raji Burkitt's lymphoma cells. {sup 177}Lu-conjugated antibodies were administered at a single dose of 9.5 MBq per mouse. For dual-targeted therapy, rituximab was injected at weekly intervals (0.5 - 1.0 mg). Tumour accumulation of RICs was monitored by planar scintigraphy. Conjugation of CHX-A''-DTPA resulted in highly stable RICs with excellent antigen-binding properties. Biodistribution experiments revealed higher tumour uptake of the {sup 177}Lu-labelled anti-CD22 IgG than of {sup 177}Lu-labelled rituximab. Treatment with {sup 177}Lu-conjugated huRFB4 resulted in increased tumour growth inhibition and significantly longer survival than treatment with {sup 177}Lu-conjugated rituximab. The therapeutic efficacy of the anti-CD22 RIC could be markedly enhanced by combination with unlabelled rituximab. These findings suggest that dual targeting with {sup 177}Lu-based CD22-specific RIT in combination with rituximab is a promising new treatment option for

  20. Chemoradiation With Paclitaxel and Carboplatin in High-Risk Cervical Cancer Patients After Radical Hysterectomy: A Korean Gynecologic Oncology Group Study

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Taek Sang [Department of Obstetrics and Gynecology, SMG-SNU Boramae Medical Center, Seoul (Korea, Republic of); Kang, Soon Beom, E-mail: tslee70@gmail.com [Department of Obstetrics and Gynecology, Konkuk University Medical Center, Seoul (Korea, Republic of); Kim, Young Tak [Department of Obstetrics and Gynecology, Asan Medical Center, Seoul (Korea, Republic of); Park, Byung Joo [Department of Preventive Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Yong Man [Department of Obstetrics and Gynecology, Asan Medical Center, Seoul (Korea, Republic of); Lee, Jong Min [Department of Obstetrics and Gynecology, Kyung Hee University Hospital at Gangdong, Seoul (Korea, Republic of); Kim, Seok Mo [Department of Obstetrics and Gynecology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Kim, Young Tae [Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Jae Hoon [Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Seoul (Korea, Republic of); Kim, Kyung Tai [Department of Obstetrics and Gynecology, Hanyang University Medical Center, Seoul (Korea, Republic of)

    2013-06-01

    Purpose: To evaluate the efficacy and toxicity of concurrent chemoradiation with paclitaxel and carboplatin in patients with high-risk cervical cancer. Methods and Materials: Patients after radical hysterectomy for cervical cancer, with at least 1 high-risk characteristic, were administered paclitaxel 135 mg/m{sup 2}, carboplatin area under the curve = 5 every 3 weeks for 3 cycles concomitant with radiation therapy as adjuvant treatment. Results: This prospective study enrolled 71 consecutive patients. Sixty-six patients (93%) completed the planned treatment. The majority of grade 3/4 neutropenia or nonhematologic toxicities were usually self-limited. Diarrhea grades 3/4 were observed in 4 patients (5.6%). One patient developed anaphylactic shock after infusion of paclitaxel. With a median follow-up of 57 months, recurrences occurred in 16 patients. Multivariable analysis indicated that common iliac lymph node involvement is an independent risk factor for disease recurrence (odds ratio 13.48; 95% confidence interval 2.93-62.03). In the intent-to-treat population (n=71), the estimated 5-year disease-free survival and overall survival rates were 77.3% and 80.3% respectively. In the per-protocol population (n=62), disease-free survival was 78.9% and overall survival was 83.9%. Conclusions: Concurrent chemoradiation with paclitaxel/carboplatin is well tolerated and seems to be effective for patients who undergo radical hysterectomy. Therefore, a prospective, randomized controlled study should be designed to evaluate efficacy of this approach for patients with high-risk cervical cancer.

  1. Concomitant Chemoradiotherapy Using Carboplatin, Tegafur-Uracil and Leucovorin for Stage III and IV Head-and-Neck Cancer: Results of GORTEC Phase II Study

    International Nuclear Information System (INIS)

    Fesneau, Melanie; Pointreau, Yoann; Chapet, Sophie; Martin, Laurent; Pommier, Pascal; Alfonsi, Marc; Laguerre, Brigitte; Feham, Nasreddine; Berger, Christine; Garaud, Pascal; Calais, Gilles

    2010-01-01

    Purpose: Concomitant chemoradiotherapy is the standard treatment of locally advanced, nonresectable, head-and-neck squamous cell carcinoma. However, the optimal chemotherapy regimen is still controversial. The objective of this Phase II study was to evaluate the feasibility and efficacy of a concomitant treatment using tegafur-uracil, leucovorin, carboplatin, and radiotherapy. Methods and Materials: A total of 77 patients with head-and-neck squamous cell carcinoma Stage III and IVA were enrolled between October 2003 and July 2005. Of the 77 patients, 72 were eligible. They were treated with tegafur-uracil (300 mg/m 2 /d) and leucovorin (75 mg/d) from Days 1 to 19 and from Days 29 to 47 and carboplatin (70 mg/m 2 intravenously for 4 consecutive days), in three cycles every 21 days. Conventional radiotherapy was delivered to a total dose of 70 Gy in 35 fractions. Results: With a mean follow-up of 22.8 months, the 3-year locoregional control, overall survival and disease-free survival actuarial rate was 33.1%, 41.9%, and 27.2%, respectively. The compliance of the treatment was correct. The main acute toxicity was mucositis, with 62% Grade 3-4. Three patients (4.2%) died of acute toxicity. The incidence and severity of late toxicity was acceptable, with 32% Grade 3 and no Grade 4 toxicity. Conclusion: The protocol of concomitant chemoradiotherapy using tegafur-uracil, leucovorin, and carboplatin for locally advanced unresectable head-and-neck squamous cell carcinoma is feasible. The compliance was correct. The incidence and severity of the acute and late toxicities were acceptable, but not improved. The efficacy of this regimen seems equivalent to the main protocols of concurrent chemoradiotherapy. It represents a possible alternative for patients without an intravenous catheter.

  2. A phase ii study of concurrent accelerated hyperfractionated radiotherapy and carboplatin/oral etoposide for elderly patients with stage iii non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Jeremic, Branislav; Shibamoto, Yuta; Milicic, Biljana; Milisavljevic, Slobodan; Nikolic, Nebojsa; Dagovic, Aleksandar; Aleksandrovic, Jasna; Radosavljevic-Asic, Gordana

    1999-01-01

    Purpose: To investigate feasibility, toxicity, and efficacy of accelerated hyperfractionated radiation therapy and concurrent carboplatin/oral etoposide in elderly (> 70 years) patients with stage III non-small-cell lung cancer. Methods and Materials: Between January 1988 and June 1993, a total of 58 patients entered a phase II study. Carboplatin (400 mg/m 2 ) was given intravenously on days 1 and 29, and etoposide (50 mg/m 2 ) was given orally on days 1-21 and 29-42. Accelerated hyperfractionated radiotherapy was administered starting on day 1, with a total dose of 51 Gy in 34 fractions over 3.5 weeks. Results: In 55 evaluable patients, the complete response rate was 27% and the overall response rate was 65%. For the 55 patients, the median survival time was 10 months, and the 1-, 2-, and 5-year survival rates were 45%, 24%, and 9.1%, respectively. The median time until relapse was 8 months and the 1-, 2-, and 5-year relapse-free survival rates were 45%, 20%, and 9.1%, respectively. The median time to local recurrence was 14 months and the 5-year local control rate was 13%; the median time to distant metastasis was 18 months and the 5-year distant metastasis-free rate was 15%. Hematological, esophageal, and bronchopulmonary acute grade 3 or 4 toxicities were observed in 22%, 7%, and 4% of the patients, respectively. There was no grade 5 toxicity or late grade ≥ 3 toxicity. Conclusion: Concurrent accelerated hyperfractionated radiotherapy and carboplatin/oral etoposide produced relatively low and acceptable toxicity. The survival results appeared to be comparable to those obtained in nonelderly patients with stage III non-small-cell lung cancer treated by full-dose radiation

  3. Evaluation of paclitaxel and carboplatin versus combination chemotherapy with fluorouracil doxorubicin and cyclophosphamide as a neoadjuvant therapy in patients with inoperable breast cancer

    International Nuclear Information System (INIS)

    Akhtar, M.S.; Kausar, F.

    2010-01-01

    To compare the results of patients with locally advanced breast cancer receiving two different regimens Fluorouracil, Doxorubicin and Cyclophosphamide (FAC) and Paclitaxel and Carboplatin. Study Design: Comparative study. Place and Duration of Study: The Oncology Department, Institute of Nuclear Medicine and Oncology (INMOL), Lahore, from March 2007 to September 2008. Methodology: Patients with inoperable locally advanced breast cancer of stage were included. Sixteen patients were given FAC regimen and 9 patients were given Paclitaxel and Carboplatin, each combination was cycled after 21 days for four times. Before enrollment, detailed medical histories, physical examinations and performance status assessments were done as well as post chemotherapy evaluation with regular follow-up visits was done. Complete Response (CR, 100%) is defined as the disappearance of all known disease parameter i.e. disappearance in detectable tumour size, node free disease and surgery is possible. Paratial Response (PR, > 50%) was defined by 50% or greater decrease in the sum of the areas of bidimensionally measured lesions i.e. change of N2 to N1 or no status and some surgical procedure is possible to down stage the disease. Minor Response (MR) was defined as a decrease in the tumour insufficient to quality for partial resp once. Static disease or no evaluable reflected no significant change in disease and no evidence of new disease. Progression of disease (> 25%) was defined as a 25% or greater increase in the area of any lesion > 2 cm or in the sum of the products of the individual lesions or the appearance of new malignant lesions, surgery not possible. Results: Twenty five patients completed neoadjuvant chemotherapy. Sixteen (66%) patients received FAC and 9 (37%) patients received PC chemotherapy. Overall CR (breast and axilla) was 54%, PR was 16% and minor response (MR) was 8%. FAC treatment induced more emesis, mucositis, alopecia and cardiotoxicity. No death occurred

  4. Rituximab, alkylating agents or combination therapy for gastric mucosa-associated lymphoid tissue lymphoma: a monocentric non-randomised observational study.

    Science.gov (United States)

    Amiot, A; Lévy, M; Copie-Bergman, C; Dupuis, J; Szablewski, V; Le Baleur, Y; Baia, M; Belhadj, K; Sobhani, I; Leroy, K; Haioun, C; Delchier, J-C

    2014-03-01

    There is no consensus on the standard treatment of gastric mucosa-associated lymphoid tissue (MALT) lymphoma for Helicobacter pylori-negative patients and for patients with persistent disease despite H. pylori eradication. To evaluate the comparative efficacy and safety of alkylating agents and rituximab alone or in combination. In this monocentric retrospective study, which included 106 patients who had not been previously treated with anti-cancer agents, we evaluated the efficacy and safety of oral alkylating agents monotherapy (n = 48), rituximab monotherapy (n = 28) and the therapy combining both drugs (n = 30). Evaluations were performed at weeks 6 (W6), 25 (W25), and 52 (W52) and after 2 years (W104). After a median follow-up period of 4.9 years (range 0.4-17.2 years), complete remission and overall response were significantly higher in patients in the combination therapy group at W104 (92% and 100% respectively) compared with patients treated with alkylating agents alone (66% and 68%) and rituximab alone (64% and 73%). The 5-year progression-free survival probabilities were 68%, 70% and 89% in patients treated with alkylating agents alone, rituximab alone and combination therapy respectively. Haematological adverse events were reported in 32 (30%) patients (mostly grade 1) and were more frequent in the two groups receiving alkylating agents (P = 0.05 and P alkylating agents alone. Rituximab has a better safety profile than regimens containing alkylating agents. © 2014 John Wiley & Sons Ltd.

  5. Validation of a treatment satisfaction questionnaire in non-Hodgkin lymphoma: assessing the change from intravenous to subcutaneous administration of rituximab.

    Science.gov (United States)

    Theodore-Oklota, Christina; Humphrey, Louise; Wiesner, Christof; Schnetzler, Gabriel; Hudgens, Stacie; Campbell, Alicyn

    2016-01-01

    A subcutaneous (SC) formulation of rituximab (MabThera ® /Rituxan ® ) has been developed that could reduce administration time and improve patient satisfaction with treatment. The Rituximab Administration Satisfaction Questionnaire (RASQ) was created to assess patients' perceptions and satisfaction with rituximab SC (RASQ-SC) or rituximab intravenous (RASQ-IV). We assessed the content validity and psychometric properties of RASQ in patients with non-Hodgkin lymphoma. Face and content validity of RASQ-SC and RASQ-IV were qualitatively assessed using 60-minute combined concept elicitation and cognitive debriefing interviews. Psychometric validation of RASQ (item performance and reliability) was assessed quantitatively against the established Cancer Therapy Satisfaction Questionnaire (CTSQ), using questionnaire data from the PrefMab (NCT01724021) and MabCute (NCT01461928) clinical studies. RASQ-IV demonstrated excellent coverage of concepts relevant to patients' (n=10) own treatment experiences and no new concepts were identified. Patients' expectations of rituximab SC were conceptually consistent with items included in the RASQ-SC, suggesting that the tool is also conceptually adequate. In 1,051 patients from PrefMab and MabCute, correlations with domains such as "RASQ: Physical Impacts" and "CTSQ: Feelings About Side Effects", "RASQ: Physical Impacts" and "CTSQ: Satisfaction With Therapy", and "RASQ: Satisfaction" and "CTSQ: Satisfaction With Therapy", achieved moderate-to-high correlations (>0.4) for convergent domains and <0.3 for divergent domains. This study supports the qualitative face and content validity and psychometric validity of RASQ-IV and RASQ-SC. Minor revisions were made to the questionnaires to enhance clarity and aid consistent reporting.

  6. Activatory and Inhibitory Fcγ Receptors Augment Rituximab-mediated Internalization of CD20 Independent of Signaling via the Cytoplasmic Domain*

    Science.gov (United States)

    Vaughan, Andrew T.; Chan, Claude H. T.; Klein, Christian; Glennie, Martin J.; Beers, Stephen A.; Cragg, Mark S.

    2015-01-01

    Type I anti-CD20 mAb such as rituximab and ofatumumab engage with the inhibitory FcγR, FcγRIIb on the surface of B cells, resulting in immunoreceptor tyrosine-based inhibitory motif (ITIM) phosphorylation. Internalization of the CD20·mAb·FcγRIIb complex follows, the rate of which correlates with FcγRIIb expression. In contrast, although type II anti-CD20 mAb such as tositumomab and obinutuzumab also interact with and activate FcγRIIb, this interaction fails to augment the rate of CD20·mAb internalization, raising the question of whether ITIM phosphorylation plays any role in this process. We have assessed the molecular requirements for the internalization process and demonstrate that in contrast to internalization of IgG immune complexes, FcγRIIb-augmented internalization of rituximab-ligated CD20 occurs independently of the FcγRIIb ITIM, indicating that signaling downstream of FcγRIIb is not required. In transfected cells, activatory FcγRI, FcγRIIa, and FcγRIIIa augmented internalization of rituximab-ligated CD20 in a similar manner. However, FcγRIIa mediated a slower rate of internalization than cells expressing equivalent levels of the highly homologous FcγRIIb. The difference was maintained in cells expressing FcγRIIa and FcγRIIb lacking cytoplasmic domains and in which the transmembrane domains had been exchanged. This difference may be due to increased degradation of FcγRIIa, which traffics to lysosomes independently of rituximab. We conclude that the cytoplasmic domain of FcγR is not required for promoting internalization of rituximab-ligated CD20. Instead, we propose that FcγR provides a structural role in augmenting endocytosis that differs from that employed during the endocytosis of immune complexes. PMID:25568316

  7. Different impact of excision repair cross-complementation group 1 on survival in male and female patients with inoperable non-small-cell lung cancer treated with carboplatin and gemcitabine

    DEFF Research Database (Denmark)

    Holm, Bente; Mellemgaard, Anders; Skov, Torsten

    2009-01-01

    PURPOSE: The excision repair cross-complementation group 1 (ERCC1) status was assessed in patients receiving carboplatin and gemcitabine for inoperable non-small-cell lung cancer (NSCLC). We analyzed the association between the ERCC1 status and the overall survival after the chemotherapy. PATIENTS...... AND METHODS: We retrospectively identified 163 patients with inoperable NSCLC and sufficient tumor tissue for ERCC1 analysis, who had received carboplatin and gemcitabine as first-line treatment. Immunohistochemistry was used to assess the expression of ERCC1. RESULTS: One hundred sixty-three patients were...

  8. Docetaxel-carboplatin in combination with erlotinib and/or bevacizumab in patients with non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Boutsikou E

    2013-03-01

    Full Text Available Eftimia Boutsikou,1 Theodoros Kontakiotis,1 Paul Zarogoulidis,1 Kaid Darwiche,2 Ellada Eleptheriadou,1 Konstantinos Porpodis,1 Grammati Galaktidou,3 Leonidas Sakkas,4 Wolfgang Hohenforst-Schmidt,5 Kosmas Tsakiridis,6 Theodoros Karaiskos,7 Konstantinos Zarogoulidis11Pulmonary Department-Oncology Unit, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Greece; 2University Pulmonary Department-Interventional Unit, Ruhrland Klinic, University of Duisburg-Essen, Essen, Germany; 3Theagenio Anticancer Institute Research Laboratory, 4Department of Pathology, G Papanikolaou Hospital, Thessaloniki, Greece; 5II Medical Clinic, Hospital Coburg, University of Wuerzburg, Coburg, Germany; 6Cardiothoracic Surgery Department, Saint Luke Private Hospital, Panorama, 7Cardiothoracic Surgery Department, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, GreeceBackground: Bevacizumab and erlotinib have been demonstrated to prolong overall survival in patients with non-squamous non-small cell lung cancer (NSCLC. We designed a four-arm Phase III trial to evaluate the efficacy and toxicity of the combination of docetaxel, carboplatin, bevacizumab, and erlotinib in the first-line treatment of patients with NSCLC.Methods: A total of 229 patients with stage IIIb/IV non-squamous NSCLC were treated with two cycles of carboplatin (area under the concentration-time curve 5.5 and docetaxel 100 mg/m2 as chemotherapy. After completion of two treatment cycles, patients were evaluated for response and divided into four groups: 61/229 continued with four more cycles of chemotherapy (control group, 52/229 received chemotherapy plus erlotinib 150 mg daily, 56/229 received chemotherapy plus bevacizumab 7.5 mg/kg, and 60/229 were treated with the combination of chemotherapy, erlotinib, and bevacizumab until disease progression. The primary endpoint was overall survival.Results: Over 4 years of follow-up, there was no statistically

  9. Continuous-Course Reirradiation With Concurrent Carboplatin and Paclitaxel for Locally Recurrent, Nonmetastatic Squamous Cell Carcinoma of the Head-and-Neck

    Energy Technology Data Exchange (ETDEWEB)

    Kharofa, Jordan [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Choong, Nicholas [Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Wang, Dian; Firat, Selim; Schultz, Christopher [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Sadasiwan, Chitra [Medical College of Wisconsin, Milwaukee, WI (United States); Wong, Stuart, E-mail: Swong@mcw.edu [Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI (United States)

    2012-06-01

    Purpose: To examine the efficacy and toxicity of continuous-course, conformal reirradiation with weekly paclitaxel and carboplatin for the treatment of locally recurrent, nonmetastatic squamous cell carcinoma of the head and neck (SCCHN) in a previously irradiated field. Methods and Materials: Patients treated with continuous course-reirradiation with concurrent carboplatin and paclitaxel at the Medical College of Wisconsin and the Clement J. Zablocki VA from 2001 through 2009 were retrospectively reviewed. Patients included in the analysis had prior radiation at the site of recurrence of at least 45 Gy. The analysis included patients who received either intensity-modulated radiotherapy (RT) or three-dimensional conformal RT techniques. All patients received weekly concurrent carboplatin (AUC2) and paclitaxel (30-50 mg/m{sup 2}). Results: Thirty-eight patients with nonmetastatic SCCHN met the entry criteria for analysis. The primary sites at initial diagnosis were oropharyngeal or laryngeal in most patients (66%). Median reirradiation dose was 60 Gy (range, 54-70 Gy). Acute toxicity included Grade 2 neutropenia (5%), Grade 3 neutropenia (15%), and Grade 1/2 thrombocytopenia (8%). No deaths occurred from hematologic toxicity. Chemotherapy doses held (50%) was more prevalent than radiation treatment break (8%). Sixty-eight percent of patients required a gastrostomy tube in follow-up. Significant late toxicity was experienced in 6 patients (16%): 1 tracheoesophageal fistula, 1 pharyngocutaneous fistula, 3 with osteoradionecrosis, and 1 patient with a lingual artery bleed. Patients treated with three-dimensional conformal RT had more frequent significant late toxicites than patients treated with intensity-modulated RT (44% and 7% respectively, p < 0.05). The median time to progression was 7 months and progression-free rates at 1, 2, and 5 years was 44%, 34%, and 29% respectively. The median overall survival was 16 months. Overall survival at 1, 3, and 5 years was 54

  10. L-Carnitine halts apoptosis and myelosuppression induced by carboplatin in rat bone marrow cell cultures (BMC).

    Science.gov (United States)

    Abd-Allah, Adel R A; Al-Majed, Abdulhakeem A; Al-Yahya, Abdulaziz A; Fouda, Soliman I; Al-Shabana, Othman A

    2005-07-01

    Carboplatin (CP), a second generation platinum compound, is effective against various types of cancers, producing less nephrotoxicity and ototoxicity but more myelotoxicity than cisplatinum. CP-myelosuppression is the rate-limiting step of its clinical use. Prevention of CP-myelosuppression is a major target in the field of chemotherapy. Therefore, the present study investigates the use of L-carnitine (LCR)-an antioxidant, cardioprotective, neuroprotective, and immunostimulant nontoxic natural compound-to protect against CP-induced myelosuppression. The viability of BMC was studied using a trypan blue exclusion technique following incubation with CP and/or LCR as a function of time and concentration. Apoptosis was tested for by detecting the amount of DNA fragmentation and the visualization of DNA ladders upon gel electrophoresis. Bone marrow progenitor cell function was examined by colony forming unit assay. Cellular contents of glutathione (GSH) and malondialdehyde (MDA) were also estimated. Results revealed that LC50 of CP is 4.7 mM and the highest safe concentration of LCR is 5 mM. Co-exposure of LCR+CP rescued BMC viability by 37% compared to the CP-treated cultures. The LCR halts CP-induced apoptosis and it significantly improves the function of the bone marrow progenitors by increasing the number of colony-forming units as a response to granulocyte/macrophage colony stimulating factors. Finally, LCR restores CP-induced GSH depletion and prevents MDA elevation in BMC. In summary, the results suggest that LCR is able to protect against CP-induced myelosuppression, which suggests its use as an adjuvant therapy. This finding merits further investigation into the mechanism(s) of such protection as well as its interaction with CP antitumor activity.

  11. Intensity-Modulated Whole Abdominal Radiotherapy After Surgery and Carboplatin/Taxane Chemotherapy for Advanced Ovarian Cancer: Phase I Study

    International Nuclear Information System (INIS)

    Rochet, Nathalie; Sterzing, Florian; Jensen, Alexandra D.; Dinkel, Julien; Herfarth, Klaus K.; Schubert, Kai; Eichbaum, Michael H.; Schneeweiss, Andreas; Sohn, Christof; Debus, Juergen; Harms, Wolfgang

    2010-01-01

    Purpose: To assess the feasibility and toxicity of consolidative intensity-modulated whole abdominal radiotherapy (WAR) after surgery and chemotherapy in high-risk patients with advanced ovarian cancer. Methods and Materials: Ten patients with optimally debulked ovarian cancer International Federation of Gynecology and Obstetrics Stage IIIc were treated in a Phase I study with intensity-modulated WAR up to a total dose of 30 Gy in 1.5-Gy fractions as consolidation therapy after adjuvant carboplatin/taxane chemotherapy. Treatment was delivered using intensity-modulated radiotherapy in a step-and-shoot technique (n = 3) or a helical tomotherapy technique (n = 7). The planning target volume included the entire peritoneal cavity and the pelvic and para-aortal node regions. Organs at risk were kidneys, liver, heart, vertebral bodies, and pelvic bones. Results: Intensity-modulated WAR resulted in an excellent coverage of the planning target volume and an effective sparing of the organs at risk. The treatment was well tolerated, and no severe Grade 4 acute side effects occurred. Common Toxicity Criteria Grade III toxicities were as follows: diarrhea (n = 1), thrombocytopenia (n = 1), and leukopenia (n = 3). Radiotherapy could be completed by all the patients without any toxicity-related interruption. Median follow-up was 23 months, and 4 patients had tumor recurrence (intraperitoneal progression, n = 3; hepatic metastasis, n = 1). Small bowel obstruction caused by adhesions occurred in 3 patients. Conclusions: The results of this Phase I study showed for the first time, to our knowledge, the clinical feasibility of intensity-modulated whole abdominal radiotherapy, which could offer a new therapeutic option for consolidation treatment of advanced ovarian carcinoma after adjuvant chemotherapy in selected subgroups of patients. We initiated a Phase II study to further evaluate the toxicity of this intensive multimodal treatment.

  12. Intensity-modulated whole abdominal radiotherapy after surgery and carboplatin/taxane chemotherapy for advanced ovarian cancer: phase I study.

    Science.gov (United States)

    Rochet, Nathalie; Sterzing, Florian; Jensen, Alexandra D; Dinkel, Julien; Herfarth, Klaus K; Schubert, Kai; Eichbaum, Michael H; Schneeweiss, Andreas; Sohn, Christof; Debus, Juergen; Harms, Wolfgang

    2010-04-01

    To assess the feasibility and toxicity of consolidative intensity-modulated whole abdominal radiotherapy (WAR) after surgery and chemotherapy in high-risk patients with advanced ovarian cancer. Ten patients with optimally debulked ovarian cancer International Federation of Gynecology and Obstetrics Stage IIIc were treated in a Phase I study with intensity-modulated WAR up to a total dose of 30 Gy in 1.5-Gy fractions as consolidation therapy after adjuvant carboplatin/taxane chemotherapy. Treatment was delivered using intensity-modulated radiotherapy in a step-and-shoot technique (n = 3) or a helical tomotherapy technique (n = 7). The planning target volume included the entire peritoneal cavity and the pelvic and para-aortal node regions. Organs at risk were kidneys, liver, heart, vertebral bodies, and pelvic bones. Intensity-modulated WAR resulted in an excellent coverage of the planning target volume and an effective sparing of the organs at risk. The treatment was well tolerated, and no severe Grade 4 acute side effects occurred. Common Toxicity Criteria Grade III toxicities were as follows: diarrhea (n = 1), thrombocytopenia (n = 1), and leukopenia (n = 3). Radiotherapy could be completed by all the patients without any toxicity-related interruption. Median follow-up was 23 months, and 4 patients had tumor recurrence (intraperitoneal progression, n = 3; hepatic metastasis, n = 1). Small bowel obstruction caused by adhesions occurred in 3 patients. The results of this Phase I study showed for the first time, to our knowledge, the clinical feasibility of intensity-modulated whole abdominal radiotherapy, which could offer a new therapeutic option for consolidation treatment of advanced ovarian carcinoma after adjuvant chemotherapy in selected subgroups of patients. We initiated a Phase II study to further evaluate the toxicity of this intensive multimodal treatment.

  13. Macroglobulinemia de Waldenström - remissão completa após tratamento com rituximabe Successful outcome in Waldenström's macroglobulinemia treated with rituximab

    Directory of Open Access Journals (Sweden)

    Flavia C. F. Pimenta

    2008-10-01

    Full Text Available A macroglobulinemia de Waldenström (MW é uma patologia rara dos linfócitos B caracterizada pela produção monoclonal de IgM, e que pode manifestar-se clinicamente com fadiga, astenia, perda de peso, sangramento de mucosas e do trato gastrintestinal, lifonodonomegalias, hepatoesplenomegalia e alterações neurológicas. A doença é mais comum em pacientes idosos, e seus sintomas são decorrentes da hiperviscosidade sangüínea. Na MW observa-se hipergamaglobulinemia com pico monoclonal na eletroforese de proteínas séricas, níveis elevados de IgM e demais imunoglobulinas normais ou diminuídas, imunofenotipagem com linfócitos B CD19+, CD20+ e CD24+, aspirado de medula óssea hipercelular, e biópsia de medula óssea hipercelular com infiltração difusa de linfócitos, linfócitos plasmocitóides e plasmócitos. Atualmente, anticorpos monoclonais estão sendo usados na terapêutica da MW com grande sucesso. O rituximabe, anticorpo monoclonal anti -CD20, tem mostrado excelentes resultados no tratamento da MW, inclusive naqueles indivíduos que não obtiveram resposta adequada ao tratamento convencional. Nós reportamos o caso de uma mulher de 78 anos de idade com história de fadiga, astenia, anorexia, sonolência, inquietação, urticária, dificuldade para deambular e perda excessiva de peso, aproximadamente 22 kg em um período de cinco meses, cujo tratamento foi realizado com rituximabe. O objetivo deste relato é apresentar uma paciente com diagnóstico de MW e revisar aspectos clínicos e terapêutico atual da doença.Waldenström's macroglobulinemia is a rare pathology of B lymphocytes characterized by the production of monoclonal IgM, causing clinical manifestations which may include fatigue, asthenia, weight loss, bleeding of the mucosa and intestinal tract, lymphadenomegaly, hepatosplenomegaly and neurological alterations. The disease is more frequent among elderly patients and its symptoms are a result of the hyperviscosity of

  14. Rituximab for the treatment of refractory simultaneous anti-glomerular basement membrane (anti-GBM) and membranous nephropathy.

    Science.gov (United States)

    Bandak, Ghassan; Jones, Bruce A; Li, Jian; Yee, Jerry; Umanath, Kausik

    2014-02-01

    Antibody-mediated anti-glomerular basement membrane (anti-GBM) disease occurs rarely in the presence of another B-cell disorder, membranous nephropathy. The coexistence of these two autoimmune disorders would be anticipated to require differing, specific therapies targeted to each disease process. We describe a case of concomitant membranous nephropathy and anti-GBM disease in which conventional therapy, including steroids, plasmapheresis and cyclophosphamide, failed to attenuate the anti-GBM disease, yet responded to an alternative treatment of rituximab. This B-cell directed, monoclonal, chimeric antibody treatment substantially reduced anti-GBM antibody titers and led to discontinuation of plasmapheresis, while maintaining the remission of membranous nephropathy and anti-GBM disease.

  15. Radiolabeling of rituximab with {sup 188}Re and {sup 99m}Tc using the tricarbonyl technology

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Carla Roberta [Instituto de Pesquisas Energeticas e Nucleares, Av. Professor Lineu Prestes 2242, 05508-000 Sao Paulo (Brazil); Jeger, Simone [Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI (Switzerland); Osso, Joao Alberto [Instituto de Pesquisas Energeticas e Nucleares, Av. Professor Lineu Prestes 2242, 05508-000 Sao Paulo (Brazil); Mueller, Cristina; De Pasquale, Christine; Hohn, Alexander; Waibel, Robert [Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI (Switzerland); Schibli, Roger, E-mail: roger.schibli@psi.c [Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI (Switzerland); Department of Chemistry and Applied Biosciences of the ETH, 8093 Zurich (Switzerland)

    2011-01-15

    Introduction: The most successful clinical studies of immunotherapy in patients with non-Hodgkin's lymphoma (NHL) use the antibody rituximab (RTX) targeting CD20{sup +} B-cell tumors. Rituximab radiolabeled with {beta}{sup -} emitters could potentiate the therapeutic efficacy of the antibody by virtue of the particle radiation. Here, we report on a direct radiolabeling approach of rituximab with the {sup 99m}Tc- and {sup 188}Re-tricarbonyl core (IsoLink technology). Methods: The native format of the antibody (RTX{sub wt}) as well as a reduced form (RTX{sub red}) was labeled with {sup 99m}Tc/{sup 188}Re(CO){sub 3}. The partial reduction of the disulfide bonds to produce free sulfhydryl groups (-SH) was achieved with 2-mercaptoethanol. Radiolabeling efficiency, in vitro human plasma stability as well as transchelation toward cysteine and histidine was investigated. The immunoreactivity and binding affinity were determined on Ramos and/or Raji cells expressing CD20. Biodistribution was performed in mice bearing subcutaneous Ramos lymphoma xenografts. Results: The radiolabeling efficiency and kinetics of RTX{sub red} were superior to that of RTX{sub wt} ({sup 99m}Tc: 98% after 3 h for RTX{sub red} vs. 70% after 24 h for RTX{sub wt}). {sup 99m}Tc(CO){sub 3}-RTX{sub red} was used without purification for in vitro and in vivo studies whereas {sup 188}Re(CO){sub 3}-RTX{sub red} was purified to eliminate free {sup 188}Re-precursor. Both radioimmunoconjugates were stable in human plasma for 24 h at 37{sup o}C. In contrast, displacement experiments with excess cysteine/histidine showed significant transchelation in the case of {sup 99m}Tc(CO){sub 3}-RTX{sub red} but not with pre-purified {sup 188}Re(CO){sub 3}-RTX{sub red}. Both conjugates revealed high binding affinity to the CD20 antigen (K{sub d}=5-6 nM). Tumor uptake of {sup 188}Re(CO){sub 3}-RTX{sub red} was 2.5 %ID/g and 0.8 %ID/g for {sup 99m}Tc(CO){sub 3}-RTX{sub red} 48 h after injection. The values for other

  16. Combination therapy with rituximab, low-dose cyclophosphamide, and prednisone for idiopathic membranous nephropathy: a case series.

    Science.gov (United States)

    Cortazar, Frank B; Leaf, David E; Owens, Charles T; Laliberte, Karen; Pendergraft, William F; Niles, John L

    2017-02-01

    Membranous nephropathy is a common cause of the nephrotic syndrome. Treatment with standard regimens fails to induce complete remission in most patients. We evaluated the efficacy of combination therapy with rituximab, low-dose, oral cyclophosphamide, and an accelerated prednisone taper (RCP) for the treatment of idiopathic membranous nephropathy. We analyzed 15 consecutive patients with idiopathic membranous nephropathy treated with RCP at Massachusetts General Hospital. Seven patients (47%) received RCP as initial therapy, and the other eight patients (53%) received RCP for relapsing or refractory disease. All patients had at least 1 year of follow-up. The co-primary outcomes were attainment of partial and complete remission. Partial remission was defined as a urinary protein to creatinine ratio (UPCR) RCP resulted in high rates of complete remission. Larger studies evaluating this regimen are warranted.

  17. Rearrangements of MYC gene facilitate risk stratification in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

    DEFF Research Database (Denmark)

    Tzankov, Alexandar; Xu-Monette, Zijun Y; Gerhard, Marc

    2014-01-01

    In order to address the debatable prognostic role of MYC rearrangements in diffuse large B-cell lymphoma patients treated with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone, we evaluated MYC rearrangements by fluorescence in situ hybridization in 563 cases using...... with the dual-fusion probes, 15 detectable only with the break-apart probes and 20 detectable with both dual-fusion probes and break-apart probes. MYC rearrangements correlated with germinal center B-cell origin (P=0.02), MYC protein expression (P=0.032), and larger tumor mass size (P=0.0003). Patients with MYC...... was prognostically additive. Radiotherapy seemed to diminish the prognostic effects of MYC rearrangements in diffuse large B-cell lymphoma patients since only 2/10 irradiated patients with MYC rearrangements died of/with disease, compared with 16/28 non-irradiated patients with MYC rearrangements. We conclude...

  18. Vinorelbine and gemcitabine vs vinorelbine and carboplatin as first-line treatment of advanced NSCLC. A phase III randomised controlled trial by the Norwegian Lung Cancer Study Group

    DEFF Research Database (Denmark)

    Fløtten, Ø; Grønberg, B H; Bremnes, R

    2012-01-01

    BACKGROUND: Platinum-based doublet chemotherapy is the standard first-line treatment for advanced non-small cell lung cancer (NSCLC), but earlier studies have suggested that non-platinum combinations are equally effective and better tolerated. We conducted a national, randomised study to compare...... a non-platinum with a platinum combination. METHODS: Eligible patients had stage IIIB/IV NSCLC and performance status (PS) 0-2. Patients received up to three cycles of vinorelbine 60 mg m(-2) p.o.+gemcitabine 1000 mg m(-2) i.v. day 1 and 8 (VG) or vinorelbine 60 mg m(-2) p.o. day 1 and 8+carboplatin...... was 65 years, 58% were men and 25% had PS 2. Median survival was VG: 6.3 months; VC: 7.0 months, P=0.802. Vinorelbine plus carboplatin patients had more grade III/IV nausea/vomiting (VG: 4%, VC: 12%, P=0.008) and grade IV neutropenia (VG: 7%, VC: 19%, P

  19. The impact of carboplatin and toceranib phosphate on serum vascular endothelial growth factor (VEGF) and metalloproteinase-9 (MMP-9) levels and survival in canine osteosarcoma.

    Science.gov (United States)

    Gieger, Tracy L; Nettifee-Osborne, Julie; Hallman, Briana; Johannes, Chad; Clarke, Dawn; Nolan, Michael W; Williams, Laurel E

    2017-07-01

    In this pilot study, 10 dogs with osteosarcoma (OSA) were treated with amputation and subsequent carboplatin chemotherapy (300 mg/m 2 IV q3wk × 4 doses) followed by toceranib phosphate (2.75 mg/kg PO q48h starting at day 14 post carboplatin). Monthly clinical monitoring and serum measurements of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were acquired. No dogs were removed from the study due to toxicity. Levels of VEGF and MMP-9 did not change over time. Seven dogs died related to local recurrence and/or pulmonary or bone metastasis and the remainder died of other causes. Median OSA-free survival was 238 d with 34% 1-year progression-free survival. Median overall survival was 253 d with 30% alive at 1.5 y and 10% alive at 2 y. Although this regimen was well-tolerated, survival times did not exceed previously published data from dogs treated with amputation plus chemotherapy alone.

  20. Phase 1 trial of the oral AKT inhibitor MK-2206 plus carboplatin/paclitaxel, docetaxel, or erlotinib in patients with advanced solid tumors.

    Science.gov (United States)

    Molife, L Rhoda; Yan, Li; Vitfell-Rasmussen, Joanna; Zernhelt, Adriane M; Sullivan, Daniel M; Cassier, Philippe A; Chen, Eric; Biondo, Andrea; Tetteh, Ernestina; Siu, Lillian L; Patnaik, Amita; Papadopoulos, Kyriakos P; de Bono, Johann S; Tolcher, Anthony W; Minton, Susan

    2014-01-03

    Inhibition of AKT with MK-2206 has demonstrated synergism with anticancer agents. This phase 1 study assessed the MTD, DLTs, PK, and efficacy of MK-2206 in combination with cytotoxic and targeted therapies. Advanced solid tumor patients received oral MK-2206 45 or 60 mg (QOD) with either carboplatin (AUC 6.0) and paclitaxel 200 mg/m2 (arm 1), docetaxel 75 mg/m2 (arm 2), or erlotinib 100 or 150 mg daily (arm 3); alternative schedules of MK-2206 135-200 mg QW or 90-250 mg Q3W were also tested. MTD of MK-2206 (N = 72) was 45 mg QOD or 200 mg Q3W (arm 1); MAD was 200 mg Q3W (arm 2) and 135 mg QW (arm 3). DLTs included skin rash (arms 1, 3), febrile neutropenia (QOD, arms 1, 2), tinnitus (Q3W, arm 2), and stomatitis (QOD, arm 3). Common drug-related toxicities included fatigue (68%), nausea (49%), and rash (47%). Two patients with squamous cell carcinoma of the head and neck (arm 1; Q3W) demonstrated a complete and partial response (PR); additional PRs were observed in patients (1 each) with melanoma, endometrial, neuroendocrine prostate, NSCLC, and cervical cancers. Six patients had stable disease ≥6 months. MK-2206 plus carboplatin and paclitaxel, docetaxel, or erlotinib was well-tolerated, with early evidence of antitumor activity.

  1. The translational blocking of α5 and α6 integrin subunits affects migration and invasion, and increases sensitivity to carboplatin of SKOV-3 ovarian cancer cell line

    Energy Technology Data Exchange (ETDEWEB)

    Villegas-Pineda, Julio César, E-mail: jcvillegas@cinvestav.mx; Toledo-Leyva, Alfredo, E-mail: toledo_leyva@hotmail.com; Osorio-Trujillo, Juan Carlos, E-mail: clostrujillo2@yahoo.com.mx; Hernández-Ramírez, Verónica Ivonne, E-mail: arturomvi@hotmail.com; Talamás-Rohana, Patricia, E-mail: ptr@cinvestav.mx

    2017-02-15

    Epithelial ovarian cancer is the most lethal gynecologic malignancy. Integrins, overexpressed in cancer, are involved in various processes that favor the development of the disease. This study focused on determining the degree of involvement of α5, α6 and β3 integrin subunits in the establishment/development of epithelial ovarian cancer (EOC), such as proliferation, migration, invasion, and response to carboplatin. The translation of the α5, α6 and β3 integrins was blocked using morpholines, generating morphant cells for these proteins, which were corroborated by immunofluorescence assays. WST-1 proliferation assay showed that silencing of α5, α6, and β3 integrins does not affect the survival of morphants. Wound healing and transwell chamber assays showed that blocking α5 and α6 integrins decrease, in lesser and greater level respectively, the migratory and the invasive capacity of SKOV-3 cells. Finally, blocking α5 and α6 integrins partially sensitized the cells response to carboplatin, while blocking integrin β3 generated resistance to this drug. Statistical analyses were performed with the GraphPad Prism 5.0 software employing one way and two-way ANOVA tests; data are shown as average±SD. Results suggest that α5 and α6 integrins could become good candidates for chemotherapy targets in EOC.

  2. Randomized phase II study of vandetanib alone or with paclitaxel and carboplatin as first-line treatment for advanced non-small-cell lung cancer.

    Science.gov (United States)

    Heymach, John V; Paz-Ares, Luis; De Braud, Filippo; Sebastian, Martin; Stewart, David J; Eberhardt, Wilfried E E; Ranade, Anantbhushan A; Cohen, Graham; Trigo, Jose Manuel; Sandler, Alan B; Bonomi, Philip D; Herbst, Roy S; Krebs, Annetta D; Vasselli, James; Johnson, Bruce E

    2008-11-20

    Vandetanib is a once-daily, oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling. The antitumor activity of vandetanib monotherapy or vandetanib with paclitaxel and carboplatin (VPC) was compared with paclitaxel and carboplatin (PC) in previously untreated patients with non-small-cell lung cancer (NSCLC). All NSCLC histologies and previously treated CNS metastases were permitted in this partially blinded, placebo-controlled, randomized phase II study. Patients were randomly assigned 2:1:1 to receive vandetanib, VPC, or PC. Progression-free survival (PFS) was the primary end point, and the study was powered to detect a reduced risk of progression with VPC versus PC (hazard ratio = 0.70; one-sided P 1.33 v PC). Overall survival was not significantly different between patients receiving VPC or PC. Rash, diarrhea, and hypertension were common adverse events; no pulmonary or CNS hemorrhage events required intervention. VPC could be safely administered to patients with NSCLC, including those with squamous cell histology and treated brain metastases. Compared with the PC control arm, patients receiving VPC had longer PFS, meeting the prespecified study end point, whereas those receiving vandetanib monotherapy had shorter PFS.

  3. An inflammation-based cumulative prognostic score system in patients with diffuse large B cell lymphoma in rituximab era.

    Science.gov (United States)

    Sun, Feifei; Zhu, Jia; Lu, Suying; Zhen, Zijun; Wang, Juan; Huang, Junting; Ding, Zonghui; Zeng, Musheng; Sun, Xiaofei

    2018-01-02

    Systemic inflammatory parameters are associated with poor outcomes in malignant patients. Several inflammation-based cumulative prognostic score systems were established for various solid tumors. However, there is few inflammation based cumulative prognostic score system for patients with diffuse large B cell lymphoma (DLBCL). We retrospectively reviewed 564 adult DLBCL patients who had received rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) therapy between Nov 1 2006 and Dec 30 2013 and assessed the prognostic significance of six systemic inflammatory parameters evaluated in previous studies by univariate and multivariate analysis:C-reactive protein(CRP), albumin levels, the lymphocyte-monocyte ratio (LMR), the neutrophil-lymphocyte ratio(NLR), the platelet-lymphocyte ratio(PLR)and fibrinogen levels. Multivariate analysis identified CRP, albumin levels and the LMR are three independent prognostic parameters for overall survival (OS). Based on these three factors, we constructed a novel inflammation-based cumulative prognostic score (ICPS) system. Four risk groups were formed: group ICPS = 0, ICPS = 1, ICPS = 2 and ICPS = 3. Advanced multivariate analysis indicated that the ICPS model is a prognostic score system independent of International Prognostic Index (IPI) for both progression-free survival (PFS) (p systemic inflammatory status was associated with clinical outcomes of patients with DLBCL in rituximab era. The ICPS model was shown to classify risk groups more accurately than any single inflammatory prognostic parameters. These findings may be useful for identifying candidates for further inflammation-related mechanism research or novel anti-inflammation target therapies.

  4. Multicenter Retrospective Analysis of the Effectiveness and Safety of Rituximab in Korean Patients with Refractory Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    So-Young Bang

    2012-01-01

    Full Text Available Objective. Although two recent randomized placebo-controlled trials of rituximab (RTX failed to demonstrate efficacy in systemic lupus erythematosus (SLE, clinicians continue to use off-label RTX for cases refractory to current treatments. We evaluated the effectiveness and safety of rituximab for patients with refractory SLE in Korea. Methods. We retrospectively analyzed multicenter patients treated with RTX in Korea. Results. 39 SLE patients treated with RTX were included in the following manner: lupus nephritis 43.6%, hematologic 33.3%, arthritis 7.8%, myositis 7.8%, and others 7.7%. All patients had responded poorly to at least one conventional immunosuppressive agent (mean 2.5 ± 1.1, cyclophosphamide 43.6%, mycophenolate mofetil 48.7%, and other drugs before RTX. Clinical improvements (complete or partial remission occurred in patients with renal disease, hematologic disease, arthritis, myositis, and other manifestations at 6 months after RTX. The SLEDAI score was significantly decreased from 10.8±7.1 at baseline to 6.7±4.0 at 6 months, 6.2±4.1 at 12 months, and 5.5±3.6 at 24 months after RTX (P<0.05. Among 28 clinical responders, 4 patients experienced a relapse of disease at 25±4 months. Infections were noted in 3 patients (7.7%. Conclusion. RTX could be an effective and relatively safe therapeutic option in patients with severe refractory SLE until novel B-cell depletion therapy is available.

  5. Analysis of anti-HLA antibodies in sensitized kidney transplant candidates subjected to desensitization with intravenous immunoglobulin and rituximab.

    Science.gov (United States)

    Lobashevsky, Andrew L; Higgins, Nancy G; Rosner, Kevin M; Mujtaba, Muhammad A; Goggins, William C; Taber, Tim E

    2013-07-27

    Preexisting donor-specific antibodies against human leukocyte antigens are major risk factors for acute antibody-mediated and chronic rejection of kidney transplant grafts. Immunomodulation (desensitization) protocols may reduce antibody concentration and improve the success of transplant. We investigated the effect of desensitization with intravenous immunoglobulin and rituximab on the antibody profile in highly sensitized kidney transplant candidates. In 31 transplant candidates (calculated panel-reactive antibody [cPRA], 34%-99%), desensitization included intravenous immunoglobulin on days 0 and 30 and a single dose of rituximab on day 15. Anti-human leukocyte antigen antibodies were analyzed before and after desensitization. Reduction of cPRA from 25% to 50% was noted for anti-class I (5 patients, w