"Time sequential high dose of Cytarabine in acute myelocytic leukemia "

Directory of Open Access Journals (Sweden)

Ghavamzadeh A

2003-05-01

Full Text Available Given preliminary evidence of timed, sequential chemotherapy of high dose cytosine arabinoside the current study was initiated to assess the side effects and efficacy of this regimen in patients with newly acute myelocytic leukemia (AML. Nineteen adults who referred to Hematology-Oncology and Bone Marrow Transplantation (BMT research center of Tehran University of Medical Sciences were enrolled in a trial from Aug 1999 to Nov 2000. All patients had a Karnofski classification above 60%. At this time induction therapy consisted of daunorubicin or idarubicin given at a dose of 60 mg/m² and 12 mg/m² IV respectively on days 1-3, and cytarabine (Ara-C 100 mg/m² intravenously by continuous infusion on days 1-7, followed by Ara-C 1000 mg/m² given on day 8-10 every 12 hours by IV infusion. Consolidation therapy started after 35th day. Of 19 fully evaluable patients, 10 patients achieved a complete remission, whereas 36.6% patients succumbed to death due to regeneration failure. The clinical data show that the overall survival rate from diagnosis 55.5% (95% CI, 30.8-78.5 at 6 months for the entire cohort of the patients. Disease free survival is also 50% (95% CI, 26-74. Mean duration of death due to treatment was 20 days (range 17-29 after beginning the regimen. Presenting WBC counts, French-American-British (FAB classification, sex and age were not useful prognostic variables. Fever, diarrhea, nausea and vomiting and GI hemorrhage were seen in 19, 6, 4, 7 patients respectively. It seems the 3+7+3 regimen is a promising approach for the AML patients regarding to high complete remission rate, but more supportive care should be considered. Furthermore any, benefit in long-term outcome can’t be determined regardless to the choice of post remission therapy (e.g., GCSF, appropriate antibiotics and etc.

High-dose 8% capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy: single-center experience.

Science.gov (United States)

Filipczak-Bryniarska, Iwona; Krzyzewski, Roger M; Kucharz, Jakub; Michalowska-Kaczmarczyk, Anna; Kleja, Justyna; Woron, Jarosław; Strzepek, Katarzyna; Kazior, Lucyna; Wordliczek, Jerzy; Grodzicki, Tomasz; Krzemieniecki, Krzysztof

2017-08-17

High-dose capsaicin patch is effective in treatment of neuropathic pain in HIV-associated neuropathy and diabetic neuropathy. There are no studies assessing effectiveness of high-dose capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy. We sought to determine the effectiveness of treatment of pain associated with chemotherapy-induced peripheral neuropathy with high-dose capsaicin patch. Our study group consisted of 18 patients with clinically confirmed oxaliplatin-induced neuropathy. Baseline characteristic including underling disease, received cumulative dose of neurotoxic agent, neuropathic symptoms, prior treatment and initial pain level were recorded. Pain was evaluated with Numeric Rating Scale prior to treatment with high-dose capsaicin and after 1.8 day and after 8 and 12 weeks after introducing treatment. Patients were divided into two groups accordingly to the amount of neurotoxic agent that caused neuropathy (high sensitivity and low sensitivity group). Most frequent symptoms of chemotherapy-induced neuropathy were: pain (88.89%), paresthesis (100%), sock and gloves sensation (100%) and hypoesthesis (100%). Initial pain level was 7.45 ± 1.14. Mean cumulative dose of oxaliplatin after which patients developed symptoms was 648.07 mg/m 2 . Mean pain level after 12 weeks of treatment was 0.20 ± 0.41. When examined according to high and low sensitivity to neurotoxic agent patients with low sensitivity had higher pain reduction, especially after 8 days after introducing treatment (69.55 ± 12.09 vs. 49.40 ± 20.34%; p = 0.02) and after 12 weeks (96.96 ± 5.56 vs. 83.93 ± 18.59%; p = 0.04). High-dose capsaicin patch is an effective treatment for pain associated with chemotherapy-induced neuropathy in patients treated with oxaliplatin. Patients with lower sensitivity to neurotoxic agents have better response to treatment and pain reduction.

Effect of cryoablation sequential chemotherapy on patients with advanced non-small cell lung cancer

Directory of Open Access Journals (Sweden)

Shu-Hui Yao

2016-03-01

Full Text Available Objective: To evaluate the effect of cryoablation sequential chemotherapy on patients with advanced non-small cell lung cancer. Methods: A total of 39 cases with advanced non-small cell lung cancer who received cryoablation sequential chemotherapy and 39 cases with advanced non-small cell lung cancer who received chemotherapy alone were selected and enrolled in sequential group and control group, disease progression and survival of two groups were followed up, and contents of tumor markers and angiogenesis molecules in serum as well as contents of T-lymphocyte subsets in peripheral blood were detected. Results: Progressionfree survival and median overall survival (mOS of sequential group were longer than those of control group, and cumulative cases of tumor progression at various points in time were significantly less than those of control group (P<0.05; 1 month after treatment, serum tumor markers CEA, CYFRA21-1 and NSE contents, serum angiogenesis molecules PCDGF, VEGF and HDGF contents as well as CD3+CD4-CD8+CD28-T cell content in peripheral blood of sequential group were significantly lower than those of control group (P<0.05, and contents of CD3+CD4+CD8-T cell and CD3+CD4-CD8+CD28+T cell in peripheral blood were higher than those of control group (P<0.05. Conclusions: Cryoablation sequential chemotherapy can improve the prognosis of patients with advanced non-small cell lung cancer, delay disease progression, prolong survival time, inhibit angiogenesis and improve immune function.

HIGH-DOSE CHEMOTHERAPY WITH STEM-CELL REINFUSION AND GROWTH-FACTOR SUPPORT FOR SOLID TUMORS

NARCIS (Netherlands)

DEVRIES, EGE; DEGRAAF, H; VANDERGRAAF, WTA; MULDER, NH; Boonstra, A.

1995-01-01

With the help of stem cell reinfusion and hematopoietic growth factors, it is possible to get up to a ten-fold dose increase for certain chemotherapeutic drugs, A number of reasons may have made high-dose chemotherapy less dangerous and the fore more acceptable in a more upfront treatment setting,

High-dose chemotherapy : studies on supportive care, quality of life and late effects of treatment

NARCIS (Netherlands)

Nieboer, Peter

2008-01-01

Drug resistance is a major problem in the treatment of malignancies. Based on steep dose-response relationship for certain chemotherapeutic drugs in vitro on tumor cell survival, high-dose chemotherapy was considered of interest for the treatment of malignancies. Introduction of autologous

Efficacy of high-dose alkylating chemotherapy in HER2/neu-negative breast cancer

NARCIS (Netherlands)

Rodenhuis, S.; Bontenbal, M.; Hoesel, Q.G.C.M. van; Smit, W.M.; Nooij, M.A.; Voest, E.E.; Wall, E. van der; Hupperets, P.; Tinteren, H. van; Peterse, J.L.; Vijver, M.J. van de; Vries, E.G.E. de

2006-01-01

Background: High-dose chemotherapy in the adjuvant treatment of breast cancer has been abandoned by many. Patients and methods: 885 patients with stage III primary breast cancer and four or more axillary lymph node metastases were randomised to receive either five courses of FEC (fluorouracil,

Efficacy of high-dose alkylating chemotherapy in HER2/neu-negative breast cancer

NARCIS (Netherlands)

Rodenhuis, S; Bontenbal, M; van Hoesel, QGCM; Smit, WM; Nooij, MA; Voest, EE; van der Wall, E; Hupperets, P; van Tinteren, H; Peterse, JL; van de Vijver, MJ; de Vries, EGE

Background: High-dose chemotherapy in the adjuvant treatment of breast cancer has been abandoned by many. Patients and methods: 885 patients with stage III primary breast cancer and four or more axillary lymph node metastases were randomised to receive either five courses of FEC (fluorouracil,

Adjuvant chemotherapy with sequential or concurrent anthracycline and docetaxel: Breast International Group 02-98 randomized trial

DEFF Research Database (Denmark)

Francis, P.; Crown, J.; Di, Leo A.

2008-01-01

BACKGROUND: Docetaxel is more effective than doxorubicin for patients with advanced breast cancer. The Breast International Group 02-98 randomized trial tested the effect of incorporating docetaxel into anthracycline-based adjuvant chemotherapy and compared sequential vs concurrent administration....... However, important differences may be related to doxorubicin and docetaxel scheduling, with sequential but not concurrent administration, appearing to produce better DFS than anthracycline-based chemotherapy Udgivelsesdato: 2008/1/16...

Clinical approaches involving thrombopoietin to shorten the period of thrombocytopenia after high-dose chemotherapy

NARCIS (Netherlands)

Tijssen, Marloes R.; van der Schoot, C. Ellen; Voermans, Carlijn; Zwaginga, Jaap Jan

2006-01-01

High-dose chemotherapy followed by a peripheral blood stem cell transplant is successfully used for a wide variety of malignancies. A major drawback, however, is the delay in platelet recovery. Several clinical strategies using thrombopoietin (Tpo) have been developed in an attempt to speed up

Delivery of adjuvant sequential dose-dense FEC-Doc to patients with breast cancer is feasible, but dose reductions and toxicity are dependent on treatment sequence.

Science.gov (United States)

Wildiers, H; Dirix, L; Neven, P; Prové, A; Clement, P; Squifflet, P; Amant, F; Skacel, T; Paridaens, R

2009-03-01

This study prospectively investigates the impact of dose densification and altering sequence of fluorouracil, epirubicin and cyclophosphamide [FEC(100)] and docetaxel [Doc] on dose delivery and tolerability of adjuvant chemotherapy in breast cancer patients. 117 patients with high-risk primary operable breast cancer were randomized (1:1:2:2) to conventional (three cycles of 3-weekly FEC(100) then three cycles of 3-weekly Doc 100 mg/m(2) or reverse sequence) or dose-dense (dd) treatment (four 10- to 11-day cycles of FEC(75) then four 2-weekly cycles of Doc 75 mg/m(2), or the reverse). In the dd arms, pegfilgrastim was given on day 2 of each cycle, but only as secondary prophylaxis in conventional arms. The primary endpoint was the proportion of patients completing intended cycles at relative dose intensity >or=85% and this was achieved by 95% of patients in each group except for the ddDoc-->FEC group (90%). Dose intensity in the dd arms increased by 48% for FEC and 11% for docetaxel, compared with the conventional arms (both P Doc dose reductions were more frequent with dd treatment and when Doc was given after FEC. Grade 3-4 neutropenia was significantly more frequent with conventional treatment, while fatigue and hand-foot syndrome were numerically more common with dd treatment, particularly when Doc was given after FEC. Discussion Delivery of adjuvant sequential ddFEC and Doc is feasible with growth factor support, and chemotherapy sequence appeared to affect delivery of target doses and toxicity.

Effect of Tailored Dose-Dense Chemotherapy vs Standard 3-Weekly Adjuvant Chemotherapy on Recurrence-Free Survival Among Women With High-Risk Early Breast Cancer: A Randomized Clinical Trial.

Science.gov (United States)

Foukakis, Theodoros; von Minckwitz, Gunter; Bengtsson, Nils-Olof; Brandberg, Yvonne; Wallberg, Birgitta; Fornander, Tommy; Mlineritsch, Brigitte; Schmatloch, Sabine; Singer, Christian F; Steger, Günther; Egle, Daniel; Karlsson, Eva; Carlsson, Lena; Loibl, Sibylle; Untch, Michael; Hellström, Mats; Johansson, Hemming; Anderson, Harald; Malmström, Per; Gnant, Michael; Greil, Richard; Möbus, Volker; Bergh, Jonas

2016-11-08

Standard dosing of chemotherapy based on body surface area results in marked interpatient variation in pharmacokinetics, toxic effects, and efficacy. Whether tailored dosing can improve outcomes is unknown, as is the role of dose-dense adjuvant chemotherapy. To determine whether tailored dose-dense adjuvant chemotherapy improves the outcomes of early breast cancer compared with a standard 3-weekly chemotherapy schedule. A randomized, open-label, phase 3 trial of women aged 65 years and younger who had surgery for nonmetastatic node-positive or high-risk node-negative breast cancer at 86 sites in Sweden, Germany, and Austria between February 20, 2007, and September 14, 2011. Patients were randomized 1:1 either to 4 cycles of leukocyte nadir-based tailored and dose-dense adjuvant epirubicin and cyclophosphamide every 2 weeks followed by 4 cycles of tailored dose-dense docetaxel every 2 weeks, or to standard-interval chemotherapy with 3 cycles of fluorouracil and epirubicin-cyclophosphamide every 3 weeks followed by 3 cycles of docetaxel every 3 weeks. The primary end point was breast cancer recurrence-free survival (BCRFS). Secondary end points included 5-year event-free survival (EFS), distant disease-free survival (DDFS), overall survival (OS), and rates of grade 3 or 4 toxic effects. Among 2017 randomized patients (1006 in the tailored dose-dense group and 1011 in the control group; median [IQR] age, 51 [45-58] years; 80% with hormone receptor-positive tumors; 97% with node-positive disease), 2000 received study treatment (≥1 cycle of chemotherapy; 1001 in the tailored dose-dense group and 999 in the control group). After a median follow-up of 5.3 years (IQR, 4.5-6.1 years), 269 BCRFS events were reported, 118 in the tailored dose-dense group and 151 in the control group (HR, 0.79; 95% CI, 0.61-1.01; log-rank P = .06; 5-year BCRFS, 88.7% vs 85.0%). The tailored dose-dense group had significantly better EFS than the control group (HR, 0.79; 95% CI, 0

Sequential response patterns to chemotherapy and radiotherapy in head and neck cancer

International Nuclear Information System (INIS)

Hong, W.K.; O'Donoghue, G.M.; Sheetz, S.

1985-01-01

Surgery and/or radiotherapy have been the standard therapies for locally advanced squamous cell carcinoma of the head and neck region. Despite major improvement in these therapeutic techniques, the control rate in cases of advanced cancer remains poor. More recently, induction chemotherapy as initial treatment has been used in previously untreated squamous cell carcinoma of the head and neck. For the last 6 years at the Boston Veterans Administration (V.A.) Medical Center, initial induction chemotherapy followed by surgery and/or radiotherapy has been employed in the treatment of advanced head and neck cancer. The use of chemotherapy and radiotherapy has allowed the authors to monitor and correlate sequential response patterns produced by each modality of treatment. The authors have observed that responders to chemotherapy can be predicted to have further response to subsequent radiotherapy

Evaluation of an every-other-day palonosetron schedule to control emesis in multiple-day high-dose chemotherapy.

Science.gov (United States)

Mirabile, Aurora; Celio, Luigi; Magni, Michele; Bonizzoni, Erminio; Gianni, Alessandro Massimo; Di Nicola, Massimo

2014-12-01

Efficacy of intermittent palonosetron dosing in patients undergoing multiple-day, high-dose chemotherapy (HDC) was investigated. Fifty-eight patients received palonosetron (0.25 mg intravenous [iv.]) every other day plus daily dexamethasone (8 mg iv. twice daily) dosing. The primary end point was complete control (CC; no emesis, no rescue anti-emetics, and no more than mild nausea) in the overall acute-period (until 24 h after chemotherapy completion). Acute-period CC occurred in 81% and 50% of patients receiving palonosetron and ondansetron (historical control cohort), respectively. Palonosetron (odds ratio [OR]: 4.37; p = 0.001) and a longer duration of HDC regimen (OR: 3.47; p = 0.011) independently predicted a better anti-emetic outcome. Palonosetron every other day plus daily dexamethasone is an effective anti-emetic coverage in patients undergoing HDC.

Sequential versus "sandwich" sequencing of adjuvant chemoradiation for the treatment of stage III uterine endometrioid adenocarcinoma.

Science.gov (United States)

Lu, Sharon M; Chang-Halpenny, Christine; Hwang-Graziano, Julie

2015-04-01

To compare the efficacy and tolerance of adjuvant chemotherapy and radiotherapy delivered in sequential (chemotherapy followed by radiation) versus "sandwich" fashion (chemotherapy, interval radiation, and remaining chemotherapy) after surgery in patients with FIGO stage III uterine endometrioid adenocarcinoma. From 2004 to 2011, we identified 51 patients treated at our institution fitting the above criteria. All patients received surgical staging followed by adjuvant chemoradiation (external-beam radiation therapy (EBRT) with or without high-dose rate (HDR) vaginal brachytherapy (VB)). Of these, 73% and 27% of patients received their adjuvant therapy in sequential and sandwich fashion, respectively. There were no significant differences in clinical or pathologic factors between patients treated with either regimen. Thirty-nine (76%) patients had stage IIIC disease. The majority of patients received 6 cycles of paclitaxel with carboplatin or cisplatin. Median EBRT dose was 45 Gy and 54% of patients received HDR VB boost (median dose 21 Gy). There were no significant differences in the estimated 5-year overall survival, local progression-free survival, and distant metastasis-free survival between the sequential and sandwich groups: 87% vs. 77% (p=0.37), 89% vs. 100% (p=0.21), and 78% vs. 85% (p=0.79), respectively. No grade 3-4 genitourinary or gastrointestinal toxicities were reported in either group. There was a trend towards higher incidence of grade 3-4 hematologic toxicity in the sandwich group. Adjuvant chemoradiation for FIGO stage III endometrioid uterine cancer given in either sequential or sandwich fashion appears to offer equally excellent early clinical outcomes and acceptably low toxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

Concurrent and sequential initiation of ovarian function suppression with chemotherapy in premenopausal women with endocrine-responsive early breast cancer: an exploratory analysis of TEXT and SOFT.

Science.gov (United States)

Regan, M M; Walley, B A; Francis, P A; Fleming, G F; Láng, I; Gómez, H L; Colleoni, M; Tondini, C; Pinotti, G; Salim, M; Spazzapan, S; Parmar, V; Ruhstaller, T; Abdi, E A; Gelber, R D; Coates, A S; Goldhirsch, A; Pagani, O

2017-09-01

Recent breast cancer treatment guidelines recommend that higher-risk premenopausal patients should receive ovarian function suppression (OFS) as part of adjuvant endocrine therapy. If chemotherapy is also given, it is uncertain whether to select concurrent or sequential OFS initiation. We analyzed 1872 patients enrolled in the randomized phase III TEXT and SOFT trials who received adjuvant chemotherapy for hormone receptor-positive, HER2-negative breast cancer and upon randomization to an OFS-containing adjuvant endocrine therapy, initiated gonadotropin-releasing-hormone-agonist triptorelin. Breast cancer-free interval (BCFI) was compared between patients who received OFS concurrently with chemotherapy in TEXT (n = 1242) versus sequentially post-chemotherapy in SOFT (n = 630). Because timing of trial enrollment relative to adjuvant chemotherapy differed, we implemented landmark analysis re-defining BCFI beginning 1 year after final dose of chemotherapy (median, 15.5 and 8.1 months from enrollment to landmark in TEXT and SOFT, respectively). As a non-randomized treatment comparison, we implemented comparative-effectiveness propensity score methodology with weighted Cox modeling. Distributions of several clinico-pathologic characteristics differed between groups. Patients who were premenopausal post-chemotherapy in SOFT were younger on average. The median duration of adjuvant chemotherapy was 18 weeks in both groups. There were 231 (12%) BC events after post-landmark median follow-up of about 5 years. Concurrent use of triptorelin with chemotherapy was not associated with a significant difference in post-landmark BCFI compared with sequential triptorelin post-chemotherapy, either in the overall population (HR = 1.11, 95% CI 0.72-1.72; P = 0.72; 4-year BCFI 89% in both groups), or in the subgroup of 692 women SOFT after about 5 years median follow-up, with limited statistical power especially for the subgroup <40 years, neither

Sequential radiotherapy and chemotherapy using CDDP and 5-FU for advanced head and neck cancer

International Nuclear Information System (INIS)

Takamura, Akio; Arimoto, Takuro; Mizoe, Jun-etsu; Tomita, Masayoshi; Kitahara, Toshihiro; Irie, Goro; Matsuoka, Yoshisuke.

1991-01-01

From April 1989 to January 1990, nine patients with locally advanced stage IV squamous cell carcinoma of the head and neck underwent combined chemotherapy and radiotherapy (RT). Chemotherapy consisted of two cycles of CDDP (100 mg/m 2 , day 1) + 5-FU (1 g/m 2 , days 1-5, continuous infusion) every five weeks. RT was interdigitated with chemotherapy after the second course of chemotherapy. Each course was initiated two or three days after interrupting chemotherapy. RT was delivered at 65 or 70 Gy for 8 weeks. Of the 7 patients completing the treatment, 29% responded totally, and 43% responded partially. Seven patients died: two due to acute treatment-related toxicity; four due to locoregional progression; and one due to an unrelated cause. Two patients are still alive (10 and 12 months); one is free of tumor, the other has a metastatic bone tumor. Though sequential use of CT might be considered effective for some patients, acute toxicity was moderate to severe and patients with poor performance (≤70%), elderly (≥70 yr) and renal dysfunction (creatinine clearance<80 ml/min) patients must be considered as high risk for treatment by our combined regimen. (author)

Long-term brain structural magnetic resonance imaging and cognitive functioning in children treated for acute lymphoblastic leukemia with high-dose methotrexate chemotherapy alone or combined with CNS radiotherapy at reduced total dose to 12 Gy

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Zajac-Spychala, Olga; Pilarczyk, Jakub; Derwich, Katarzyna; Wachowiak, Jacek [Poznan University of Medical Sciences, Department of Pediatric Oncology, Hematology and Transplantology, Poznan (Poland); Pawlak, Mikolaj A. [Poznan University of Medical Sciences, Department of Neurology and Cerebrovascular Disorders, Poznan (Poland); Karmelita-Katulska, Katarzyna [Poznan University of Medical Sciences, Department of Neuroradiology, Poznan (Poland)

2017-02-15

The aim of this study was to assess the long-term side effects of central nervous system prophylaxis (high-dose chemotherapy alone vs chemotherapy and CNS radiotherapy) according to the ALL IC-BFM 2002. Thirty-tree children aged 6.7-19.9 years have been studied. The control group consisted of 12 children newly diagnosed with acute lymphoblastic leukemia. We assessed subcortical gray matter volume using automatic MRI segmentation and cognitive performance to identify differences between two therapeutic schemes and patients prior to treatment. Patients treated with chemotherapy and CNS radiotherapy had smaller hippocampi than two other subgroups and lower IQ score than patients treated with chemotherapy alone. Both treated groups, whether with chemotherapy only or in combination with CNS radiotherapy, had significantly lower volumes of caudate nucleus and performed significantly worse on measures of verbal fluency in comparison with patients prior to treatment. There were no differences in the mean volumes of total white matter, total gray matter, thalamus, putamen, and amygdala between the studied groups. In all children treated according to the ALL IC-BFM 2002 with high-dose chemotherapy, both decreased volume of selected subcortical structures and cognitive impairment was observed, especially in children who received chemotherapy in combination with reduced dose CNS radiotherapy. In all children treated according to the ALL IC-BFM 2002 with high-dose chemotherapy, both decreased volume of selected subcortical structures and cognitive impairment were observed, especially in children who received chemotherapy in combination with CNS radiotherapy. (orig.)

Long-term brain structural magnetic resonance imaging and cognitive functioning in children treated for acute lymphoblastic leukemia with high-dose methotrexate chemotherapy alone or combined with CNS radiotherapy at reduced total dose to 12 Gy

International Nuclear Information System (INIS)

Zajac-Spychala, Olga; Pilarczyk, Jakub; Derwich, Katarzyna; Wachowiak, Jacek; Pawlak, Mikolaj A.; Karmelita-Katulska, Katarzyna

2017-01-01

The aim of this study was to assess the long-term side effects of central nervous system prophylaxis (high-dose chemotherapy alone vs chemotherapy and CNS radiotherapy) according to the ALL IC-BFM 2002. Thirty-tree children aged 6.7-19.9 years have been studied. The control group consisted of 12 children newly diagnosed with acute lymphoblastic leukemia. We assessed subcortical gray matter volume using automatic MRI segmentation and cognitive performance to identify differences between two therapeutic schemes and patients prior to treatment. Patients treated with chemotherapy and CNS radiotherapy had smaller hippocampi than two other subgroups and lower IQ score than patients treated with chemotherapy alone. Both treated groups, whether with chemotherapy only or in combination with CNS radiotherapy, had significantly lower volumes of caudate nucleus and performed significantly worse on measures of verbal fluency in comparison with patients prior to treatment. There were no differences in the mean volumes of total white matter, total gray matter, thalamus, putamen, and amygdala between the studied groups. In all children treated according to the ALL IC-BFM 2002 with high-dose chemotherapy, both decreased volume of selected subcortical structures and cognitive impairment was observed, especially in children who received chemotherapy in combination with reduced dose CNS radiotherapy. In all children treated according to the ALL IC-BFM 2002 with high-dose chemotherapy, both decreased volume of selected subcortical structures and cognitive impairment were observed, especially in children who received chemotherapy in combination with CNS radiotherapy. (orig.)

Fatigue and Relating Factors in High-Risk Breast Cancer Patients Treated With Adjuvant Standard or High-Dose Chemotherapy: A Longitudinal Study

NARCIS (Netherlands)

Nieboer, P.; Buijs, C.; Rodenhuis, S.; Seynaeve, C.; Beex, L.V.A.M.; Wall, E. van der; Richel, D.J.; Nooij, M.A.; Voest, E.E.; Hupperets, P.; Mulder, N.H.; Graaf, W.T.A. van der; TenVergert, E.M.; Tinteren, H. van; Vries, E.G.E. de

2005-01-01

PURPOSE Determine whether standard or high-dose chemotherapy leads to changes in fatigue, hemoglobin (Hb), mental health, muscle and joint pain, and menopausal status from pre- to posttreatment and to evaluate whether fatigue is associated with these factors in disease-free breast cancer patients.

Fatigue and relating factors in high-risk breast cancer patients treated with adjuvant standard or high-dose chemotherapy: a longitudinal study.

NARCIS (Netherlands)

Nieboer, P.; Buijs, C.; Rodenhuis, S.; Seynaeve, C.; Beex, L.V.A.M.; Wall, E. van der; Richel, D.J.; Nooij, M.A.; Voest, E.E.; Hupperets, P.S.G.J.; Mulder, N.H.; Graaf, W.T.A. van der; Vergert, E.M. ten; Tinteren, H.L.G. van; Vries, E.G.F. de

2005-01-01

PURPOSE: Determine whether standard or high-dose chemotherapy leads to changes in fatigue, hemoglobin (Hb), mental health, muscle and joint pain, and menopausal status from pre- to post-treatment and to evaluate whether fatigue is associated with these factors in disease-free breast cancer patients.

Fatigue and relating factors in high-risk breast cancer patients treated with adjuvant standard or high-dose chemotherapy: a longitudinal study

NARCIS (Netherlands)

Nieboer, Peter; Buijs, Ciska; Rodenhuis, Sjoerd; Seynaeve, Caroline; Beex, Louk V. A. M.; van der Wall, Elsken; Richel, Dick J.; Nooij, Marianne A.; Voest, Emile E.; Hupperets, Pierre; Mulder, Nanno H.; van der Graaf, Winette T. A.; TenVergert, Els M.; van Tinteren, Harm; de Vries, Elisabeth G. E.

2005-01-01

PURPOSE: Determine whether standard or high-dose chemotherapy leads to changes in fatigue, hemoglobin (Hb), mental health, muscle and joint pain, and menopausal status from pre- to post-treatment and to evaluate whether fatigue is associated with these factors in disease-free breast cancer patients.

Fatigue and relating factors in high-risk breast cancer patients treated with adjuvant standard or high-dose chemotherapy : A longitudinal study

NARCIS (Netherlands)

Nieboer, P; Buijs, C; Rodenhuis, S; Seynaeve, C; Beex, LVAM; van der Wall, E; Richel, DJ; Nooij, MA; Voest, EE; Hupperets, P; Mulder, NH; van der Graaf, WTA; TenVergert, EM; van Tinteren, H; de Vries, EGE

2005-01-01

Purpose Determine whether standard or high-dose chemotherapy leads to changes in fatigue, hemoglobin (Hb), mental health, muscle and joint pain, and menopausal status from pre- to post-treatment and to evaluate whether fatigue is associated with these factors in disease-free breast cancer patients.

Late effects of high-dose adjuvant chemotherapy on white and gray matter in breast cancer survivors: Converging results from multimodal magnetic resonance imaging

NARCIS (Netherlands)

de Ruiter, Michiel B.; Reneman, Liesbeth; Boogerd, Willem; Veltman, Dick J.; Caan, Matthan; Douaud, Gwenaëlle; Lavini, Cristina; Linn, Sabine C.; Boven, Epie; van Dam, Frits S. A. M.; Schagen, Sanne B.

2012-01-01

The neural substrate underlying cognitive impairments after chemotherapy is largely unknown. Here, we investigated very late (>9 years) effects of adjuvant high-dose chemotherapy on brain white and gray matter in primary breast cancer survivors (n = 17) with multimodal magnetic resonance imaging

Administration of Concurrent Vaginal Brachytherapy During Chemotherapy for Treatment of Endometrial Cancer

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Nagar, Himanshu; Boothe, Dustin; Parikh, Amar; Yondorf, Menachem; Parashar, Bhupesh [Department of Radiation Oncology, Weill Cornell Medical College of Cornell University, New York, New York (United States); Gupta, Divya; Holcomb, Kevin; Caputo, Thomas [Division of Gynecological Oncology, Department of Obstetrics and Gynecology, Weill Cornell Medical College of Cornell University, New York, New York (United States); Chao, K. S. Clifford; Nori, Dattatreyudu [Department of Radiation Oncology, Weill Cornell Medical College of Cornell University, New York, New York (United States); Wernicke, A. Gabriella, E-mail: gaw9006@med.cornell.edu [Department of Radiation Oncology, Weill Cornell Medical College of Cornell University, New York, New York (United States)

2013-11-15

Purpose: To evaluate the tolerability and toxicity of administering vaginal brachytherapy (VB) concurrently during chemotherapy compared with the sequential approach for patients with endometrial cancer. Methods and Materials: A retrospective analysis of 372 surgically staged patients with endometrial cancer American Joint Committee on Cancer 2009 stages I to IV treated with adjuvant postoperative radiation therapy (RT) at our institution from 2001 to 2012 was conducted. All patients received VB + external beam RT (EBRT) + 6 cycles of adjuvant carboplatin- and paclitaxel-based chemotherapy. The VB mean dose was 15.08 Gy (range, 15-20 Gy), with 3 to 4 weekly applications, and the EBRT mean dose was 45 Gy delivered with 3-dimensional or intensity modulated RT techniques. Hematologic, gastrointestinal (GI), and genitourinary (GU) toxicities were assessed by Common Toxicity Criteria (CTC) and compared between sequential and concurrent chemotherapy and VB schedules. Results: Among patients who received RT and adjuvant chemotherapy, 180 of 372 patients (48%) received RT sandwiched between cycles 3 and 4 of chemotherapy. A separate group of 192 patients (52%) were treated with VB during the first 3 cycles of chemotherapy, with a weekly application on nonchemotherapy days, and received the EBRT portion in a sandwiched fashion. Patients treated with VB during chemotherapy had a decreased overall treatment time by 4 weeks (P<.001; 95% confidence interval: 3.99-4.02) and sustained no difference in CTC-graded acute hematologic, GI, or GU toxicities in comparison with the patients treated with VB and chemotherapy in a sequential manner (P>.05). CTC grade 3 or 4 hematologic, GI, and GU toxicities were zero. Conclusions: VB during chemotherapy is well tolerated, decreases overall treatment time, and does not render more toxicity than the sequential regimen.

Full dose CHOP chemotherapy

International Nuclear Information System (INIS)

Tominaga, Shinichi; Kondo, Makoto; Ando, Yutaka; Yamashita, Shoji; Uematsu, Minoru; Shigematsu, Naoyuki; Nishiguchi, Iku; Hashimoto, Shozo

1985-01-01

Since 1982, we have performed 125 courses of CHOP chemotherapy for 27 patients of malignancy, adhering to the original regimen as strictly as possible. CHOP chemotherapy consisted of Cyclophosphamide 750 mg/m 2 , iv, on day 1; Adriamycin 50 mg/m 2 , iv, on day 1; Vincristine 1.4 mg/m 2 , iv, on day 1 (maximum single dose 2.0 mg) and Prednisolone 50 mg/m 2 , po, day 1 through 5. The cycle was repeated every 21 days. As side effects, myelosuppression, hair loss, fever, nausea, vomiting, liver dysfunction, stomatitis, neuropathy, herpes zoster, arrhythmia and hemorrhagic cystitis were seen. Due to myelosuppression, twenty patients experienced febrile episodes at each nadir of WBC counts on 40 courses. However, any febrile patient did not have life threatening infection. Other side effects were also reversible. The radiotherapy of most patients was carried out as initially scheduled, except for 3 patients in whom irradiation was interrupted due to severe stomatitis or herpes zoster. We consider that CHOP chemotherapy is excellent in feasibility even when combined with radiotherapy. (author)

Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

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Selle, F.; Gligorov, J.; Richard, S.; Khalil, A.; Alexandre, I.; Avenin, D.; Provent, S.; Soares, D.G.; Lotz, J.P.

2014-01-01

Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis

Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

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Selle, F.; Gligorov, J. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France); Richard, S.; Khalil, A. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Alexandre, I. [Medical Oncology Department, Hospital Centre of Bligny, Briis-sous-Forges (France); Avenin, D.; Provent, S.; Soares, D.G. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Lotz, J.P. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France)

2014-11-04

Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis.

Dosing of cytotoxic chemotherapy: impact of renal function estimates on dose.

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Dooley, M J; Poole, S G; Rischin, D

2013-11-01

Oncology clinicians are now routinely provided with an estimated glomerular filtration rate on pathology reports whenever serum creatinine is requested. The utility of using this for the dose determination of renally excreted drugs compared with other existing methods is needed to inform practice. Renal function was determined by [Tc(99m)]DTPA clearance in adult patients presenting for chemotherapy. Renal function was calculated using the 4-variable Modification of Diet in Renal Disease (4v-MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Cockcroft and Gault (CG), Wright and Martin formulae. Doses for renal excreted cytotoxic drugs, including carboplatin, were calculated. The concordance of the renal function estimates according to the CKD classification with measured Tc(99m)DPTA clearance in 455 adults (median age 64.0 years: range 17-87 years) for the 4v-MDRD, CKD-EPI, CG, Martin and Wright formulae was 47.7%, 56.3%, 46.2%, 56.5% and 60.2%, respectively. Concordance for chemotherapy dose for these formulae was 89.0%, 89.5%, 85.1%, 89.9% and 89.9%, respectively. Concordance for carboplatin dose specifically was 66.4%, 71.4%, 64.0%, 73.8% and 73.2%. All bedside formulae provide similar levels of concordance in dosage selection for the renal excreted chemotherapy drugs when compared with the use of a direct measure of renal function.

Adjuvant sequential chemo and radiotherapy improves the oncological outcome in high risk endometrial cancer

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Signorelli, Mauro; Lissoni, Andrea Alberto; De Ponti, Elena; Grassi, Tommaso; Ponti, Serena

2015-01-01

Objective Evaluation of the impact of sequential chemoradiotherapy in high risk endometrial cancer (EC). Methods Two hundred fifty-four women with stage IB grade 3, II and III EC (2009 FIGO staging), were included in this retrospective study. Results Stage I, II, and III was 24%, 28.7%, and 47.3%, respectively. Grade 3 tumor was 53.2% and 71.3% had deep myometrial invasion. One hundred sixty-five women (65%) underwent pelvic (+/- aortic) lymphadenectomy and 58 (22.8%) had nodal metastases. Ninety-eight women (38.6%) underwent radiotherapy, 59 (23.2%) chemotherapy, 42 (16.5%) sequential chemoradiotherapy, and 55 (21.7%) were only observed. After a median follow-up of 101 months, 78 women (30.7%) relapsed and 91 women (35.8%) died. Sequential chemoradiotherapy improved survival rates in women who did not undergo nodal evaluation (disease-free survival [DFS], p=0.040; overall survival [OS], p=0.024) or pelvic (+/- aortic) lymphadenectomy (DFS, p=0.008; OS, p=0.021). Sequential chemoradiotherapy improved both DFS (p=0.015) and OS (p=0.014) in stage III, while only a trend was found for DFS (p=0.210) and OS (p=0.102) in stage I-II EC. In the multivariate analysis, only age (≤65 years) and sequential chemoradiotherapy were statistically related to the prognosis. Conclusion Sequential chemoradiotherapy improves survival rates in high risk EC compared with chemotherapy or radiotherapy alone, in particular in stage III. PMID:26197768

Simultaneous adjuvant radiation therapy and chemotherapy in high-risk breast cancer--toxicity and dose modification: a trans-tasman radiation oncology group multi-institution study

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Denham, James W.; Hamilton, Christopher S.; Christie, David; O'Brien, Maree; Bonaventura, Antonino; Stewart, John F.; Ackland, Stephen P.; Lamb, David S.; Spry, Nigel A.; Dady, Peter; Atkinson, Christopher H.; Wynne, Christopher; Joseph, David J.

1995-01-01

Purpose: To establish the toxicity profile of simultaneously administered postoperative radiation therapy and CMF chemotherapy as a prelude to a randomized controlled study addressing the sequencing of the two modalities. Methods and Materials: One hundred and thirty eight breast cancer patients at high risk of locoregional, as well as systemic relapse, who were referred to three centers in Australia and New Zealand were treated with postoperative radiation therapy and chemotherapy simultaneously. Acute toxicity and dose modifications in these patients were compared with 83 patients treated over the same time frame with chemotherapy alone. In a separate study the long-term radiation and surgical effects in 24 patients treated simultaneously with radiation therapy and chemotherapy at Newcastle (Australia) following conservative surgery were compared with 23 matched patients treated at Newcastle with radiation therapy alone. Results: Myelotoxicity was increased in patients treated simultaneously with radiation therapy and chemotherapy. The effect was not great, but may have contributed to chemotherapy dose reductions. Lymphopenia was observed to be the largest factor in total white cell depressions caused by the simultaneous administration of radiation therapy. Postsurgical appearances were found to so dominate long-term treatment effects on the treated breast that the effect of radiation therapy dose and additional chemotherapy was difficult to detect. Conclusion: Studies addressing the sequencing of radiation therapy and chemotherapy will necessarily be large because adverse effects from administering the two modalities simultaneously are not great. The present study has endorsed the importance in future studies of stratification according to the extent and type of surgery and adherence to a single strict policy of chemotherapy dose modification

Marked improvement by high-dose chemotherapy and autologous stem cell transplantation in a case of light chain deposition disease.

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Matsuzaki, Keiichi; Ohsawa, Isao; Nishitani, Tomohito; Takeda, Yukihiko; Inoshita, Hiroyuki; Ishii, Masaya; Takagi, Miyuki; Horikoshi, Satoshi; Tomino, Yasuhiko

2011-01-01

A 55-year-old woman presented with heavy proteinuria (6.2 g/day) in April 2007. Because monoclonal IgG-k was detected in serum and urine samples, bone marrow aspiration and renal biopsy were performed. She was diagnosed with plasma cell dyscrasia because a bone marrow aspiration specimen showed plasma cells at 6.1%. Renal tissues revealed the formation of nodular glomerulosclerosis which was negative for Congo-red staining. Renal immunohistochemistry showed positive staining for kappa light chains in the nodular lesions, proximal tubules and part of Bowman's capsules. Her renal involvement was diagnosed as light chain deposition disease. Proteinuria disappeared and renal function stabilized after high-dose chemotherapy and autologous stem cell transplantation. It appears that an early initiation of active therapy such as high-dose chemotherapy and autologous stem cell transplantation may be beneficial for patients with light chain deposition disease.

Administration of Concurrent Vaginal Brachytherapy During Chemotherapy for Treatment of Endometrial Cancer

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Nagar, Himanshu; Boothe, Dustin; Parikh, Amar; Yondorf, Menachem; Parashar, Bhupesh; Gupta, Divya; Holcomb, Kevin; Caputo, Thomas; Chao, K. S. Clifford; Nori, Dattatreyudu; Wernicke, A. Gabriella

2013-01-01

Purpose: To evaluate the tolerability and toxicity of administering vaginal brachytherapy (VB) concurrently during chemotherapy compared with the sequential approach for patients with endometrial cancer. Methods and Materials: A retrospective analysis of 372 surgically staged patients with endometrial cancer American Joint Committee on Cancer 2009 stages I to IV treated with adjuvant postoperative radiation therapy (RT) at our institution from 2001 to 2012 was conducted. All patients received VB + external beam RT (EBRT) + 6 cycles of adjuvant carboplatin- and paclitaxel-based chemotherapy. The VB mean dose was 15.08 Gy (range, 15-20 Gy), with 3 to 4 weekly applications, and the EBRT mean dose was 45 Gy delivered with 3-dimensional or intensity modulated RT techniques. Hematologic, gastrointestinal (GI), and genitourinary (GU) toxicities were assessed by Common Toxicity Criteria (CTC) and compared between sequential and concurrent chemotherapy and VB schedules. Results: Among patients who received RT and adjuvant chemotherapy, 180 of 372 patients (48%) received RT sandwiched between cycles 3 and 4 of chemotherapy. A separate group of 192 patients (52%) were treated with VB during the first 3 cycles of chemotherapy, with a weekly application on nonchemotherapy days, and received the EBRT portion in a sandwiched fashion. Patients treated with VB during chemotherapy had a decreased overall treatment time by 4 weeks (P .05). CTC grade 3 or 4 hematologic, GI, and GU toxicities were zero. Conclusions: VB during chemotherapy is well tolerated, decreases overall treatment time, and does not render more toxicity than the sequential regimen

Non-Cross Resistant Sequential Single Agent Chemotherapy in First-Line Advanced Non-Small Cell Lung Cancer Patients: Results of a Phase II Study

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V. Surmont

2009-01-01

Full Text Available Background. sequential chemotherapy can maintain dose intensity and preclude cumulative toxicity by increasing drug diversity. Purpose. to investigate the toxicity and efficacy of the sequential regimen of gemcitabine followed by paclitaxel in first line advanced stage non-small cell lung cancer (NSCLC patients with good performance status (PS. Patients and methods. gemcitabine 1250 mg/m2 was administered on day 1 and 8 of course 1 and 2; Paclitaxel 150 mg/m2 on day 1 and 8 of course 3 and 4. Primary endpoint was response rate (RR, secondary endpoints toxicity and time to progression (TTP. Results. Of the 21 patients (median age 56, range 38–80 years; 62% males, 38% females 10% (2/21 had stage IIIB, 90% (19/21 stage IV, 15% PS 0, 85% PS 1. 20% of patients had a partial response, 30% stable disease, 50% progressive disease. Median TTP was 12 weeks (range 6–52 weeks, median overall survival (OS 8 months (range 1–27 months, 1-year survival was 33%. One patient had grade 3 hematological toxicity, 2 patients a grade 3 peripheral neuropathy. Conclusions. sequential administration of gemcitabine followed by paclitaxel in first line treatment of advanced NSCLC had a favourable toxicity profile, a median TTP and OS comparable with other sequential trials and might , therefore, be a treatment option for NSCLC patients with high ERCC1 expression.

Pre-operative combined 5-FU, low dose leucovorin, and sequential radiation therapy for unresectable rectal cancer

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Minsky, B.D.; Cohen, A.M.; Kemeny, N.; Enker, W.E.; Kelsen, D.P.; Schwartz, G.; Saltz, L.; Dougherty, J.; Frankel, J.; Wiseberg, J.

1993-01-01

The authors performed a Phase 1 trial to determine the maximum tolerated dose of combined pre-operative radiation (5040 cGy) and 2 cycles (bolus daily x 5) of 5-FU and low dose LV (20 mg/m2), followed by surgery and 10 cycles of post-operative LV/5-FU in patients with unresectable primary or recurrent rectal cancer. Twelve patients were entered. The initial dose of 5-FU was 325 mg/m2. 5-FU was to be escalated while the LV remained constant at 20 mg/m2. Chemotherapy began on day 1 and radiation on day 8. The post-operative chemotherapy was not dose escalated; 5-FU: 425 mg/m2 and LV: 20 mg/m2. The median follow-up was 14 months (7--16 months). Following pre-operative therapy, the resectability rate with negative margins was 91% and the pathologic complete response rate was 9%. For the combined modality segment (preoperative) the incidence of any grade 3+ toxicity was diarrhea: 17%, dysuria: 8%, mucositis: 8%, and erythema: 8%. The median nadir counts were WBC: 3.1, HGB: 8.8, and PLT: 153000. The maximum tolerated dose of 5-FU for pre-operative combined LV/5-FU/RT was 325 mg/m2 with no escalation possible. Therefore, the recommended dose was less than 325 mg/m2. Since adequate doses of 5-FU to treat systemic disease could not be delivered until at least 3 months (cycle 3) following the start of therapy, the authors do not recommend that this 5-FU, low dose LV, and sequential radiation therapy regimen be used as presently designed. However, given the 91% resectability rate they remain encouraged with this approach. 31 refs., 1 fig., 2 tabs

High-dose chemotherapy and auto-SCT for relapsed and refractory Hodgkin's lymphoma patients refractory to first-line salvage chemotherapy but responsive to second-line salvage chemotherapy.

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Rauf, Muhammad Shahzad; Maghfoor, Irfan; Elhassan, Tusneem Ahmed M; Akhtar, Saad

2015-01-01

Relapsed or primary refractory Hodgkin's lymphoma (HL) patients refractory to first-line salvage chemotherapy (first salvage) and unable to undergo high-dose chemotherapy (HDC) and autologous stem cell transplant (auto-SCT) have very poor outcome. Some patients are offered second-line salvage chemotherapy (second salvage), if they are responsive and may receive HDC auto-SCT. We identified 31 patients (18 males, 13 females) from 1996-2012 who received second salvage prior to auto-SCT. Median age at auto-SCT is 22 years. Patients were grouped as (1) relapsed-refractory (Rel:Ref): patients with prior complete response (CR) and on relapse found refractory to first salvage and received second salvage and (2) refractory-refractory (Ref:Ref): patients refractory to both primary treatment and first salvage and received second salvage. Median follow-up is 63 months (18-170). Disease status after second salvage prior to HDC was CR 16 %, partial response (PR) 71 % and stable disease 13 %. After HDC auto-SCT, CR:PR: progressive disease was observed in 18 (58 %): four (12 %): nine (29 %) patients, respectively. Five-year overall survival (OS) for whole group is 57 % (Rel:Ref vs. Ref:Ref, 73 % vs. 48 %, p = 0.48). Progression-free survival (PFS) for whole group is 52 % (Rel:Ref vs. Ref:Ref, 73 % vs. 40 % respectively, p = 0.11). Second-line salvage is a valid approach with no long-term side effects for those HL patients who do not respond to first-line salvage chemotherapy and they can be candidate of HDC and stem cell transplant with a high ORR, the PFS and OS in relapse-refractory and refractory-refractory group of patients.

Sequential versus simultaneous use of chemotherapy and gonadotropin-releasing hormone agonist (GnRHa) among estrogen receptor (ER)-positive premenopausal breast cancer patients: effects on ovarian function, disease-free survival, and overall survival.

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Zhang, Ying; Ji, Yajie; Li, Jianwei; Lei, Li; Wu, Siyu; Zuo, Wenjia; Jia, Xiaoqing; Wang, Yujie; Mo, Miao; Zhang, Na; Shen, Zhenzhou; Wu, Jiong; Shao, Zhimin; Liu, Guangyu

2018-04-01

To investigate ovarian function and therapeutic efficacy among estrogen receptor (ER)-positive, premenopausal breast cancer patients treated with gonadotropin-releasing hormone agonist (GnRHa) and chemotherapy simultaneously or sequentially. This study was a phase 3, open-label, parallel, randomized controlled trial (NCT01712893). Two hundred sixteen premenopausal patients (under 45 years) diagnosed with invasive ER-positive breast cancer were enrolled from July 2009 to May 2013 and randomized at a 1:1 ratio to receive (neo)adjuvant chemotherapy combined with sequential or simultaneous GnRHa treatment. All patients were advised to receive GnRHa for at least 2 years. The primary outcome was the incidence of early menopause, defined as amenorrhea lasting longer than 12 months after the last chemotherapy or GnRHa dose, with postmenopausal or unknown follicle-stimulating hormone and estradiol levels. The menstrual resumption period and survivals were the secondary endpoints. The median follow-up time was 56.9 months (IQR 49.5-72.4 months). One hundred and eight patients were enrolled in each group. Among them, 92 and 78 patients had complete primary endpoint data in the sequential and simultaneous groups, respectively. The rates of early menopause were 22.8% (21/92) in the sequential group and 23.1% (18/78) in the simultaneous group [simultaneous vs. sequential: OR 1.01 (95% CI 0.50-2.08); p = 0.969; age-adjusted OR 1.13; (95% CI 0.54-2.37); p = 0.737]. The median menstruation resumption period was 12.0 (95% CI 9.3-14.7) months and 10.3 (95% CI 8.2-12.4) months for the sequential and simultaneous groups, respectively [HR 0.83 (95% CI 0.59-1.16); p = 0.274; age-adjusted HR 0.90 (95%CI 0.64-1.27); p = 0.567]. No significant differences were evident for disease-free survival (p = 0.290) or overall survival (p = 0.514) between the two groups. For ER-positive premenopausal patients, the sequential use of GnRHa and chemotherapy showed ovarian preservation

High dose lansoprazole combined with metronomic chemotherapy: a phase I/II study in companion animals with spontaneously occurring tumors.

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Spugnini, Enrico P; Buglioni, Sabrina; Carocci, Francesca; Francesco, Menicagli; Vincenzi, Bruno; Fanciulli, Maurizio; Fais, Stefano

2014-08-21

The treatment of human cancer has been seriously hampered for decades by resistance to chemotherapeutic drugs. A very efficient mechanism of tumor resistance to drugs is the proton pumps-mediated acidification of tumor microenvironment. Metronomic chemotherapy has shown efficacy in adjuvant fashion as well as in the treatment of pets with advanced disease. Moreover, we have shown in veterinary clinical settings that pre-treatment with proton-pumps inhibitors (PPI) increases tumor responsiveness to chemotherapeutics. In this study pet with spontaneously occurring cancer have been recruited to be treated by a combination of metronomic chemotherapy and high dose PPIs and their responses have been matched to those of a historical control of ten patients treated with metronomic chemotherapy alone. Single arm, non randomized phase II open study, with historical control group, evaluating safety and efficacy of the combination of metronomic chemotherapy and alkalization. Twenty-four companion animals (22 dogs and 2 cats) were treated adding to their metronomic chemotherapy protocol the pump inhibitor lansoprazole at high dose, and a water alkalizer. Their responses have been evaluated by clinical and instrumental evaluation and matched to those of the control group. The protocol was overall well tolerated, with only two dogs experiencing side effects due to gastric hypochlorhydria consisting with vomiting and or diarrhea. In terms of overall response, in the alkalized cohort, 18 out of 24 had partial or complete responses (75%), two patients had a stable disease and the remaining patients experienced no response or progressive disease. On the other hand, only one patient in the control group experienced a complete response (10%) and three other experienced short lived responses. Median time to terminal event was 34 weeks for the experimental group versus 2 weeks in the controls (p= 0.042). Patient alkalization has shown to be well tolerated and to increase tumor response

An aCGH classifier derived from BRCA1-mutated breast cancer and benefit of high-dose platinum-based chemotherapy in HER2-negative breast cancer patients

NARCIS (Netherlands)

Vollebergh, M. A.; Lips, E. H.; Nederlof, P. M.; Wessels, L. F. A.; Schmidt, M. K.; van Beers, E. H.; Cornelissen, S.; Holtkamp, M.; Froklage, F. E.; de Vries, E. G. E.; Schrama, J. G.; Wesseling, J.; van de Vijver, M. J.; van Tinteren, H.; de Bruin, M.; Hauptmann, M.; Rodenhuis, S.; Linn, S. C.

Patients and methods: We evaluated this classifier in stage III breast cancer patients, who had been randomly assigned between adjuvant high-dose platinum-based (HD-PB) chemotherapy, a DSB-inducing regimen, and conventional anthracycline-based chemotherapy. Additionally, we assessed BRCA1 loss

Anti-tumor activity of high-dose EGFR tyrosine kinase inhibitor and sequential docetaxel in wild type EGFR non-small cell lung cancer cell nude mouse xenografts

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Tang, Ning; Zhang, Qianqian; Fang, Shu; Han, Xiao; Wang, Zhehai

2017-01-01

Treatment of non-small-cell lung cancer (NSCLC) with wild-type epidermal growth factor receptor (EGFR) is still a challenge. This study explored antitumor activity of high-dose icotinib (an EGFR tyrosine kinase inhibitor) plus sequential docetaxel against wild-type EGFR NSCLC cells-generated nude mouse xenografts. Nude mice were subcutaneously injected with wild-type EGFR NSCLC A549 cells and divided into different groups for 3-week treatment. Tumor xenograft volumes were monitored and recorded, and at the end of experiments, tumor xenografts were removed for Western blot and immunohistochemical analyses. Compared to control groups (negative control, regular-dose icotinib [IcoR], high-dose icotinib [IcoH], and docetaxel [DTX]) and regular icotinib dose (60 mg/kg) with docetaxel, treatment of mice with a high-dose (1200 mg/kg) of icotinib plus sequential docetaxel for 3 weeks (IcoH-DTX) had an additive effect on suppression of tumor xenograft size and volume (P Icotinib-containing treatments markedly reduced phosphorylation of EGFR, mitogen activated protein kinase (MAPK), and protein kinase B (Akt), but only the high-dose icotinib-containing treatments showed an additive effect on CD34 inhibition (P icotinib plus docetaxel had a similar effect on mouse weight loss (a common way to measure adverse reactions in mice), compared to the other treatment combinations. The study indicate that the high dose of icotinib plus sequential docetaxel (IcoH-DTX) have an additive effect on suppressing the growth of wild-type EGFR NSCLC cell nude mouse xenografts, possibly through microvessel density reduction. Future clinical trials are needed to confirm the findings of this study. PMID:27852073

Clinical Study on Prospective Efficacy of All-Trans Acid, Realgar-Indigo Naturalis Formula Combined with Chemotherapy as Maintenance Treatment of Acute Promyelocytic Leukemia

Directory of Open Access Journals (Sweden)

Li Xiang-Xin

2014-01-01

Full Text Available Objectives. To test the efficiency and safety of sequential application of retinoic acid (ATRA, Realgar-Indigo naturalis formula (RIF and chemotherapy (CT were used as the maintenance treatment in patients with acute promyelocytic leukemia (APL. Methods. This was a retrospective study of 98 patients with newly diagnosed APL who accepted two different maintenance treatments. After remission induction and consolidation chemotherapy according to their Sanz scores, patients received two different kinds of maintenance scheme. The first regimen was using ATRA, RIF, and standard dose of CT sequentially (ATRA/RIF/CT regimen, while the second one was using ATRA and low dose of chemotherapy with methotrexate (MTX plus 6-mercaptopurine (6-MP alternately (ATRA/CTlow regimen. The OS, DFS, relapse rate, minimal residual disease, and adverse reactions in two groups were monitored and evaluated. Results. ATRA/RIF/CT regimen could effectively reduce the chance of relapse in different risk stratification of patients, but there was no significant difference in 5-year DFS rate and OS rate between the two groups. Besides, the patients in the experimental group suffered less severe adverse reactions than those in the control group. Conclusions. The repeated sequential therapeutic regimen to APL with ATRA, RIF, and chemotherapy is worth popularizing for its high effectiveness and low toxicity.

Early lymphocyte recovery after intensive timed sequential chemotherapy for acute myelogenous leukemia: peripheral oligoclonal expansion of regulatory T cells.

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Kanakry, Christopher G; Hess, Allan D; Gocke, Christopher D; Thoburn, Christopher; Kos, Ferdynand; Meyer, Christian; Briel, Janet; Luznik, Leo; Smith, B Douglas; Levitsky, Hyam; Karp, Judith E

2011-01-13

Few published studies characterize early lymphocyte recovery after intensive chemotherapy for acute myelogenous leukemia (AML). To test the hypothesis that lymphocyte recovery mirrors ontogeny, we characterized early lymphocyte recovery in 20 consecutive patients undergoing induction timed sequential chemotherapy for newly diagnosed AML. Recovering T lymphocytes were predominantly CD4(+) and included a greatly expanded population of CD3(+)CD4(+)CD25(+)Foxp3(+) T cells. Recovering CD3(+)CD4(+)CD25(+)Foxp3(+) T cells were phenotypically activated regulatory T cells and showed suppressive activity on cytokine production in a mixed lymphocyte reaction. Despite an initial burst of thymopoiesis, most recovering regulatory T cells were peripherally derived. Furthermore, regulatory T cells showed marked oligoclonal skewing, suggesting that their peripheral expansion was antigen-driven. Overall, lymphocyte recovery after chemotherapy differs from ontogeny, specifically identifying a peripherally expanded oligoclonal population of activated regulatory T lymphocytes. These differences suggest a stereotyped immunologic recovery shared by patients with newly diagnosed AML after induction timed sequential chemotherapy. Further insight into this oligoclonal regulatory T-cell population will be fundamental toward developing effective immunomodulatory techniques to improve survival for patients with AML.

Chemotherapy dosing in achondroplastic dwarfism: a case report and review of literature.

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Elsoueidi, R; Gresham, C; Michael, L; Chaney, D; Mourad, H

2016-12-01

CASE DESCRIPTION: A 74-year-old female with achondroplastic dwarfism was diagnosed with ER-, BR- and HER2- breast cancer. No guideline currently exists to direct chemotherapy dosing in this population. She received neoadjuvant chemotherapy based on body surface area utilizing actual height and weight with dose-dense doxorubicin and cyclophosphamide followed by paclitaxel with the use of granulocyte colony-stimulating factor. Satisfactory clinical response and remission were achieved, and treatment proceeded without any significant toxicity or delays. In the absence of guideline recommendations, dosing chemotherapy based on actual height and weight in patients with achondroplastic dwarfism may be safe and appropriate. © 2016 John Wiley & Sons Ltd.

Bismuth adjuvant ameliorates adverse effects of high-dose chemotherapy in patients with multiple myeloma and malignant lymphoma undergoing autologous stem cell transplantation

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Hansen, Per Boye; Penkowa, Milena

2017-01-01

show for the first time that bismuth significantly reduces grade 2 stomatitis, febrile neutropenia and infections caused by melphalan in multiple myeloma, where adverse effects also were significantly linked to gender. In lymphoma patients, bismuth significantly reduces diarrhoea relative to placebo......PURPOSE: High-dose chemotherapy prior to autologous stem cell transplantation (ASCT) leads to adverse effects including mucositis, neutropenia and bacteremia. To reduce the toxicity, we treated myeloma and lymphoma patients with peroral bismuth as an adjuvant to chemotherapy to convey...

High-dose chemotherapy with stem cell rescue in the primary treatment of metastatic and pelvic osteosarcoma: final results of the ISG/SSG II study.

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Boye, Kjetil; Del Prever, Adalberto Brach; Eriksson, Mikael; Saeter, Gunnar; Tienghi, Amelia; Lindholm, Paula; Fagioli, Franca; Skjeldal, Sigmund; Ferrari, Stefano; Hall, Kirsten Sundby

2014-05-01

Patients with metastatic osteosarcoma at diagnosis or axial primary tumors have a poor prognosis. The aim of the study was to evaluate the feasibility and efficacy of intensified treatment with high-dose chemotherapy (HDCT) and stem cell rescue in this group. From May 1996 to August 2004, 71 patients were included in a Scandinavian-Italian single arm phase II study. Preoperative chemotherapy included methotrexate, doxorubicin, cisplatin and ifosfamide, and postoperative treatment consisted of two cycles of doxorubicin, one cycle of cyclophosphamide and etoposide and two courses of high-dose etoposide and carboplatin with stem cell rescue. Twenty-nine patients (43%) received two courses and 10 patients (15%) received one course of HDCT. HDCT was associated with significant toxicity, but no treatment-related deaths were recorded. Fourteen patients (20%) had disease progression before completion of the study protocol, and only 29/71 patients (41%) received the full planned treatment. Median event-free survival (EFS) was 18 months, and estimated 5-year EFS was 27%. Median overall survival (OS) was 34 months, and estimated 5-year OS was 31%. When patients who did not receive HDCT due to disease progression were excluded, there was no difference in EFS (P = 0.72) or OS (P = 0.49) between patients who did or did not receive HDCT. The administration of high-dose chemotherapy with stem cell rescue was feasible, but associated with significant toxicity. Patient outcome seemed comparable to previous studies using conventional chemotherapy. We conclude that HDCT with carboplatin and etoposide should not be further explored as a treatment strategy in high-risk osteosarcoma. © 2013 Wiley Periodicals, Inc.

Treatment of small cell carcinoma of lung with combined high dose mediastinal irradiation, whole brain prophylaxis and chemotherapy

International Nuclear Information System (INIS)

Shank, B.; Natale, R.B.; Hilaris, B.S.; Wittes, R.E.

1981-01-01

Survival of patients with small cell carcinoma of lung, treated on a new combined radiotherapy-chemotherapy protocol, compares favorably with other regimens in the literature and our own previous combined approaches. Radiation, given after induction chemotherapy, consisted of whole brain prophylaxis in all 44 evaluable patients. Patients with limited disease were also treated to the primary and mediastinum to a high dose (5000 rad equivalent) using multiple fields. The new chemotherapy regimen consisted of induction with cyclophosphamide, doxorubicin, and vincristine alternated with cis-platinum and VP-16 (an epipodophyllotoxin) for two cycles, followed by consolidation with low dose cyclophosphamide and vincristine concurrent with irradiation. Patients with limited disease who achieved less than complete response, and all patients with extensive disease were not continued on maintenance chemotherapy. Out of 24 evaluable patients with limited disease, there was 73% survival at 1 year by life-table analysis, measured from treatment initiation. After induction, 16/24 of these limited disease patients were CR (complete responders): 20/24 were CR at completion of their irradiation. Out of 20 evaluable patients with extensive disease, there was 59% survival at 1 year by life-table analysis. Only 4/44 (9%) brain parenchymal relapses occurred, one at 3 months and one at 6 months after local failure and two in patients who did not become CRs, implicating a possible re-seeding mechanism. Five patients had central nervous system relapses outside of brain parenchyma (spinal epidural and leptomeningeal); in three patients this was the initial site of failure. Significant complications included leukopenia (50%) and thrombocytopenia (24%) primarily during induction, and chronic pulmonary fibrosis (25%), possibly contributing to two deaths

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

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...

Feasibility of sequential adjuvant chemotherapy with a 3-month oxaliplatin-based regimen followed by 3 months of capecitabine in patients with stage III and high-risk stage II colorectal cancer: JSWOG-C2 study.

Science.gov (United States)

Tsuruta, Atsushi; Yamashita, Kazuki; Tanioka, Hiroaki; Tsuji, Akihito; Inukai, Michio; Yamakawa, Toshiki; Yamatsuji, Tomoki; Yoshimitsu, Masanori; Toyota, Kazuhiro; Yamano, Taketoshi; Nagasaka, Takeshi; Okajima, Masazumi

2016-01-01

Six months of oxaliplatin-based chemotherapy is the standard adjuvant chemotherapy for completely resected stage III colorectal cancer (CRC). Also, patients with stage II CRC who are considered to be at high risk of disease recurrence often receive the same adjuvant chemotherapy treatment. We prospectively investigated the extent and degree of neuropathy suffered by stage III and high-risk stage II resectable CRC patients who underwent sequential approach involving 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine. Patients with completely resected stage III and high-risk stage II CRC aged ≥20 years were eligible. Patients were treated with folinic acid, fluorouracil, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX) for 3 months followed by capecitabine (2,500 mg/m 2 on days 1-14 every 3 weeks) for 3 months. Primary end points were frequency and the grade of oxaliplatin-induced neurotoxicity as evaluated using the physician-based Common Terminology Criteria for Adverse Events version 4.0 (CTCAE) grading and the patient-based scale, self-reported Patient Neurotoxicity Questionnaire. Ninety-one patients were enrolled and 86 patients assessed. Eighty-four percent of patients completed the planned oxaliplatin-based therapy for 3 months, and 63% of patients completed all treatments for the full 6 months. Overall incidences of grade 3 or 4 peripheral sensory or motor neuropathy according to the CTCAE were 3.5% and 1.2%, respectively. Regarding the peripheral sensory neuropathy, the proportion of Patient Neurotoxicity Questionnaire (grade C-E) and CTCAE (grade 2-4) at months 1.5/3/6 were 11.3/22.1/29.4% and 5.3/4.4/11.3%, respectively (Spearman correlation coefficient: 0.47). A sequential approach to adjuvant chemotherapy with 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine was tolerated by patients and associated with a low incidence of neuropathy.

The effect of weight-based chemotherapy dosing in a cohort of gynecologic oncology patients.

Science.gov (United States)

Hansen, Jean; Stephan, Jean-Marie; Freesmeier, Michele; Bender, David; Button, Anna; Goodheart, Michael J

2015-07-01

Many clinicians limit chemotherapy doses based on a maximum body surface area (BSA) of 2m(2). We sought to determine how chemotherapy-related toxicities compared between groups of patients that varied with respect to BSA. We hypothesized that obese patients receiving weight-based (WB) dosing would not have significantly higher chemotherapy-related toxicities than control groups. We performed a retrospective review of patients with BSA≥2m(2) who received WB chemotherapy for a gynecologic cancer between January and August 2013. Subjects were matched with two controls: patients with BSAGynecologic cancer patients with BSA≥2m(2) treated with WB chemotherapy had no increase in hematologic or non-hematologic toxicities when compared to controls. Consideration should be given to using WB dosing in obese patients with gynecologic malignancies. Further investigation is required to determine the effect of WB dosing on progression-free and overall survival in obese gynecologic cancer patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Timed sequential chemotherapy of cytoxan-refractory multiple myeloma with cytoxan and adriamycin based on induced tumor proliferation.

Science.gov (United States)

Karp, J E; Humphrey, R L; Burke, P J

1981-03-01

Malignant plasma cell proliferation and induced humoral stimulatory activity (HSA) occur in vivo at a predictable time following drug administration. Sequential sera from 11 patients with poor-risk multiple myeloma (MM) undergoing treatment with Cytoxan (CY) 2400 mq/sq m were assayed for their in vitro effects on malignant bone marrow plasma cell tritiated thymidine (3HTdR) incorporation. Peak HSA was detected day 9 following CY. Sequential changes in marrow malignant plasma cell 3HTdR-labeling indices (LI) paralleled changes in serum activity, with peak LI occurring at the time of peak HS. An in vitro model of chemotherapy demonstrated that malignant plasma cell proliferation was enhanced by HSA, as determined by 3HTdR incorporation assay, 3HTdR LI, and tumor cells counts, and that stimulated plasma cells were more sensitive to cytotoxic effects of adriamycin (ADR) than were cells cultured in autologous pretreatment serum. Based on these studies, we designed a clinical trial to treat 12 CY-refractory poor-risk patients with MM in which ADR (60 mg/sq m) was administered at the time of peak HSA and residual tumor cell LI (day 9) following initial CY, 2400 mg/m (CY1ADR9). Eight of 12 (67%) responded to timed sequential chemotherapy with a greater than 50% decrement in monoclonal protein marker and a median survival projected to be greater than 8 mo duration (range 4-21+ mo). These clinical results using timed sequential CY1ADR9 compare favorably with results obtained using ADR in nonsequential chemotherapeutic regimens.

Reinfusion of autologous lymphocytes with granulocyte-macrophage colony-stimulating factor induces rapid recovery of CD4+ and CD8+ T cells after high-dose chemotherapy for metastatic breast cancer

NARCIS (Netherlands)

de Gast, G. C.; Vyth-Dreese, F. A.; Nooijen, W.; van den Bogaard, C. J. C.; Sein, J.; Holtkamp, M. M. J.; Linthorst, G. A. M.; Baars, J. W.; Schornagel, J. H.; Rodenhuis, S.

2002-01-01

PURPOSE: Repeated high-dose chemotherapy (HDCT) followed by peripheral-blood progenitor cell (PBPC) transplantation can induce a complete remission in patients with metastatic breast cancer sensitive to standard chemotherapy (CT), but the majority of patients relapse within 1 to 2 years. The immune

Role of sequential hemi-body irradiation in multiple myeloma: preliminary observations

International Nuclear Information System (INIS)

Kumar, H.S.; Chaudhary, R.K.; Kumar, Vanita

1993-01-01

Ten patients with multiple myeloma presenting in a highly painful condition were included in the study. They were treated by sequential hemi-body irradiation. A dose of 600 cGy was delivered to the upper hemi-body and 800 c Gy to the lower hemi-body. All patients has appreciable relief from pain. The maximum effect was achieved within 24 to 48 hours of treatment. 9 out of the 10 patients has an improvement in the performance status. All these patients were later subjected to combination chemotherapy. (author). 9 refs., 3 tabs

High-dose rapid and standard induction chemotherapy for patients aged over 1 year with stage 4 neuroblastoma: a randomised trial.

Science.gov (United States)

Pearson, Andrew D J; Pinkerton, C Ross; Lewis, Ian J; Imeson, John; Ellershaw, Caroline; Machin, David

2008-03-01

The current standard treatment for patients with high-risk neuroblastoma includes initial induction chemotherapy with a 21-day interval between induction treatments. We aimed to assess whether an intensive chemotherapy protocol that had a 10-day interval between treatments would improve event-free survival (EFS) in patients aged 1 year or over with high-risk neuroblastoma. Between Oct 30, 1990, and March 18, 1999, patients with stage 4 neuroblastoma who had not received previous chemotherapy were enrolled from 29 centres in Europe. Patients were randomly assigned to rapid treatment (cisplatin [C], vincristine [O], carboplatin [J], etoposide [E], and cyclophosphamide [C], known as COJEC) or standard treatment (vincristine [O], cisplatin [P], etoposide [E], and cyclophosphamide [C], ie, OPEC, alternated with vincristine [O], carboplatin [J], etoposide [E], and cyclophosphamide [C], ie, OJEC). Both regimens used the same total cumulative doses of each drug (except vincristine), but the dose intensity of the rapid regimen was 1.8-times higher than that of the standard regimen. The standard regimen was given every 21 days if patients showed haematological recovery, whereas the rapid regimen was given every 10 days irrespective of haematological recovery. Response to chemotherapy was assessed according to the conventional International Neuroblastoma Response Criteria (INRC). In responders, surgical excision of the primary tumour was attempted, followed by myeloablation (with 200 mg/m2 of melphalan) and haemopoietic stem-cell rescue. Primary endpoints were 3-year, 5-year, and 10-year EFS. Data were analysed by intention to treat. This trial is registered on the clinical trials site of the US National Cancer Institute website, number NCT00365755, and also as EU-20592 and CCLG-NB-1990-11. 262 patients, of median age 2.95 years (range 1.03-20.97), were randomly assigned-132 patients to standard and 130 patients to rapid treatment. 111 patients in the standard group and 109

Application of biological effective dose (BED) to estimate the duration of symptomatic relief and repopulation dose equivalent in palliative radiotherapy and chemotherapy

International Nuclear Information System (INIS)

Jones, Bleddyn; Cominos, Matilda; Dale, Roger G.

2003-01-01

Purpose: To investigate the potential for mathematic modeling in the assessment of symptom relief in palliative radiotherapy and cytotoxic chemotherapy. Methods: The linear quadratic model of radiation effect with the overall treatment time and the daily dose equivalent of repopulation is modified to include the regrowth time after completion of therapy. Results: The predicted times to restore the original tumor volumes after treatment are dependent on the biological effective dose (BED) delivered and the repopulation parameter (K); it is also possible to estimate K values from analysis of palliative treatment response durations. Hypofractionated radiotherapy given at a low total dose may produce long symptom relief in slow-growing tumors because of their low α/β ratios (which confer high fraction sensitivity) and their slow regrowth rates. Cancers that have high α/β ratios (which confer low fraction sensitivity), and that are expected to repopulate rapidly during therapy, are predicted to have short durations of symptom control. The BED concept can be used to estimate the equivalent dose of radiotherapy that will achieve the same duration of symptom relief as palliative chemotherapy. Conclusion: Relatively simple radiobiologic modeling can be used to guide decision-making regarding the choice of the most appropriate palliative schedules and has important implications in the design of radiotherapy or chemotherapy clinical trials. The methods described provide a rationalization for treatment selection in a wide variety of tumors

Is High Dose Therapy Superior to Conventional Dose Therapy as Initial Treatment for Relapsed Germ Cell Tumors? The TIGER Trial

Directory of Open Access Journals (Sweden)

Darren R. Feldman, Robert Huddart, Emma Hall, Jörg Beyer, Thomas Powles

2011-01-01

Full Text Available Metastatic germ cell tumours (GCTs are usually cured with cisplatin based chemotherapy and standard treatment algorithms are established. However when this treatment fails and the disease relapses, standard treatment is much more uncertain. Both conventional dose therapy (CDT and high dose therapy (HDT are widely used, due to the lack of conclusive data supporting one specific approach. A recent retrospective analysis focusing on this population suggested a significant benefit for HDT. Retrospective analyses are prone to bias, and therefore while this data is provocative it is by no mean conclusive. For this reason the international community is supporting a prospective randomised trial in this area comparing CDT(TIP with sequential HDT (TICE. The planned open labelled randomised phase III study (TIGER is due to open in 2011 and will recruit 390 patients to detect a 13% difference in 2 year progression free survival (primary endpoint. It is hoped that this large study will conclusively resolve the uncertainty which currently exists.

Early stage cost-effectiveness analysis of a BRCA1-like test to detect triple negative breast cancers responsive to high dose alkylating chemotherapy

NARCIS (Netherlands)

Miquel-Cases, Anna; Steuten, Lotte Maria Gertruda; Retel, Valesca P.; van Harten, Willem H.

2015-01-01

Purpose Triple negative breast cancers (TNBC) with a BRCA1-like profile may benefit from high dose alkylating chemotherapy (HDAC). This study examines whether BRCA1-like testing to target effective HDAC in TNBC patients can be more cost-effective than treating all patients with standard

Mobilization of peripheral blood progenitor cells by chemotherapy and granulocyte-macrophage colony-stimulating factor for hematologic support after high-dose intensification for breast cancer.

Science.gov (United States)

Elias, A D; Ayash, L; Anderson, K C; Hunt, M; Wheeler, C; Schwartz, G; Tepler, I; Mazanet, R; Lynch, C; Pap, S

1992-06-01

High-dose therapy with autologous marrow support results in durable complete remissions in selected patients with relapsed lymphoma and leukemia who cannot be cured with conventional dose therapy. However, substantial morbidity and mortality result from the 3- to 6-week period of marrow aplasia until the reinfused marrow recovers adequate hematopoietic function. Hematopoietic growth factors, particularly used after chemotherapy, can increase the number of peripheral blood progenitor cells (PBPCs) present in systemic circulation. The reinfusion of PBPCs with marrow has recently been reported to reduce the time to recovery of adequate marrow function. This study was designed to determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF)-mobilized PBPCs alone (without marrow) would result in rapid and reliable hematopoietic reconstitution. Sixteen patients with metastatic breast cancer were treated with four cycles of doxorubicin, 5-fluorouracil, and methotrexate (AFM induction). Patients responding after the first two cycles were administered GM-CSF after the third and fourth cycles to recruit PBPCs for collection by two leukapheresis per cycle. These PBPCs were reinfused as the sole source of hematopoietic support after high doses of cyclophosphamide, thiotepa, and carboplatin. No marrow or hematopoietic cytokines were used after progenitor cell reinfusion. Granulocytes greater than or equal to 500/microL was observed on a median of day 14 (range, 8 to 57). Transfusion independence of platelets greater than or equal to 20,000/microL occurred on a median day of 12 (range, 8 to 134). However, three patients required the use of a reserve marrow for slow platelet engraftment. In retrospect, these patients were characterized by poor baseline bone marrow cellularity and poor platelet recovery after AFM induction therapy. When compared with 29 historical control patients who had received the same high-dose intensification chemotherapy using autologous

Feasibility Study of Sequentially Alternating EGFR-TKIs and Chemotherapy for Patients with Non-small Cell Lung Cancer.

Science.gov (United States)

Takemura, Yoshizumi; Chihara, Yusuke; Morimoto, Yoshie; Tanimura, Keiko; Imabayashi, Tatsuya; Seko, Yurie; Kaneko, Yoshiko; Date, Koji; Ueda, Mikio; Arimoto, Taichiro; Iwasaki, Yoshinobu; Takayama, Koichi

2018-04-01

The purpose of this trial was to evaluate the feasibility and efficacy of alternating platinum-based doublet chemotherapy with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with EGFR-mutant non-small cell lung cancer (NSCLC). Chemotherapy-naive patients with advanced NSCLC harboring an EGFR mutation were enrolled. All patients underwent induction chemotherapy by sequentially alternating pemetrexed/cisplatin/bevacizumab and EGFR-TKIs followed by maintenance therapy with pemetrexed/bevacizumab and EGFR-TKIs. The primary outcome was the completion rate of the induction therapy. Eighteen eligible patients were enrolled between May 2011 and March 2016. The completion rate of induction therapy was 72.2% (13/18). Unfortunately, one patient developed grade 4 acute renal injury, but no other serious complications concerning this protocol were observed. Furthermore, diarrhea, rashes, and hematological adverse effects were mild. The completion rate of induction therapy was promising. Alternating chemotherapy and EGFR-TKIs should be further investigated regarding feasibility and efficacy. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Busulfan and melphalan versus carboplatin, etoposide, and melphalan as high-dose chemotherapy for high-risk neuroblastoma (HR-NBL1/SIOPEN): an international, randomised, multi-arm, open-label, phase 3 trial.

Science.gov (United States)

Ladenstein, Ruth; Pötschger, Ulrike; Pearson, Andrew D J; Brock, Penelope; Luksch, Roberto; Castel, Victoria; Yaniv, Isaac; Papadakis, Vassilios; Laureys, Geneviève; Malis, Josef; Balwierz, Walentyna; Ruud, Ellen; Kogner, Per; Schroeder, Henrik; de Lacerda, Ana Forjaz; Beck-Popovic, Maja; Bician, Pavel; Garami, Miklós; Trahair, Toby; Canete, Adela; Ambros, Peter F; Holmes, Keith; Gaze, Mark; Schreier, Günter; Garaventa, Alberto; Vassal, Gilles; Michon, Jean; Valteau-Couanet, Dominique

2017-04-01

High-dose chemotherapy with haemopoietic stem-cell rescue improves event-free survival in patients with high-risk neuroblastoma; however, which regimen has the greatest patient benefit has not been established. We aimed to assess event-free survival after high-dose chemotherapy with busulfan and melphalan compared with carboplatin, etoposide, and melphalan. We did an international, randomised, multi-arm, open-label, phase 3 cooperative group clinical trial of patients with high-risk neuroblastoma at 128 institutions in 18 countries that included an open-label randomised arm in which high-dose chemotherapy regimens were compared. Patients (age 1-20 years) with neuroblastoma were eligible to be randomly assigned if they had completed a multidrug induction regimen (cisplatin, carboplatin, cyclophosphamide, vincristine, and etoposide with or without topotecan, vincristine, and doxorubicin) and achieved an adequate disease response. Patients were randomly assigned (1:1) to busulfan and melphalan or to carboplatin, etoposide, and melphalan by minimisation, balancing age at diagnosis, stage, MYCN amplification, and national cooperative clinical group between groups. The busulfan and melphalan regimen comprised oral busulfan (150 mg/m 2 given on 4 days consecutively in four equal doses); after Nov 8, 2007, intravenous busulfan was given (0·8-1·2 mg/kg per dose for 16 doses according to patient weight). After 24 h, an intravenous melphalan dose (140 mg/m 2 ) was given. Doses of busulfan and melphalan were modified according to bodyweight. The carboplatin, etoposide, and melphalan regimen consisted of carboplatin continuous infusion of area under the plasma concentration-time curve 4·1 mg/mL per min per day for 4 days, etoposide continuous infusion of 338 mg/m 2 per day for 4 days, and melphalan 70 mg/m 2 per day for 3 days, with doses for all three drugs modified according to bodyweight and glomerular filtration rate. Stem-cell rescue was given after the last dose of

High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

Directory of Open Access Journals (Sweden)

L John Hoffer

Full Text Available Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail.We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement.Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type

High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

Science.gov (United States)

Hoffer, L John; Robitaille, Line; Zakarian, Robert; Melnychuk, David; Kavan, Petr; Agulnik, Jason; Cohen, Victor; Small, David; Miller, Wilson H

2015-01-01

Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC) could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail. We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement. Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type, chemotherapy

Strategies to eradicate minimal residual disease in small cell lung cancer: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

Science.gov (United States)

Krug, L M; Grant, S C; Miller, V A; Ng, K K; Kris, M G

1999-10-01

In the last 25 years, treatment for small cell lung cancer (SCLC) has improved with advances in chemotherapy and radiotherapy. Standard chemotherapy regimens can yield 80% to 90% response rates and some cures when combined with thoracic irradiation in limited-stage patients. Nonetheless, small cell lung cancer has a high relapse rate due to drug resistance; this has resulted in poor survival for most patients. Attacking this problem requires a unique approach to eliminate resistant disease remaining after induction therapy. This review will focus on three potential strategies: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

Multidisciplinary approach for the esophageal carcinoma with intent to conserve the esophagus centering on high-dose radiotherapy and concurrent chemotherapy

International Nuclear Information System (INIS)

Murakami, Masao; Kuroda, Yasumasa; Okamoto, Yoshiaki

1997-01-01

Forty-seven patients with operable squamous cell carcinoma of the thoracic esophagus were treated by initial concurrent chemoradiotherapy (CDDP-5 FU-44 Gy) followed by definitive high-dose of radiotherapy (CRT group: 35 patients) or surgery (CRT-S group: 12 patients). Clinical CR rate showed 86% in CRT group; and pathological CR rate 18% in CRT-S group. The overall median survival was 45 months, survival at 1, 3, 5 years being 96%, 52%, 48%, respectively. No treatment-related mortality was observed. The rate of the 'esophagus conservation' was 66%. Our results demonstrated that the multidisciplinary approach with intent to conserve the esophagus centering on high-dose radiotherapy and concurrent chemotherapy provides a significant improvement of both survival and quality of life in patients with operable esophageal carcinoma. (author)

Acute Complications After High-Dose Chemotherapy and Stem-Cell Rescue in Pediatric Patients With High-Risk Neuroblastoma Treated in Countries With Different Resources

Directory of Open Access Journals (Sweden)

Mahmoud M. Elzembely

2018-03-01

Full Text Available Purpose: High-dose chemotherapy with autologous stem-cell rescue (SCR is a key component of high-risk neuroblastoma (HRNB therapy. Carboplatin, etoposide, and melphalan (CEM or busulfan and melphalan (Bu/Mel are the most evaluated, effective high-dose chemotherapy for HRNB on the basis of results from major cooperative group studies. Toxicity profiles vary between these regimens, and practice variation exists regarding the preferred high-dose therapy (HDT. We sought to evaluate the safety of HDT and autologous SCR for HRNB in a resource-limited country (Egypt compared with the resource-rich United States. Patients and Methods: We performed a retrospective comparative review of single CEM-based HDT/SCR outcomes through day 100 for HRNB at the Fred Hutchinson Cancer Research Center (FH in the United States (2005 to 2015 versus Bu/Mel-based HDT at El-Sheikh Zayed Specialized Hospital (SZ in Egypt (2009 to 2015. Results: Forty-four patients at FH and 77 patients at SZ were reviewed. Pretransplant hepatic comorbidities were significantly higher at SZ (29 of 77 v nine of 44; P = .05, with 19 of 77 patients at SZ having hepatitis infection. Engraftment was delayed after SZ-Bu/Mel therapy compared with FH-CEM therapy for neutrophils (median 12 days v 10 days, respectively; P < .001 and platelets (median 20 days v 18 days, respectively; P < .001. Sinusoidal obstruction syndrome occurred later, after SZ-Bu/Mel therapy (median 19 days v 7 days; P = .033, and four of eight cases were fatal (six of eight patients had underlying hepatitis infection, whereas three of three cases after FH-CEM therapy were moderately severe. Resource utilization associated with the number of days with fever, antibiotic use, and the number of transfusions administered was significantly higher after FH-CEM therapy than after SZ-Bu/Mel therapy. Conclusion: Use of autologous stem-cell transplantation is feasible in the context of a resource-limited country.

Optimal Intermittent Dose Schedules for Chemotherapy Using Genetic Algorithm

Directory of Open Access Journals (Sweden)

Nadia ALAM

2013-08-01

Full Text Available In this paper, a design method for optimal cancer chemotherapy schedules via genetic algorithm (GA is presented. The design targets the key objective of chemotherapy to minimize the size of cancer tumor after a predefined time with keeping toxic side effects in limit. This is a difficult target to achieve using conventional clinical methods due to poor therapeutic indices of existing anti-cancer drugs. Moreover, there are clinical limitations in treatment administration to maintain continuous treatment. Besides, carefully decided rest periods are recommended to for patient’s comfort. Three intermittent drug scheduling schemes are presented in this paper where GA is used to optimize the dose quantities and timings by satisfying several treatment constraints. All three schemes are found to be effective in total elimination of cancer tumor after an agreed treatment length. The number of cancer cells is found zero at the end of the treatment for all three cases with tolerable toxicity. Finally, two of the schemes, “Fixed interval variable dose (FIVD and “Periodic dose” that are periodic in characteristic have been emphasized due to their additional simplicity in administration along with friendliness to patients. responses to the designed treatment schedules. Therefore the proposed design method is capable of planning effective, simple, patient friendly and acceptable chemotherapy schedules.

Metronomic chemotherapy – promising therapeutical approach for recurrent/ refractory high risk tumours in children

International Nuclear Information System (INIS)

Deak, L.; Feketeova, J.; Haluskova, V.; Sencakova, I.; Jenco, I.; Oravkinova, I.

2011-01-01

Despite a great progress in the treatment of pediatric malignancies, the outcome of children with high risk refractory or relapsed tumours, as are some types of brain tumours or metastatic sarcomas, remain poor. In contrast to dose – intensified chemotherapy, utilizing „maximal tolerated doses“ of chemotherapy, the metronomic chemotherapy (MC) is based on chronic administration of significantly lower doses of chemotherapy in an uninterrupted manner, for prolonged periods. Because of different mechanism of action against conventional chemotherapy and no cross- resistance, this treatment modality is effective also in refractory and recurrent tumours. The predominant mechanism of action of MC is antiangiogenic. In last decades several studies confirmed the efficacy and low toxicity of this new treatment modality. It can be delivered on outpatient basis and is well tolerated even in heavily pretreated patients. The authors present an overview of studies on MC in pediatric oncology and their own experience. (author)

Impact of Dose Reductions, Delays Between Chemotherapy Cycles, and/or Shorter Courses of Adjuvant Chemotherapy in Stage II and III Colorectal Cancer Patients: a Single-Center Retrospective Study.

Science.gov (United States)

Sgouros, Joseph; Aravantinos, Gerasimos; Kouvatseas, George; Rapti, Anna; Stamoulis, George; Bisvikis, Anastasios; Res, Helen; Samantas, Epameinondas

2015-12-01

Most stage II or III colorectal cancer patients are receiving nowadays a 4 to 6-month course of adjuvant chemotherapy. However, delays between cycles, reductions in the doses of chemotherapy drugs, or even permanent omissions of chemotherapy cycles might take place due to side effects or patient's preference. We examined the impact of these treatment modifications on recurrence-free survival (RFS) and overall survival (OS). We retrospectively collected data from colorectal cancer patients who had received adjuvant chemotherapy in our Department. Patients were categorized in five groups based on whether they had or not delays between chemotherapy cycles, dose reductions, and permanent omissions of chemotherapy cycles. Three-year RFS and OS of the five different groups were compared using the log-rank test and the Sidak approach. Five hundred and eight patients received treatment. Twenty seven percent of the patients had the full course of chemotherapy; the others had delays, dose reductions, or early termination of the treatment. No statistically significant differences were observed in 3-year RFS and OS between the five groups. A trend for worse RFS was noticed with early termination of treatment. A similar trend was also noticed for OS but only for stage II patients. In colorectal cancer patients, receiving adjuvant chemotherapy, delays between chemotherapy cycles, dose reductions of chemotherapy drugs, or even early termination of the treatment course do not seem to have a negative impact in 3-year RFS and OS; however, due to the trend of worse RFS in patients receiving shorter courses of chemotherapy, further studies are needed.

Randomised study of sequential versus combination chemotherapy with capecitabine, irinotecan and oxaliplatin in advanced colorectal cancer, an interim safety analysis. A Dutch Colorectal Cancer Group (DCCG) phase III study.

NARCIS (Netherlands)

Koopman, M.; Antonini, N.; Douma, J.; Wals, J.; Honkoop, A.H.; Erdkamp, F.L.; Jong, R.S. de; Rodenburg, C.J.; Vreugdenhil, G.R.; Akkermans-Vogelaar, J.M.; Punt, C.J.A.

2006-01-01

BACKGROUND: Results on overall survival in randomised studies of mono- versus combination chemotherapy in advanced colorectal cancer patients may have been biased by an imbalance in salvage treatments. This is the first randomised study that evaluates sequential versus combination chemotherapy with

Randomised study of sequential versus combination chemotherapy with capecitabine, irinotecan and oxaliplatin in advanced colorectal cancer, an interim safety analysis. A Dutch Colorectal Cancer Group (DCCG) phase III study

NARCIS (Netherlands)

Koopman, M.; Antonini, N. F.; Douma, J.; Wals, J.; Honkoop, A. H.; Erdkamp, F. L. G.; de Jong, R. S.; Rodenburg, C. J.; Vreugdenhil, G.; Akkermans-Vogelaar, J. M.; Punt, C. J. A.

2006-01-01

Results on overall survival in randomised studies of mono- versus combination chemotherapy in advanced colorectal cancer patients may have been biased by an imbalance in salvage treatments. This is the first randomised study that evaluates sequential versus combination chemotherapy with a

Motivation for Different Types and Doses of Exercise During Breast Cancer Chemotherapy: a Randomized Controlled Trial.

Science.gov (United States)

Courneya, Kerry S; Segal, Roanne J; Vallerand, James R; Forbes, Cynthia C; Crawford, Jennifer J; Dolan, Lianne B; Friedenreich, Christine M; Reid, Robert D; Gelmon, Karen; Mackey, John R; McKenzie, Donald C

2016-08-01

Exercise is beneficial for breast cancer patients during chemotherapy, but their motivation to perform different types and doses of exercise is unknown. The purpose of this study was to examine the anticipated and experienced motivation of breast cancer patients before and after three different exercise programs during chemotherapy. Breast cancer patients initiating chemotherapy (N = 301) were randomized to a standard dose of 25-30 min of aerobic exercise, a higher dose of 50-60 min of aerobic exercise, or a combined dose of 50-60 min of aerobic and resistance exercise. Patient preference and motivational outcomes from the theory of planned behavior (i.e., perceived benefit, enjoyment, support, difficulty, and motivation) were assessed before and after the interventions. At pre-randomization, breast cancer patients were significantly (p types and doses of exercise during chemotherapy varied considerably at pre-randomization, but the motivational outcomes experienced after the three interventions were similar. Clinicians can recommend any of the three exercise interventions to breast cancer patients knowing that positive motivational outcomes will result. Clinicaltrials.gov identifier: NCT00249015 .

Final report of Intergroup Trial 0122 (ECOG PE-289, RTOG 90-12): Phase II trial of neoadjuvant chemotherapy plus concurrent chemotherapy and high-dose radiation for squamous cell carcinoma of the esophagus

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Minsky, Bruce D.; Neuberg, Donna; Kelsen, David P.; Pisansky, Thomas M.; Ginsberg, Robert J.; Pajak, Thomas; Salter, Merle; Benson, Al

1999-01-01

Purpose: To determine the outcome of neoadjuvant chemotherapy followed by concurrent chemotherapy plus high-dose radiation therapy in patients with local/regional squamous cell carcinoma of the esophagus. Methods and Materials: Forty-five patients with clinical Stage T1-4N0-1M0 squamous cell carcinoma were entered on a prospective single-arm study, of which 38 were eligible. Patients received 3 monthly cycles of 5-FU (1000 mg/m 2 /24 h x 5 days) and cisplatin (100 mg/m 2 day 1; neoadjuvant segment) followed by 2 additional monthly cycles of 5-FU (1000 mg/m 2 /24 h x 5 days) and cisplatin (75 mg/m 2 day 1) plus concurrent 6480 cGy (combined modality segment). The median follow-up in surviving patients was 59 months. Results: For the 38 eligible patients, the primary tumor response rate was 47% complete, 8% partial, and 3% stable disease. The first site of clinical failure was 39% local/regional and 24% distant. For the total patient group, there were 6 deaths during treatment, of which 9% (4/45) were treatment related. The median survival was 20 months. Actuarial survival at 3 years was 30%, and at 5 years, 20%. Conclusion: This intensive neoadjuvant approach does not appear to offer a benefit compared with conventional doses and techniques of combined modality therapy. However, high dose radiation (6480 cGy) appears to be tolerable, and is being tested further in Intergroup Trial INT 0123

Reduced cerebral glucose metabolism and increased brain capillary permeability following high-dose methotrexate chemotherapy: a positron emission tomographic study

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Phillips, P.C.; Dhawan, V.; Strother, S.C.; Sidtis, J.J.; Evans, A.C.; Allen, J.C.; Rottenberg, D.A.

1987-01-01

Regional glucose metabolic rate constants and blood-to-brain transport of rubidium were estimated using positron emission tomography in an adolescent patient with a brain tumor, before and after chemotherapy with intravenous high-dose methotrexate. Widespread depression of cerebral glucose metabolism was apparent 24 hours after drug administration, which may reflect reduced glucose phosphorylation, and the influx rate constant for 82 Rb was increased, indicating a drug-induced alteration in blood-brain barrier function. Associated changes in neuropsychological performance, electroencephalogram, and plasma amino acid concentration were identified in the absence of evidence of systemic methotrexate toxicity, suggesting primary methotrexate neurotoxicity

Prognostic impact of hemoglobin level and other factors in patients with high-grade gliomas treated with postoperative radiochemotherapy and sequential chemotherapy based on temozolomide. A 10-year experience at a single institution

International Nuclear Information System (INIS)

Ausili Cefaro, Giampiero; Genovesi, Domenico; Vinciguerra, Annamaria; Trignani, Marianna; Taraborrelli, Maria; Augurio, Antonietta; Buonaguidi, Roberto; Galzio, Renato J.; Di Nicola, Marta

2011-01-01

To evaluate the influence of serum hemoglobin level prior to radiotherapy and other prognostic factors on survival in patients with high-grade gliomas. From 2001-2010, we retrospectively evaluated a total of 48 patients with malignant glioma treated with surgery and postoperative radiochemotherapy with temozolomide. A total of 37 of 48 patients received sequential temozolomide. Hemoglobin levels were assayed before radiotherapy in all patients. The Kaplan-Meier method was applied to estimate the overall survival, while the log-rank test was applied to evaluate the differences on survival probability between prognostic subgroups. Results were assessed in 43 patients. The median overall survival time was 18 months (95% confidence interval: 12-40 months). The 1- and 2-year survival rates were 62.2% and 36.3%, respectively. The prognostic factors analyzed were gender, age, extent of surgery, performance status before and after radiotherapy, sequential chemotherapy, hemoglobin level, and methylation of the O-6-methylguanine-DNA methyltransferase gene (MGMT). In univariate analysis, the variables significantly related to survival were performance status before and after radiotherapy, sequential chemotherapy, and hemoglobin level. The median overall survival in patients with a hemoglobin level ≤ 12 g/dl was 12 months and 23 months in patients with a hemoglobin level > 12 g/dl. The 1- and 2-year survival rates were 46.7% and 20.0%, respectively, for patients with a hemoglobin level ≤ 12 mg/dl and 69.6% and 45.7%, respectively, for patients with a hemoglobin level > 12 g/dl. Our results confirm the impact of well-known prognostic factors on survival. In this research, it was found that a low hemoglobin level before radiotherapy can adversely influence the prognosis of patients with malignant gliomas.

Five-year follow-up of survival and relapse in patients who received cryotherapy during high-dose chemotherapy for stem cell transplantation shows no safety concerns.

Science.gov (United States)

Svanberg, A; Ohrn, K; Birgegård, G

2012-11-01

We have previously published a randomised controlled study of the efficacy of cryotherapy in preventing acute oral mucositis after high-dose chemotherapy for stem cell transplantation. The present study is a 5-year follow-up safety study of survival in these patients. In the previously published study oral cryotherapy (cooling of the oral cavity) during high-dose chemotherapy significantly reduced mucositis grade and opiate use in the treated group. All patients were followed up for at least 5 years with regard to relapse and death rates. Baseline data, transplant complications and mucositis data were compared. Significantly more patients (25/39) who received oral cryotherapy were alive after 5 years compared to 15/39 in the control group (P= 0.025). Relapse rates were similar. The only baseline difference was a lower proportion of patients in complete remission at transplantation in the control group (6 vs. 13, P= 0.047). This 5-year follow-up study gave no support for safety concerns with cryotherapy. © 2012 Blackwell Publishing Ltd.

Sequential hemi-body radiotherapy in advanced multiple myeloma

International Nuclear Information System (INIS)

Jaffe, J.P.; Bosch, A.; Raich, P.C.

1979-01-01

Eleven patients with advanced multiple myeloma refractory to standard chemotherapy were treated with a regimen of sequential hemi-body radiotherapy consisting of 800 rad midplane in a single dose to each half. 9/10 patients experienced significant relief of skeletal pain and there were 5/11 objective tumor responses with one complete remission. Treatment-related morbidity was significant and consisted primarily of nausea and emesis, bone marrow suppression, and pneumonitis. This therapy is helpful in the management of advanced myeloma, and should be studied earlier in the course of the disease

Can high-dose fotemustine reverse MGMT resistance in glioblastoma multiforme?

Science.gov (United States)

Gallo, Chiara; Buonerba, Carlo; Di Lorenzo, Giuseppe; Romeo, Valeria; De Placido, Sabino; Marinelli, Alfredo

2010-11-01

Glioblastoma multiforme (GBM), the highest grade malignant glioma, is associated with a grim prognosis-median overall survival is in the range 12-15 months, despite optimum treatment. Surgery to the maximum possible extent, external beam radiotherapy, and systemic temozolomide chemotherapy are current standard treatments for newly diagnosed GBM, with intracerebral delivery of carmustine wafers (Gliadel). Unfortunately, the effectiveness of chemotherapy can be hampered by the DNA repair enzyme O6-methylguanine methyltransferase (MGMT), which confers resistance both to temozolomide and nitrosoureas, for example fotemustine and carmustine. MGMT activity can be measured by PCR and immunohistochemistry, with the former being the current validated technique. High-dose chemotherapy can deplete MGMT levels in GBM cells and has proved feasible in various trials on temozolomide, in both newly diagnosed and recurrent GBM. We here report the unique case of a GBM patient, with high MGMT expression by immunohistochemistry, who underwent an experimental, high-dose fotemustine schedule after surgery and radiotherapy. Although treatment caused two episodes of grade 3-4 thrombocytopenia, a complete response and survival of more than three years were achieved, with a 30% increase in dose intensity compared with the standard fotemustine schedule.

Long-term follow-up in patients treated with larynx preservation approach using sequential chemotherapy and radiation therapy: the Memorial Hospital experience

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Maluf, Fernando; Sherman, Eric J.; Bosl, George J.; Pfister, David G. [Memorial Sloan-Kettering Cancer Center, New York, NY (United States). Dept. of Medicine. Div. of Solid Tumor Oncology; Kraus, Dennis H.; Shaha, Ashok; Shah, Jatin P. [Memorial Sloan-Kettering Cancer Center, New York, NY (United States).Dept. of Surgery. Head and Neck Service; Zelefsky, Michael J. [Memorial Sloan-Kettering Cancer Center, New York, NY (United States). Dept. of Radiation Oncology]. E-mail: pfisterd@mskcc.org

2000-06-01

While many combined modality, organ preservation programs are reported in the literature, few provide long-term follow-up with functional outcomes. The goal of this report is to provide this outcome data for patients treated with a sequential chemotherapy/radiotherapy (CT/RT) approach - the only strategy successfully compared to surgery and RT in randomized trials to date - treated at our institution with a median follow-up of over 10 years. Eligible patients had advanced, resectable, histologically-confirmed squamous cell carcinomas of larynx or pharynx for which standard surgical management would have jeopardized the larynx. Treatment occurred as part of three consecutive larynx preservation protocols and consisted of three cycles of induction, cisplatin-based chemotherapy followed, if the primary site had a major response, by definitive dose radiation therapy (65-70 Gy to sites of initial disease bulk) via conventional fractionation (1.8-2 Gy fraction). If the tumor did not respond to the induction chemotherapy or persisted after radiation therapy, appropriate locoregional treatment was pursued. Response to induction chemotherapy, initial rendered disease-free rate, local control with a functional larynx (without any surgery except biopsy to the primary site, permanent tracheostomy or gastrostomy - LCLP), and actuarial survival rates were calculated. A multivariate assessment of prognostic variables was performed using Cox-proportional hazards model to evaluate for predictors of successful larynx preservation. One hundred and ten patients (109 evaluable) with cancer of the larynx (40%), hypopharynx (29%), and oropharynx (30%) were enrolled from 1983 to 1990. The median age was 60 years With a median Karnofsky Performance Status of 80%. The stage of the patients consisted of 33% T4, 74% node positive, and 69% stage IV. The major response rate at the primary site to induction chemotherapy was 74% (complete response in 36%). Seventy-eight percent were rendered

Long-term follow-up in patients treated with larynx preservation approach using sequential chemotherapy and radiation therapy: the Memorial Hospital experience

International Nuclear Information System (INIS)

Maluf, Fernando; Sherman, Eric J.; Bosl, George J.; Pfister, David G.; Kraus, Dennis H.; Shaha, Ashok; Shah, Jatin P.; Zelefsky, Michael J.

2000-01-01

While many combined modality, organ preservation programs are reported in the literature, few provide long-term follow-up with functional outcomes. The goal of this report is to provide this outcome data for patients treated with a sequential chemotherapy/radiotherapy (CT/RT) approach - the only strategy successfully compared to surgery and RT in randomized trials to date - treated at our institution with a median follow-up of over 10 years. Eligible patients had advanced, resectable, histologically-confirmed squamous cell carcinomas of larynx or pharynx for which standard surgical management would have jeopardized the larynx. Treatment occurred as part of three consecutive larynx preservation protocols and consisted of three cycles of induction, cisplatin-based chemotherapy followed, if the primary site had a major response, by definitive dose radiation therapy (65-70 Gy to sites of initial disease bulk) via conventional fractionation (1.8-2 Gy fraction). If the tumor did not respond to the induction chemotherapy or persisted after radiation therapy, appropriate locoregional treatment was pursued. Response to induction chemotherapy, initial rendered disease-free rate, local control with a functional larynx (without any surgery except biopsy to the primary site, permanent tracheostomy or gastrostomy - LCLP), and actuarial survival rates were calculated. A multivariate assessment of prognostic variables was performed using Cox-proportional hazards model to evaluate for predictors of successful larynx preservation. One hundred and ten patients (109 evaluable) with cancer of the larynx (40%), hypopharynx (29%), and oropharynx (30%) were enrolled from 1983 to 1990. The median age was 60 years With a median Karnofsky Performance Status of 80%. The stage of the patients consisted of 33% T4, 74% node positive, and 69% stage IV. The major response rate at the primary site to induction chemotherapy was 74% (complete response in 36%). Seventy-eight percent were rendered

Effective treatment of Stage I uterine papillary serous carcinoma with high dose-rate vaginal apex radiation (192Ir) and chemotherapy

International Nuclear Information System (INIS)

Turner, Bruce C.; Knisely, Jonathan P. S.; Kacinski, Barry M.; Haffty, Bruce G.; Gumbs, Andrew A.; Roberts, Kenneth B.; Frank, Alex H.; Peschel, Richard E.; Rutherford, Thomas J.; Edraki, Babak; Kohorn, Ernest I.; Chambers, Setsuko K.; Schwartz, Peter E.; Wilson, Lynn D.

1998-01-01

Purpose: Uterine papillary serous carcinoma (UPSC) is a morphologically distinct variant of endometrial carcinoma that is associated with a poor prognosis, high recurrence rate, frequent clinical understaging, and poor response to salvage treatment. We retrospectively analyzed local control, actuarial overall survival (OS), actuarial disease-free survival (DFS), salvage rate, and complications for patients with Federation International of Gynecology and Obstetrics (FIGO) (1988) Stage I UPSC. Methods and Materials: This retrospective analysis describes 38 patients with FIGO Stage I UPSC who were treated with the combinations of radiation therapy, chemotherapy, total abdominal hysterectomy, and bilateral salpingo-oophorectomy (TAH/BSO), with or without a surgical staging procedure. Twenty of 38 patients were treated with a combination of low dose-rate (LDR) uterine/vaginal brachytherapy using 226 Ra or 137 Cs and conventional whole-abdomen radiation therapy (WART) or whole-pelvic radiation therapy (WPRT). Of 20 patients (10%) in this treatment group, 2 received cisplatin chemotherapy. Eighteen patients were treated with high dose-rate (HDR) vaginal apex brachytherapy using 192 Ir with an afterloading device and cisplatin, doxorubicin, and cyclophosphamide (CAP) chemotherapy (5 of 18 patients). Only 6 of 20 UPSC patients treated with combination LDR uterine/vaginal brachytherapy and conventional external beam radiotherapy underwent complete surgical staging, consisting of TAH/BSO, pelvic/para-aortic lymph node sampling, omentectomy, and peritoneal fluid analysis, compared to 15 of 18 patients treated with HDR vaginal apex brachytherapy. Results: The 5-year actuarial OS for patients with complete surgical staging and adjuvant radiation/chemotherapy treatment was 100% vs. 61% for patients without complete staging (p = 0.002). The 5-year actuarial OS for all Stage I UPSC patients treated with postoperative HDR vaginal apex brachytherapy and systemic chemotherapy was 94

Radiation effects of high and low doses

International Nuclear Information System (INIS)

El-Naggar, A.M.

1998-01-01

The extensive proliferation of the uses and applications of atomic and nuclear energy resulted in possible repercussions on human health. The prominent features of the health hazards that may be incurred after exposure to high and low radiation doses are discussed. The physical and biological factors involved in the sequential development of radiation health effects and the different cellular responses to radiation injury are considered. The main criteria and features of radiation effects of high and low doses are comprehensively outlined

High-dose chemotherapy followed by autologous stem cell transplantation for metastatic rhabdomyosarcoma--a systematic review.

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Frank Peinemann

Full Text Available INTRODUCTION: Patients with metastatic rhabdomyosarcoma (RMS have a poor prognosis. The aim of this systematic review is to investigate whether high-dose chemotherapy (HDCT followed by autologous hematopoietic stem cell transplantation (HSCT in patients with metastatic RMS has additional benefit or harm compared to standard chemotherapy. METHODS: Systematic literature searches were performed in MEDLINE, EMBASE, and The Cochrane Library. All databases were searched from inception to February 2010. PubMed was searched in June 2010 for a last update. In addition to randomized and non-randomized controlled trials, case series and case reports were included to complement results from scant data. The primary outcome was overall survival. A meta-analysis was performed using the hazard ratio as primary effect measure, which was estimated from Cox proportional hazard models or from summary statistics of Kaplan Meier product-limit estimations. RESULTS: A total of 40 studies with 287 transplant patients with metastatic RMS (age range 0 to 32 years were included in the assessment. We identified 3 non-randomized controlled trials. The 3-year overall survival ranged from 22% to 53% in the transplant groups vs. 18% to 55% in the control groups. Meta-analysis on overall survival in controlled trials showed no difference between treatments. Result of meta-analysis of pooled individual survival data of case series and case reports, and results from uncontrolled studies with aggregate data were in the range of those from controlled data. The risk of bias was high in all studies due to methodological flaws. CONCLUSIONS: HDCT followed by autologous HSCT in patients with RMS remains an experimental treatment. At present, it does not appear justifiable to use this treatment except in appropriately designed controlled trials.

High-dose chemotherapy for patients with high-risk breast cancer: a clinical and economic assessment using a quality-adjusted survival analysis.

Science.gov (United States)

Marino, Patricia; Roché, Henri; Moatti, Jean-Paul

2008-04-01

The benefit of high-dose chemotherapy (HDC) has not been clearly demonstrated. It may offer disease-free survival improvement at the expense of major toxicity and increasing cost. We evaluated the trade-offs between toxicity, relapse, and costs using a quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis. The analysis was conducted in the context of a randomized trial (PEGASE 01) evaluating the benefit of HDC for 314 patients with high-risk breast cancer. A Q-TWiST analysis was first performed to compare HDC with standard chemotherapy. We then used the results of this Q-TWiST analysis to inform a cost per quality-adjusted life-year (QALY) comparison between treatments. Q-TWiST durations were in favor of HDC, whatever the weighting coefficients used for the analysis. This benefit was significant when the weighting coefficient related to the time spent after relapse was low (0.78), HDC offered no benefit. For intermediate values, the results depended on the weighting coefficient attributed to the toxicity period. The incremental cost per QALY ranged from 12,691euro/QALY to 26,439euro/QALY, according to the coefficients used to weight toxicity and relapse. The benefits of HDC outweigh the burdens of treatment for a wide range of utility coefficients. Economic impact is not a barrier to HDC diffusion in this situation. Nevertheless, no significant benefit was demonstrated for a certain range of utility values.

Chemotherapy for head and neck cancer

International Nuclear Information System (INIS)

Pfister, David G.

1997-01-01

Purpose/Objective: The role of chemotherapy in the management of squamous cell carcinoma of the upper aerodigestive tract is undergoing rapid evolution. Historically, the use of chemotherapy was limited to patients with incurable disease who had exhausted all surgical and radiation therapy options. The results of recent randomized trials, however, suggest an increasing role for chemotherapy as part of primary management in patients with unresectable disease; advanced larynx or hypopharynx cancer with the intent of larynx preservation, or advanced nasopharynx cancer. This refresher course will provide a comprehensive overview of the current indications for chemotherapy in the management of these malignancies, and will highlight areas of controversy and future directions of investigation. More specifically, the following areas will be emphasized. 1. The identification of drugs commonly used in the management of head and neck cancer, their customary dosing and side effects. 2. The impact of induction and/or adjuvant chemotherapy combined with surgery and radiation therapy as defined by randomized trials, including a discussion of the Head and Neck Contracts program and the Intergroup adjuvant trial. 3. The development of larynx/function preservation treatment programs, including a review of the Veterans Administration and EORTC larynx preservation studies. 4. The evolving role of chemotherapy as part of innovative combined modality programs, especially in patients with unresectable disease. The rationale and utility of sequential versus concomitant/alternating chemotherapy-radiation strategies, and relevant randomized clinical trials comparing the different strategies will be discussed. 5. The appropriate application of chemotherapy in the palliative setting, including a discussion of the relative merits of single-agent versus combination chemotherapy

Chemotherapy for head and neck cancer

International Nuclear Information System (INIS)

Pfister, David G.

1995-01-01

Purpose/Objective: The role of chemotherapy in the management of squamous cell carcinoma of the upper aerodigestive tract is undergoing rapid evolution. Historically, the use of chemotherapy was limited to patients with incurable disease who had exhausted all surgical and radiation therapy options. The results of recent randomized trials, however, suggest an increasing role for chemotherapy as part of primary management in patients seeking to avoid potentially morbid surgical procedures or with unresectable disease. This refresher course will provide a comprehensive overview of the current indications for chemotherapy in the management of these malignancies, and will highlight areas of controversy and future directions of investigation. More specifically, the following areas will be emphasized. 1. The identification of drugs commonly used in the management of head and neck cancer, their customary dosing and side effects. 2. The impact of induction and/or adjuvant chemotherapy combined with surgery and radiation therapy as defined by randomized trials, including a discussion of the Head and Neck Contracts program and the Intergroup adjuvant trial. 3. The development of larynx/function preservation treatment programs, including a review of the Memorial Hospital experience with larynx preservation and the Veterans Administration larynx preservation study. 4. The evolving role of chemotherapy as part of innovative combined modality programs, especially in patients with unresectable disease. The rationale and utility of sequential versus concomitant/alternating chemotherapy-radiation strategies, and relevant randomized clinical trials comparing the different strategies will be discussed. 5. The appropriate application of chemotherapy in the palliative setting, including a discussion of the relative merits of single-agent versus combination chemotherapy

Combined radiotherapy and chemotherapy for head and neck cancer

International Nuclear Information System (INIS)

Inuyama, Yukio; Fujii, Masato; Tanaka, Juichi; Takaoka, Tetsuro; Hosoda, Hyonosuke; Kawaura, Mitsuhiro; Toji, Masao

1988-01-01

There are 4 modalities of combined radiotherapy and chemotherapy which include (1) concurrent radiotherapy and chemotherapy, (2) sequential use of radiotherapy and chemotherapy (pre-radiation chemotherapy), (3) pre-radiation chemotherapy followed by concurrent radiation and chemotherapy, and (4) alternating use of radiotherapy and chemotherapy based upon Looney's hypothesis. We studied concurrent use of radiotherapy and UFT by means of animal experimentation and clinical trials. The results obtained revealed that UFT was a most suitable agent together with 5-fluorouracil for concurrent application of radiotherapy and chemotherapy. Neo-adjuvant chemotherapy including pre-radiation chemotherapy was also studied in cases of maxillary sinus carcinoma and nasopharyngeal carcinoma. From the results, it seemed desirable to use cisplatin and bleomycin analogs sequentially in combined chemotherapy and radiotherapy. Neo-adjuvant chemotherapy should be studied successively to improve local tumor control rates and prevent distant metastases. For future perspectives, new trials of alternating radiotherapy and chemotherapy based upon Looney's hypothesis seem necessary. (author)

Health related quality of life in locally advanced NSCLC treated with high dose radiotherapy and concurrent chemotherapy or cetuximab – Pooled results from two prospective clinical trials

International Nuclear Information System (INIS)

Hallqvist, Andreas; Bergman, Bengt; Nyman, Jan

2012-01-01

Background: In non-small cell lung cancer (NSCLC) stage III, data on patient reported health-related quality of life (HRQL) are scarce, especially regarding concurrent chemoradiotherapy. Aims: To evaluate HRQL in patients treated with high dose radiotherapy combined with concurrent chemotherapy or the antibody cetuximab. Methods: The study population comprised all patients enroled in either of two phase II trials in locally advanced NSCLC performed in Sweden 2002–2007. The RAKET trial investigated three different ways of increasing local control (accelerated hyperfractionated treatment or concurrent daily or weekly chemotherapy). The Satellite trial evaluated the addition of cetuximab to thoracic irradiation. HRQL was measured at four time points: At baseline, before radiotherapy, 4–6 weeks after radiotherapy and at 3 months follow-up, using the EORTC QLQ-C30 and LC14 set of questionnaires. Results: 154/220 patients (65%) who completed HRQL assessments at all time points were included in the longitudinal study. There was a significant decline over time regarding most functioning measures. Dyspnoea and fatigue gradually deteriorated without recovery after completed treatment. Chemotherapy related symptoms showed a transient deterioration, whereas radiotherapy related esophagitis had not fully recovered at 3 months. Patients with stage IIIA disease tended to recover better regarding global QL, fatigue and dyspnoea compared to patients with stage IIIB. Patients with WHO performance status (PS) 0 reported improved global QL and less fatigue over time compared with PS 1. Concurrent chemotherapy was associated with more pronounced fatigue and dysphagia, and worse global QL compared with concurrent cetuximab. Baseline physical functioning was an independent predictor of overall survival. Conclusion: Patients undergoing high dose thoracic radiotherapy combined with chemotherapy or cetuximab reported a gradual deterioration in functioning, dyspnoea and fatigue, while

Preliminary results of concurrent chemotherapy and radiation therapy using high-dose-rate brachytherapy for cervical cancer

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Lee, Kyung Ja; Lee, Ji Hye; Lee, Re Na; Suh, Hyun Suk [Ewha Womans University College of Medicine, Seoul (Korea, Republic of)

2006-09-15

To determine the efficacy and safety of concurrent chemotherapy and radiation therapy with high-dose-rate brachytherapy for cervical cancer. From January 2001 to December 2002, 30 patients with cervical cancer were treated with concurrent chemotherapy (cisplatin and 5-FU) and definitive radiation therapy. The median age was 58 (range 34 {approx} 74) year old. The pathology of the biopsy sections was squamous cell carcinoma in 29 patients and one was adenocarcinoma. The distribution to FIGO staging system was as follow: stage IB, 7 (23%); IIA, 3 (10%); IIB, 12 (40%); IIIA, 3 (10%); IIIB, 5 (17%). All patients received pelvic external beam irradiation (EBRT) to a total dose of 45 {approx} 50.4 Gy (median: 50.4 Gy) over 5 {approx} 5.5 weeks. Ir-192 HDR intracavity brachytherapy (ICBT) was given after a total dose of 41.1 Gy. HDR-ICBT was performed twice a week, with a fraction point. A dose of 4 Gy and median dose to point A was 28 Gy (range: 16 {approx} 32 Gy) in 7 fractions. The median cumulative biologic effective dose (BED) at point A (EBRT + ICBT) was 88 Gy{sub 10} (range:77 {approx} 94 Gy{sub 10}). The median cumulative BED at ICRU 38 reference point (EBRT + ICBT) was 131 Gy{sub 3} (range: 122 {approx} 140 Gy{sub 3}) at point A, 109 Gy{sub 3} (range:88{approx} 125 Gy{sub 3}) at the rectum and 111 Gy{sub 3} (range: 91 {approx} 123 Gy{sub 3}) at the urinary bladder. Cisplatin (60 mg/m{sup 2}) and 5-FU (1,000 mg/m{sup 2}) was administered intravenously at 2 weeks interval from the first day of radiation for median 5 (range:2 {approx} 6) cycles. The assessment was performed at 1 month after completion of radiation therapy by clinical examination and CT scan. The median follow-up time was 36 months (range:8{approx} 50 months). The complete response rate after concurrent chemo radiation therapy was 93.3%. The 3-yr actuarial pelvic control rate was 87% and 3-yr actuarial overall survival and disease-free survival rate was 93% and 87%, respectively. The local failure

Preliminary results of concurrent chemotherapy and radiation therapy using high-dose-rate brachytherapy for cervical cancer

International Nuclear Information System (INIS)

Lee, Kyung Ja; Lee, Ji Hye; Lee, Re Na; Suh, Hyun Suk

2006-01-01

To determine the efficacy and safety of concurrent chemotherapy and radiation therapy with high-dose-rate brachytherapy for cervical cancer. From January 2001 to December 2002, 30 patients with cervical cancer were treated with concurrent chemotherapy (cisplatin and 5-FU) and definitive radiation therapy. The median age was 58 (range 34 ∼ 74) year old. The pathology of the biopsy sections was squamous cell carcinoma in 29 patients and one was adenocarcinoma. The distribution to FIGO staging system was as follow: stage IB, 7 (23%); IIA, 3 (10%); IIB, 12 (40%); IIIA, 3 (10%); IIIB, 5 (17%). All patients received pelvic external beam irradiation (EBRT) to a total dose of 45 ∼ 50.4 Gy (median: 50.4 Gy) over 5 ∼ 5.5 weeks. Ir-192 HDR intracavity brachytherapy (ICBT) was given after a total dose of 41.1 Gy. HDR-ICBT was performed twice a week, with a fraction point. A dose of 4 Gy and median dose to point A was 28 Gy (range: 16 ∼ 32 Gy) in 7 fractions. The median cumulative biologic effective dose (BED) at point A (EBRT + ICBT) was 88 Gy 10 (range:77 ∼ 94 Gy 10 ). The median cumulative BED at ICRU 38 reference point (EBRT + ICBT) was 131 Gy 3 (range: 122 ∼ 140 Gy 3 ) at point A, 109 Gy 3 (range:88∼ 125 Gy 3 ) at the rectum and 111 Gy 3 (range: 91 ∼ 123 Gy 3 ) at the urinary bladder. Cisplatin (60 mg/m 2 ) and 5-FU (1,000 mg/m 2 ) was administered intravenously at 2 weeks interval from the first day of radiation for median 5 (range:2 ∼ 6) cycles. The assessment was performed at 1 month after completion of radiation therapy by clinical examination and CT scan. The median follow-up time was 36 months (range:8∼ 50 months). The complete response rate after concurrent chemo radiation therapy was 93.3%. The 3-yr actuarial pelvic control rate was 87% and 3-yr actuarial overall survival and disease-free survival rate was 93% and 87%, respectively. The local failure rate was 13% and distant metastatic rate was 3.3%. The crude rate of minor hematologic

A phase III randomized study on the sequencing of radiotherapy and chemotherapy in the conservative management of early-stage breast cancer

International Nuclear Information System (INIS)

Arcangeli, Giorgio; Pinnaro, Paola; Rambone, Rita; Giannarelli, Diana; Benassi, Marcello

2006-01-01

Purpose: To compare two different timings of radiation treatment in patients with breast cancer who underwent conservative surgery and were candidates to receive adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy. Methods and Materials: A total of 206 patients who had quadrantectomy and axillary dissection for breast cancer and were planned to receive adjuvant CMF chemotherapy were randomized to concurrent or sequential radiotherapy. Radiotherapy was delivered only to the whole breast through tangential fields to a dose of 50 Gy in 20 fractions over 4 weeks, followed by an electron boost of 10-15 Gy in 4-6 fractions to the tumor bed. Results: No differences in 5-year breast recurrence-free, metastasis-free, disease-free, and overall survival were observed in the two treatment groups. All patients completed the planned radiotherapy. No evidence of an increased risk of toxicity was observed between the two arms. No difference in radiotherapy and in the chemotherapy dose intensity was observed in the two groups. Conclusions: In patients with negative surgical margins receiving adjuvant chemotherapy, radiotherapy can be delayed to up to 7 months. Concurrent administration of CMF chemotherapy and radiotherapy is safe and might be reserved for patients at high risk of local recurrence, such as those with positive surgical margins or larger tumor diameters

High-dose Extended-Field Irradiation and High-Dose-Rate Brachytherapy With Concurrent Chemotherapy for Cervical Cancer With Positive Para-Aortic Lymph Nodes

International Nuclear Information System (INIS)

Kim, Young Seok; Kim, Jong Hoon; Ahn, Seung Do; Lee, Sang-wook; Shin, Seong Soo; Nam, Joo-Hyun; Kim, Young-Tak; Kim, Yong-Man; Kim, Jong-Hyeok; Choi, Eun Kyung

2009-01-01

Purpose: To determine the efficacy and toxicity of extended-field radiotherapy (RT) with concurrent platinum-based chemotherapy in patients with uterine cervical carcinoma and positive para-aortic nodes. Methods and Materials: We retrospectively reviewed the results for 33 women with Stage IB-IVB cervical cancer. Each patient had received 59.4 Gy, including a three-dimensional conformal boost to the para-aortic lymph nodes and 41.4-50.4 Gy of external beam radiotherapy to the pelvis. Each patient also underwent six or seven applications of high-dose-rate brachytherapy (median, 5 Gy to point A at each session). Results: The median follow-up period of surviving patients was 39 months. The most common acute toxicity was hematologic, observed in 23 women. Severe acute and late gastrointestinal toxicity was observed in 3 and 4 patients, respectively. More than three-quarters of patients showed a complete response, encompassing the primary mass, metastatic pelvic, and para-aortic lymph nodes. Of the 33 women, 15 had no evidence of disease, 6 had persistent disease, 4 developed in-field failures, and 6 developed distant failures. The 5-year overall and disease-free survival rate was 47% and 42%, respectively. Conclusion: Concurrent chemoradiotherapy with extended-field radiotherapy is feasible in women with uterine cervical carcinoma and positive para-aortic lymph nodes, with acceptable late morbidity and a high survival rate, although it was accompanied by substantial acute toxicity.

Combination chemotherapy concurrent with small dose radiation therapy for small cell carcinoma of the lung

International Nuclear Information System (INIS)

Tada, Toshihiko; Fujita, Hiroji; Shintomi, Takenori

1987-01-01

Forty consecutive patients with small cell carcinoma of the lung were treated with chemotherapy, radiotherapy or both. Of 34 patients treated with chemotherapy, 24 were treated with combination chemotherapy, containing cyclophosphamide vincristine methotrexate and procarbazine, concurrent with small dose radiation therapy (500 cGy/5 fraction) as a chemosensitizer (COMPrt). The response rate to this regimen was 81 % (29 % complete) and the 2 year survival rate was 28.6 %. These results have been superior to other regimens and the toxicity was not see to be any higher. After completion of COMPrt regimen, 10 patients were treated with intrathoracic radiation therapy (average dose 3000 cGy) and 3 recieved surgical treatment. Radiation therapy improved the 2-year survival rate (42.2 %) when compared with those patients who received no radiation therapy (18.2 %). Three patients received surgical treatment were considered to be disease-free for 23, 17, and 9 months respectively, after induction of chemotherapy. (author)

Sequencing chemotherapy and radiotherapy in locoregional advanced breast cancer patients after mastectomy – a retrospective analysis

International Nuclear Information System (INIS)

Piroth, Marc D; Pinkawa, Michael; Gagel, Bernd; Stanzel, Sven; Asadpour, Branka; Eble, Michael J

2008-01-01

Combined chemo- and radiotherapy are established in breast cancer treatment. Chemotherapy is recommended prior to radiotherapy but decisive data on the optimal sequence are rare. This retrospective analysis aimed to assess the role of sequencing in patients after mastectomy because of advanced locoregional disease. A total of 212 eligible patients had a stage III breast cancer and had adjuvant chemotherapy and radiotherapy after mastectomy and axillary dissection between 1996 and 2004. According to concerted multi-modality treatment strategies 86 patients were treated sequentially (chemotherapy followed by radiotherapy) (SEQgroup), 70 patients had a sandwich treatment (SW-group) and 56 patients had simultaneous chemoradiation (SIM-group) during that time period. Radiotherapy comprised the thoracic wall and/or regional lymph nodes. The total dose was 45–50.4 Gray. As simultaneous chemoradiation CMF was given in 95.4% of patients while in sequential or sandwich application in 86% and 87.1% of patients an anthracycline-based chemotherapy was given. Concerning the parameters nodal involvement, lymphovascular invasion, extracapsular spread and extension of the irradiated region the three treatment groups were significantly imbalanced. The other parameters, e.g. age, pathological tumor stage, grading and receptor status were homogeneously distributed. Looking on those two groups with an equally effective chemotherapy (EC, FEC), the SEQ- and SW-group, the sole imbalance was the extension of LVI (57.1 vs. 25.6%, p < 0.0001). 5-year overall- and disease free survival were 53.2%/56%, 38.1%/32% and 64.2%/50%, for the sequential, sandwich and simultaneous regime, respectively, which differed significantly in the univariate analysis (p = 0.04 and p = 0.03, log-rank test). Also the 5-year locoregional or distant recurrence free survival showed no significant differences according to the sequence of chemo- and radiotherapy. In the multivariate analyses the sequence had no

Comparison of fluorouracil with additional levamisole, higher-dose folinic acid, or both, as adjuvant chemotherapy for colorectal cancer: a randomised trial. QUASAR Collaborative Group.

Science.gov (United States)

2000-05-06

Standard adjuvant chemotherapy for colorectal cancer consists of fluorouracil with folinic acid or levamisole. The large QUASAR randomised trial aimed to investigate (in a two x two design) whether use of a higher dose of folinic acid or addition of levamisole to fluorouracil and folinic acid improved survival. Patients with colorectal cancer, without evident residual disease, were randomly assigned fluorouracil (370 mg/m2) with high-dose (175 mg) or low-dose (25 mg) L-folinic acid and either active or placebo levamisole. The fluorouracil and folinic acid could be given either as six 5-day courses with 4 weeks between the start of the courses or as 30 once-weekly doses. Levamisole (50 mg) or placebo was given three times daily for 3 days repeated every 2 weeks for 12 courses. The primary endpoint was mortality from any cause. Analyses were by intention to treat. Between 1994 and 1997, 4,927 patients were enrolled. 1,776 had recurrences and 1,576 died. Survival was similar with high-dose and low-dose folinic acid (70.1% vs 71.0% at 3 years; p=0-43), as were 3-year recurrence rates (36.0% vs 35.8%; p=0.94). Survival was worse with levamisole than with placebo (69.4% vs 71.5% at 3 years; p=0.06), and there were more recurrences with the active drug (37.0% vs 34.9% at 3 years; p=0.16). The inclusion of levamisole in chemotherapy regimens for colorectal cancer does not delay recurrence or improve survival. Higher-dose folinic acid produced no extra benefit in these regimens over that from low-dose folinic acid. Trials of chemotherapy versus no chemotherapy will show whether these four treatments are equally effective or equally ineffective.

Statistical analysis of dose heterogeneity in circulating blood: Implications for sequential methods of total body irradiation

International Nuclear Information System (INIS)

Molloy, Janelle A.

2010-01-01

Purpose: Improvements in delivery techniques for total body irradiation (TBI) using Tomotherapy and intensity modulated radiation therapy have been proven feasible. Despite the promise of improved dose conformality, the application of these ''sequential'' techniques has been hampered by concerns over dose heterogeneity to circulating blood. The present study was conducted to provide quantitative evidence regarding the potential clinical impact of this heterogeneity. Methods: Blood perfusion was modeled analytically as possessing linear, sinusoidal motion in the craniocaudal dimension. The average perfusion period for human circulation was estimated to be approximately 78 s. Sequential treatment delivery was modeled as a Gaussian-shaped dose cloud with a 10 cm length that traversed a 183 cm patient length at a uniform speed. Total dose to circulating blood voxels was calculated via numerical integration and normalized to 2 Gy per fraction. Dose statistics and equivalent uniform dose (EUD) were calculated for relevant treatment times, radiobiological parameters, blood perfusion rates, and fractionation schemes. The model was then refined to account for random dispersion superimposed onto the underlying periodic blood flow. Finally, a fully stochastic model was developed using binomial and trinomial probability distributions. These models allowed for the analysis of nonlinear sequential treatment modalities and treatment designs that incorporate deliberate organ sparing. Results: The dose received by individual blood voxels exhibited asymmetric behavior that depended on the coherence among the blood velocity, circulation phase, and the spatiotemporal characteristics of the irradiation beam. Heterogeneity increased with the perfusion period and decreased with the treatment time. Notwithstanding, heterogeneity was less than ±10% for perfusion periods less than 150 s. The EUD was compromised for radiosensitive cells, long perfusion periods, and short treatment times

Statistical analysis of dose heterogeneity in circulating blood: implications for sequential methods of total body irradiation.

Science.gov (United States)

Molloy, Janelle A

2010-11-01

Improvements in delivery techniques for total body irradiation (TBI) using Tomotherapy and intensity modulated radiation therapy have been proven feasible. Despite the promise of improved dose conformality, the application of these "sequential" techniques has been hampered by concerns over dose heterogeneity to circulating blood. The present study was conducted to provide quantitative evidence regarding the potential clinical impact of this heterogeneity. Blood perfusion was modeled analytically as possessing linear, sinusoidal motion in the craniocaudal dimension. The average perfusion period for human circulation was estimated to be approximately 78 s. Sequential treatment delivery was modeled as a Gaussian-shaped dose cloud with a 10 cm length that traversed a 183 cm patient length at a uniform speed. Total dose to circulating blood voxels was calculated via numerical integration and normalized to 2 Gy per fraction. Dose statistics and equivalent uniform dose (EUD) were calculated for relevant treatment times, radiobiological parameters, blood perfusion rates, and fractionation schemes. The model was then refined to account for random dispersion superimposed onto the underlying periodic blood flow. Finally, a fully stochastic model was developed using binomial and trinomial probability distributions. These models allowed for the analysis of nonlinear sequential treatment modalities and treatment designs that incorporate deliberate organ sparing. The dose received by individual blood voxels exhibited asymmetric behavior that depended on the coherence among the blood velocity, circulation phase, and the spatiotemporal characteristics of the irradiation beam. Heterogeneity increased with the perfusion period and decreased with the treatment time. Notwithstanding, heterogeneity was less than +/- 10% for perfusion periods less than 150 s. The EUD was compromised for radiosensitive cells, long perfusion periods, and short treatment times. However, the EUD was

Differential response of immunohistochemically defined breast cancer subtypes to anthracycline-based adjuvant chemotherapy with or without paclitaxel.

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George Fountzilas

Full Text Available BACKGROUND: The aim of the present study was to investigate the efficacy of adjuvant dose-dense sequential chemotherapy with epirubicin, paclitaxel, and CMF in subgroups of patients with high-risk operable breast cancer, according to tumor subtypes defined by immunohistochemistry (IHC. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded (FFPE tumor tissue samples from 1,039 patients participating in two adjuvant dose-dense sequential chemotherapy phase III trials were centrally assessed in tissue micro-arrays by IHC for 6 biological markers, that is, estrogen receptor (ER, progesterone receptor (PgR, HER2, Ki67, cytokeratin 5 (CK5, and EGFR. The majority of the cases were further evaluated for HER2 amplification by FISH. Patients were classified as: luminal A (ER/PgR-positive, HER2-negative, Ki67(low; luminal B (ER/PgR-positive, HER2-negative, Ki67(high; luminal-HER2 (ER/PgR-positive, HER2-positive; HER2-enriched (ER-negative, PgR-negative, HER2-positive; triple-negative (TNBC (ER-negative, PgR-negative, HER2-negative; and basal core phenotype (BCP (TNBC, CK5-positive and/or EGFR-positive. RESULTS: After a median follow-up time of 105.4 months the 5-year disease-free survival (DFS and overall survival (OS rates were 73.1% and 86.1%, respectively. Among patients with HER2-enriched tumors there was a significant benefit in both DFS and OS (log-rank test; p = 0.021 and p = 0.006, respectively for those treated with paclitaxel. The subtype classification was found to be of both predictive and prognostic value. Setting luminal A as the referent category, the adjusted for prognostic factors HR for relapse for patients with TNBC was 1.91 (95% CI: 1.31-2.80, Wald's p = 0.001 and for death 2.53 (95% CI: 1.62-3.60, p<0.001. Site of and time to first relapse differed according to subtype. Locoregional relapses and brain metastases were more frequent in patients with TNBC, while liver metastases were more often seen in patients with HER2-enriched tumors

Olanzapine is effective for refractory chemotherapy-induced nausea and vomiting irrespective of chemotherapy emetogenicity.

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Vig, Sierra; Seibert, Laurel; Green, Myke R

2014-01-01

The role of olanzapine added to a dopamine antagonist and benzodiazepine for the treatment of refractory chemotherapy-induced nausea and vomiting (CINV) is incompletely characterized in all levels of chemotherapy emetogenicity. This retrospective study evaluated the efficacy of the addition of olanzapine in adults experiencing refractory CINV stratified by chemotherapy emetogenicity. Thirty-three adults who experienced CINV refractory to guideline-recommended prophylaxis and breakthrough antiemetics (dopamine antagonists and benzodiazepines) and received at least one dose of olanzapine 5-10 mg per os were evaluated. Failure was defined as >5 emesis events in 24 h or more than 10 cumulative doses of rescue antiemetics following first olanzapine dose per treatment cycle. Post hoc analyses investigated variables impacting olanzapine efficacy. The addition of olanzapine demonstrated an overall success rate of 70 %. This success rate did not differ between chemotherapy regimens of high versus low-to-moderate emetogenicity (p = 0.79), prophylaxis with serotonin antagonist plus corticosteroid and aprepitant versus serotonin antagonist alone (p = 0.77), or age over 50 versus ≤50 years (p > 0.99). A trend toward greater benefit was seen in women (p = 0.08). The addition of olanzapine to a dopamine antagonist and benzodiazepine demonstrated high efficacy rates for refractory CINV irrespective of chemotherapy emetogenicity. The high success rates among all groups suggests that incomplete resolution of CINV with prophylactic serotonin antagonists and breakthrough dopamine antagonists plus benzodiazepine may benefit from the addition of olanzapine regardless of gender, degree of chemotherapy emetogenicity, number of prophylactic antiemetics, or age. The trend toward greater control of emesis in women merits further investigation.

Treatment of aggressive multiple myeloma by high-dose chemotherapy and total body irradiation followed by blood stem cells autologous graft

International Nuclear Information System (INIS)

Fermand, J.P.; Levy, Y.; Gerota, J.; Benbunan, M.; Cosset, J.M.; Castaigne, S.; Seligmann, M.; Brouet, J.C.

1989-01-01

Eight patients with stage III aggressive multiple myeloma, refractory to current chemotherapy in six cases, were treated by high-dose chemotherapy (nitrosourea, etoposide, and melphalan) (HDC) and total body irradiation (TBI), followed by autografting with blood stem cells. These cells were previously collected by leukapheresis performed during hematologic recovery following cytotoxic drug-induced bone marrow aplasia. Seven patients were alive 9 to 17 months after HDC-TBI and graft. One died at day 40 from cerebral bleeding. All living patients achieved a 90% or greater reduction in tumor mass. In two cases, a complete remission (CR) has persisted at a follow-up of 15 and 16 months. Three patients have been well and off therapy with stable minimal residual disease (RD) since 10, 11, and 17 months, respectively. A patient in apparent CR and another with RD have relapsed 9 to 12 months posttreatment. Autologous blood-derived hematopoietic stem cells induced successful and sustained engraftment in all living patients. These results, although still preliminary, indicate that HDC and TBI, followed by blood stem cells autograft, which has both practical and theoretical interest over allogeneic or autologous bone marrow transplantation, deserve consideration in selected patients with multiple myeloma

A phase I study of different doses and frequencies of pegylated recombinant human granulocyte-colony stimulating factor (PEG rhG-CSF) in patients with standard-dose chemotherapy-induced neutropenia.

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Qin, Yan; Han, Xiaohong; Wang, Lin; Du, Ping; Yao, Jiarui; Wu, Di; Song, Yuanyuan; Zhang, Shuxiang; Tang, Le; Shi, Yuankai

2017-10-01

The recommended dose of prophylactic pegylated recombinant human granulocyte-colony stimulating factor (PEG rhG-CSF) is 100 μg/kg once per cycle for patients receiving intense-dose chemotherapy. However, few data are available on the proper dose for patients receiving less-intense chemotherapy. The aim of this phase I study is to explore the proper dose and administration schedule of PEG rhG-CSF for patients receiving standard-dose chemotherapy. Eligible patients received 3-cycle chemotherapy every 3 weeks. No PEG rhG-CSF was given in the first cycle. Patients experienced grade 3 or 4 neutropenia would then enter the cycle 2 and 3. In cycle 2, patients received a single subcutaneous injection of prophylactic PEG rhG-CSF on d 3, and received half-dose subcutaneous injection in cycle 3 on d 3 and d 5, respectively. Escalating doses (30, 60, 100 and 200 μg/kg) of PEG rhG-CSF were investigated. A total of 26 patients were enrolled and received chemotherapy, in which 24 and 18 patients entered cycle 2 and cycle 3 treatment, respectively. In cycle 2, the incidence of grade 3 or 4 neutropenia for patients receiving single-dose PEG rhG-CSF of 30, 60, 100 and 200 μg/kg was 66.67%, 33.33%, 22.22% and 0, respectively, with a median duration less than 1 (0-2) d. No grade 3 or higher neutropenia was noted in cycle 3 in all dose cohorts. The pharmacokinetic and pharmacodynamic profiles of PEG rhG-CSF used in cancer patients were similar to those reported, as well as the safety. Double half dose administration model showed better efficacy result than a single dose model in terms of grade 3 neutropenia and above. The single dose of 60 μg/kg, 100 μg/kg and double half dose of 30 μg/kg were recommended to the phase II study, hoping to find a preferable method for neutropenia treatment.

Anti-tumor activity of high-dose EGFR tyrosine kinase inhibitor and sequential docetaxel in wild type EGFR non-small cell lung cancer cell nude mouse xenografts

OpenAIRE

Tang, Ning; Zhang, Qianqian; Fang, Shu; Han, Xiao; Wang, Zhehai

2016-01-01

Treatment of non-small-cell lung cancer (NSCLC) with wild-type epidermal growth factor receptor (EGFR) is still a challenge. This study explored antitumor activity of high-dose icotinib (an EGFR tyrosine kinase inhibitor) plus sequential docetaxel against wild-type EGFR NSCLC cells-generated nude mouse xenografts. Nude mice were subcutaneously injected with wild-type EGFR NSCLC A549 cells and divided into different groups for 3-week treatment. Tumor xenograft volumes were monitored and record...

Subgroup effects in a randomised trial of different types and doses of exercise during breast cancer chemotherapy.

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Courneya, K S; McKenzie, D C; Mackey, J R; Gelmon, K; Friedenreich, C M; Yasui, Y; Reid, R D; Vallerand, J R; Adams, S C; Proulx, C; Dolan, L B; Wooding, E; Segal, R J

2014-10-28

The Combined Aerobic and Resistance Exercise Trial tested different types and doses of exercise in breast cancer patients receiving chemotherapy. Here, we explore potential moderators of the exercise training responses. Breast cancer patients initiating chemotherapy (N=301) were randomly assigned to three times a week, supervised exercise of a standard dose of 25-30 min of aerobic exercise, a higher dose of 50-60 min of aerobic exercise, or a higher dose of 50-60 min of combined aerobic and resistance exercise. Outcomes were patient-reported symptoms and health-related fitness. Moderators were baseline demographic, exercise/fitness, and cancer variables. Body mass index moderated the effects of the exercise interventions on bodily pain (P for interaction=0.038), endocrine symptoms (P for interaction=0.029), taxane/neuropathy symptoms (P for interaction=0.013), aerobic fitness (P for interaction=0.041), muscular strength (P for interaction=0.007), and fat mass (P for interaction=0.005). In general, healthy weight patients responded better to the higher-dose exercise interventions than overweight/obese patients. Menopausal status, age, and baseline fitness moderated the effects on patient-reported symptoms. Premenopausal, younger, and fitter patients achieved greater benefits from the higher-dose exercise interventions. Healthy weight, fitter, and premenopausal/younger breast cancer patients receiving chemotherapy are more likely to benefit from higher-dose exercise interventions.

Postoperative Chemotherapy Followed by Conformal Concomitant Chemoradiotherapy in High-Risk Gastric Cancer

International Nuclear Information System (INIS)

Quero, Laurent; Bouchbika, Zineb; Kouto, Honorine; Baruch-Hennequin, Valerie; Gornet, Jean-Marc; Munoz, Nicolas; Cojean-Zelek, Isabelle; Houdart, Remi; Panis, Yves; Valleur, Patrice; Aparicio, Thomas; Maylin, Claude; Hennequin, Christophe

2012-01-01

Purpose: To analyze the efficacy, toxicity, and pattern of relapse after adjuvant cisplatin-based chemotherapy followed by three-dimensional irradiation and concomitant LV5FU2 chemotherapy (high-dose leucovorin and 5-fluorouracil bolus plus continuous infusion) in the treatment of completely resected high-risk gastric cancer. Methods and Materials: This was a retrospective analysis of 52 patients with high-risk gastric cancer initially treated by total/partial gastrectomy and lymphadenectomy between January 2002 and June 2007. Median age was 54 years (range, 36–75 years). Postoperative treatment consisted of 5-fluorouracil and cisplatin chemotherapy. Adjuvant chemotherapy was followed by three-dimensional conformal radiotherapy in the tumor bed and regional lymph nodes at 4500 cGy/25 fractions in association with concomitant chemotherapy. Concomitant chemotherapy consisted of a 2-h infusion of leucovorin (200 mg/m²) followed by a bolus of 5-fluorouracil (400 mg/m²) and then a 44-h continuous infusion of 5-fluorouracil (2400–3600 mg/m²) given every 14 days, for three cycles (LV5FU2 protocol). Results: Five-year overall and disease-free survival were 50% and 48%, respectively. Distant metastases and peritoneal spread were the most frequent sites of relapse (37% each). After multivariate analysis, only pathologic nodal status was significantly associated with disease-free and overall survival. Acute toxicities were essentially gastrointestinal and hematologic. One myocardial infarction and one pulmonary embolism were also reported. Eighteen patients had a radiotherapy program interruption because of acute toxicity. All patients but 2 have completed radiotherapy. Conclusion: Postoperative cisplatin-based chemotherapy followed by conformal radiotherapy in association with concurrent 5-fluorouracil seemed to be feasible and resulted in successful locoregional control.

Phase 1 Dose Escalation Study of Accelerated Radiation Therapy With Concurrent Chemotherapy for Locally Advanced Lung Cancer

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Kelsey, Chris R., E-mail: christopher.kelsey@duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Das, Shiva [Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina (United States); Gu, Lin [Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina (United States); Dunphy, Frank R.; Ready, Neal E. [Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, North Carolina (United States); Marks, Lawrence B. [Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina (United States)

2015-12-01

Purpose: To determine the maximum tolerated dose of radiation therapy (RT) given in an accelerated fashion with concurrent chemotherapy using intensity modulated RT. Methods and Materials: Patients with locally advanced lung cancer (non-small cell and small cell) with good performance status and minimal weight loss received concurrent cisplatin and etoposide with RT. Intensity modulated RT with daily image guidance was used to facilitate esophageal avoidance and delivered using 6 fractions per week (twice daily on Fridays with a 6-hour interval). The dose was escalated from 58 Gy to a planned maximum dose of 74 Gy in 4 Gy increments in a standard 3 + 3 trial design. Dose-limiting toxicity (DLT) was defined as acute grade 3-5 nonhematologic toxicity attributed to RT. Results: A total of 24 patients were enrolled, filling all dose cohorts, all completing RT and chemotherapy as prescribed. Dose-limiting toxicity occurred in 1 patient at 58 Gy (grade 3 esophagitis) and 1 patient at 70 Gy (grade 3 esophageal fistula). Both patients with DLTs had large tumors (12 cm and 10 cm, respectively) adjacent to the esophagus. Three additional patients were enrolled at both dose cohorts without further DLT. In the final 74-Gy cohort, no DLTs were observed (0 of 6). Conclusions: Dose escalation and acceleration to 74 Gy with intensity modulated RT and concurrent chemotherapy was tolerable, with a low rate of grade ≥3 acute esophageal reactions.

A multicenter randomized trial of the effects of exercise dose and type on psychosocial distress in breast cancer patients undergoing chemotherapy.

Science.gov (United States)

Courneya, Kerry S; McKenzie, Donald C; Gelmon, Karen; Mackey, John R; Reid, Robert D; Yasui, Yutaka; Friedenreich, Christine M; Forbes, Cynthia C; Trinh, Linda; Jespersen, Diana; Cook, Diane; Proulx, Carolyn; Wooding, Evyanne; Dolan, Lianne B; Segal, Roanne J

2014-05-01

Exercise may improve psychosocial distress in patients with cancer; however, few studies have examined the effects of different types or doses of exercise, or whether exercise effects are related to baseline depression levels. In a multicenter trial in Canada, we randomized 301 patients with breast cancer initiating chemotherapy to thrice weekly, supervised exercise consisting of either a standard dose of 25 to 30 minutes of aerobic exercise (STAN; n = 96), a higher dose of 50 to 60 minutes of aerobic exercise (HIGH; n = 101), or a combined dose of 50 to 60 minutes of aerobic and resistance exercise (COMB; n = 104). The primary endpoint was depression assessed by the Center for Epidemiological Studies-Depression scale at baseline, twice during chemotherapy, and postchemotherapy. Secondary endpoints were anxiety, perceived stress, and self-esteem. Repeated measures ANOVA indicated that neither HIGH [mean difference = -0.9; 95% confidence interval (CI), +0.0 to -1.8; P = 0.061] nor COMB (mean difference = -0.4; 95% CI, +0.5 to -1.3; P = 0.36) was superior to STAN for managing depressive symptoms. In a planned subgroup analysis, there was a significant interaction with baseline depression levels (P interaction = 0.027) indicating that COMB and HIGH were effective for managing depressive symptoms in patients with clinical levels of depressive symptoms at baseline. Compared with a standard volume of aerobic exercise, higher volumes of exercise did not help manage depressive symptoms in unselected patients with breast cancer receiving chemotherapy, but they were effective in patients with clinical levels of depressive symptoms at baseline. A phase III exercise trial targeting depressed patients with breast cancer is warranted. ©2014 AACR.

Breakthrough therapy for peritoneal carcinomatosis of gastric cancer: Intraperitoneal chemotherapy with taxanes.

Science.gov (United States)

Yamaguchi, Hironori; Kitayama, Joji; Ishigami, Hironori; Kazama, Shinsuke; Nozawa, Hiroaki; Kawai, Kazushige; Hata, Keisuke; Kiyomatsu, Tomomichi; Tanaka, Toshiaki; Tanaka, Junichiro; Nishikawa, Takeshi; Otani, Kensuke; Yasuda, Koji; Ishihara, Soichiro; Sunami, Eiji; Watanabe, Toshiaki

2015-11-15

The effect of chemotherapy on peritoneal carcinomatosis (PC) of gastric cancer remains unclear. Recently, the intraperitoneal (IP) administration of taxanes [e.g., paclitaxel (PTX) and docetaxel (DOC)] during the perioperative period has shown promising results. Herein, we summarized the rationale and methodology for using IP chemotherapy with taxanes and reviewed the clinical results. IP administered taxanes remain in the IP space at an extremely high concentration for 48-72 h. The drug directly infiltrates peritoneal metastatic nodules from the surface and then produces antitumor effects, making it ideal for IP chemotherapy. There are two types of perioperative IP chemotherapy with taxanes: neoadjuvant intraperitoneal and systemic chemotherapy and sequential perioperative intraperitoneal chemotherapy (SPIC). In SPIC, patients receive neoadjuvant IP chemotherapy and the same regimen of IP chemotherapy after cytoreductive surgery (CRS) until disease progression. Usually, a taxane dissolved in 500-1000 mL of saline at ordinary temperature is administered through an IP access port on an outpatient basis. According to phase I studies, the recommended doses (RD) are as follows: IP DOC, 45-60 mg/m(2); IP PTX [without intravenous (IV) PTX], 80 mg/m(2); and IP PTX (with IV PTX), 20 mg/m(2). Phase II studies have reported a median survival time of 14.4-24.6 mo with a 1-year overall survival of 67%-78%. A phase III study comparing S-1 in combination with IP and IV PTX to S-1 with IV cisplatin started in 2011. The prognosis of patients who underwent CRS was better than that of those who did not; however, this was partly due to selection bias. Although several phase II studies have shown promising results, a randomized controlled study is needed to validate the effectiveness of IP chemotherapy with taxanes for PC of gastric cancer.

Dose finding study of granisetron in patients receiving high-dose cisplatin chemotherapy. The Granisetron Study Group.

Science.gov (United States)

Riviere, A.

1994-01-01

The efficacy and safety of three different doses of granisetron (2 micrograms kg-1, group A; 10 micrograms kg-1, group B; 40 micrograms kg-1, group C) were compared in a randomised, double-blind study of 157 patients due to receive high-dose cisplatin therapy (mean dose > 97 mg m-2). In each group, up to two 3 mg rescue doses of granisetron were allowed if more than mild nausea or vomiting occurred. In group A 30.8%, in group B 61.5% and in group C 67.9% of patients were complete responders (i.e. no vomiting or nothing worse than mild nausea) during the first 24 h. These differences are significant between groups A and B, and A and C. There were no statistically significant differences in any efficacy variable between the 10 micrograms kg-1 and 40 micrograms kg-1 groups, although in each case the trend favoured the higher dose. Additional rescue doses resulted in resolved or improved symptoms in 95.3% for the first rescue dose and 93.3% for the second. Over the 7 days of the study, 82.7%, 82.7% and 86.8% of patients in groups A, B and C respectively were treated with granisetron alone. Headache was the most common side-effect, reported by 9.6% of patients; the majority of headaches were mild. There was no difference between the treatment groups regarding the adverse event rate. We concluded that prophylactic doses of 10 or 40 micrograms kg-1 lead to a safe and satisfactory degree of control of nausea and vomiting induced by high-dose cisplatin. PMID:8180032

Low-dose pressurized intraperitoneal aerosol chemotherapy (PIPAC) as an alternative therapy for ovarian cancer in an octogenarian patient.

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Giger-Pabst, Urs; Solass, Wiebke; Buerkle, Bernd; Reymond, Marc-André; Tempfer, Clemens B

2015-04-01

Octogenarians with ovarian cancer limited to the abdomen may not be willing or able to undergo systemic chemotherapy. Low-dose pressurized intraperitoneal aerosol chemotherapy (PIPAC) with cisplatin and doxorubicin is a form of intra-abdominal chemotherapy which can be applied repeatedly and potentially prevents from the systemic side-effects of chemotherapy. We present the case of an 84-year-old woman with laparoscopically and histologically confirmed ovarian cancer who refused to undergo systemic chemotherapy. She was treated with eight courses q 28-104 days of low-dose PIPAC with cisplatin at 7.5 mg/m(2) and doxorubicin at 1.5 mg/m(2) at 12 mmHg and 37 °C for 30 min. Objective tumor response was noted, defined as tumor regression on histology, and stable disease noted by peritoneal carcinomatosis index on repeated video-laparoscopy and abdominal computed tomographic scan. The treatment was well-tolerated with no Common Terminology Criteria for Adverse Events (CTCAE) CTCAE >2. With a follow-up of 15 months, the patient is alive and clinically stable. The quality of life measured by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 demonstrated improvement over 5-6 months (global physical score, global health score, global quality of live) without cumulative increase of gastrointestinal toxicity. Low-dose PIPAC is a new form of intraperitoneal chemotherapy which may be applied repeatedly in octogenarian patients. PIPAC may be an alternative and well-tolerated treatment for selected octogenarian patients with ovarian cancer limited to the abdomen who cannot be treated with systemic chemotherapy. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Metronomic chemotherapy.

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Mutsaers, Anthony J

2009-08-01

Chemotherapy drugs are usually administered at doses that are high enough to result in an obligatory break period to allow for the observation of potential side effects and institution of supportive care, if required. In recent years, efforts to administer chemotherapy on a more continuous basis, with a much shorter break period, or none at all, have received increased interest, and the practice has come to be known as metronomic chemotherapy. The basis for success with this currently investigational approach may be rooted in continuous drug exposure to susceptible cancer cells, inhibition of tumor blood vessel growth-a process known as tumor angiogenesis, and/or alterations in tumor immunology. Increased benefit also appears to occur when metronomic chemotherapy is used in combination with newer, targeted antiangiogenic agents, and therefore represents a promising approach to combination therapy, particularly as targeted oncology drugs make their way into veterinary oncology applications. There is still much to be learned in this field, especially with regard to optimization of the proper drugs, dose, schedule, and tumor applications. However, the low cost, ease of administration, and acceptable toxicity profiles potentially associated with this therapeutic strategy make metronomic chemotherapy protocols attractive and suitable to veterinary applications. Preliminary clinical trial results have now been reported in both human and veterinary medicine, including adjuvant treatment of canine splenic hemangiosarcoma and incompletely resected soft tissue sarcoma, and, further, more powerful studies are currently ongoing.

Feasibility of sequential adjuvant chemotherapy with a 3-month oxaliplatin-based regimen followed by 3 months of capecitabine in patients with stage III and high-risk stage II colorectal cancer: JSWOG-C2 study

Directory of Open Access Journals (Sweden)

Tsuruta A

2016-11-01

Full Text Available Atsushi Tsuruta,1,* Kazuki Yamashita,2,* Hiroaki Tanioka,3 Akihito Tsuji,4,5 Michio Inukai,6 Toshiki Yamakawa,7 Tomoki Yamatsuji,8 Masanori Yoshimitsu,9 Kazuhiro Toyota,10 Taketoshi Yamano,11 Takeshi Nagasaka,12 Masazumi Okajima13 On behalf of the Japan Southwest Oncology Group (JSWOG 1Department of Digestive Surgery, Kawasaki Medical School Hospital, 2Department of Surgery, 3Department of Medical Oncology, Okayama Rosai Hospital, Okayama, 4Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, 5Department of Clinical Oncology, Faculty of Medicine, Kagawa University Hospital, Kagawa, 6Department of Medicine, Okayama Saiseikai General Hospital, Okayama, 7Department of Surgery, Kagawa Prefectural Central Hospital, Takamatsu, 8Department of General Surgery, Kawasaki Medical School, Okayama, 9Department of Surgery, Hiroshima City Asa Hospital, Hiroshima, 10Department of Surgery, National Hospital Organization Higashihirosima Medical Center, Higashihiroshima, 11Department of Surgery, Kurashiki Medical Center, 12Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 13Department of Surgery, Hiroshima City Hospital, Hiroshima, Japan *These authors contributed equally to this work Background: Six months of oxaliplatin-based chemotherapy is the standard adjuvant chemotherapy for completely resected stage III colorectal cancer (CRC. Also, patients with stage II CRC who are considered to be at high risk of disease recurrence often receive the same adjuvant chemotherapy treatment. We prospectively investigated the extent and degree of neuropathy suffered by stage III and high-risk stage II resectable CRC patients who underwent sequential approach involving 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine. Patients and methods: Patients with completely resected stage III and high-risk stage II CRC aged ≥20 years were

High-doses of proton pump inhibitors in refractory gastro-intestinal cancer: A case series and the state of art.

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Falcone, Rosa; Roberto, Michela; D'Antonio, Chiara; Romiti, Adriana; Milano, Annalisa; Onesti, Concetta Elisa; Marchetti, Paolo; Fais, Stefano

2016-12-01

In recent years, proton pump inhibitors (PPIs) have been investigated at high-dose to modulate tumour microenvironment acidification thus restoring chemotherapeutic sensitivity. Moreover, several clinical data supports the role of cytotoxic drugs at low-dose continuously delivered as anticancer therapy. Clinical records of three patients affected with gastrointestinal cancer refractory to standard treatments, who had received a combination of high-dose rabeprazole and metronomic chemotherapy were reviewed. The first case, a 78-year-old man was treated for lung metastasis from colon adenocarcinoma. The second case, a 73-year-old man was treated for metastatic rectal cancer to the liver. The third one, a 68-year-old man, underwent the combination regimen for colon cancer with lung, liver and peritoneal metastases. Despite the failure of previous standard chemotherapy for metastatic disease, good clinical outcome was shown in these patients treated with an unconventional association of high-dose PPIs and metronomic chemotherapy. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Gemcitabine concurrent with thoracic radiotherapy after induction chemotherapy with gemcitabine/vinorelbine in locally advanced non-small cell lung cancer. A phase I study

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Gagel, B.; Piroth, M.; Pinkawa, M.; Fischedik, K.; Asadpour, B.; Schmachtenberg, A.; Eble, M.J. [Dept. of Radiotherapy, RWTH Aachen (Germany); Reinartz, P.; Zimny, M.; Buell, U. [Dept. of Nuclear Medicine, RWTH Aachen (Germany); Stanzel, S. [Inst. for Medical Statistics, RWTH Aachen (Germany); Breuer, C.; Skobel, E. [Dept. of Internal Medicine I, RWTH Aachen (Germany)

2006-05-15

Purpose: to determine the maximum tolerated dose (MTD) of gemcitabine every 2 weeks to a concurrent radiotherapy administered during an aggressive program of sequential and simultaneous radio-/chemotherapy for locally advanced, unresectable non-small cell lung cancer (NSCLC). Patients and methods: ten patients with histologically confirmed NSCLC were observed and treated in accordance with a combined radio-/chemotherapy protocol. This included two cycles of induction chemotherapy with gemcitabine (1,200 mg/m{sup 2}) and vinorelbine (30 mg/m{sup 2}) at days 1, 8 and 22, 29, followed by concurrent radiotherapy including [{sup 18}F] fluorodeoxyglucose positron emission tomography-(FDG-PET-) based target volume definition (2.0 Gy/d; total dose 66.0 Gy) and chemotherapy with gemcitabine every 2 weeks at days 43, 57, and 71. The initial dose was 300 mg/m{sup 2}. The dose of gemcitabine was increased by 100 mg/m{sup 2} until the MTD was realized. Three patients were enrolled for each dose level. Results: dose-limiting toxicity (DLT) was identified for the patient group receiving gemcitabine 500 mg/m{sup 2}, due to grade 2 esophagitis (next to grade 3) in all patients. 6 weeks after the completion of radio-/chemotherapy, most patients still presented treatment-induced esophagitis. In accordance with expected complications, such as esophagitis, dysphagia and odynophagia, the MTD was defined at this dose level, although no DLT grade 3 was reached. Conclusion: after induction chemotherapy, the MTD and frequency of gemcitabine in locally advanced NSCLC is 500 mg/m{sup 2} every 2 weeks during a maximum of 7 weeks of thoracic radiotherapy. (orig.)

High dose rate brachytherapy for the treatment of soft tissue sarcoma of the extremity

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Speight, J.L.; Streeter, O.E.; Chawla, S.; Menendez, L.E.

1996-01-01

Purpose: we examined the role of preoperative neoadjuvant chemoradiation and adjuvant high-dose rate brachytherapy on the management of prognostically unfavorable soft tissue sarcomas of the extremities. Our goal was to examine the effect of high dose rate interstitial brachytherapy (HDR IBT) on reducing the risk of local recurrence following limb-sparing resection, as well as shortening treatment duration. Materials and methods: eleven patients, ranging in age from 31 to 73 years old, with soft tissue sarcoma of the extremity were treated at USC/Norris Comprehensive Cancer Center during 1994 and 1995. All patients had biopsy proven soft tissue sarcoma, and all were suitable candidates for limb-sparing surgery. All lesions were greater than 5cm in size and were primarily high grade. Tumor histologies included malignant fibrous histiocytoma (45%), liposarcoma (18%) and leiomyosarcoma, synovial cell sarcoma and spindle cell sarcoma (36%). Sites of tumor origin were the lower extremity (55%), upper extremity (18%) and buttock (9%), 1 patient (9%) had lesions in both the upper and lower extremity. Patients received HDR IBT following combined chemotherapy and external beam irradiation (EBRT) and en bloc resection of the sarcoma. Neoadjuvant chemotherapy consisted of three to four cycles of either Ifosfamide/Mesna with or without Adriamycin, or Mesna, Adriamycin, Ifosfamide and Dacarbazine. One patient received Cis-platin in addition to Ifos/Adr. A minimum of two cycles of chemotherapy were administered prior to EBRT. Additional cycles of chemotherapy were completed concurrently with EBRT but prior to HDR IBT. Preoperative EBRT doses ranging from 40 to 59.4 Gy were given in daily fractions of 180 to 200cGy. Following en bloc resection, HDR IBT was administered using the Omnitron tm 2000 remote afterloading system. Doses ranging from 13 to 30 Gy were delivered to the surgical tumor bed at depths of 0.5mm to 0.75mm from the radioactive source. Results: median follow-up was

Distribution of 99Tcm-rh-Annexin vin tumor and expression relationship of bcl-2, bax after a single dose of chemotherapy

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Zhang Xin; Li Yaming; Zhang Yanjun; Tao Li; Zhu Yi; Yang Chun; Ji Xiaopeng; Zhao Ming; Tian Aijuan; Zhang Jianying; Zhao Zhenzhen

2007-01-01

The expression of bcl-2 and bax after the single dose of chemotherapy with 99 Tc m -rh-Annexin V as the tracer of tumor apoptosis imaging is studied. tumor cell apoptosis is examined by TUNEL methods, and the expression of bcl-2 and bax in tumor are determined by immunohistochemical methods. Single dose of chemotherapy significantly increased the tumor uptake of 99 Tc m -rh-annexin V and the positive number of TUNEL, as well as the expression of bax (P 99 Tc m -rh-annexin V in tumor reflectes not only the degree of apoptosis of tumor cells, but also the change of bax expression after the single dose of chemotherapy. (authors)

Systematic overview of preoperative (neoadjuvant) chemoradiotherapy trials in oesophageal cancer: Evidence of a radiation and chemotherapy dose response

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Geh, J. Ian; Bond, Simon J.; Bentzen, Soren M.; Glynne-Jones, Robert

2006-01-01

Background and purpose: Numerous trials have shown that pathological complete response (pCR) following preoperative chemoradiotherapy (CRT) and surgery for oesophageal cancer is associated with improved survival. However, different radiotherapy doses and fractionations and chemotherapy drugs, doses and scheduling were used, which may account for the differences in observed pCR and survival rates. A dose-response relationship may exist between radiotherapy and chemotherapy dose and pCR. Patients and methods: Trials using a single radiotherapy and chemotherapy regimen (5FU, cisplatin or mitomycin C-based) and providing information on patient numbers, age, resection and pCR rates were eligible. The endpoint used was pCR and the covariates analysed were prescribed radiotherapy dose, radiotherapy dosexdose per fraction, radiotherapy treatment time, prescribed chemotherapy (5FU, cisplatin and mitomycin C) dose and median age of patients within the trial. The model used was a multivariate logistic regression. Results: Twenty-six trials were included (1335 patients) in which 311 patients (24%) achieved pCR. The probability of pCR improved with increasing dose of radiotherapy (P=0.006), 5FU (P=0.003) and cisplatin (P=0.018). Increasing radiotherapy treatment time (P=0.035) and increasing median age (P=0.019) reduced the probability of pCR. The estimated α/β ratio of oesophageal cancer was 4.9 Gy (95% confidence interval (CI) 1.5-17 Gy) and the estimated radiotherapy dose lost per day was 0.59 Gy (95% CI 0.18-0.99 Gy). One gram per square metre of 5FU was estimated to be equivalent to 1.9 Gy (95% CI 0.8-5.2 Gy) of radiation and 100 mg/m 2 of cisplatin was estimated to be equivalent to 7.2 Gy (95% CI 2.1-28 Gy). Mitomycin C dose did not appear to influence pCR rates (P=0.60). Conclusions: There was evidence of a dose-response relationship between increasing protocol prescribed radiotherapy, 5FU and cisplatin dose and pCR. Additional significant factors were radiotherapy

Effective chemotherapy of acute myelocytic leukemia occurring after alkylating agent or radiation therapy for prior malignancy

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Vaughan, W.P.; Karp, J.E.; Burke, P.J.

1983-01-01

Eleven consecutive patients with acute myelocytic leukemia occurring as a second malignancy were treated with high-dose, timed, sequential chemotherapy. Eight of the patients were felt to have ''secondary'' acute leukemia because they had received an alkylating agent or radiation therapy. The other three patients were considered controls. Despite a median age of 65, four of the eight secondary leukemia patients achieved complete remission with this regimen. One of the three control patients also achieved complete remission. This remission rate and duration are comparable to what was achieved with this treatment of ''primary'' acute myelocytic leukemia during the same period of time. These results suggest that patients with leukemia occurring after an alkylating agent or radiation therapy are not at especially high risk if treated aggressively

Brachytherapy treatment with high dose rate

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Santana Rodriguez, Sergio Marcelino; Rodriguez Rodriguez, Lissi Lisbet; Ciscal Chiclana, Onelio Alberto

2009-01-01

Retrospectively analyze results and prognostic factors of cervical cancer patients treated with radio concomitant cisplatin-based chemotherapy, radiation therapy combined modality. Methods: From January 2003 to December 2007, 198 patients with invasive cervical cancer were treated at the Oncology Department of Hospital Robau Celestino Hernandez (brachytherapy performed at INOR). The most common age group was 31 to 40 years. The histology in squamous cell carcinoma accounted for 84.3% of cases. The treatment consisted of external pelvic irradiation and vaginal brachytherapy, high dose rate. Concomitant chemotherapy consisted of cisplatin 40 mg/m2 weekly with a maximum of 70 mg for 5 weeks. Results: 66.2% of patients completed 5 cycles of chemotherapy. The median overall survival was 39 months, overall survival, disease-free survival and survival free of locoregional recurrence at 5 years of 78%, 76% and 78.6% respectively .. We found that clinical stage, histological type (adenocarcinoma worst outcome) were statistically related to level of response. Conclusions: Treatment with external pelvic radiation, brachytherapy and concurrent weekly cisplatin in patients with stage IIIB cervical cancer is feasible in the Chilean public health system, well tolerated and results comparable to international literature. (Author)

A Contralateral Esophagus-Sparing Technique to Limit Severe Esophagitis Associated With Concurrent High-Dose Radiation and Chemotherapy in Patients With Thoracic Malignancies

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Al-Halabi, Hani; Paetzold, Peter; Sharp, Gregory C.; Olsen, Christine; Willers, Henning

2015-01-01

Purpose: Severe (Radiation Therapy Oncology Group [RTOG] grade 3 or greater) esophagitis generally occurs in 15% to 25% of non–small cell lung cancer (NSCLC) patients undergoing concurrent chemotherapy and radiation therapy (CCRT), which may result in treatment breaks that compromise local tumor control and pose a barrier to dose escalation. Here, we report a novel contralateral esophagus-sparing technique (CEST) that uses intensity modulated radiation therapy (IMRT) to reduce the incidence of severe esophagitis. Methods and Materials: We reviewed consecutive patients with thoracic malignancies undergoing curative CCRT in whom CEST was used. The esophageal wall contralateral (CE) to the tumor was contoured as an avoidance structure, and IMRT was used to guide a rapid dose falloff gradient beyond the target volume in close proximity to the esophagus. Esophagitis was recorded based on the RTOG acute toxicity grading system. Results: We identified 20 consecutive patients treated with CCRT of at least 63 Gy in whom there was gross tumor within 1 cm of the esophagus. The median radiation dose was 70.2 Gy (range, 63-72.15 Gy). In all patients, ≥99% of the planning and internal target volumes was covered by ≥90% and 100% of prescription dose, respectively. Strikingly, no patient experienced grade ≥3 esophagitis (95% confidence limits, 0%-16%) despite the high total doses delivered. The median maximum dose, V45, and V55 of the CE were 60.7 Gy, 2.1 cc, and 0.4 cc, respectively, indicating effective esophagus cross-section sparing by CEST. Conclusion: We report a simple yet effective method to avoid exposing the entire esophagus cross-section to high doses. By using proposed CE dose constraints of V45 <2.5 cc and V55 <0.5 cc, CEST may improve the esophagus toxicity profile in thoracic cancer patients receiving CCRT even at doses above the standard 60- to 63-Gy levels. Prospective testing of CEST is warranted

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...

Breast conserving treatment of breast carcinoma T2 ({<=} 4 cm) and T3 by neoadjuvant chemotherapy, quadrantectomy, high dose rate brachytherapy as a boost, external beam radiotherapy and adjuvant chemotherapy: local control and overall survival analysis; Tratamento conservador do cancer de mama T2 ({<=} 4 cm) e T3 por quimioterapia neoadjuvante, quadrantectomia, braquiterapia com alta taxa de dose como reforco de dose, teleterapia complementar e quimioterapia adjuvante: analise de controle local e sobrevida global

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Soares, Celia Regina; Miziara Filho, Miguel Abrao; Fogaroli, Ricardo Cesar; Baraldi, Helena Espindola; Pellizzon, Antonio Cassio Assis; Pelosi, Edilson Lopes [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil). Servico de Radioterapia], e-mail: celiarsoares@terra.com.br; Fristachi, Carlos Elias [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil). Servico de Onco-Ginecologia e Mastologia; Paes, Roberto Pinto [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil)

2008-12-15

Objective: to assess the treatment of breast cancer T2 ({<=} 4 cm) and T3 through neoadjuvant chemotherapy, quadrantectomy and high dose rate brachytherapy as a boost, complementary radiotherapy and adjuvant chemotherapy, considering local control and overall survival. Material and method: this clinical prospective descriptive study was based on the evaluation of 88 patients ranging from 30 to 70 years old, with infiltrating ductal carcinoma, clinical stage IIb and IIIa, responsive to the neoadjuvant chemotherapy, treated from June/1995 to December/2006. Median follow-up was 58 months. Using clinical methods the tumor was evaluated before and after three or four cycles of chemotherapy based on anthracyclines. Overall survival and local control were assessed according to Kaplan-Meier methodology. Results: Local control and overall survival in five years were 90% and 73.5%, respectively. Conclusion: local control and overall survival were comparable to other forms of treatment. (author)

Dealing with initial chemotherapy doses: a new basis for treatment optimization in limited small-cell lung cancer

International Nuclear Information System (INIS)

Le Chevalier, T.; Le Cesne, A.; Arriagada, R.

1995-01-01

Treatment of patients with small-cell lung cancer (SCLC) remains disappointing despite high initial complete response rates. The dramatic initial chemosensitivity of tumor cells is frustrated by the early emergence of chemoresistant clonogenic cells, regardless of front line treatments. Although the dose relationship is fairly well established regarding the response rate, its effect on survival is inconclusive. From 1980 to 1988, 202 patients with limited SCLC were included in four consecutive protocols using an alternating schedule of thoracic radiotherapy and chemotherapy. Despite an increase of chemotherapy and/or total radiation doses, no significant difference was observed between the four protocols in terms of response rate, disease free and overall survival. However, a retrospective analysis performed on a total of 131 consecutive patients led us to propose the hypothesis that a moderate increase in the initial dose, ie first course, of cisplatin and cyclophosphamide could improve overall survival. From 1988 to 1991, 105 patients were subsequently included in a large randomized trial raising this question. The treatment difference only concerned the initial doses of cisplatin (80 vs 100 mg/m 2 ) and cyclophosphamide (900 vs 1200 mg/m 2 ). The trial was closed after inclusion of 105 patients, 32 months after the start of the study because at that time overall survival was significantly better in the higher-dose group (p = 0.001). The emergence of this debatable concept opens new directions in the therapeutic strategy of SCLC and the contribution of hematopoietic growth factors may be a great interest in the management of this disease. (authors). 27 refs., 1 tab

Pharmacokinetics, safety, and efficacy of APF530 (extended-release granisetron) in patients receiving moderately or highly emetogenic chemotherapy: results of two Phase II trials

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Gabrail, Nashat; Yanagihara, Ronald; Spaczyński, Marek; Cooper, William; O’Boyle, Erin; Smith, Carrie; Boccia, Ralph

2015-01-01

Despite advances with new therapies, a significant proportion of patients (>30%) suffer delayed-onset chemotherapy-induced nausea and vomiting (CINV) despite use of antiemetics. APF530 is a sustained-release subcutaneous (SC) formulation of granisetron for preventing CINV. APF530 pharmacokinetics, safety, and efficacy were studied in two open-label, single-dose Phase II trials (C2005-01 and C2007-01, respectively) in patients receiving moderately emetogenic chemotherapy or highly emetogenic chemotherapy. In C2005-01, 45 patients received APF530 250, 500, or 750 mg SC (granisetron 5, 10, or 15 mg, respectively). In C2007-01, 35 patients were randomized to APF530 250 or 500 mg SC. Injections were given 30 to 60 minutes before single-day moderately emetogenic chemotherapy or highly emetogenic chemotherapy. Plasma granisetron was measured from predose to 168 hours after study drug administration. Safety and efficacy were also evaluated. APF530 pharmacokinetics were dose proportional, with slow absorption and elimination of granisetron after a single SC dose. Median time to maximum plasma concentration and half-life were similar for APF530 250 and 500 mg in both trials, with no differences between the groups receiving moderately and highly emetogenic chemotherapy. Exposure to granisetron was maintained at a therapeutic level over the delayed-onset phase, at least 168 hours. Adverse events in both trials were as expected for granisetron; injection site reactions (eg, erythema and induration) were predominantly mild and seen in ≤20% of patients. Complete responses (no emesis, with no rescue medication) were obtained in the acute, delayed, and overall phases in ≥80% and ≥75% of patients in both trials with the 250 and 500 mg doses, respectively. After a single injection of APF530, there were dose-proportional pharmacokinetics and sustained concentrations of granisetron over 168 hours. The 250 and 500 mg doses were well tolerated and maintained therapeutic granisetron

A non-randomised, single-centre comparison of induction chemotherapy followed by radiochemotherapy versus concomitant chemotherapy with hyperfractionated radiotherapy in inoperable head and neck carcinomas

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Graf, Reinhold; Hildebrandt, Bert; Tilly, Wolfgang; Riess, Hanno; Felix, Roland; Budach, Volker; Wust, Peter

2006-01-01

The application of induction chemotherapy failed to provide a consistent benefit for local control in primary treatment of advanced head and neck (H&N) cancers. The aim of this study was to compare the results of concomitant application of radiochemotherapy for treating locally advanced head-and-neck carcinoma in comparison with the former standard of sequential radiochemotherapy. Between 1987 and 1995 we treated 122 patients with unresectable (stage IV head and neck) cancer by two different protocols. The sequential protocol (SEQ; 1987–1992) started with two courses of neoadjuvant chemotherapy (cisplatin [CDDP] + 120-h continuous infusions (c.i.) of folinic acid [FA] and 5-fluorouracil [5-FU]), followed by a course of radiochemotherapy using conventional fractionation up to 70 Gy. The concomitant protocol (CON; since 1993) combined two courses of FA/5-FU c.i. plus mitomycin (MMC) concomitantly with a course of radiotherapy up to 30 Gy in conventional fractionation, followed by a hyperfractionated course up to 72 Gy. Results from the two groups were compared. Patient and tumor characteristics were balanced (SEQ = 70, CON = 52 pts.). Mean radiation dose achieved (65.3 Gy vs. 71.6 Gy, p = 0.00), response rates (67 vs. 90 % for primary, p = 0.02), and local control (LC; 17.6% vs. 41%, p = 0.03), were significantly lower in the SEQ group, revealing a trend towards lower disease-specific (DSS; 19.8% vs. 31.4%, p = 0.08) and overall (14.7% vs. 23.7%, p = 0.11) survival rates after 5 years. Mucositis grades III and IV prevailed in the CON group (54% versus 44%). Late toxicity was similar in both groups. Concurrent chemotherapy seemed more effective in treating head and neck tumors than induction chemotherapy followed by chemoradiation, resulting in better local control and a trend towards improved survival

A non-randomised, single-centre comparison of induction chemotherapy followed by radiochemotherapy versus concomitant chemotherapy with hyperfractionated radiotherapy in inoperable head and neck carcinomas

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Felix Roland

2006-02-01

Full Text Available Abstract Background The application of induction chemotherapy failed to provide a consistent benefit for local control in primary treatment of advanced head and neck (H&N cancers. The aim of this study was to compare the results of concomitant application of radiochemotherapy for treating locally advanced head-and-neck carcinoma in comparison with the former standard of sequential radiochemotherapy. Methods Between 1987 and 1995 we treated 122 patients with unresectable (stage IV head and neck cancer by two different protocols. The sequential protocol (SEQ; 1987–1992 started with two courses of neoadjuvant chemotherapy (cisplatin [CDDP] + 120-h continuous infusions (c.i. of folinic acid [FA] and 5-fluorouracil [5-FU], followed by a course of radiochemotherapy using conventional fractionation up to 70 Gy. The concomitant protocol (CON; since 1993 combined two courses of FA/5-FU c.i. plus mitomycin (MMC concomitantly with a course of radiotherapy up to 30 Gy in conventional fractionation, followed by a hyperfractionated course up to 72 Gy. Results from the two groups were compared. Results Patient and tumor characteristics were balanced (SEQ = 70, CON = 52 pts.. Mean radiation dose achieved (65.3 Gy vs. 71.6 Gy, p = 0.00, response rates (67 vs. 90 % for primary, p = 0.02, and local control (LC; 17.6% vs. 41%, p = 0.03, were significantly lower in the SEQ group, revealing a trend towards lower disease-specific (DSS; 19.8% vs. 31.4%, p = 0.08 and overall (14.7% vs. 23.7%, p = 0.11 survival rates after 5 years. Mucositis grades III and IV prevailed in the CON group (54% versus 44%. Late toxicity was similar in both groups. Conclusion Concurrent chemotherapy seemed more effective in treating head and neck tumors than induction chemotherapy followed by chemoradiation, resulting in better local control and a trend towards improved survival.

Pulmonary Toxicity in Stage III Non-Small Cell Lung Cancer Patients Treated With High-Dose (74 Gy) 3-Dimensional Conformal Thoracic Radiotherapy and Concurrent Chemotherapy Following Induction Chemotherapy: A Secondary Analysis of Cancer and Leukemia Group B (CALGB) Trial 30105

International Nuclear Information System (INIS)

Salama, Joseph K.; Stinchcombe, Thomas E.; Gu Lin; Wang Xiaofei; Morano, Karen; Bogart, Jeffrey A.; Crawford, Jeffrey C.; Socinski, Mark A.; Blackstock, A. William; Vokes, Everett E.

2011-01-01

Purpose: Cancer and Leukemia Group B (CALGB) 30105 tested two different concurrent chemoradiotherapy platforms with high-dose (74 Gy) three-dimensional conformal radiotherapy (3D-CRT) after two cycles of induction chemotherapy for Stage IIIA/IIIB non–small cell lung cancer (NSCLC) patients to determine if either could achieve a primary endpoint of >18-month median survival. Final results of 30105 demonstrated that induction carboplatin and gemcitabine and concurrent gemcitabine 3D-CRT was not feasible because of treatment-related toxicity. However, induction and concurrent carboplatin/paclitaxel with 74 Gy 3D-CRT had a median survival of 24 months, and is the basis for the experimental arm in CALGB 30610/RTOG 0617/N0628. We conducted a secondary analysis of all patients to determine predictors of treatment-related pulmonary toxicity. Methods and Materials: Patient, tumor, and treatment-related variables were analyzed to determine their relation with treatment-related pulmonary toxicity. Results: Older age, higher N stage, larger planning target volume (PTV)1, smaller total lung volume/PTV1 ratio, larger V20, and larger mean lung dose were associated with increasing pulmonary toxicity on univariate analysis. Multivariate analysis confirmed that V20 and nodal stage as well as treatment with concurrent gemcitabine were associated with treatment-related toxicity. A high-risk group comprising patients with N3 disease and V20 >38% was associated with 80% of Grades 3-5 pulmonary toxicity cases. Conclusions: Elevated V20 and N3 disease status are important predictors of treatment related pulmonary toxicity in patients treated with high-dose 3D-CRT and concurrent chemotherapy. Further studies may use these metrics in considering patients for these treatments.

Pulmonary Toxicity in Stage III Non-Small Cell Lung Cancer Patients Treated With High-Dose (74 Gy) 3-Dimensional Conformal Thoracic Radiotherapy and Concurrent Chemotherapy Following Induction Chemotherapy: A Secondary Analysis of Cancer and Leukemia Group B (CALGB) Trial 30105

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Salama, Joseph K., E-mail: joseph.salama@duke.edu [Duke University Medical Center, Durham, NC (United States); Stinchcombe, Thomas E. [University of North Carolina at Chapel Hill, Chapel Hill, NC (United States); Gu Lin; Wang Xiaofei [CALGB Statistical Center, Duke University Medical Center, Durham, NC (United States); Morano, Karen [Quality Assurance Review Center, Lincoln, RI (United States); Bogart, Jeffrey A. [State University of New York Upstate Medical University, Syracuse, NY (United States); Crawford, Jeffrey C. [Duke University Medical Center, Durham, NC (United States); Socinski, Mark A. [University of North Carolina at Chapel Hill, Chapel Hill, NC (United States); Blackstock, A. William [Wake Forest University School of Medicine, Winston-Salem, NC (United States); Vokes, Everett E. [University of Chicago, Chicago, IL (United States)

2011-11-15

Purpose: Cancer and Leukemia Group B (CALGB) 30105 tested two different concurrent chemoradiotherapy platforms with high-dose (74 Gy) three-dimensional conformal radiotherapy (3D-CRT) after two cycles of induction chemotherapy for Stage IIIA/IIIB non-small cell lung cancer (NSCLC) patients to determine if either could achieve a primary endpoint of >18-month median survival. Final results of 30105 demonstrated that induction carboplatin and gemcitabine and concurrent gemcitabine 3D-CRT was not feasible because of treatment-related toxicity. However, induction and concurrent carboplatin/paclitaxel with 74 Gy 3D-CRT had a median survival of 24 months, and is the basis for the experimental arm in CALGB 30610/RTOG 0617/N0628. We conducted a secondary analysis of all patients to determine predictors of treatment-related pulmonary toxicity. Methods and Materials: Patient, tumor, and treatment-related variables were analyzed to determine their relation with treatment-related pulmonary toxicity. Results: Older age, higher N stage, larger planning target volume (PTV)1, smaller total lung volume/PTV1 ratio, larger V20, and larger mean lung dose were associated with increasing pulmonary toxicity on univariate analysis. Multivariate analysis confirmed that V20 and nodal stage as well as treatment with concurrent gemcitabine were associated with treatment-related toxicity. A high-risk group comprising patients with N3 disease and V20 >38% was associated with 80% of Grades 3-5 pulmonary toxicity cases. Conclusions: Elevated V20 and N3 disease status are important predictors of treatment related pulmonary toxicity in patients treated with high-dose 3D-CRT and concurrent chemotherapy. Further studies may use these metrics in considering patients for these treatments.

Mean esophageal radiation dose is predictive of the grade of acute esophagitis in lung cancer patients treated with concurrent radiotherapy and chemotherapy

International Nuclear Information System (INIS)

Ozgen, A.; Hayran, M.; Kahraman, F.

2012-01-01

The intention of this research was to define the predictive factors for acute esophagitis (AE) in lung cancer patients treated with concurrent chemotherapy and three-dimensional conformal radiotherapy. The data for 72 lung cancer patients treated with concurrent chemoradiotherapy between 2008 and 2010 were prospectively evaluated. Mean lung dose, mean dose of esophagus, volume of esophagus irradiated and percentage of esophagus volume treated were analysed according to esophagitis grades. The mean esophageal dose was associated with an increased risk of esophageal toxicity (Kruskal-Wallis test, P<0.001). However, the mean lung dose and the volume of esophagus irradiated were not associated with an increased risk of esophageal toxicity (Kruskal-Wallis test, P=0.50 and P=0.41, respectively). The mean radiation dose received by the esophagus was found to be highly correlated with the duration of Grade 2 esophagitis (Spearman test, r=0.82, P<0.001). The mean dose of esophagus ≥28 Gy showed statistical significance with respect to AE Grade 2 or worse (receiver operating characteristic curve analysis, 95% confidence interval (CI), 0.929-1.014). In conclusion, the mean esophageal dose was significantly associated with a risk of esophageal toxicity in patients with lung cancer treated with concurrent radiotherapy and chemotherapy. (author)

Sequential measurements of spectrum and dose for cosmic-ray neutrons on the ground

International Nuclear Information System (INIS)

Hirabayashi, N.; Nunomiya, T.; Suzuki, H.; Nakamura, T.

2002-01-01

The earth is continually bathed in high-energy particles that come from outside the solar system, known as galactic cosmic rays. When these particles penetrate the magnetic fields of the solar system and the Earth and reach the Earth's atmosphere, they collide with atomic nuclei in air and secondary cosmic rays of every kind. On the other hand, levels of accumulation of the semiconductor increase recently, and the soft error that the cosmic-ray neutrons cause has been regarded as questionable. There have been long-term measurements of cosmic-ray neutron fluence at several places in the world, but no systematic study on cosmic-ray neutron spectrum measurements. This study aimed to measure the cosmic-ray neutron spectrum and dose on the ground during the solar maximum period of 2000 to 2002. Measurements have been continuing in a cabin of Tohoku University Kawauchi campus, by using five multi-moderator spectrometers (Bonner sphere), 12.7 cm diam by 12.7 cm long NE213 scintillator, and rem counter. The Bonner sphere uses a 5.08 cm diam spherical 3 He gas proportional counter and the rem counter uses a 12.7 cm diam 3 He gas counter. The neutron spectra were obtained by unfolding from the count rates measured with the Bonner sphere using the SAND code and the pulse height spectra measured with the NE213 scintillator using the FORIST code . The cosmic- ray neutron spectrum and ambient dose rates have been measured sequentially from April 2001. Furthermore, the correlation between ambient dose rate and the atmospheric pressure was investigated with a barometer. We are also very much interested in the variation of neutron spectrum following big solar flares. From the sequential measurements, we found that the cosmic-ray neutron spectrum has two peaks at around 1 MeV and at around 100 MeV, and the higher energy peak increases with a big solar flare

A Randomized, Double-Blind Pilot Study of Dose Comparison of Ramosetron to Prevent Chemotherapy-Induced Nausea and Vomiting

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Ka-Rham Kim

2015-01-01

Full Text Available Purpose. This study was conducted to determine the optimal dose titration of ramosetron to prevent the Rhodes Index of Nausea, Vomiting, and Retching (RINVR. Methods. Patients treated with folic acid, 5-fluorouracil, and oxaliplatin were randomized into three groups (0.3 mg, 0.45 mg, and 0.6 mg ramosetron before chemotherapy. The pharmacokinetics and pharmacodynamics using RINVR were evaluated. Results. Seventeen, 15, and 18 patients received ramosetron at doses of 0.3 mg, 0.45 mg, and 0.6 mg, respectively. Tmax (h, Cmax (ng/mL, and AUClast (ng·h/mL were associated with dose escalation significantly, showing a reverse correlation with the RINVR during chemotherapy. Acute CINV was observed in four patients (22.2%, two patients (14.3%, and one (5.6% patient and a delayed CINV on day 7 was found in eight (47%, three (21.4%, and five (27.8% patients in each group. The complete response rate was increased with dose escalation (35.3%, 50.0%, and 72.2% in each group and also showed the tendency for decreasing moderate-to-severe CINV. Conclusions. This study shows a trend regarding the dose-response relationship for ramosetron to prevent CINV, including delayed emesis. It suggested that dose escalation should be considered in patients with CINV in a subsequent cycle of chemotherapy, and an individual approach using RINVR could be useful to monitor CINV.

Treatment for non-Hodgkin's lymphoma (stage I, II) of the elderly : usefulness of local and regional irradiation and brief reduced-dose chemotherapy

International Nuclear Information System (INIS)

Oguchi, Masahiko; Izuno, Itaru; Takei, Kazuyoshi; Shikama, Naoto; Sasaki, Shigeru; Gomi, Koutarou; Kiyono, Kunihiro; Takizawa, Masaomi; Sone, Shusuke

1996-01-01

Purpose: To examine the usefulness and safety of a new treatment regimen consisting of irradiation to the involved area and adjacent lymph-node area, and reduced-dose chemotherapy for elderly patients with non-Hodgkin's lymphoma. Materials and Methods: The core of this study was 38 elderly patients older than 65 years old with intermediate or high grade NHL, and concomitantly suffering from some other geriatric disease. They received involved-area irradiation (40 Gy), adjacent lymph-node irradiation (30 Gy), and reduced-dose chemotherapy (50-70 % ACOP 2 cycles or 70 % MACOP-B 4 weeks). Results: The completion rate of the treatment regimen was 100 %. The 5-year local control rate was 98 %. The 5-year disease free survival rate and the 5-year cause-specific survival rate for all patients were 70 % and 82 %, respectively. No treatment deaths were observed, and the rate of serious complications arising from the treatment was 3 %. Conclusion: Chemotherapy with a dose reduced to 50% or 70% of that prescribed in the original ACOP or MACOP-B, and irradiation to both the involved area and the adjacent lymph-node area are useful for treating elderly patients with Stage I, II intermediate B-cell NHL, who are at the same time suffering from some other geriatric disease

Adjuvant endocrine and chemotherapy for early breast cancer

International Nuclear Information System (INIS)

Henderson, I. Craig

1996-01-01

Objective: Present the results of the 1995 World Overview which will be held in Oxford England two weeks before ASTRO. Discuss the interpretation and application of these results. Review current research topics on the use of adjuvant endocrine and chemotherapy for early breast cancer. The survival benefits from adjuvant chemotherapy in premenopausal women and adjuvant tamoxifen in postmenopausal women are well established. Each will reduce the annual odds of death by about 25% resulting in a 10 year survival difference of 8-10%. By the time of this presentation, the results of the 1995 Adjuvant Therapy Overview should be with 10+ years of follow-up, and if possible these will be summarized. Current efforts to improve on previous results are focused on the following areas: Optimal chemotherapy dose. Decreasing dose will compromise patient survival. It is not as certain that increasing dose will have as much impact in improving survival. The NSABP was unable to demonstrate an improvement in survival by modestly increasing the dose of cyclophosphamide alone. However, recent results of a Canadian study of CEF (cyclophosphamide, epidoxorubicin, and 5-fluorouracil) and an Intergroup trial of an intense 16 week polychemotherapy program keep alive the possibility that dose escalation is still a very important question. An NSABP trial evaluating even greater cyclophosphamide dose escalation, an Intergroup evaluation of different doxorubicin doses, and two Intergroup trials evaluating very high dose chemotherapy and bone marrow transplantation should provide definitive evidence regarding the importance of dose. Drug sequence. A study from Milan suggests that initial treatment with single agent doxorubicin followed by CMF will be superior to alternating doxorubicin and CMF. This has not been confirmed yet, and the reason for increased benefit from such a sequence is not entirely clear. This concept is being explored further in an Intergroup trial comparing four cycles of

Pre-Irradiation Chemotherapy in High Risk Medulloblastoma

International Nuclear Information System (INIS)

Abd-El-Aal, H.

2006-01-01

Rationale: The present study evaluates the effect of pre-irradiation chemotherapy in pediatric patients with high risk medulloblastoma. Twenty-four (24) pediatric patients attended the pediatric unit of Kasr-EI-Aini Center of Radiation Oncology and Nuclear Medicine (NEMROCK) from January 2000 to January 2003. Patients and Methods: Our patients were 13 boys and II girls aged 3-12 years with a median of 6.5 years. According to Chang staging system 6 cases had T2, 14 cases had T3 A and 4 cases had T3 B, 20 cases were M0, 3 cases were M I and I case was M2. All patients were treated by initial surgery, 2 cycles of pre-irradiation chemotherapy followed by craniospinal radiation then by 4 cycles of post-radiation chemotherapy. Results: Fifteen out of the 20 patients with M0 had objective response (10CR + 5PR) and no one had disease progression after pre-irradiation chemotherapy. Among 4 patients with M0 disease, 2 patients had PR and 2 had S.D. There was no disease progression among patients who received pre-irradiation chemotherapy. The 3-year overall survival and 3-year progression-free survival; (PFS) were 50% and 51 %, respectively, Myelosuppression was the main toxic effect observed during pre-irradiation chemotherapy; however, there was no delay or interruption of craniospinal irradiation. Conclusion: Pre-irradiation chemotherapy is effective in high risk medulloblastoma and is associated with acceptable side effects. The delay in craniospinal irradiation (CSI) for about 5 weeks to receive 2 courses of chemotherapy will not significantly increase disease progression. Multiple cycles of post-irradiation chemotherapy can be given safely after C51. A larger number of patients and longer follow-up is needed to confirm the results

Attitudes and practice patterns for maintaining relative dose intensity of chemotherapy in outpatient clinics: results of a Japanese web-based survey

International Nuclear Information System (INIS)

Sakai, Hitomi; Katsumata, Noriyuki; Kadokura, Genmu

2015-01-01

This analysis was undertaken to evaluate the practice patterns of Japanese physicians regarding curative-intent chemotherapy, especially in outpatient settings, and to define factors negatively affecting the maintenance of relative dose intensity (RDI). We performed a web-based questionnaire survey of Japanese physicians involved in malignant lymphoma chemotherapy (Group ML) or in breast cancer chemotherapy (Group BC). The questionnaire inquired how they manage low-risk febrile neutropenia (FN) caused by initial chemotherapy for diffuse large B-cell lymphoma(DLBCL) or by adjuvant chemotherapy for breast cancer in an outpatient setting. Valid responses were obtained from 185 physicians in Group ML and 160 in Group BC. In Group ML, 76 % (n = 141) of the physicians were board-certified hematologists, while 82 % (n = 131) of the physicians in Group BC were board-certified surgeons. A significantly higher proportion of physicians in Group ML responded that “dose reduction is not required for the subsequent course of chemotherapy after the first episode of FN” than in Group BC (ML versus BC; 77 % versus 31 %; P < 0.001). Significantly higher proportions of physicians in Group ML were more likely to prophylactically administer antibiotics or granulocyte-colony stimulating factor (G-CSF; ML versus BC; antibiotics: 36 % versus 26 %, P = 0.049; G-CSF: 25 % versus 16 %, P = 0.047). Eighty six percent (n = 159) of Group ML and 70 % (n = 112) of Group BC responded that “emergency outpatient unit is open at all hours”. Japanese physicians are more likely to administer reduced doses of chemotherapy to patients with breast cancer than to patients with malignant lymphoma. Supportive infrastructures should be improved to ensure the provision of adequate chemotherapy to all cancer patients

Dose-Dependent Cortical Thinning After Partial Brain Irradiation in High-Grade Glioma

Energy Technology Data Exchange (ETDEWEB)

Karunamuni, Roshan [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Bartsch, Hauke; White, Nathan S. [Department of Radiology, University of California San Diego, La Jolla, California (United States); Moiseenko, Vitali; Carmona, Ruben; Marshall, Deborah C.; Seibert, Tyler M. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); McDonald, Carrie R. [Department of Psychiatry, University of California San Diego, La Jolla, California (United States); Farid, Nikdokht; Krishnan, Anithapriya; Kuperman, Joshua [Department of Radiology, University of California San Diego, La Jolla, California (United States); Mell, Loren [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Brewer, James B.; Dale, Anders M. [Department of Radiology, University of California San Diego, La Jolla, California (United States); Hattangadi-Gluth, Jona A., E-mail: jhattangadi@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States)

2016-02-01

Purpose: Radiation-induced cognitive deficits may be mediated by tissue damage to cortical regions. Volumetric changes in cortex can be reliably measured using high-resolution magnetic resonance imaging (MRI). We used these methods to study the association between radiation therapy (RT) dose and change in cortical thickness in high-grade glioma (HGG) patients. Methods and Materials: We performed a voxel-wise analysis of MRI from 15 HGG patients who underwent fractionated partial brain RT. Three-dimensional MRI was acquired pre- and 1 year post RT. Cortex was parceled with well-validated segmentation software. Surgical cavities were censored. Each cortical voxel was assigned a change in cortical thickness between time points, RT dose value, and neuroanatomic label by lobe. Effects of dose, neuroanatomic location, age, and chemotherapy on cortical thickness were tested using linear mixed effects (LME) modeling. Results: Cortical atrophy was seen after 1 year post RT with greater effects at higher doses. Estimates from LME modeling showed that cortical thickness decreased by −0.0033 mm (P<.001) for every 1-Gy increase in RT dose. Temporal and limbic cortex exhibited the largest changes in cortical thickness per Gy compared to that in other regions (P<.001). Age and chemotherapy were not significantly associated with change in cortical thickness. Conclusions: We found dose-dependent thinning of the cerebral cortex, with varying neuroanatomical regional sensitivity, 1 year after fractionated partial brain RT. The magnitude of thinning parallels 1-year atrophy rates seen in neurodegenerative diseases and may contribute to cognitive decline following high-dose RT.

Sequential hemi-body radiotherapy in advanced multiple myeloma. [Side effects of indicated x-ray therapy

Energy Technology Data Exchange (ETDEWEB)

Jaffe, J.P.; Bosch, A.; Raich, P.C.

1979-01-01

Eleven patients with advanced multiple myeloma refractory to standard chemotherapy were treated with a regimen of sequential hemi-body radiotherapy consisting of 800 rad midplane in a single dose to each half. 9/10 patients experienced significant relief of skeletal pain and there were 5/11 objective tumor responses with one complete remission. Treatment-related morbidity was significant and consisted primarily of nausea and emesis, bone marrow suppression, and pneumonitis. This therapy is helpful in the management of advanced myeloma, and should be studied earlier in the course of the disease.

Sequential multi-nuclide emission rate estimation method based on gamma dose rate measurement for nuclear emergency management

International Nuclear Information System (INIS)

Zhang, Xiaole; Raskob, Wolfgang; Landman, Claudia; Trybushnyi, Dmytro; Li, Yu

2017-01-01

Highlights: • Sequentially reconstruct multi-nuclide emission using gamma dose rate measurements. • Incorporate a priori ratio of nuclides into the background error covariance matrix. • Sequentially augment and update the estimation and the background error covariance. • Suppress the generation of negative estimations for the sequential method. • Evaluate the new method with twin experiments based on the JRODOS system. - Abstract: In case of a nuclear accident, the source term is typically not known but extremely important for the assessment of the consequences to the affected population. Therefore the assessment of the potential source term is of uppermost importance for emergency response. A fully sequential method, derived from a regularized weighted least square problem, is proposed to reconstruct the emission and composition of a multiple-nuclide release using gamma dose rate measurement. The a priori nuclide ratios are incorporated into the background error covariance (BEC) matrix, which is dynamically augmented and sequentially updated. The negative estimations in the mathematical algorithm are suppressed by utilizing artificial zero-observations (with large uncertainties) to simultaneously update the state vector and BEC. The method is evaluated by twin experiments based on the JRodos system. The results indicate that the new method successfully reconstructs the emission and its uncertainties. Accurate a priori ratio accelerates the analysis process, which obtains satisfactory results with only limited number of measurements, otherwise it needs more measurements to generate reasonable estimations. The suppression of negative estimation effectively improves the performance, especially for the situation with poor a priori information, where it is more prone to the generation of negative values.

Sequential multi-nuclide emission rate estimation method based on gamma dose rate measurement for nuclear emergency management

Energy Technology Data Exchange (ETDEWEB)

Zhang, Xiaole, E-mail: zhangxiaole10@outlook.com [Institute for Nuclear and Energy Technologies, Karlsruhe Institute of Technology, Karlsruhe, D-76021 (Germany); Institute of Public Safety Research, Department of Engineering Physics, Tsinghua University, Beijing, 100084 (China); Raskob, Wolfgang; Landman, Claudia; Trybushnyi, Dmytro; Li, Yu [Institute for Nuclear and Energy Technologies, Karlsruhe Institute of Technology, Karlsruhe, D-76021 (Germany)

2017-03-05

Highlights: • Sequentially reconstruct multi-nuclide emission using gamma dose rate measurements. • Incorporate a priori ratio of nuclides into the background error covariance matrix. • Sequentially augment and update the estimation and the background error covariance. • Suppress the generation of negative estimations for the sequential method. • Evaluate the new method with twin experiments based on the JRODOS system. - Abstract: In case of a nuclear accident, the source term is typically not known but extremely important for the assessment of the consequences to the affected population. Therefore the assessment of the potential source term is of uppermost importance for emergency response. A fully sequential method, derived from a regularized weighted least square problem, is proposed to reconstruct the emission and composition of a multiple-nuclide release using gamma dose rate measurement. The a priori nuclide ratios are incorporated into the background error covariance (BEC) matrix, which is dynamically augmented and sequentially updated. The negative estimations in the mathematical algorithm are suppressed by utilizing artificial zero-observations (with large uncertainties) to simultaneously update the state vector and BEC. The method is evaluated by twin experiments based on the JRodos system. The results indicate that the new method successfully reconstructs the emission and its uncertainties. Accurate a priori ratio accelerates the analysis process, which obtains satisfactory results with only limited number of measurements, otherwise it needs more measurements to generate reasonable estimations. The suppression of negative estimation effectively improves the performance, especially for the situation with poor a priori information, where it is more prone to the generation of negative values.

Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in patients with high-risk soft-tissue sarcomas (ISG-STS 1001): an international, open-label, randomised, controlled, phase 3, multicentre trial.

Science.gov (United States)

Gronchi, Alessandro; Ferrari, Stefano; Quagliuolo, Vittorio; Broto, Javier Martin; Pousa, Antonio Lopez; Grignani, Giovanni; Basso, Umberto; Blay, Jean-Yves; Tendero, Oscar; Beveridge, Robert Diaz; Ferraresi, Virginia; Lugowska, Iwona; Merlo, Domenico Franco; Fontana, Valeria; Marchesi, Emanuela; Donati, Davide Maria; Palassini, Elena; Palmerini, Emanuela; De Sanctis, Rita; Morosi, Carlo; Stacchiotti, Silvia; Bagué, Silvia; Coindre, Jean Michelle; Dei Tos, Angelo Paolo; Picci, Piero; Bruzzi, Paolo; Casali, Paolo Giovanni

2017-06-01

Previous trials from our group suggested an overall survival benefit with five cycles of adjuvant full-dose epirubicin plus ifosfamide in localised high-risk soft-tissue sarcoma of the extremities or trunk wall, and no difference in overall survival benefit between three cycles versus five cycles of the same neoadjuvant regimen. We aimed to show the superiority of the neoadjuvant administration of histotype-tailored regimen to standard chemotherapy. For this international, open-label, randomised, controlled, phase 3, multicentre trial, patients were enrolled from 32 hospitals in Italy, Spain, France, and Poland. Eligible patients were aged 18 years or older with localised, high-risk (high malignancy grade, 5 cm or longer in diameter, and deeply located according to the investing fascia), soft-tissue sarcoma of the extremities or trunk wall and belonging to one of five histological subtypes: high-grade myxoid liposarcoma, leiomyosarcoma, synovial sarcoma, malignant peripheral nerve sheath tumour, and undifferentiated pleomorphic sarcoma. Patients were randomly assigned (1:1) to receive three cycles of full-dose standard chemotherapy (epirubicin 60 mg/m 2 per day [short infusion, days 1 and 2] plus ifosfamide 3 g/m 2 per day [days 1, 2, and 3], repeated every 21 days) or histotype-tailored chemotherapy: for high-grade myxoid liposarcoma, trabectedin 1·3 mg/m 2 via 24-h continuous infusion, repeated every 21 days; for leiomyosarcoma, gemcitabine 1800 mg/m 2 on day 1 intravenously over 180 min plus dacarbazine 500 mg/m 2 on day 1 intravenously over 20 min, repeated every 14 days; for synovial sarcoma, high-dose ifosfamide 14 g/m 2 , given over 14 days via an external infusion pump, every 28 days; for malignant peripheral nerve sheath tumour, intravenous etoposide 150 mg/m 2 per day (days 1, 2, and 3) plus intravenous ifosfamide 3 g/m 2 per day (days 1, 2, and 3), repeated every 21 days; and for undifferentiated pleomorphic sarcoma, gemcitabine 900 mg/m 2 on days 1 and

Prospective Phase I-II Trial of Helical Tomotherapy With or Without Chemotherapy for Postoperative Cervical Cancer Patients

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Schwarz, Julie K., E-mail: jschwarz@radonc.wustl.edu [Department of Radiation Oncology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO (United States); Department of Cell Biology and Physiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO (United States); Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO (United States); Wahab, Sasa [Cobb Center for Radiation Oncology Center, Austell, GA (United States); Grigsby, Perry W. [Department of Radiation Oncology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO (United States); Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO (United States); Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO (United States); Department of Obstetrics and Gynecology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO (United States)

2011-12-01

Purpose: To investigate, in a prospective trial, the acute and chronic toxicity of patients with cervical cancer treated with surgery and postoperative intensity-modulated radiotherapy (RT) delivered using helical tomotherapy, with or without the administration of concurrent chemotherapy. Patients and Methods: A total of 24 evaluable patients entered the study between March 2006 and August 2009. The indications for postoperative RT were tumor size, lymphovascular space invasion, and the depth of cervical stromal invasion in 15 patients; 9 patients underwent postoperative RT because of surgically positive lymph nodes. All patients underwent pelvic RT delivered with helical tomotherapy and intracavitary high-dose-rate brachytherapy. Treatment consisted of concurrent weekly platinum in 17, sequential carboplatin/Taxol in 1, and RT alone in 6. The patients were monitored for acute and chronic toxicity using the Common Toxicity Criteria, version 3.0. Results: The median follow-up was 24 months (range, 4-49). At the last follow-up visit, 23 patients were alive and disease free. Of the 24 patients, 12 (50%) experienced acute Grade 3 gastrointestinal toxicity (anorexia in 5, diarrhea in 4, and nausea in 3). One patient developed acute Grade 4 genitourinary toxicity (vesicovaginal fistula). For patients treated with concurrent chemotherapy, the incidence of acute Grade 3 and 4 hematologic toxicity was 71% and 24%, respectively. For patients treated without concurrent chemotherapy, the incidence of acute Grade 3 and 4 hematologic toxicity was 29% and 14%, respectively. Two long-term toxicities occurred (vesicovaginal fistula at 25 months and small bowel obstruction at 30 months). The overall and progression-free survival rate at 3 years for all patients was 100% and 89%, respectively. Conclusion: The results of our study have shown that postoperative external RT for cervical cancer delivered with helical tomotherapy and high-dose-rate brachytherapy and with or without

Prospective Phase I-II Trial of Helical Tomotherapy With or Without Chemotherapy for Postoperative Cervical Cancer Patients

International Nuclear Information System (INIS)

Schwarz, Julie K.; Wahab, Sasa; Grigsby, Perry W.

2011-01-01

Purpose: To investigate, in a prospective trial, the acute and chronic toxicity of patients with cervical cancer treated with surgery and postoperative intensity-modulated radiotherapy (RT) delivered using helical tomotherapy, with or without the administration of concurrent chemotherapy. Patients and Methods: A total of 24 evaluable patients entered the study between March 2006 and August 2009. The indications for postoperative RT were tumor size, lymphovascular space invasion, and the depth of cervical stromal invasion in 15 patients; 9 patients underwent postoperative RT because of surgically positive lymph nodes. All patients underwent pelvic RT delivered with helical tomotherapy and intracavitary high-dose-rate brachytherapy. Treatment consisted of concurrent weekly platinum in 17, sequential carboplatin/Taxol in 1, and RT alone in 6. The patients were monitored for acute and chronic toxicity using the Common Toxicity Criteria, version 3.0. Results: The median follow-up was 24 months (range, 4–49). At the last follow-up visit, 23 patients were alive and disease free. Of the 24 patients, 12 (50%) experienced acute Grade 3 gastrointestinal toxicity (anorexia in 5, diarrhea in 4, and nausea in 3). One patient developed acute Grade 4 genitourinary toxicity (vesicovaginal fistula). For patients treated with concurrent chemotherapy, the incidence of acute Grade 3 and 4 hematologic toxicity was 71% and 24%, respectively. For patients treated without concurrent chemotherapy, the incidence of acute Grade 3 and 4 hematologic toxicity was 29% and 14%, respectively. Two long-term toxicities occurred (vesicovaginal fistula at 25 months and small bowel obstruction at 30 months). The overall and progression-free survival rate at 3 years for all patients was 100% and 89%, respectively. Conclusion: The results of our study have shown that postoperative external RT for cervical cancer delivered with helical tomotherapy and high-dose-rate brachytherapy and with or without

Concurrent chemotherapy and radiation therapy for unresectable locally advanced carcinoma of the esophagus. Phase II study and clinical review on literature

International Nuclear Information System (INIS)

Fritz, P.; Stoll, P.; Wannenmacher, M.; Zierhut, D.

2003-01-01

Background: Neither surgical advances nor those in therapeutic radiology have been able to significantly reduce the mortality related to esophageal carcinomas. The results of combining: first surgery, then radiation therapy, which have been dissatisfactory for decades, encourage therapeutic concepts involving a variety of modalities. Patients and Methods: For 50 patients with unresectable locally advanced esophageal carcinomas, a palliative concurrent chemotherapy and radiation therapy was carried out according to the ''intent to treat'' principle. The aim was a minimal dose of 40 Gy. The concurrent chemotherapy was carried out using cisplatin/5-FU during the 1st and 4th weeks of radiation therapy. In the case of partial or complete remission, the chemotherapy was to be continued as maintenance therapy with a maximum of four cycles. In the case of no change or minor response, instead of maintenance chemotherapy, the dose of local radiation was to be increased by means of brachytherapy. Results: The median survival rate for the entire population under study was 8.7 months. The survival rates of 1, 2, 3, 4, and 5 years were, respectively, 38%, 20.5%, 13.7%, 6.8%, and 6.8%. The remission rates were as follows: NC: 14 patients (28%), PR: 32 patients (64%), CR: 4 patients (8%). 17 patients (34%) tolerated the full concurrent chemotherapy; only twelve patients (24%) tolerated supportive chemotherapy. The following factors exhibited a significant correlation to survival: the intensity of the chemotherapy, the Karnofsky index, the age of the patients, and the improvement of oral food intake. Conclusions: The concurrent chemotherapy was toxic and the benefit to the patients questionable. At best, meta-analyses of randomized studies along the lines of ''evidence-based medicine'' demonstrate for concurrent chemotherapy and radiation therapy an improvement of 2-year survival rates, but with these also involving a high level of toxicity. Due to the heterogeneous data available

A Phase II Study of Fixed-Dose Rate Gemcitabine Plus Low-Dose Cisplatin Followed by Consolidative Chemoradiation for Locally Advanced Pancreatic Cancer

International Nuclear Information System (INIS)

Ko, Andrew H.; Quivey, Jeanne M.; Venook, Alan P.; Bergsland, Emily K.; Dito, Elizabeth R.N.; Schillinger, Brian R.N.; Tempero, Margaret A.

2007-01-01

Purpose: The optimal strategy for treating locally advanced pancreatic cancer remains controversial, including the respective roles and timing of chemotherapy and radiation. We conducted a Phase II nonrandomized trial to evaluate sequential chemotherapy followed by chemoradiation in this patient population. Methods and Materials: Chemotherapy naive patients with locally advanced pancreatic adenocarcinoma were treated with fixed-dose rate gemcitabine (1,000 mg/m 2 at 10 mg/m 2 /min) plus cisplatin 20 mg/m 2 on Days 1 and 15 of a 28-day cycle. Those without evidence of extrapancreatic metastases after six cycles of chemotherapy received radiation (5,040 cGy over 28 fractions) with concurrent capecitabine (800 mg/m 2 orally twice daily on the day of radiation) as a radiosensitizer. Results: A total of 25 patients were enrolled with a median follow-up time of 656 days. Twelve patients (48%) successfully received all six cycles of chemotherapy plus chemoradiation. Eight patients (32%) progressed during chemotherapy, including 7 with extrapancreatic metastases. Grade 3/4 hematologic toxicities were uncommon. Two patients sustained myocardial infarctions during chemotherapy, and 4 were hospitalized for infectious complications, although none in the setting of neutropenia. Median time to progression was 10.5 months and median survival was 13.5 months, with an estimated 1-year survival rate of 62%. Patients receiving all components of therapy had a median survival of 17.0 months. Conclusions: A strategy of initial fixed-dose rate gemcitabine-based chemotherapy, followed by chemoradiation, shows promising efficacy for treatment of locally advanced disease. A substantial proportion of patients will be identified early on as having extrapancreatic disease and spared the potential toxicities associated with radiation

Breast conserving treatment of locally advanced carcinoma T2 and T3 after neoadjuvant chemotherapy followed by quadrantectomy and high dose-rate brachytherapy, as a boost, complementary teletherapy and adjuvant chemotherapy

International Nuclear Information System (INIS)

Fristachi, Carlos Elias

2005-01-01

Objective: to assess the treatment of breast cancer T2 and T3(T > = 4 cm), through neoadjuvant chemotherapy, quadrantectomy and high-dose-rate (HDR) brachytherapy as a boost, complementary radiotherapy and adjuvant chemotherapy, considering its method problems, its esthetics results, the aspect of local control, overall survival, and disease-free survival. Patients and method: this clinical prospective descriptive study was based on the evaluation of 26 patients ranging from 30 to 70 years old, with infiltrating ductal carcinoma, clinical stage IIB and IIIA, responsive to the neoadjuvant chemotherapy. Early and late radiotherapy complications were evaluated according to the criteria established by the RTOG/EORTC (Radiotherapy and Oncology Group /European Organization for Research and Treatment of Cancer) groups. Esthetics evaluation was done in accordance with the criteria set by a plastic surgeon. Local control was evaluated by clinical method, mammography and ultrasonography. Overall survival (OS) and the disease-free survival (DFS) were assessed according to Kaplan-Meier methodology. All the patients were treated at the Dr. Arnaldo Vieira de Carvalho Cancer Institute, from June/1995 to November/2001, and evaluated in March, 2002, with median follow-up of 28.7 months. Results: early complications were observed in 8 patients (30.6%). Two patients were classified as G3 and G4 (RTOG/EORTC). Six patients had late complications and three of them (11.5%) were classified as G3 and G4. One patient (3.8%) had local recurrence, 64 months after having local treatment. Esthetics results were considered good or regular in 16 patients (60.5%) out of 24 patients who were examined. Overall survival and disease-free survival in 24, 36 and 60 months were 100%, 92.3% and 83.1% respectively. Conclusion: early and late radiotherapy complications were considerate high when compared to literature, but esthetic results were considered acceptable. RL, OS and DFS were comparable to other

The effect of endocrine responsiveness on high-risk breast cancer treated with dose-intensive chemotherapy : results of International Breast Cancer Study Group Trial 15-95 after prolonged follow-up

NARCIS (Netherlands)

Colleoni, M.; Sun, Z.; Martinelli, G.; Basser, R. L.; Coates, A. S.; Gelber, R. D.; Green, M. D.; Peccatori, F.; Cinieri, S.; Aebi, S.; Viale, G.; Price, K. N.; Goldhirsch, A.

Patients and methods: Three hundred and forty-four patients were randomized to receive seven courses of standard-dose chemotherapy (SD-CT) or three cycles of dose-intensive epirubicin and cyclophosphamide (epirubicin 200 mg/m(2) plus cyclophosphamide 4 mg/m(2) with filgrastim and progenitor cell

Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma. Final results of phase III US Intergroup Trial S9321

International Nuclear Information System (INIS)

Kim, Sung-Won; Tobinai, Kensei

2007-01-01

The outline of the title trial is described in comparison with outcomes of other randomized controlled trials. The S9321 trial in US started in 1993 by Southwest Oncology Group, Eastern Cooperative Oncology Group and Cancer and Leukemia Group B, including 11 institutions for performance status 0-2 untreated patients of symptomatic multiple myeloma (MM). Patients were randomized to either group receiving the standard dose therapy (SDT) or high-dose therapy with autologous heamatopoietic stem cell transplantation group (HDT). The former essentially underwent the chemotherapy with vincristine, carmustine, melphalan (MEL) and predonisolone after the remission treatment and the latter, whole body irradiation of total 12 Gy (8 fractions/4 days) as well. An appropriate part of the latter group also received the transplantation of allogenic heamatopoietic stem cells previously treated with MEL and 12-Gy radiation. Patients younger than 70 y of age, 899 cases, were registered in the trial, 86 of whom were eliminated before the remission treatment and 248, at that treatment end. No statistical significance was seen between SDT and HDT in efficacy. It is concluded that, despite the present outcome, HDT should be taken into consideration because novel medicals are being under development and MM is a symptomatic disease originated from different molecular bases. (T.I.)

Infectious Complications during Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Children with High-Risk or Recurrent Solid Tumors.

Directory of Open Access Journals (Sweden)

Young Bae Choi

Full Text Available We retrospectively analyzed infectious complications during tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT in children and adolescents with high-risk or recurrent solid tumors. A total of 324 patients underwent their first HDCT/auto-SCT between October 2004 and September 2014, and 283 of them proceeded to their second HDCT/auto-SCT (a total of 607 HDCT/auto-SCTs. During the early transplant period of 607 HDCT/auto-SCTs (from the beginning of HDCT to day 30 post-transplant, bacteremia, urinary tract infection (UTI, respiratory virus infection, and varicella zoster virus (VZV reactivation occurred in 7.1%, 2.3%, 13.0%, and 2.5% of HDCT/auto-SCTs, respectively. The early transplant period of the second HDCT/auto-SCT had infectious complications similar to the first HDCT/auto-SCT. During the late transplant period of HDCT/auto-SCT (from day 31 to 1 year post-transplant, bacteremia, UTI, and VZV reactivation occurred in 7.5%, 2.5%, and 3.9% of patients, respectively. Most infectious complications in the late transplant period occurred during the first 6 months post-transplant. There were no invasive fungal infections during the study period. Six patients died from infectious complications (4 from bacterial sepsis and 2 from respiratory virus infection. Our study suggests that infectious complications are similar following second and first HDCT/auto-SCT in children.

Effect of low dose pre-irradiation on DNA damage and genetic material damage caused by high dosage of cyclophosphamide

International Nuclear Information System (INIS)

Yu Hongsheng; Zhu Jingjuan; Shang Qingjun; Wang Zhuomin; Cui Fuxian

2007-01-01

Objective: To study the effect of low dose γ-rays pre-irradiation on the induction of DNA damage and genetic material damage in peripheral lymphocytes by high dosage of cyclophosphamide (CTX). Methods: Male Kunming strain mice were randomly divided into five groups: control group, sham-irradiated group, low dose irradiated group(LDR group), cyclophosphamide chemotherapy group(CTX group) and low dose irradiation combined with chemotherapy group(LDR + CTX group). After being feeded for one week, all the mice were implanted subcutaneously with S180 cells in the left groin (control group excluded). On days 8 and 11, groups of LDR and LDR + CTX were administered with 75 mGy of whole-body irradiation, 30 h later groups CTX and LDR + CTX were injected intraperitoneally 3.0 mg cyclophosphamide. All the mice were sacrificed on day 13. DNA damage of the peripheral lymphocytes was analyzed using single cell gel electrophoresis (SCGE). Genetic material damage was analyzed using micronucleus frequency(MNF) of polychromatoerythrocytes(PCE) in bone marrow. Results: (1) Compared with control group and sham-irradiated group, the DNA damage of peripheral lymphocytes in CTX group were increased significantly (P 0.05). Conclusions: (1) High- dosage of CTX chemotherapy can cause DNA damage in peripheral lymphocytes. 75 mGy y-irradiation before chemotherapy may have certain protective effect on DNA damage. (2) CTX has potent mutagenic effect, giving remarkable rise to MNF of PCE. 75 mGy γ-ray pre-irradiation has not obvious protection against genetic toxicity of high-dose CTX chemotherapy. (authors)

Defining the dose of gemtuzumab ozogamicin in combination with induction chemotherapy in acute myeloid leukemia

DEFF Research Database (Denmark)

Burnett, Alan; Cavenagh, Jamie; Russell, Nigel

2016-01-01

Arecent source data meta-analysis of randomized trials in adults assessing the immunoconjugate gemtuzumab ozogamicin combined with standard chemotherapy in acute myeloid leukemia showed a significant survival benefit in patients without an adverse karyotype. It is not clear whether the optimal dose...

Dose-dependent deterioration of swallowing function after induction chemotherapy and definitive chemoradiotherapy for laryngopharyngeal cancer

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Haderlein, M.; Semrau, S.; Ott, O.; Speer, S.; Fietkau, R. [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany); Bohr, C. [University Hospital Erlangen, Department of Otorhinolaryngology, Head and Neck Surgery, Erlangen (Germany)

2014-02-15

To evaluate the influence of clinical, treatment- and dose-dependent factors on posttreatment swallowing function after induction chemotherapy and definitive chemoradiotherapy in a group of homogeneously treated laryngopharyngeal cancer patients. From 28 May 2008 to 15 February 2013, 45 patients with borderline inoperable laryngopharyngeal cancer that had responded well to induction chemotherapy were treated with definitive chemoradiotherapy. Median follow-up was 22 months. Swallowing function and clinical data were prospectively analyzed using the EORTC QLQ-C30 questionnaire. Swallowing structures were retrospectively delineated on the original treatment planning CT. Dose-volume histograms were calculated for swallowing structures and D{sub mean}, D{sub max} and V50-V64 values (in 2 Gy increments) were determined for each patient. Tumor volume and infiltration of the swallowing apparatus was defined by CT before induction chemotherapy. Of the 45 patients, 26 (57.8 %) fully regained swallowing function after chemoradiotherapy. A further 12 patients (26.7 %) were able to manage soft, pureed and/or liquid foods; the remaining 7 (15.6 %) were completely dependent on percutaneous endoscopic gastrostomy (PEG). Posttreatment swallowing function was significantly influenced by D{sub mean} to the superior pharyngeal constrictor muscle (PCM, p = 0.041). Correlations between late dysphagia and dose-volume relationships in the superior PCM and soft palate were also observed, which were significant from V60 (p = 0.043) and V58 for the soft palate and superior PCM, respectively. Of the evaluated clinical and tumor-related factors, only alcohol abuse (p = 0.024) had an influence on posttreatment swallowing function. Almost 50 % of patients had deterioration of swallowing function after definitive chemoradiotherapy for laryngopharyngeal cancer. The dose to anatomical structures responsible for swallowing function appears to play a role. Therefore, in selected patients, target

Dose-dependent deterioration of swallowing function after induction chemotherapy and definitive chemoradiotherapy for laryngopharyngeal cancer

International Nuclear Information System (INIS)

Haderlein, M.; Semrau, S.; Ott, O.; Speer, S.; Fietkau, R.; Bohr, C.

2014-01-01

To evaluate the influence of clinical, treatment- and dose-dependent factors on posttreatment swallowing function after induction chemotherapy and definitive chemoradiotherapy in a group of homogeneously treated laryngopharyngeal cancer patients. From 28 May 2008 to 15 February 2013, 45 patients with borderline inoperable laryngopharyngeal cancer that had responded well to induction chemotherapy were treated with definitive chemoradiotherapy. Median follow-up was 22 months. Swallowing function and clinical data were prospectively analyzed using the EORTC QLQ-C30 questionnaire. Swallowing structures were retrospectively delineated on the original treatment planning CT. Dose-volume histograms were calculated for swallowing structures and D mean , D max and V50-V64 values (in 2 Gy increments) were determined for each patient. Tumor volume and infiltration of the swallowing apparatus was defined by CT before induction chemotherapy. Of the 45 patients, 26 (57.8 %) fully regained swallowing function after chemoradiotherapy. A further 12 patients (26.7 %) were able to manage soft, pureed and/or liquid foods; the remaining 7 (15.6 %) were completely dependent on percutaneous endoscopic gastrostomy (PEG). Posttreatment swallowing function was significantly influenced by D mean to the superior pharyngeal constrictor muscle (PCM, p = 0.041). Correlations between late dysphagia and dose-volume relationships in the superior PCM and soft palate were also observed, which were significant from V60 (p = 0.043) and V58 for the soft palate and superior PCM, respectively. Of the evaluated clinical and tumor-related factors, only alcohol abuse (p = 0.024) had an influence on posttreatment swallowing function. Almost 50 % of patients had deterioration of swallowing function after definitive chemoradiotherapy for laryngopharyngeal cancer. The dose to anatomical structures responsible for swallowing function appears to play a role. Therefore, in selected patients, target volume

Sequential charged particle reaction

International Nuclear Information System (INIS)

Hori, Jun-ichi; Ochiai, Kentaro; Sato, Satoshi; Yamauchi, Michinori; Nishitani, Takeo

2004-01-01

The effective cross sections for producing the sequential reaction products in F82H, pure vanadium and LiF with respect to the 14.9-MeV neutron were obtained and compared with the estimation ones. Since the sequential reactions depend on the secondary charged particles behavior, the effective cross sections are corresponding to the target nuclei and the material composition. The effective cross sections were also estimated by using the EAF-libraries and compared with the experimental ones. There were large discrepancies between estimated and experimental values. Additionally, we showed the contribution of the sequential reaction on the induced activity and dose rate in the boundary region with water. From the present study, it has been clarified that the sequential reactions are of great importance to evaluate the dose rates around the surface of cooling pipe and the activated corrosion products. (author)

Interstitial high-dose rate brachytherapy as boost for anal canal cancer

International Nuclear Information System (INIS)

Falk, Alexander Tuan; Claren, Audrey; Benezery, Karen; François, Eric; Gautier, Mathieu; Gerard, Jean-Pierre; Hannoun-Levi, Jean-Michel

2014-01-01

To assess clinical outcomes of patients treated with a high-dose rate brachytherapy boost for anal canal cancer (ACC). From August 2005 to February 2013, 28 patients presenting an ACC treated by split-course external beam radiotherapy (EBRT) and HDR brachytherapy with or without chemotherapy in a French regional cancer center in Nice were retrospectively analyzed. Median age was 60.6 years [34 – 83], 25 patients presented a squamous cell carcinoma and 3 an adenocarcinoma; 21 received chemotherapy. Median dose of EBRT was 45 Gy [43.2 – 52]. Median dose of HDR brachytherapy was 12 Gy [10 - 15] with a median duration of 2 days. Median overall treatment time was 63 days and median delay between EBRT and brachytherapy was 20 days. Two-year local relapse free, metastatic free, disease free and overall survivals were 83%, 81.9%, 71.8% and 87.7% respectively. Acute toxicities were frequent but not severe with mostly grade 1 toxicities: 37% of genito-urinary, 40.7% of gastro-intestinal and 3.7% of cutaneous toxicities. Late toxicities were mainly G1 (43.1%) and G2 (22%). Two-year colostomy-free survival was 75.1%, one patient had a definitive sphincter amputation. High-dose rate brachytherapy for anal canal carcinoma as boost represents a feasible technique compared to low or pulsed-dose rate brachytherapy. This technique remains an excellent approach to precisely boost the tumor in reducing the overall treatment time

High frequency of streptococcal bacteraemia during childhood AML therapy irrespective of dose of cytarabine

DEFF Research Database (Denmark)

Johannsen, Katrine Helle; Handrup, Mette Møller; Lausen, Birgitte Frederiksen

2013-01-01

of cytarabine and more chemotherapy series (n = 6) than other protocols with the potential increased risk of severe VGS infections. PROCEDURE: Medical records of all Danish children enrolled on the NOPHO-AML-2004 protocol between January 2004 and September 2011 (n = 45) were retrospectively reviewed and all...... rate of VGS seemed independent of high-dose cytarabine but was more likely caused by the intensive chemotherapy treatment leading to severe mucositis and neutropenia....

Female fertility following dose-adjusted EPOCH-R chemotherapy in primary mediastinal B-cell lymphomas.

Science.gov (United States)

Gharwan, Helen; Lai, Catherine; Grant, Cliona; Dunleavy, Kieron; Steinberg, Seth M; Shovlin, Margaret; Fojo, Tito; Wilson, Wyndham H

2016-07-01

We assessed fertility/gonadal function in premenopausal women treated with dose-adjusted EPOCH-Rituximab for untreated primary mediastinal B-cell lymphoma (PMBL). Eligible patents were ≤ 50 years and premenopausal. Serial reproductive histories were obtained and hormonal assays were performed on serum samples before, at the end of treatment and 4-18 months later. Twenty-eight eligible women had a median age (range) of 31 (21-50) years and were followed a median of 7.3 years. Of 23 patients who completed a questionnaire, 19 (83%) were and four were not menstruating prior to chemotherapy. Amenorrhea developed in 12 patients during chemotherapy. At > 1-year follow-up, 14/19 (74%) patients were menstruating, all years old, and six (43%) of these patients delivered healthy children. Hormonal assays showed ovarian dysfunction during chemotherapy in all patients with varying recovery at 4-18 months after treatment. Fertility was preserved in most women with ovarian failure confined to patients > 40 years old.

Consolidation Radiotherapy in Primary Central Nervous System Lymphomas: Impact on Outcome of Different Fields and Doses in Patients in Complete Remission After Upfront Chemotherapy

International Nuclear Information System (INIS)

Ferreri, Andres Jose Maria; Verona, Chiara; Politi, Letterio Salvatore; Chiara, Anna; Perna, Lucia; Villa, Eugenio; Reni, Michele

2011-01-01

Purpose: Avoidance radiotherapy or reduction of irradiation doses in patients with primary central nervous system lymphoma (PCNSL) in complete remission (CR) after high-dose methotrexate (HD-MTX)-based chemotherapy has been proposed to minimize the neurotoxicity risk. Nevertheless, no study has focused on the survival impact of radiation parameters, as far as we know, and the optimal radiation schedule remains to be defined. Methods and Materials: The impact on outcome and neurologic performance of different radiation fields and doses was assessed in 33 patients with PCNSL who achieved CR after MTX-containing chemotherapy and were referred to consolidation whole-brain irradiation (WBRT). Patterns of relapse were analyzed on computed tomography-guided treatment planning, and neurologic impairment was assessed by the Mini Mental Status Examination. Results: At a median follow-up of 50 months, 21 patients are relapse-free (5-year failure-free survival [FFS], 51%). WBRT doses ≥40 Gy were not associated with improved disease control in comparison with a WBRT dose of 30 to 36 Gy (relapse rate, 46% vs. 30%; 5-year FFS, 51% vs. 50%; p = 0.26). Disease control was not significantly different between patients irradiated to the tumor bed with 45 to 54 Gy or with 36 to 44 Gy, with a 5-year FFS of 35% and 44% (p = 0.43), respectively. Twenty patients are alive (5-year overall survival, 54%); WB and tumor bed doses did not have an impact on survival. Impairment as assessed by the Mini Mental Status Examination was significantly more common in patients treated with a WBRT dose ≥40 Gy. Conclusion: Consolidation with WBRT 36 Gy is advisable in patients with PCNSL in CR after HD-MTX-based chemotherapy. Higher doses do not change the outcome and could increase the risk of neurotoxicity.

Predictors of pulmonary toxicity in limited stage small cell lung cancer patients treated with induction chemotherapy followed by concurrent platinum-based chemotherapy and 70 Gy daily radiotherapy: CALGB 30904.

Science.gov (United States)

Salama, Joseph K; Pang, Herbert; Bogart, Jeffrey A; Blackstock, A William; Urbanic, James J; Hogson, Lydia; Crawford, Jeffrey; Vokes, Everett E

2013-12-01

Standard therapy for limited stage small cell lung cancer (L-SCLC) is concurrent chemotherapy and radiotherapy followed by prophylactic cranial radiotherapy. Predictors of post chemoradiotherapy pulmonary toxicity in limited stage (LS) small cell lung cancer (SCLC) patients are not well defined. Current guidelines are derived from non-small cell lung cancer regimens, and do not account for the unique biology of this disease. Therefore, we analyzed patients on three consecutive CALGB LS-SCLC trials treated with concurrent chemotherapy and daily high dose radiotherapy (70 Gy) to determine patient and treatment related factors predicting for post-treatment pulmonary toxicity. Patients treated on CALGB protocols 39808, 30002, 30206 investigating two cycles of chemotherapy followed by concurrent chemotherapy and 70 Gy daily thoracic radiation therapy were pooled. Patient, tumor, and treatment related factors were evaluated to determine predictors of grade 3–5 pulmonary toxicities after concurrent chemoradiotherapy. 100 patients were included. No patient experienced grade 4–5 post-treatment pulmonary toxicity. Patients who experienced post-treatment pulmonary toxicity were more likely to be older (median age 69 vs 60, p = 0.09) and have smaller total lung volumes (2565 cc vs 3530 cc, p = 0.05).). Furthermore,exposure of larger volumes of lung to lower (median V5 = 70%, p = 0.09, median V10 = 63%, p = 0.07), inter-mediate (median V20 = 50, p = 0.04) and high (median V60 = 25%, p = 0.01) doses of radiation were all associated with post-treatment grade 3 pulmonary toxicity, as was a larger mean lung radiation dose(median 31 Gy) p = 0.019. Post-treatment pulmonary toxicity following the completion of 2 cycles of chemotherapy followed by concurrent chemotherapy and high dose daily radiation therapy was uncommon. Care should be taken to minimize mean lung radiation exposure, as well as volumes of low, intermediate and high doses of radiation.

Intra-individual diagnostic image quality and organ-specific-radiation dose comparison between spiral cCT with iterative image reconstruction and z-axis automated tube current modulation and sequential cCT

International Nuclear Information System (INIS)

Wenz, Holger; Maros, Máté E.; Meyer, Mathias; Gawlitza, Joshua; Förster, Alex; Haubenreisser, Holger; Kurth, Stefan; Schoenberg, Stefan O.; Groden, Christoph; Henzler, Thomas

2016-01-01

•Superiority of spiral versus sequential cCT in image quality and organ-specific-radiation dose.•Spiral cCT: lower organ-specific-radiation-dose in eye lense compared to tilted sequential cCT.•State-of-the-art IR spiral cCT techniques has significant advantages over sequential cCT techniques. Superiority of spiral versus sequential cCT in image quality and organ-specific-radiation dose. Spiral cCT: lower organ-specific-radiation-dose in eye lense compared to tilted sequential cCT. State-of-the-art IR spiral cCT techniques has significant advantages over sequential cCT techniques. To prospectively evaluate image quality and organ-specific-radiation dose of spiral cranial CT (cCT) combined with automated tube current modulation (ATCM) and iterative image reconstruction (IR) in comparison to sequential tilted cCT reconstructed with filtered back projection (FBP) without ATCM. 31 patients with a previous performed tilted non-contrast enhanced sequential cCT aquisition on a 4-slice CT system with only FBP reconstruction and no ATCM were prospectively enrolled in this study for a clinical indicated cCT scan. All spiral cCT examinations were performed on a 3rd generation dual-source CT system using ATCM in z-axis direction. Images were reconstructed using both, FBP and IR (level 1–5). A Monte-Carlo-simulation-based analysis was used to compare organ-specific-radiation dose. Subjective image quality for various anatomic structures was evaluated using a 4-point Likert-scale and objective image quality was evaluated by comparing signal-to-noise ratios (SNR). Spiral cCT led to a significantly lower (p < 0.05) organ-specific-radiation dose in all targets including eye lense. Subjective image quality of spiral cCT datasets with an IR reconstruction level 5 was rated significantly higher compared to the sequential cCT acquisitions (p < 0.0001). Consecutive mean SNR was significantly higher in all spiral datasets (FBP, IR 1–5) when compared to sequential cCT with a mean

Pharmacokinetics, safety, and efficacy of APF530 (extended-release granisetron in patients receiving moderately or highly emetogenic chemotherapy: results of two Phase II trials

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Gabrail N

2015-03-01

Full Text Available Nashat Gabrail,1 Ronald Yanagihara,2 Marek Spaczyński,3 William Cooper,4 Erin O'Boyle,5 Carrie Smith,1 Ralph Boccia6 1Gabrail Cancer Center, Canton, OH, USA; 2St Louise Regional Hospital, Gilroy, CA, USA; 3Department of Gynecology, Obstetrics and Gynecologic Oncology, University of Medical Sciences, Poznan, Poland; 4TFS International, Flemington, NJ, USA; 5FibroGen, Inc., San Francisco, CA, USA; 6Center for Cancer and Blood Disorders, Bethesda, MD, USA Background: Despite advances with new therapies, a significant proportion of patients (>30% suffer delayed-onset chemotherapy-induced nausea and vomiting (CINV despite use of antiemetics. APF530 is a sustained-release subcutaneous (SC formulation of granisetron for preventing CINV. APF530 pharmacokinetics, safety, and efficacy were studied in two open-label, single-dose Phase II trials (C2005-01 and C2007-01, respectively in patients receiving moderately emetogenic chemotherapy or highly emetogenic chemotherapy. Methods: In C2005-01, 45 patients received APF530 250, 500, or 750 mg SC (granisetron 5, 10, or 15 mg, respectively. In C2007-01, 35 patients were randomized to APF530 250 or 500 mg SC. Injections were given 30 to 60 minutes before single-day moderately emetogenic chemotherapy or highly emetogenic chemotherapy. Plasma granisetron was measured from predose to 168 hours after study drug administration. Safety and efficacy were also evaluated. Results: APF530 pharmacokinetics were dose proportional, with slow absorption and elimination of granisetron after a single SC dose. Median time to maximum plasma concentration and half-life were similar for APF530 250 and 500 mg in both trials, with no differences between the groups receiving moderately and highly emetogenic chemotherapy. Exposure to granisetron was maintained at a therapeutic level over the delayed-onset phase, at least 168 hours. Adverse events in both trials were as expected for granisetron; injection site reactions (eg, erythema

Low dose combined chemotherapy/radiotherapy in the management of locally advanced urethral squamous cell carcinoma

International Nuclear Information System (INIS)

Johnson, D.W.; Kessler, J.F.; Ferrigni, R.G.; Anderson, J.D.

1989-01-01

The successful treatment of a patient with bulky squamous cell carcinoma of the urethra using low dose preoperative radiation therapy and concurrent chemotherapy is described. Dramatic rapid tumor response facilitated surgical resection of the remaining microscopic disease. This clinical behavior is remarkably similar to that seen with squamous cell carcinoma of the anal canal and esophagus when a similar regimen is used. At the latter tumor sites the successful use of combination radiotherapy and chemotherapy has reduced the morbidity of subsequent surgery, and in selected cases has obviated the need for a radical operation. Further investigation of such combination treatment is warranted for urethral carcinoma

Intensity Modulated Radiation Therapy With Dose Painting to Treat Rhabdomyosarcoma

International Nuclear Information System (INIS)

Yang, Joanna C.; Dharmarajan, Kavita V.; Wexler, Leonard H.; La Quaglia, Michael P.; Happersett, Laura; Wolden, Suzanne L.

2012-01-01

Purpose: To examine local control and patterns of failure in rhabdomyosarcoma patients treated with intensity modulated radiation therapy (RT) with dose painting (DP-IMRT). Patients and Methods: A total of 41 patients underwent DP-IMRT with chemotherapy for definitive treatment. Nineteen also underwent surgery with or without intraoperative RT. Fifty-six percent had alveolar histologic features. The median interval from beginning chemotherapy to RT was 17 weeks (range, 4-25). Very young children who underwent second-look procedures with or without intraoperative RT received reduced doses of 24-36 Gy in 1.4-1.8-Gy fractions. Young adults received 50.4 Gy to the primary tumor and lower doses of 36 Gy in 1.8-Gy fractions to at-risk lymph node chains. Results: With 22 months of median follow-up, the actuarial local control rate was 90%. Patients aged ≤7 years who received reduced overall and fractional doses had 100% local control, and young adults had 79% (P=.07) local control. Three local failures were identified in young adults whose primary target volumes had received 50.4 Gy in 1.8-Gy fractions. Conclusions: DP-IMRT with lower fractional and cumulative doses is feasible for very young children after second-look procedures with or without intraoperative RT. DP-IMRT is also feasible in adolescents and young adults with aggressive disease who would benefit from prophylactic RT to high-risk lymph node chains, although dose escalation might be warranted for improved local control. With limited follow-up, it appears that DP-IMRT produces local control rates comparable to those of sequential IMRT in patients with rhabdomyosarcoma.

Focal Radiation Therapy Dose Escalation Improves Overall Survival in Locally Advanced Pancreatic Cancer Patients Receiving Induction Chemotherapy and Consolidative Chemoradiation

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Krishnan, Sunil, E-mail: skrishnan@mdanderson.org [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States); Chadha, Awalpreet S. [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States); Suh, Yelin [Department of Radiation Physics, The University of Texas, Houston, Texas (United States); Chen, Hsiang-Chun [Department of Biostatistics, MD Anderson Cancer Center, Houston, Texas (United States); Rao, Arvind [Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, Texas (United States); Das, Prajnan; Minsky, Bruce D.; Mahmood, Usama; Delclos, Marc E. [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States); Sawakuchi, Gabriel O. [Department of Radiation Physics, The University of Texas, Houston, Texas (United States); Graduate School of Biomedical Sciences, The University of Texas, Houston, Texas (United States); Beddar, Sam [Department of Radiation Physics, The University of Texas, Houston, Texas (United States); Katz, Matthew H.; Fleming, Jason B. [Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Javle, Milind M.; Varadhachary, Gauri R.; Wolff, Robert A. [Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Crane, Christopher H. [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States)

2016-03-15

Purpose: To review outcomes of locally advanced pancreatic cancer (LAPC) patients treated with dose-escalated intensity modulated radiation therapy (IMRT) with curative intent. Methods and Materials: A total of 200 patients with LAPC were treated with induction chemotherapy followed by chemoradiation between 2006 and 2014. Of these, 47 (24%) having tumors >1 cm from the luminal organs were selected for dose-escalated IMRT (biologically effective dose [BED] >70 Gy) using a simultaneous integrated boost technique, inspiration breath hold, and computed tomographic image guidance. Fractionation was optimized for coverage of gross tumor and luminal organ sparing. A 2- to 5-mm margin around the gross tumor volume was treated using a simultaneous integrated boost with a microscopic dose. Overall survival (OS), recurrence-free survival (RFS), local-regional and distant RFS, and time to local-regional and distant recurrence, calculated from start of chemoradiation, were the outcomes of interest. Results: Median radiation dose was 50.4 Gy (BED = 59.47 Gy) with a concurrent capecitabine-based (86%) regimen. Patients who received BED >70 Gy had a superior OS (17.8 vs 15.0 months, P=.03), which was preserved throughout the follow-up period, with estimated OS rates at 2 years of 36% versus 19% and at 3 years of 31% versus 9% along with improved local-regional RFS (10.2 vs 6.2 months, P=.05) as compared with those receiving BED ≤70 Gy. Degree of gross tumor volume coverage did not seem to affect outcomes. No additional toxicity was observed in the high-dose group. Higher dose (BED) was the only predictor of improved OS on multivariate analysis. Conclusion: Radiation dose escalation during consolidative chemoradiation therapy after induction chemotherapy for LAPC patients improves OS and local-regional RFS.

Management of chemotherapy induced diarrhea (abstract)

International Nuclear Information System (INIS)

Qureshi, A.M.

1998-01-01

Diarrhoea is seen with many tumors and following several chemotherapy regimen esp. those containing 5-fluorouracil and high dose folinic acid it causes debility even death, delays cancer treatment, reduces compliance increases cost. It causes dehydration, renal failure volume depletion. Quality of life is worsened and hospitalization may be needed in multifactorial, with secretion; absorption imbalance due to mucosal damage, necrosis or inflammation. Local infection is set up by opportunistic organism and cell necrosis. The large volume of fluid and electrolytes overwhelms colonic absorptive capacity. Agent usually used for treatment is opioids (such as Diphenoxylate / Loperamide]. Bismuth (for inflammatory diarrhea). NSAIDs or alpha 2-agonists. For optimal management, the cause and severity should be assessed and treatment planned. Advice is given about certain dietary restraints and avoidance of some drugs. Fever, infection, dehydration and electrolyte losses are treated, pain relieved. Diphenoxylate / Loperamide (later is more effective; 4 mg, STAT, then 2mg every 4 hours or even 2 hourly) may be used. It is moderately effective in CID. Octreotide is useful in carcinoid. VIPoma, AIDS idiopathic secretary diarrhea, ileostomy, dumping syndrome. It acts directly on epithelial cells to reduce secretin, motilin pancreatic polypeptide. It slows transit time, reduces fluid and electrolyte secretin, increases absorption of electrolytes. It is effective in 5 FU and high dose chemotherapy with a 90% response rates seen after 3 days treatment. High Dose Chemotherapy and total body irradiation - induced diarrhea usually resolves within 72 hours. (author)

High dose melphalan in the treatment of advanced neuroblastoma: results of a randomised trial (ENSG-1) by the European Neuroblastoma Study Group

NARCIS (Netherlands)

Pritchard, Jon; Cotterill, Simon J.; Germond, Shirley M.; Imeson, John; de Kraker, Jan; Jones, David R.

2005-01-01

High dose myeloablative chemotherapy ("megatherapy"), with haematopoietic stem cell support, is now widely used to consolidate response to induction chemotherapy in patients with advanced neuroblastoma. In this study (European Neuroblastoma Study Group, ENSG1), the value of melphalan myeloablative

Intravenous administration of high-dose Paclitaxel reduces gut-associated lymphoid tissue cell number and respiratory immunoglobulin A concentrations in mice.

Science.gov (United States)

Moriya, Tomoyuki; Fukatsu, Kazuhiko; Noguchi, Midori; Okamoto, Koichi; Murakoshi, Satoshi; Saitoh, Daizoh; Miyazaki, Masaru; Hase, Kazuo; Yamamoto, Junji

2014-02-01

Chemotherapy remains a mainstay of treatment for cancer patients. However, anti-cancer drugs frequently cause a wide range of side effects, including leukopenia and gastrointestinal toxicity. These adverse effects can lead to treatment delays or necessitate temporary dose reductions. Although chemotherapy-related changes in gut morphology have been demonstrated, the influences of chemotherapeutic regimens on gut immunity are understood poorly. This study aimed to examine whether the anti-cancer drug paclitaxel (PTX) impairs gut immunity in mice. Male ICR mice were randomized into three groups: Control, low-dose PTX (low PTX; 2 mg/kg), or high-dose PTX (high PTX; 4 mg/kg). A single intravenous dose was given. On day seven after the injection, lymphocytes from Peyer patches (PP), intraepithelial (IE) spaces, and the lamina propria (LP) were counted and analyzed by flow cytometry (CD4(+), CD8(+), αβTCR(+), γδTCR(+), B220(+)). Immunoglobulin A (IgA) concentrations were measured in small intestinal and respiratory tract washings. Total, CD4(+) and γδTCR(+) lymphocyte numbers in PPs were significantly lower in the high PTX than in the control group. The CD4(+) lymphocyte numbers in the IE spaces were significantly lower in both PTX groups than in the control group. Respiratory tract IgA concentrations were lower in the high PTX than in the control group. The present data suggest high-dose PTX impairs mucosal immunity, possibly rendering patients more vulnerable to infection. Careful dose selection and new therapies may be important for maintaining mucosal immunity during PTX chemotherapy.

Improved survival of multiple myeloma patients with late relapse after high-dose treatment and stem cell support, a population-based study of 348 patients in Denmark in 1994-2004

DEFF Research Database (Denmark)

Vangsted, Annette Juul; Klausen, Tobias W; Andersen, Niels F

2010-01-01

To analyse if patients with early relapse after high-dose chemotherapy with stem cell support (HDT) benefit from new treatment strategies in a population-based setting.......To analyse if patients with early relapse after high-dose chemotherapy with stem cell support (HDT) benefit from new treatment strategies in a population-based setting....

Simultaneous integrated vs. sequential boost in VMAT radiotherapy of high-grade gliomas.

Science.gov (United States)

Farzin, Mostafa; Molls, Michael; Astner, Sabrina; Rondak, Ina-Christine; Oechsner, Markus

2015-12-01

In 20 patients with high-grade gliomas, we compared two methods of planning for volumetric-modulated arc therapy (VMAT): simultaneous integrated boost (SIB) vs. sequential boost (SEB). The investigation focused on the analysis of dose distributions in the target volumes and the organs at risk (OARs). After contouring the target volumes [planning target volumes (PTVs) and boost volumes (BVs)] and OARs, SIB planning and SEB planning were performed. The SEB method consisted of two plans: in the first plan the PTV received 50 Gy in 25 fractions with a 2-Gy dose per fraction. In the second plan the BV received 10 Gy in 5 fractions with a dose per fraction of 2 Gy. The doses of both plans were summed up to show the total doses delivered. In the SIB method the PTV received 54 Gy in 30 fractions with a dose per fraction of 1.8 Gy, while the BV received 60 Gy in the same fraction number but with a dose per fraction of 2 Gy. All of the OARs showed higher doses (Dmax and Dmean) in the SEB method when compared with the SIB technique. The differences between the two methods were statistically significant in almost all of the OARs. Analysing the total doses of the target volumes we found dose distributions with similar homogeneities and comparable total doses. Our analysis shows that the SIB method offers advantages over the SEB method in terms of sparing OARs.

Simultaneous optimization of sequential IMRT plans

International Nuclear Information System (INIS)

Popple, Richard A.; Prellop, Perri B.; Spencer, Sharon A.; Santos, Jennifer F. de los; Duan, Jun; Fiveash, John B.; Brezovich, Ivan A.

2005-01-01

Radiotherapy often comprises two phases, in which irradiation of a volume at risk for microscopic disease is followed by a sequential dose escalation to a smaller volume either at a higher risk for microscopic disease or containing only gross disease. This technique is difficult to implement with intensity modulated radiotherapy, as the tolerance doses of critical structures must be respected over the sum of the two plans. Techniques that include an integrated boost have been proposed to address this problem. However, clinical experience with such techniques is limited, and many clinicians are uncomfortable prescribing nonconventional fractionation schemes. To solve this problem, we developed an optimization technique that simultaneously generates sequential initial and boost IMRT plans. We have developed an optimization tool that uses a commercial treatment planning system (TPS) and a high level programming language for technical computing. The tool uses the TPS to calculate the dose deposition coefficients (DDCs) for optimization. The DDCs were imported into external software and the treatment ports duplicated to create the boost plan. The initial, boost, and tolerance doses were specified and used to construct cost functions. The initial and boost plans were optimized simultaneously using a gradient search technique. Following optimization, the fluence maps were exported to the TPS for dose calculation. Seven patients treated using sequential techniques were selected from our clinical database. The initial and boost plans used to treat these patients were developed independently of each other by dividing the tolerance doses proportionally between the initial and boost plans and then iteratively optimizing the plans until a summation that met the treatment goals was obtained. We used the simultaneous optimization technique to generate plans that met the original planning goals. The coverage of the initial and boost target volumes in the simultaneously optimized

ROLES OF RADIATION DOSE AND CHEMOTHERAPY IN THE ETIOLOGY OF STOMACH CANCER AS A SECOND MALIGNANCY

NARCIS (Netherlands)

van den Belt-Dusebout, Alexandra W.; Aleman, Berthe M. P.; Besseling, Gijs; de Bruin, Marie L.; Hauptmann, Michael; van 't Veer, Mars B.; de Wit, Ronald; Ribot, Jacques G.; Noordijk, Evert M.; Kerst, J. Martijn; Gietema, Jourik A.; van Leeuwen, Flora E.

2009-01-01

Purpose: To evaluate the roles of radiation dose, chemotherapy, and other factors in the etiology of stomach cancer in long-term survivors of testicular cancer or Hodgkin lymphoma. Methods and Materials: We conducted a cohort study in 5,142 survivors of testicular cancer or Hodgkin lymphoma treated

Characteristics of breast cancer blood supply before and after chemotherapy with low-dose CT perfusion

International Nuclear Information System (INIS)

Zhou Juan; Lu Hong; Sheng Fugeng; Xing Xudong; Li Gongjie; Liu Baosheng

2009-01-01

Objective: To analyze the characteristics of breast cancer blood supply before and after chemotherapy with low-dose CT perfusion. Methods: Fifteen patients with breast cancer underwent CT breast perfusion examination, which was performed before and after chemotherapy within 1 week on Siemens Sensation 4 scanner with 120 kV and 50 mAs, 50 ml of nonionic contrast agent (320 mg I/ml) was injected at a flow rate of 4 ml/s with a power injector, Scan started after 8 seconds delay and data acquisition duration was 50 seconds. The blood flow (BF), blood volume (BV) and mean transfer time (MTT) of lesion and contralateral normal breast gland were calculated using Basama perfusion 3 software package before and after chemotherapy. At the same time, the tumor size before and after chemotherapy were measured and correlated with the BF values. The t test and non-parametric test were used for the statistics. Results: (1) The mean BF, BV and MTT of breast cancer were (33.20±4.17) ml·min -1 ·100 ml -1 , (8.31±2.43) ml· 100 ml -1 and (15.31±4.31) s respectively before chemotherapy, and (13.65±6.04) ml·min -1 · 100 ml -1 (5.04±2.33) ml·100 ml -1 and (25.97±9.07) s respectively after chemotherapy and there were statistically significant (P=0.000). The mean BF, BV and MTT of normal breast were (4.31±2.23) ml -1 , min -1 ·100 ml -1 , (1.38±0.75) ml·100 ml -1 and ( 19.25±3.94) s respectively before chemotherapy, and (4.03±2.35) ml·min -1 ·100 ml -1 , (1.44±0.84) ml·100 ml -1 , (22.56±7.71 ) s respectively after chemotherapy and there were not statistically significant (P>0.05). (2)The BF of breast cancer was higher than the normal breast before chemotherapy (P<0.01). (3)There was a positive correlation between the BF values and tumor size before and after chemotherapy (r=0.902, P=0.000). Conclusion: The BF value has a positive correlation with tumor size after chemotherapy, CT perfusion is more sensitive for the evaluation of chemotherapy response than morphologic

Craniospinal Germinomas in Patient with Down Syndrome Successfully Treated with Standard-Dose Chemotherapy and Craniospinal Irradiation: Case Report and Literature Review.

Science.gov (United States)

Miyake, Yohei; Adachi, Jun-Ichi; Suzuki, Tomonari; Mishima, Kazuhiko; Sasaki, Atsushi; Nishikawa, Ryo

2017-12-01

Patients with Down syndrome (DS) are more likely to develop chemotherapy-related complications. The standard treatment for these patients with cancer has not yet been established, and the risks of standard chemotherapy are unclear. In this paper, a rare case of multiple craniospinal germinomas in a patient with DS, which was successfully treated with standard-dose chemotherapy combined with craniospinal irradiation, is reported. The authors report a case of multiple craniospinal germinomas in a DS patient who presented with bilateral oculomotor and facial nerve palsy and hearing loss. The patient underwent 3 courses of combination chemotherapy using a standard dose of carboplatin and etoposide and 23.4 Gy of concurrent craniospinal irradiation. Posttreatment magnetic resonance imaging showed reduction of the tumors. Both fluorodeoxyglucose- and methionine-positron emission tomography demonstrated no uptake in the residual tumors. Follow-up magnetic resonance imaging and positron emission tomography did not reveal tumor recurrence for 18 months. As far as we know, this is the first case of multiple craniospinal germinomas in a patient with DS who achieved a successful treatment result without fatal adverse events. The literature review indicated that disseminated germinomas may need intensive treatment to reduce recurrence risk. However, intensive chemotherapy using a combination of 3 or more anticancer drugs can increase the rate of treatment-related death during the early stage. Our case indicated that multiple craniospinal germinoma of DS patients could be treated with a standard dose of carboplatin and etoposide regimen with concurrent craniospinal irradiation along with appropriate supportive therapy and careful observation. Copyright © 2017 Elsevier Inc. All rights reserved.

Correlation factor analysis between radiation pneumonitis and chemo-radiotherapy in breast cancer patients

International Nuclear Information System (INIS)

Li Huiping; Wang Junjie; Ma Liwen; Zhang Shulan; Deng Huijing; Jia Tingzhen

2004-01-01

Objective: To investigate the relationship between radiotherapy-induced lung injury and chemotherapy agents as well as other factors. Methods: A total of 85 breast cancer patients received radiotherapy with sequential or concurrent chemotherapy after surgery were analysed for radiation dose, chemotherapy schedule, age, and lung disease history. Results: Five patients had clinical symptoms of radiation pneumonitis, one of them was necessary to treat and 16 patients developed radiological changes (18.8%). Close relationship was noted between incidence of radiation pneumonitis and radiation dose, timing and drugs used in chemotherapy and lung disease history. Conclusion: High irradiation dose, concurrent chemotherapy, and lung disease history can increase the rate of radiotherapy-induced pulmonary injury in breast cancer patients. (authors)

The Influence of Dosing Modes of Coagulate on Arsenic Removal

Directory of Open Access Journals (Sweden)

Zhibin Zhang

2014-01-01

Full Text Available Three different dosing modes, including one single dosing mode and two sequential dosing modes, were applied in high-arsenic contaminated water treatment. The results illustrated that the As (V soluble and the As (V nonspecifically sorbed were the insignificant species from Fe-As (V samples in the sequential dosing mode, while they were higher in the single dosing mode. However, it could be further concluded that the mobility of the Fe-As (V in sequential dosing mode was greater than that in single dosing mode. Besides, the main arsenic speciation governing the arsenic-borne coagulates was the As (V associated with poorly crystalline hydrous oxides of Fe in sequential or single dosing mode. Moreover, the particle size distribution analysis indicated that the sequential dosing mode was more prevalent in neutralizing and adsorbing the As (V compared with the single dosing mode. In the FT-IR spectra, the presence of arsenic was highlighted by a well resolved band at 825–829 cm−1. The positions of the As–O stretching vibration bands were shifted gradually as the dosing mode changed from the single to the sequential. This result could be related to the distribution of arsenic speciation in different dosing modes.

High-dose chemotherapy and immunotherapy in adult Burkitt lymphoma: comparison of results in human immunodeficiency virus-infected and noninfected patients.

Science.gov (United States)

Oriol, Albert; Ribera, Josep-Maria; Bergua, Juan; Giménez Mesa, Eduardo; Grande, Carlos; Esteve, Jordi; Brunet, Salut; Moreno, Maria-Jose; Escoda, Lourdes; Hernandez-Rivas, Jesus-Maria; Hoelzer, Dieter

2008-07-01

It has been recognized that cure is possible for human immunodeficiency virus (HIV)-infected patients with Burkitt lymphoma/leukemia (BL) if appropriate chemotherapy is used. The introduction of rituximab in BL therapeutic schemes has been scarcely explored. The outcome and toxicity of HIV-positive patients with BL treated in a rituximab and intensive chemotherapy-based trial was evaluated. Thirty-six consecutive patients, 15 to 55 years of age, diagnosed with advanced stage BL were recruited from July 2003 to August 2006, stratified according to HIV infection status and treated with 6 cycles of intensive chemotherapy including 8 doses of rituximab. Nineteen of the patients (53%) were HIV-infected. Their clinical characteristics were comparable to those of the HIV-negative patients. Complete remission (CR) rates were 88% and 84%, respectively, for HIV-negative and -positive patients. Twenty-seven patients (82% and 68%, respectively, for HIV-negative and -positive patients) completed the 6 protocol scheduled cycles. HIV-infected patients presented higher incidences of grade 3-4 mucositis (27% vs 7% of cycles, P = .0005) and severe infectious episodes (26% vs 8%, P = .0025). However, there were no statistically significant differences in 2-year overall survival (82%, 95% confidence interval [CI], 65%-99% and 73%, 95% CI, 54%-92%, respectively) or 2-year disease-free survival (93%, 95% CI, 82%-99% and 87%, 95% CI 72%-99%, respectively). Intensive immunochemotherapy can be administered safely to patients with HIV infection. Despite a higher incidence of severe mucositis and infections the remission and survival rates are comparable to those observed in HIV-negative patients. (Copyright) 2008 American Cancer Society.

Sequential measurements of cosmic-ray neutron spectrum and dose rate at sea level in Sendai, Japan

International Nuclear Information System (INIS)

Nakamura, Takashi; Nunomiya, Tomoya; Abe, Shigeru; Terunuma, Kazutaka; Suzuki, Hiroyuki

2005-01-01

The cosmic-ray neutron energy spectrum and dose rate were measured sequentially for two years from April 2001 up to March 2003 by using three neutron detectors, a 3 He-loaded multi-moderator detector (Bonner ball), 12.7 cm diameter by 12.7 cm long NE213 organic liquid scintillator, and high-sensitivity rem (dose equivalent) counter at the Kawauchi campus of Tohoku University in Sendai, Japan of geomagnetic latitude, 29degN, and cutoff rigidity, 10.43 GV. The neutron spectrum has three major peaks, thermal energy peak, evaporation peak around 1 MeV and cascade peak around 100 MeV. The ambient neutron dose equivalent rates measured by the rem counter, and the Bonner ball keep almost constant values of 4.0 and 6.5 (nSv/h), respectively, throughout this time period, after atmospheric pressure correction, and it often decreased about 30% after a large Solar Flare, that is called as the Forbush decrease. The total neutron flux was also obtained by the Bonner ball measurements to be 7.5x10 -3 (ncm -2 ·s -1 ) in average. The altitude variation of neutron flux and dose was also investigated by comparing the measured results with other results measured at Mt. Fuji area and aboard an airplane, where the cutoff rigidities are similar. (author)

Local and regional irradiation and brief reduced-dose chemotherapy for non-Hodgkin'n lymphoma (stage IE, IIE) of Waldeyer's ring with adult diseases

International Nuclear Information System (INIS)

Oguchi, Masahiko; Shikama, Naoto; Gomi, Koutarou; Izuno, Itaru; Takei, Kazuyoshi; Sasaki, Shigeru; Kiyono, Kunihiro

1997-01-01

Usually, the middle-aged patients with non-Hodgkin's lymphoma and concomitant other adult diseases can not be tolerable for intensive chemotherapy. Then we introduced a new regimen composed of radiation for local and surrounding lymph node areas, and brief reduced-dose chemotherapy into treatment for such patients. Thirty-eight patients with Stage I E or Stage II E non-Hodgkin's lymphoma of the Waldeyer's ring were a core of this study. Histopathologically they were diagnosed as diffuse intermediate grade. In addition, they suffered from other adult diseases such as cardiovascular diseases, cereblovascular disorders, diabetes mellitus, chronic liver diseases, etc. They were treated by the combined modality composed of reduced-dose chemotherapy (70%-ACOP: 2 cycles or 70%-MACOP-B: 8 weeks) and regional lymph node irradiation (30 Gy) puls boost irradiation (10 Gy) to involved area (total 40 Gy). No relapses were observed in the radiation field, the 5-year disease-free survival rate and cause-specific survival rate for all patients were 85.7% and 91.4%, respectively. There were no differences of the 5-year disease-free survival rate between stage I E and II E , among the pathological subtypes, among the complications and etc. The regimen composed of regional lymph node irradiation (30 Gy) puls boost irradiation (10 Gy) to involved area (total 40 Gy) and reduced-dose chemotherapy (70%-dose ACOP, 70%-dose MACOP-B) is a safe and useful approach to treatment for diffuse intermediate grade of B cell lymphoma in middle-aged patients having other adult diseases. (author)

High-dose metoclopramide + lorazepam versus low-dose metoclopramide + lorazepam + dehydrobenzperidol in the treatment of cisplatin-induced nausea and vomiting

DEFF Research Database (Denmark)

Herrstedt, Jørn; Hannibal, J; Hallas, Jesper

1991-01-01

In a randomized double-blind, cross-over trial of 34 patients receiving cisplatin-based chemotherapy (20-100 mg/m2), the antiemetic effect of high-dose metoclopramide (HDM) (10 mg/kg iv. loading dose + 7 hours continuous infusion) + lorazepam (L) (2.5 mg x 4 po) was compared with low......-dose metoclopramide (LDM) (70 mg) + L (2.5 mg x 2 po) + dehydrobenzperidol (5 mg x 2 im). Among the 29 patients who completed the cross-over, HDM significantly reduced the number of vomiting episodes (p = 0.002) and the degree of nausea (p = 0.004). Seventeen patients preferred the HDM and 4 the LDM regimen (p = 0.......01). Sedation was seen in all but 1 patient, and was graded as severe in 6 patients receiving the HDM and in 2 patients receiving the LDM regimen. No extrapyramidal adverse reactions were seen. We conclude that high-dose metoclopramide + lorazepam is a safe antiemetic regimen and significantly superior to low...

Feasibility of combined modality therapy for localized high-grade soft tissue sarcomas in adults

International Nuclear Information System (INIS)

Blum, R.H.; Greenberger, J.S.; Wilson, R.E.; Corson, J.M.

1979-01-01

Seventeen consecutive patients with localized, high grade soft tissue sarcomas had resection of their primary tumor, radiation therapy and chemotherapy. The soft tissue sarcoma was primary in 14 patients and regionally recurrent in 3 patients. Chemotherapy consisted of cyclophosphamide 500 mg/M 2 day 1, Adriamycin (ADR) 60 mg/M 2 day 2, and DTIC 400 mg/M 2 days 1 and 2, given every 21 days to a maximum ADR dose of 450 mg/M 2 . Cyclophosphamide and DTIC were then given to a total duration of 1 year. Radiation therapy consisted of 4000 to 5000 rad by megavoltage photons in 5 weeks, and in selected cases, an additional 1500 to 2000 rad by electron beam boost in the tumor bed delivered over 2 additional weeks. Following surgery, 12 patients were treated sequentially with an interval of chemotherapy, radiation therapy and then the completion of chemotherapy. The added morbidity of this sequential approach is minimal: one patient of 12 had delayed primary healing of her wound, 1 of 10 patients required a break in radiation therapy because of skin erythema. Four patients were treated with intensive pre-chemotherapy radiation therapy because of inadequate surgical margins. The median time on study was 18 months from onset of treatment (range, 8 to 41 months). Although there have been no local, regional or distant recurrences, the follow-up time is inadequate to assess the therapeutic benefit of this combined modality treatment

Impact of radiation technique, radiation fraction dose, and total cisplatin dose on hearing. Retrospective analysis of 29 medulloblastoma patients

International Nuclear Information System (INIS)

Scobioala, Sergiu; Kittel, Christopher; Ebrahimi, Fatemeh; Wolters, Heidi; Eich, Hans Theodor; Parfitt, Ross; Matulat, Peter; Am Zehnhoff-Dinnesen, Antoinette

2017-01-01

To analyze the incidence and degree of sensorineural hearing loss (SNHL) resulting from different radiation techniques, fractionation dose, mean cochlear radiation dose (D mean ), and total cisplatin dose. In all, 29 children with medulloblastoma (58 ears) with subclinical pretreatment hearing thresholds participated. Radiotherapy (RT) and cisplatin had been applied sequentially according to the HIT MED Guidance. Audiological outcomes up to the latest follow-up (median 2.6 years) were compared. Bilateral high-frequency SNHL was observed in 26 patients (90%). No significant differences were found in mean hearing threshold between left and right ears at any frequency. A significantly better audiological outcome (p < 0.05) was found after tomotherapy at the 6 kHz bone-conduction threshold (BCT) and left-sided 8 kHz air-conduction threshold (ACT) than after a combined radiotherapy technique (CT). Fraction dose was not found to have any impact on the incidence, degree, and time-to-onset of SNHL. Patients treated with CT had a greater risk of SNHL at high frequencies than tomotherapy patients even though D mean was similar. Increase in severity of SNHL was seen when the total cisplatin dose reached above 210 mg/m 2 , with the highest abnormal level found 8-12 months after RT regardless of radiation technique or fraction dose. The cochlear radiation dose should be kept as low as possible in patients who receive simultaneous cisplatin-based chemotherapy. The risk of clinically relevant HL was shown when D mean exceeds 45 Gy independent of radiation technique or radiation regime. Cisplatin ototoxicity was shown to have a dose-dependent effect on bilateral SNHL, which was more pronounced in higher frequencies. (orig.) [de

Study comparing sequential (neo-adjuvant) versus concurrent chemo-radiotherapy in patients with squamous cell carcinoma

International Nuclear Information System (INIS)

Okawa, Tomohiko; Karasawa, Kumiko; Kaneyasu, Yuko; Tanaka, Makiko; Kita-Okawa, Midori; Ishii, Tetsuo

1994-01-01

Radiotherapy combined with chemotherapy is still used for standard treatment in patients with locally advanced unresectable cancer. A study was undertaken to compare a sequential (neo-adjuvant) with a simultaneous (concurrent) chemotherapy and radiotherapy program. Neo-adjuvant chemotherapy with cisplatin (80 mg/m 2 i.v. day 1) and 5FU (600 mg/m 2 continuous i.v. day 1-5) every 3 weeks prior to definitive conventional radiotherapy (60-65 Gy), or cisplatin (20 mg/m 2 i.v. day 1-5) and 5FU (250 mg/m 2 continuous i.v. infusion. day 1-14) were given simultaneously for same radiotherapy. Complete response rate was 45% in the sequential treatment and 43% in the simultaneous arm. Leukopenia and other adverse effects were slightly more frequent in the simultaneous arm, but there were no significant differences. These results suggested that individualization of treatment planning and establishment of optimum treatment were most important for combination of chemotherapy and radiotherapy. (author)

Different doses of prophylactic platelet transfusion for preventing bleeding in people with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation

Science.gov (United States)

Estcourt, Lise J; Stanworth, Simon; Doree, Carolyn; Trivella, Marialena; Hopewell, Sally; Blanco, Patricia; Murphy, Michael F

2015-01-01

Background Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in people who are thrombocytopenic due to bone marrow failure. Although considerable advances have been made in platelet transfusion therapy in the last 40 years, some areas continue to provoke debate, especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding. This is an update of a Cochrane review first published in 2004, and updated in 2012 that addressed four separate questions: prophylactic versus therapeutic-only platelet transfusion policy; prophylactic platelet transfusion threshold; prophylactic platelet transfusion dose; and platelet transfusions compared to alternative treatments. This review has now been split into four smaller reviews; this review compares different platelet transfusion doses. Objectives To determine whether different doses of prophylactic platelet transfusions (platelet transfusions given to prevent bleeding) affect their efficacy and safety in preventing bleeding in people with haematological disorders undergoing myelosuppressive chemotherapy with or without haematopoietic stem cell transplantation (HSCT). Search methods We searched for randomised controlled trials in the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 6), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 23 July 2015. Selection criteria Randomised controlled trials involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in people with malignant haematological disorders or undergoing HSCT that compared different platelet component doses (low dose 1.1 × 1011/m2 ± 25%, standard dose 2.2 × 1011/m2 ± 25%, high dose 4.4 × 1011/m2 ± 25%). Data collection and analysis We used the standard

Benefits of adjuvant chemotherapy in high-grade gliomas.

Science.gov (United States)

DeAngelis, Lisa M

2003-12-01

The current standard of care for patients with high-grade glioma is resection followed by radiotherapy. Adjuvant chemotherapy is not widely accepted because of the low sensitivity of gliomas to traditional antineoplastic agents, the poor penetration of most drugs across the blood-brain barrier, and the significant systemic toxicity associated with current agents. However, nitrosoureas and, subsequently, temozolomide (Temodar [US], Temodal [international]; Schering-Plough Corporation, Kenilworth, NJ), a novel alkylating agent, cross the blood-brain barrier and have activity against gliomas. Nitrosoureas have been studied in phase III trials in the adjuvant setting. In individual trials, chemotherapy did not increase median survival but did increase the proportion of patients surviving >/=18 months by 15%. Only with large meta-analyses did the addition of chemotherapy achieve a statistically significant improvement in median survival. Currently there is no means of identifying which patients will benefit from adjuvant chemotherapy, but nitrosoureas and temozolomide are well tolerated in most patients, justifying the administration of adjuvant chemotherapy to all newly diagnosed patients with malignant glioma.

Assessments for high dose radionuclide therapy treatment planning

International Nuclear Information System (INIS)

Fisher, D.R.

2003-01-01

Advances in the biotechnology of cell specific targeting of cancer and the increased number of clinical trials involving treatment of cancer patients with radiolabelled antibodies, peptides, and similar delivery vehicles have led to an increase in the number of high dose radionuclide therapy procedures. Optimised radionuclide therapy for cancer treatment is based on the concept of absorbed dose to the dose limiting normal organ or tissue. The limiting normal tissue is often the red marrow, but it may sometimes be the lungs, liver, intestinal tract, or kidneys. Appropriate treatment planning requires assessment of radiation dose to several internal organs and tissues, and usually involves biodistribution studies in the patient using a tracer amount of radionuclide bound to the targeting agent and imaged at sequential timepoints using a planar gamma camera. Time-activity curves are developed from the imaging data for the major organ tissues of concern, for the whole body and sometimes for selected tumours. Patient specific factors often require that dose estimates be customised for each patient. In the United States, the Food and Drug Administration regulates the experimental use of investigational new drugs and requires 'reasonable calculation of radiation absorbed dose to the whole body and to critical organs' using the methods prescribed by the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine. Review of high dose studies shows that some are conducted with minimal dosimetry, that the marrow dose is difficult to establish and is subject to large uncertainties. Despite the general availability of software, internal dosimetry methods often seem to be inconsistent from one clinical centre to another. (author)

Efficacy, safety and proper dose analysis of PEGylated granulocyte colony-stimulating factor as support for dose-dense adjuvant chemotherapy in node positive Chinese breast cancer patients.

Science.gov (United States)

Zhang, Fan; LingHu, RuiXia; Zhan, XingYang; Li, Ruisheng; Feng, Fan; Gao, Xudong; Zhao, Lei; Yang, Junlan

2017-10-03

For high-risk breast cancer patients with positive axillary lymph nodes, dose-dense every-two-week epirubicin/cyclophosphamide-paclitaxel (ddEC-P) regimen is the optimal postoperative adjuvant therapy. However, this regimen is limited by the grade 3/4 neutropenia and febrile neutropenia (FN). There is an urgent need to explore the efficacy, safety and proper dosage of PEGylated granulocyte colony-stimulating factor (PEG-G-CSF) as support for ddEC-P in Chinese breast cancer patients with positive axillary lymph nodes. Prospectively, 40 women with stage IIIA to IIIC breast cancer received ddEC-P ± trastuzumab as adjuvant treatment. PEG-G-CSF was injected subcutaneously in a dose of 6 mg or 3 mg on the 2 th day of each treatment cycle. With administration of PEG-G-CSF, all of the 40 patients completed 8 cycles of ddEC-P ± trastuzumab regimen without dose reductions or treatment delays. Moreover, no FN cases were observed. Further analysis showed that the proper dosage of PEG-G-CSF was 6 mg for ddEC treatment, and 3 mg for ddP treatment. PEG-G-CSF exhibits advantages compared with G-CSF in convenient of administration and tolerance for high risk Chinese breast cancer patients. More importantly, the proper dose of PEG-G-CSF for high risk Chinese breast cancer patients during ddEC-P chemotherapy may be 6 mg for ddEC treatment and 3 mg for ddP treatment.

Results of a randomized trial comparing high-dose chemotherapy plus Auto-SCT and R-FC in CLL at diagnosis.

Science.gov (United States)

Magni, M; Di Nicola, M; Patti, C; Scimè, R; Mulè, A; Rambaldi, A; Intermesoli, T; Viero, P; Tarella, C; Gueli, A; Bergui, L; Trentin, L; Barzan, A; Benedetti, F; Ambrosetti, A; Di Raimondo, F; Chiarenza, A; Parvis, G; Billio, A; Attolico, I; Olivieri, A; Montanari, M; Carlo-Stella, C; Matteucci, P; Devizzi, L; Guidetti, A; Viviani, S; Valagussa, P; Gianni, A M

2014-04-01

The importance of early therapy intensification in B-cell CLL (B-CLL) patients remains to be defined. Even though several studies have been published, no randomized trials comparing directly autologous stem cell transplant (ASCT) and the accepted conventional therapy (that is, rituximab, fludarabine and CY; R-FC) have been reported so far. To assess the benefit of a first-line aggressive therapy, we designed a multicenter, randomized, phase 3 trial comparing R-FC and high-dose chemotherapy supported by ASCT in patients under 65 years of age, with stage B(II) or C B-CLL. Primary end point was CR: 96 patients were enrolled (48 in each arm). On an intent-to-treat basis, the CR rates in the ASCT and R-FC arms were 62.5% and 58%, respectively. After 5 years of follow-up, PFS was 60.4% in the ASCT arm and 65.1% in the R-FC arm, time to progression 65.8 and 70.5%, and overall survival 88% vs 88.1%, respectively. Our trial demonstrates, for the first time in a randomized manner, that frontline ASCT does not translate into a survival advantage when compared with benchmark chemoimmunotherapy in B-CLL patients; the possibility of its clinical benefit in certain subgroups remains uncertain.

The effect of resveratrol in combination with irradiation and chemotherapy. Study using Merkel cell carcinoma cell lines

International Nuclear Information System (INIS)

Heiduschka, G.; Lill, C.; Brunner, M.; Thurnher, D.; Seemann, R.; Schmid, R.; Houben, R.; Bigenzahn, J.

2014-01-01

Merkel cell carcinoma (MCC) is a rare, but highly malignant tumor of the skin. In case of systemic disease, possible therapeutic options include irradiation or chemotherapy. The aim of this study was to evaluate whether the flavonoid resveratrol enhances the effect of radiotherapy or chemotherapy in MCC cell lines. The two MCC cell lines MCC13 and MCC26 were treated with increasing doses of resveratrol. Combination experiments were conducted with cisplatin and etoposide. Colony forming assays were performed after sequential irradiation with 1, 2, 3, 4, 6, and 8 Gy and apoptosis was assessed with flow cytometry. Expression of cancer drug targets was analyzed by real-time PCR array. Resveratrol is cytotoxic in MCC cell lines. Cell growth is inhibited by induction of apoptosis. The combination with cisplatin and etoposide resulted in a partially synergistic inhibition of cell proliferation. Resveratrol and irradiation led to a synergistic reduction in colony formation compared to irradiation alone. Evaluation of gene expression did not show significant difference between the cell lines. Due to its radiosensitizing effect, resveratrol seems to be a promising agent in combination with radiation therapy. The amount of chemosensitizing depends on the cell lines tested. (orig.) [de

Chemotherapy or radio-chemotherapy for advanced adenocarcinoma of the oesophagus and cardiac orifice

International Nuclear Information System (INIS)

Seitz, J.F.; Duffaud, F.; Dahan, L.; Ries, P.; Ville, E.; Laugier, R.

2001-01-01

Adenocarcinomas of esophagus and cardia represent in France approximately 20 to 40% of the esophagus cancers. They have a high risk to develop lymph nodes metastases and liver metastases. Currently, only 50 to 70% of patients may benefit from surgical curative resection at diagnosis, but more than 50% of them will recur. The standard of treatment of these metastatic adenocarcinomas is chemotherapy. Three large randomized comparative studies, between chemotherapy and supportive care, showed that chemotherapy significantly extends the median of survival (from 3-4 months to 10-12 months) and improves the quality of life. Currently, the combination of epirubicin-cisplatin-continuous 5FU (ECF) is the most effective regimen but it is difficult to administer and tolerate because of the long continuous 5FU infusion. In France, the most commonly used combination regimen still associates 5FU and cisplatin. New drugs (such as docetaxel, CPT11, oxaliplatin) used alone or in combination, especially with 5U, are very promising. Radio-chemotherapy is the preferred treatment for locoregional recurrences, because it improves dysphagia and enables to obtain complete tumor responses. Current results from concomitant radio-chemotherapy studies for esophagus cancer, based on 5FU alone, 5FU-cisplatin or 5FU-mitomycin, given as preoperative treatment or as exclusive treatment, support to use radio-chemotherapy for the treatment of loco-regional recurrences after surgical resection. Nevertheless, the optimal radio-chemotherapy schedule still remain to be defined (dose, duration, splitting of radiotherapy, choice of anticancer drugs). (authors)

Treatment for non-Hodgkin's lymphoma (stage I, II) of the elderly: usefulness of local and regional irradiation and reduced dose chemotherapy

International Nuclear Information System (INIS)

Oguchi, Masahiko; Izuno, Itaru; Takei, Kazuyoshi; Shikama, Naoto; Sasaki, Shigeru; Gomi, Koutarou; Sone, Shusuke

1997-01-01

Purpose: To examine the usefulness and safety of a new treatment regimen consisting of irradiation to the involved area and adjacent lymph node area, and reduced dose chemotherapy for elderly patients with non-Hodgkin's lymphoma. Methods and Materials: The core of this study was 38 elderly patients older than 65 years old with intermediate or high grade non-Hodgkin's lymphoma, and concomitantly suffering from some other geriatric disease. They received involved area irradiation (40 Gy), adjacent lymph node irradiation (30 Gy), and reduced dose chemotherapy (two cycles of 50-70% ACOP: Doxorubicin, Cyclophosphamide, Vincristine, Prednisone or 70% MACOP-B: Doxorubicin, Cyclophosphamide, Vincristine, Methotrexate, Bleomycin, Prednisone for 4 weeks). Results: The completion rate of the treatment regimen was 100%. The 5-year local control rate was 98%. The 5-year disease-free survival rate and the 5-year cause-specific survival rate for all patients were 70 and 82%, respectively. No treatment deaths were observed, and the rate of serious complications arising from the treatment was 3%. Conclusions: The newly conducted treatment regimen proved to be safe and useful for elderly patients with non-Hodgkin's lymphoma concomitantly suffering from some other geriatric disease

Sequential changes in bone marrow architecture during continuous low dose gamma irradiation

International Nuclear Information System (INIS)

Seed, T.M.; Chubb, G.T.; Tolle, D.V.

1981-01-01

Beagles continuously exposed to low daily doses (10 R) of whole-body 60 Co ν-radiation are prone to develop either early occurring aplasstic anemia or late occurring myeloproliferative disorders. In this study, we have examined by a combination of light microscopy and scanning and transmission electron microscopy the sequential changes in the morphology of biopsied rib bone marrow of continuously irradiated dogs that developed either aplastic anemia, myelofibrosis, or myelogenous leukemia. Characteristic modifications of key elements of marrow architecture have been observed during preclinical and clinical phases of these hemopathological conditions. These architectural changes during preclinical phases appear to be related to the pathological progression to each of the radiation-induced hemopathological end points

Primary chemotherapy and preoperative-dose irradiation for patients with stage II larger than 3 CM or locally advanced non inflammatory breast cancer

International Nuclear Information System (INIS)

Touboul, E.; Lefranc, J.P.; Blondon, J.; Deniaud, E.; Buffat, L.; Benmiloud, M.; Laugier, A.; Schlienger, M.

1995-01-01

Purpose: The aims of this prospective study were to evaluate the outcome and the possibility of breast conserving treatment for patients with stage II larger than 3 cm or locally advanced non inflammatory breast cancer, after primary chemotherapy followed by external preoperative-dose irradiation. Materials and methods: Between April 1982 and June 1990, 147 consecutive patients with large breast cancer (stage II > 3 cm [n=50], stage IIIA [n=58], stage IIIB [n=35] and stage IV with isolated clinical supraclavicular or sub-clavicular node involvement [n=4] were treated. The median age was 49 years. Mean tumor size was 6 cm (range 1 - 16 cm). Sixty percent (n=88) of the patients were postmenopausal. Histological classification was : 120 infiltrating ductal carcinomas, 21 infiltrating lobular carcinomas, 4 medullary carcinomas and 2 mucosecreting carcinomas. Grade distribution according to Scarff, Bloom and Richardson was : 14 grade 1, 72 grade 2, 30 grade 3 and 31 non classified. Median follow-up was 94 months from the beginning of the treatment. The induction treatment consisted of 4 courses of chemotherapy (doxorubicin, vincristine, cyclophosphamide, 5-fluorouracil) every 4 weeks followed by preoperative irradiation (45 Gy to the breast and nodal areas) using 60Co in 141 patients and 6 MV photons in 6 patients. A fifth course of chemotherapy was given after radiation therapy and three different locoregional approaches were proposed depending on the tumoral response. In 52 patients (35%) with residual tumor larger than 3 cm in diameter or located behind the nipple or with bifocal tumors, mastectomy and axillary dissection were performed. Ninety-five other patients (65%) benefited from conservative treatment : 48 patients (33%) achieved complete remission and received a booster dose of 25 to 30 Gy to the initial tumor bed by external photon beam or by iridium 192 implant ; 47 patients (32%) who had a residual mass less than or equal to 3 cm in diameter were treated by

Effect of pulsed dose in simultaneous and sequential irradiation of V-79 cells by 14.8-MeV neutrons and 60Co photons

International Nuclear Information System (INIS)

Higgins, P.D.; DeLuca, P.M. Jr.; Gould, M.N.

1984-01-01

The effect of irradiating V-79 Chinese hamster cells with a mixture of 40% 14.8-MeV neutrons and 60% 69 Co photons with simultaneous or sequential exposures is investigated. Sample doses are obtained by irradiating cells with alternating 3-min pulses of neutrons and photons (in the sequential case) or with mixed neutrons and photons followed by equal beam-off periods to ensure equal total exposure times for sequential and simultaneous irradiations. Differences between the survival results under each beam configuration that are consistent with previous observations with nonpulsed irradiations are observed

Sequential treatment of tyrosine kinase inhibitors and chemotherapy for EGFR-mutated non-small cell lung cancer: a meta-analysis of Phase III trials

Directory of Open Access Journals (Sweden)

Zhang Y

2013-11-01

Full Text Available Yiliang Zhang,1,* Yihua Sun,1,* Lei Wang,1 Ting Ye,1 Yunjian Pan,1 Haichuan Hu,1 Yongfu Yu,2 Naiqing Zhao,2 Yanyan Song,3 David Garfield,4 Haiquan Chen1 1Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, 2Department of Biostatistics, School of Public Health, Fudan University, 3Department of Pharmacology and Biostatistics, Institute of Medical Science, Shanghai Jiaotong University School of Medicine, 4ProMed Cancer Centers, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: This aim of this study was to compare the efficacy of first-line tyrosine kinase inhibitor therapy followed, upon progression, by chemotherapy with the reverse sequence in patients with EGFR-mutated non-small cell lung cancer (NSCLC in terms of overall survival. Methods: We performed a meta-analysis of studies that met the following criteria: Phase III clinical trial comparing the sequencing of epidermal growth factor receptor (EGFR tyrosine kinase inhibitors with chemotherapy in the treatment of advanced EGFR-mutated NSCLC; activating mutations reported; and availability of hazard ratio estimates with 95% confidence intervals (CIs for overall survival. Results: Six clinical trials were included in this study. The pooled hazard ratio for overall survival of the EGFR-mutated population that completed sequential treatment was 1.03 (95% CI 0.86–1.22, P=0.776. There was no statistically significant heterogeneity between the studies (tau2 =0; I2=0, 95% CI 0–0.37, P=0.548. Evidence of marked publication bias for the two treatment sequences was insufficient (P=0.145. Conclusion: In patients with advanced NSCLC and activating EGFR mutations, first-line chemotherapy followed upon progression by a tyrosine kinase inhibitor was not inferior in terms of overall survival compared with the inverse sequence. This may serve as an indication that

Sequential gadolinium-enhanced magnetic resonance angiography of the aortoiliac and the femoropopliteal arteries with repetitive administration of low-dose contrast agent

International Nuclear Information System (INIS)

Ito, Koichiro; Kumazaki, Tatsuo

2000-01-01

To obtain a wide-range contrast MR angiography in a single examination, we performed two sequential administrations of low-dose (0.08 mmol/kg) gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) with three dimensional inversion recovery prepared fast spoiled gradient recalled acquisition in the steady-state (3D IR-fast SPGR) sequence. Signal characteristics of the sequence were estimated by computed simulations and an in vitro study. A clinical study of 19 examinations was done with sequential MR angiography of the aortoiliac and femoropopliteal arteries. Great signal differences were observed between the high and low Gd concentrations. Higher Gd concentrations generated significantly stronger signals. Greater signals were produced at TIs of longer than 150 msec than at shorter than 100 msec. In the clinical study, the arteries were visualized with sufficient signals even with a small amount of contrast agent. Contrast-to-noise ratios between the arteries and surrounding skeletal muscles or fat tissues ranged from 10.5±9.6 to 4.7±2.2 and 6.6±2.8 to -3.1±11.2, respectively. No venous enhancement was found with diluted contrast agent on the second MR angiography. Two consecutive contrast MR angiographies can be obtained with repetitive administration of low-dose contrast agent. (author)

Sequential gadolinium-enhanced magnetic resonance angiography of the aortoiliac and the femoropopliteal arteries with repetitive administration of low-dose contrast agent

Energy Technology Data Exchange (ETDEWEB)

Ito, Koichiro [Nippon Medical School, Inba, Chiba (Japan). Chiba Hokusoh Hospital; Kumazaki, Tatsuo

2000-12-01

To obtain a wide-range contrast MR angiography in a single examination, we performed two sequential administrations of low-dose (0.08 mmol/kg) gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) with three dimensional inversion recovery prepared fast spoiled gradient recalled acquisition in the steady-state (3D IR-fast SPGR) sequence. Signal characteristics of the sequence were estimated by computed simulations and an in vitro study. A clinical study of 19 examinations was done with sequential MR angiography of the aortoiliac and femoropopliteal arteries. Great signal differences were observed between the high and low Gd concentrations. Higher Gd concentrations generated significantly stronger signals. Greater signals were produced at TIs of longer than 150 msec than at shorter than 100 msec. In the clinical study, the arteries were visualized with sufficient signals even with a small amount of contrast agent. Contrast-to-noise ratios between the arteries and surrounding skeletal muscles or fat tissues ranged from 10.5{+-}9.6 to 4.7{+-}2.2 and 6.6{+-}2.8 to -3.1{+-}11.2, respectively. No venous enhancement was found with diluted contrast agent on the second MR angiography. Two consecutive contrast MR angiographies can be obtained with repetitive administration of low-dose contrast agent. (author)

CpG island methylator phenotype is associated with the efficacy of sequential oxaliplatin- and irinotecan-based chemotherapy and EGFR-related gene mutation in Japanese patients with metastatic colorectal cancer.

Science.gov (United States)

Zhang, Xiaofei; Shimodaira, Hideki; Soeda, Hiroshi; Komine, Keigo; Takahashi, Hidekazu; Ouchi, Kota; Inoue, Masahiro; Takahashi, Masanobu; Takahashi, Shin; Ishioka, Chikashi

2016-12-01

The CpG island methylator phenotype (CIMP) with multiple promoter methylated loci has been observed in a subset of human colorectal cancer (CRC) cases. CIMP status, which is closely associated with specific clinicopathological and molecular characteristics, is considered a potential predictive biomarker for efficacy of cancer treatment. However, the relationship between the effect of standard chemotherapy, including cytotoxic drugs and anti-epidermal growth factor receptor (EGFR) antibodies, and CIMP status has not been elucidated. In 125 metastatic colorectal cancer (mCRC) patients, we investigated how clinical outcome of chemotherapy was related to CIMP status as detected by methylation-specific PCR (MSP) and to genetic status in five EGFR-related genes (KRAS, BRAF, PIK3CA, NRAS, and AKT1) as detected by direct sequencing. CIMP-positive status was significantly associated with proximal tumor location and peritoneum metastasis (all P values CIMP-positive tumors receiving sequential therapy with FOLFOX as the first-line treatment followed by irinotecan-based therapy as the second-line treatment (median = 6.6 months) was inferior to that of such patients receiving the reverse sequence (median = 15.2 months; P = 0.043). Furthermore, CIMP-positive tumors showed higher mutation frequencies for the five EGFR-related genes (74.1 %) than the CIMP-negative tumors did (50.0 %). Among the KRAS wild-type tumors, CIMP-positive tumors were associated with a worse clinical outcome than CIMP-negative tumors following anti-EGFR antibody therapy. Sequential FOLFOX followed by an irinotecan-based regimen is unfavorable in patients with CIMP-positive tumors. High frequencies of mutation in EGFR-related genes in CIMP-positive tumors may cause the lower response to anti-EGFR antibody therapy seen in patients with wild-type KRAS and CIMP-positive tumors.

Twenty-five year outcome of sequential abdominopelvic radiotherapy and alkylating agent chemotherapy for ovarian carcinoma

International Nuclear Information System (INIS)

Bellairs, Ellen E.; Twiggs, Leo B.; Potish, Roger A.

1997-01-01

Purpose: A prospective study of sequential surgery, abdominopelvic radiotherapy and single agent alkylating chemotherapy was conducted to evaluate survival and toxicity in the management of ovarian carcinoma. Methods: From 1970-1976, 95 women with stage I-III epithelial ovarian carcinoma were scheduled to receive postoperative radiotherapy consisting of 20.0 Gy to the whole abdomen (1.0 Gy/day), a 29.75 Gy pelvic boost (1.75 Gy/day) and 10 subsequent courses of Melphalan (1 mg/kg/course). Endpoints were overall survival, disease-free survival(DFS), and acute and chronic toxicity. Results: The evaluable 94 patients included 19 stage I, 25 stage II, and 50 stage III. Of the latter, 21 had no palpable disease postoperatively (IIIN) and 29 had postoperative palpable disease (IIIP). Overall survival at 5, 10, 15 and 20 years was 42%, 30%, 23% and 22%. DFS for the entire group was 54% at 5 years and remained 50% from 10 to 25 years. All but two recurrences were noted within the first 27 months. No recurrence or treatment-related deaths occurred after 8 years. After 10 years, the survival of the study group became parallel to the general population. Prognostic factors were only related to stage (p<.001) and the presence of postoperative palpable disease(p<.001). DFS at 25 years was 95 % for stage I, 71% at 5 years and 66% from 10 to 25 years for stage II, and 17% at 5 years and 11% thereafter for stage III patients(p<.001). Although no stage IIIP patients were cured, 25% lived beyond 2 years. Five year DFS was significantly better in IIIN (45%) vs. IIIP (0%) patients (p<.001). The 65 patients without postoperative palpable disease, (stage I-IIIN) achieved DFS at 5 and 25 years of 69%, and 61%, respectively. Of 31 patients undergoing a second-look surgery, 84% were found to be free of tumor. Two recurred at 3.5 and 7 years after surgery. Acute tolerance was acceptable. Chronic toxicity included an 11.7% rate of small bowel obstruction requiring surgery and a 3% rate of

The retreatment of carboplatin via high-dose intraperitoneal chemotherapy in patients with a history of a hypersensitivity reaction

NARCIS (Netherlands)

Kerkhof, M.H.; Ruiz Zapata, A.M.; Bril, H.; Bleeker, M.C.G.; Belien, J.A.M.; Stoop, R.; Helder, M.N.

2014-01-01

A hypersensitivity reaction attributed to platinum-based chemotherapy is a relatively common occurrence. Hyperthermic intraperitoneal chemotherapy potentially facilitates the safe retreatment of platinum therapy following this complication. We describe 3 ovarian cancer patients who were successfully

Influence of control group therapy on the benefit from dose-dense chemotherapy in early breast cancer: a systemic review and meta-analysis.

Science.gov (United States)

Goldvaser, Hadar; Majeed, Habeeb; Ribnikar, Domen; Šeruga, Boštjan; Ocaña, Alberto; Cescon, David W; Amir, Eitan

2018-02-08

Results from clinical trials of adjuvant dose-dense chemotherapy in patients with breast cancer are inconsistent. A systematic search of MEDLINE identified studies comparing the efficacy of dose-dense adjuvant chemotherapy to a standard treatment. The primary analysis included studies that used identical regimens in the experimental and control groups, but varied only dose density. A secondary analysis included studies that used either different drugs or doses in the experimental and the control groups. Hazard ratios (HRs) and 95% confidence intervals were computed for disease-free survival (DFS) and overall survival (OS) and pooled in a meta-analysis. Subgroup analyses and meta-regression explored drug schedules utilized in control groups and the influence of clinicopathologic variables on benefit from dose-dense therapy. The primary analysis included 5 studies comprising 9819 patients while the secondary analysis included 6 studies comprising 9679 patients. Dose-dense treatment significantly improved DFS (HR 0.85, p benefit was observed in pre-menopausal women and those with nodal involvement, but there was no influence of hormone receptor status on results. Adjuvant dose-dense regimens improve breast cancer outcomes. It remains uncertain whether the observed benefit reflects the impact of dose density or the inferiority of paclitaxel every 3 weeks as a control group.

Mining of high utility-probability sequential patterns from uncertain databases.

Directory of Open Access Journals (Sweden)

Binbin Zhang

Full Text Available High-utility sequential pattern mining (HUSPM has become an important issue in the field of data mining. Several HUSPM algorithms have been designed to mine high-utility sequential patterns (HUPSPs. They have been applied in several real-life situations such as for consumer behavior analysis and event detection in sensor networks. Nonetheless, most studies on HUSPM have focused on mining HUPSPs in precise data. But in real-life, uncertainty is an important factor as data is collected using various types of sensors that are more or less accurate. Hence, data collected in a real-life database can be annotated with existing probabilities. This paper presents a novel pattern mining framework called high utility-probability sequential pattern mining (HUPSPM for mining high utility-probability sequential patterns (HUPSPs in uncertain sequence databases. A baseline algorithm with three optional pruning strategies is presented to mine HUPSPs. Moroever, to speed up the mining process, a projection mechanism is designed to create a database projection for each processed sequence, which is smaller than the original database. Thus, the number of unpromising candidates can be greatly reduced, as well as the execution time for mining HUPSPs. Substantial experiments both on real-life and synthetic datasets show that the designed algorithm performs well in terms of runtime, number of candidates, memory usage, and scalability for different minimum utility and minimum probability thresholds.

Comparison of concurrent chemoradiotherapy versus sequential radiochemotherapy in patients with completely resected non-small cell lung cancer

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Kim, Hwan Ik; Noh, O Kyu; Oh, Young Taek; Chun, Mi Son; Kim, Sang Won; Cho, O Yeon; Heo, Jae Sung [Ajou University School of Medicine, Suwon (Korea, Republic of)

2016-09-15

Our institution has implemented two different adjuvant protocols in treating patients with non-small cell lung cancer (NSCLC): chemotherapy followed by concurrent chemoradiotherapy (CT-CCRT) and sequential postoperative radiotherapy (PORT) followed by postoperative chemotherapy (POCT). We aimed to compare the clinical outcomes between the two adjuvant protocols. From March 1997 to October 2012, 68 patients were treated with CT-CCRT (n = 25) and sequential PORT followed by POCT (RT-CT; n = 43). The CT-CCRT protocol consisted of 2 cycles of cisplatin-based POCT followed by PORT concurrently with 2 cycles of POCT. The RT-CT protocol consisted of PORT followed by 4 cycles of cisplatin-based POCT. PORT was administered using conventional fractionation with a dose of 50.4–60 Gy. We compared the outcomes between the two adjuvant protocols and analyzed the clinical factors affecting survivals. Median follow-up time was 43.9 months (range, 3.2 to 74.0 months), and the 5-year overall survival (OS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were 53.9%, 68.2%, and 51.0%, respectively. There were no significant differences in OS (p = 0.074), LRFS (p = 0.094), and DMFS (p = 0.490) between the two protocols. In multivariable analyses, adjuvant protocol remained as a significant prognostic factor for LRFS, favouring CT-CCRT (hazard ratio [HR] = 3.506, p = 0.046) over RT-CT, not for OS (HR = 0.647, p = 0.229). CT-CCRT protocol increased LRFS more than RT-CT protocol in patients with completely resected NSCLC, but not in OS. Further studies are warranted to evaluate the benefit of CCRT strategy compared with sequential strategy.

Combined radiotherapy and chemotherapy for pediatric medulloblastoma: a clinical study of 33 cases

Directory of Open Access Journals (Sweden)

Wei ZHENG

2011-06-01

Full Text Available Objective To retrospectively review the clinical characteristics of medulloblastoma,discuss the optimized treatment regimen,and analyze the prognostic influential factors.Methods Thirty-three children with pathologically certified medulloblastoma(aged 3-14 years with average of 6.5 years,admitted from Aug.2004 to Dec.2007,received radiotherapy within 3 weeks post surgery.Ratiotherapy consisted of 28~36Gy whole craniospinal radiation and a supplementary radiation aimed at tumors by three-dimensional conformal radiotherapy(3D-CRT for a total dose of 50~54Gy(conventional fraction dose of 1.8-2.0Gy.A part of patients received hyperfractionation radiotherapy(1.0Gy/f,2f/d for alleviating the tardive adverse events.Meanwhile,a synchronized chemotherapy,consisting of lomustine + vincristine + cisplatin,or isophosphamide + carboplatin + etoposide,was administered after the completion of whole craniospinal radiation,and 3-5 courses of sequential chemotherapy were given after the overall radiotherapy was finished.According to the metastasis,and the residual tumor and its size,the 33 patients were divided into 2 groups as follows: low-risk group(n=24: no metastases,total or sub-total excision of tumors(residual tumors ≤1.5cm3;high-risk group(n=9: either metastases or residual tumor > 1.5cm3.The 3-year survival rates of two groups were then compared.Results The combined radiotherapy and chemotherapy was effective to 10 of the 11 patients(90.9% with residual tumors.Out of the 33 patients,31 obtained complete remission(93.9%,and 2 patients showed partial remission or stable status(3.0%,respectively.The median survival time of 33 patients was 51 months,3-year disease free survival(DFS was 75.8%,and 3-year overall survival(OS was 78.8%,including 33.3% in high-risk group and 95.8% in low-risk group(P < 0.01.The major side effects occurred in haematological system and digestive system,such as an incidence of 21.2%(7/33 with grade Ⅲ-Ⅳ bone marrow suppression

Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: randomized, double-blind study protocol--EASE

DEFF Research Database (Denmark)

Grunberg, Steven; Chua, Daniel; Maru, Anish

2011-01-01

multiple-day NK1RA administration. Preliminary data suggested that single-dose aprepitant before chemotherapy could provide CINV protection throughout the overall risk phase (OP; 0 to 120 hours). This study compared a 3-day oral aprepitant schedule to a regimen containing a single dose of the intravenous...

Arterial occlusion precipitated by cisplatinbased chemotherapy

OpenAIRE

Joseph, D.; Dubashi, B.; Karthikeyan, B.; Jain, A.

2010-01-01

Cisplatin-based therapy is curative in testicular cancer. Adverse effects of cisplatin-based chemotherapy include dose-dependent myelosuppression, nephrotoxicity, neurotoxicity, and ototoxicity. By contrast, chemotherapy-associated vascular complications are unpredictable. Few incidents of digital gangrene with cisplatin have been reported. Here, we present a patient who developed arterial occlusion leading to gangrene of the toe after cisplatinbased chemotherapy.

Roles of radiation dose and chemotherapy in the etiology of stomach cancer as a second malignancy

DEFF Research Database (Denmark)

van den Belt-Dusebout, Alexandra W; Aleman, Berthe M P; Besseling, Gijs

2009-01-01

in the Netherlands between 1965 and 1995. In a nested case-control study, detailed information on treatment, smoking, gastrointestinal diseases, and family history was collected for 42 patients with stomach cancer and 126 matched controls. For each subject, the mean radiation dose to the stomach was estimated...... of procarbazine and related agents, needs further study, because of the relatively small numbers of chemotherapy-treated subjects....

Chemotherapy Toxicity Risk Score for Treatment Decisions in Older Adults with Advanced Solid Tumors.

Science.gov (United States)

Nishijima, Tomohiro F; Deal, Allison M; Williams, Grant R; Sanoff, Hanna K; Nyrop, Kirsten A; Muss, Hyman B

2018-05-01

The decision whether to treat older adults with advanced cancer with standard therapy (ST) or reduced therapy (RT) is complicated by heterogeneity in aging. We assessed the potential utility of the chemotherapy toxicity risk score (CTRS) [J Clin Oncol 2011;29:3457-3465] for treatment decisions in older adults. This was a prospective observational study of patients aged ≥65 years receiving first-line chemotherapy for advanced cancer for which combination chemotherapy is the standard of care. Patients were categorized as high risk (CTRS ≥10), for whom RT (dose-reduced combination or single-agent chemotherapy) is deemed appropriate, or nonhigh risk (CTRS statistic. Fifty-eight patients (median age, 71 years) were enrolled. Thirty-eight patients received ST (21 had CTRS advanced solid tumors receiving first-line chemotherapy was assessed. Little agreement was found between chemotherapy treatment decisions based on the clinical impression versus what was recommended based on the CTRS. Among patients treated with standard-dose combination chemotherapy, patients with CTRS ≥10 had a very high incidence of grade 3-4 toxicities and hospitalization, which was significantly greater than that of patients with a low CTRS (<10). These findings suggest that the addition of CTRS to the clinical impression has a potential to improve treatment decisions. © AlphaMed Press 2018.

Low- and high-dose laser irradiation effects on cell migration and destruction

Science.gov (United States)

Layton, Elivia; Gallagher, Kyra A.; Zukerman, Sara; Stevens, Brianna; Zhou, Feifan; Liu, Hong; Chen, Wei R.

2018-02-01

Metastases are the cause of more than 90 percent of cancer-related deaths. Current treatment methods, including chemotherapy, radiation, and surgery, fail to target the metastases effectively. One potential treatment for metastatic cancer is laser immunotherapy (LIT). LIT combines the use of a photothermal laser with an immunoadjuvant, Glycated Chitosan (GC). GC combined with single-walled carbon nanotubes (SWNTs) has proven to be a viable alternative to traditional cancer treatment methods, when under irradiation of laser with appropriate wavelength. In this study, the effects of low dose and high dose laser irradiation on metastatic pancreatic cancer cell migration were observed. It was found that low dose irradiation increased the migration rate, but the high dose irradiation significantly decreased the migration rate of the cancer cells. When using LIT, the goal is to kill tumor cells and to prompt the correct immune response. If the tumor were irradiated with a low dose, it would promote metastasis. If the dose of irradiation were too high, it would destroy the entire tumor and the immune response would not recognize the tumor. Therefore, the laser dose plays an important role in LIT, particularly when using SWNT as light absorbing agent. Our results from this study will delineate the optimal laser irradiation dose for destroying tumor cells and at the same time preserve and release tumor antigens as a precursor of antitumor immune response.

Risk Factors of anemia in head and neck cancer patients undergoing chemotherapy with high-dose cisplatin

Directory of Open Access Journals (Sweden)

Johan Kurnianda

2008-12-01

Full Text Available Cisplatin is well-known for its effectiveness against cancer, as well as its toxicity to human tissues. Of several documented side effects, anemia was reported to have significant association with decreased quality of life. This study was conducted to investigate development of cisplatin-induced anemia, and to identify independent factors contributing to anemia. Clinical data from head and neck cancer patients treated with high-dose cisplatin between December 2002 and December 2005 were obtained in this study. Incidence and risk factors of anemia were assessed in a model including age, sex, baseline hemoglobin level, baseline creatinine clearance, and occurrence of distant metastases. Multivariate logistic regression was used to define independent predictors of anemia. Among 86 eligible patients, 26 (30.2% developed anemia, defined as Hb level lower than 11 g/dL. Age > 55 years old (RR = 2.2, 95% CI, 1.2-4.0, female sex (RR = 2.0, 95% CI, 1.2-3.8, baseline Hb ≤ 13 g/dL (RR = 4.2, 95% CI, 1.9-9.4 and baseline CrCl < 50 mL/min (RR = 2.9, 95% CI, 1.7-5.1 were significantly correlated with incidence of anemia (P < 0.05. In multivariate analysis, baseline Hb and baseline CrCl were identified as independent risk factors for anemia. However, considerable confounding was observed in baseline CrCl after stratified by age (aRR = 2.2, 95% CI, 1.1-4.7. Thus, baseline Hb level was the strongest predictor of anemia. The findings suggested that baseline Hb and CrCl were useful to recognize cisplatin-treated patients at risk for anemia who might benefits from preventive measures. (Med J Indones 2008; 17: 248-54Keywords: anemia, cisplatin, chemotherapy, hemoglobin, creatinine clearance

High-risk bladder cancer: improving outcomes with perioperative chemotherapy

Directory of Open Access Journals (Sweden)

Daniel Y.C. Heng

2011-12-01

Full Text Available Despite treatment with radical cystectomy and pelvic lymph node dissection, muscle invasive bladder cancer has a relapse rate of 50%. Patients can develop regionally advanced or metastatic disease that ultimately leads to death. The addition of neoadjuvant or adjuvant chemotherapy to reduce the risk of relapse and death has been extensively studied over the past two decades. Two contemporary trials coupled with a recent meta-analysis evaluating neoadjuvant chemotherapy demonstrated a modest but real improvement in overall survival. This has made neoadjuvant chemotherapy a standard of care. Clinical trials evaluating adjuvant chemotherapy in patients with high-risk disease have been plagued with statistical flaws and have, therefore, been unable to define the survival impact of this approach. It is hoped that ongoing adjuvant trials that are powered to detect small but meaningful clinical differences will clarify the benefit of chemotherapy after cystectomy. Since there are theoretical advantages and disadvantages to each of these approaches, both are widely used in North America. The evidence behind each approach and potential future developments in this field will be described.

An infant with hyperalertness, hyperkinesis, and failure to thrive: a rare diencephalic syndrome due to hypothalamic anaplastic astrocytoma.

Science.gov (United States)

Stival, Alessia; Lucchesi, Maurizio; Farina, Silvia; Buccoliero, Anna Maria; Castiglione, Francesca; Genitori, Lorenzo; de Martino, Maurizio; Sardi, Iacopo

2015-09-04

Diencephalic Syndrome is a rare clinical condition of failure to thrive despite a normal caloric intake, hyperalertness, hyperkinesis, and euphoria usually associated with low-grade hypothalamic astrocytomas. We reported an unusual case of diencephalic cachexia due to hypothalamic anaplastic astrocytoma (WHO-grade III). Baseline endocrine function evaluation was performed in this patient before surgery. After histological diagnosis, he enrolled to a chemotherapy program with sequential high-dose chemotherapy followed by hematopoietic stem cell rescue. The last MRI evaluation showed a good response. The patient is still alive with good visual function 21 months after starting chemotherapy. Diencephalic cachexia can rarely be due to high-grade hypothalamic astrocytoma. We suggest that a nutritional support with chemotherapy given to high doses without radiotherapy could be an effective strategy for treatment of a poor-prognosis disease.

Practice of superselective intraarterial high-dose cisplatin chemoradiotherapy in the oral cavity

International Nuclear Information System (INIS)

Yoshida, Tomoyuki; Nakamura, Kazuhiro; Tsukahara, Kiyoaki; Inagaki, Taro; Ito, Hiroyuki; Shimizu, Akira; Takata, Daisuke; Okamoto, Isaku; Kondo, Takahito

2011-01-01

Superselective intraarterial infusion enables high-dose chemotherapeutic agents to be administered via tumor feeding vessels to neutralize and limit the adverse cisplatin effects acceptable. Between 1998 and 2008, we evaluated the efficacy of first-line therapy and adverse events in 30 subjects with oral squamous cell cancer undergoing simultaneous superselective intra arterial high-dose chemotherapy and radiotherapy. The 30 subjects- 23 men and 7 women aged 40 to 72- consisted of 3 T2, 12 T3, and 15 T4. Four patients had N0, 8 N1, 7 N2b, 8 N2c, and 3 N3 disease. Two were in CS II, 6 III, 17 IVa, and 5 IVb (III>93%, IV: 73%). Superselective intra arterial chemotherapy delivered through the femoral artery used the Seldinger technique. A single cisplatin dose of 100-550 mg/m 2 (mean 440 mg/m 2 ). Five minutes after intra arterial infusion, sodium thiosulphate (9 g/m 2 ) was administered via a peripheral cutaneous vein in the contralateral forearm. Concurrent radiotherapy started on Day 2 at 2 Gy per session for a total of 60 Gy. Two to 3 weeks later, 15 under went the second course of superselective intra arterial chemotherapy after tumor feeding vessels were visualized angiographically. Four (13.3%) subjects with Grade 3 or greater myelosuppression required granulocyte-colony stimulating factor (G-CSF). Grade 3 or greater mucositis was observed in 57% and Grade 4 mucositis occurred in 5 (16.7%). All adverse effects were reversible and no serious adverse events were prolonged. Among those responding to first-line therapy, 24 of the 30 (80%) achieved complete response (CR) and 6 (20%) partial response (PR), but no stable disease (SD) or no change (NC). Overall response was 100%. Histopathologically, 2 of 9 undergoing postchemoradiotherapy had no tumors. Clinical and pathological CR was 86.7%. Adverse events associated with this therapy associated events were considered relatively mild and within allowable limits. (author)

Phase II Trial of Radiotherapy After Hyperbaric Oxygenation With Multiagent Chemotherapy (Procarbazine, Nimustine, and Vincristine) for High-Grade Gliomas: Long-Term Results

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Ogawa, Kazuhiko, E-mail: kogawa@med.u-ryukyu.ac.jp [Department of Radiology, University of the Ryukyus, Okinawa (Japan); Ishiuchi, Shogo [Department of Neurosurgery, University of the Ryukyus, Okinawa (Japan); Inoue, Osamu [Department of Hyperbaric Medicine, University of the Ryukyus, Okinawa (Japan); Yoshii, Yoshihiko [Department of Neurosurgery, University of the Ryukyus, Okinawa (Japan); Department of Neurosurgery, Tsukuba Memorial Hospital, Tsukuba (Japan); Saito, Atsushi [Department of Neurosurgery, University of the Ryukyus, Okinawa (Japan); Department of Neurosurgery, Tsukuba Medical Center Hospital, Tsukuba (Japan); Watanabe, Takashi [Department of Neurosurgery, University of the Ryukyus, Okinawa (Japan); Iraha, Shiro [Department of Radiology, Okinawa South Medical Center, Okinawa (Japan); Department of Radiology, University of the Ryukyus, Okinawa (Japan); Toita, Takafumi; Kakinohana, Yasumasa; Ariga, Takuro; Kasuya, Goro; Murayama, Sadayuki [Department of Radiology, University of the Ryukyus, Okinawa (Japan)

2012-02-01

Purpose: To analyze the long-term results of a Phase II trial of radiotherapy given immediately after hyperbaric oxygenation (HBO) with multiagent chemotherapy in adults with high-grade gliomas. Methods and Materials: Patients with histologically confirmed high-grade gliomas were administered radiotherapy in daily 2 Gy fractions for 5 consecutive days per week up to a total dose of 60 Gy. Each fraction was administered immediately after HBO, with the time interval from completion of decompression to start of irradiation being less than 15 minutes. Chemotherapy consisting of procarbazine, nimustine, and vincristine and was administered during and after radiotherapy. Results: A total of 57 patients (39 patients with glioblastoma and 18 patients with Grade 3 gliomas) were enrolled from 2000 to 2006, and the median follow-up of 12 surviving patients was 62.0 months (range, 43.2-119.1 months). All 57 patients were able to complete a total radiotherapy dose of 60 Gy immediately after HBO with one course of concurrent chemotherapy. The median overall survival times in all 57 patients, 39 patients with glioblastoma and 18 patients with Grade 3 gliomas, were 20.2 months, 17.2 months, and 113.4 months, respectively. On multivariate analysis, histologic grade alone was a significant prognostic factor for overall survival (p < 0.001). During treatments, no patients had neutropenic fever or intracranial hemorrhage, and no serious nonhematologic or late toxicities were seen in any of the 57 patients. Conclusions: Radiotherapy delivered immediately after HBO with multiagent chemotherapy was safe, with virtually no late toxicities, and seemed to be effective in patients with high-grade gliomas.

A randomised comparison of radical radiotherapy with or without chemotherapy for patients with non-small cell lung cancer: Results from the Big Lung Trial

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Fairlamb, David; Milroy, Robert; Gower, Nicole; Parmar, Mahesh; Peake, Michael; Rudd, Robin; Souhami, Robert; Spiro, Stephen; Stephens, Richard; Waller, David

2005-01-01

Background: A meta-analysis of trials comparing primary treatment with or without chemotherapy for patients with non-small cell lung cancer published in 1995 suggested a survival benefit for cisplatin-based chemotherapy in each of the primary treatment settings studied, but it included many small trials, and trials with differing eligibility criteria and chemotherapy regimens. Methods: The Big Lung Trial was a large pragmatic trial designed to confirm the survival benefits seen in the meta-analysis, and this paper reports the findings in the radical radiotherapy setting. The trial closed before the required sample size was achieved due to slow accrual, with a total of 288 patients randomised to receive radical radiotherapy alone (146 patients) or sequential radical radiotherapy and cisplatin-based chemotherapy (142 patients). Results: There was no evidence that patients allocated sequential chemotherapy and radical radiotherapy had a better survival than those allocated radical radiotherapy alone, HR 1.07 (95% CI 0.84-1.38, P=0.57), median survival 13.0 months for the sequential group and 13.2 for the radical radiotherapy alone group. In addition, exploratory analyses could not identify any subgroup that might benefit more or less from chemotherapy. Conclusions: Despite not suggesting a survival benefit for the sequential addition of chemotherapy to radical radiotherapy, possibly because of the relatively small sample size and consequently wide confidence intervals, the results can still be regarded as consistent with the meta-analysis, and other similarly designed recently published large trials. Combining all these results suggests there may be a small median survival benefit with chemotherapy of between 2 and 8 weeks

Metformin decreases the dose of chemotherapy for prolonging tumor remission in mouse xenografts involving multiple cancer cell types.

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Iliopoulos, Dimitrios; Hirsch, Heather A; Struhl, Kevin

2011-05-01

Metformin, the first-line drug for treating diabetes, selectively kills the chemotherapy resistant subpopulation of cancer stem cells (CSC) in genetically distinct types of breast cancer cell lines. In mouse xenografts, injection of metformin and the chemotherapeutic drug doxorubicin near the tumor is more effective than either drug alone in blocking tumor growth and preventing relapse. Here, we show that metformin is equally effective when given orally together with paclitaxel, carboplatin, and doxorubicin, indicating that metformin works together with a variety of standard chemotherapeutic agents. In addition, metformin has comparable effects on tumor regression and preventing relapse when combined with a four-fold reduced dose of doxorubicin that is not effective as a monotherapy. Finally, the combination of metformin and doxorubicin prevents relapse in xenografts generated with prostate and lung cancer cell lines. These observations provide further evidence for the CSC hypothesis for cancer relapse, an experimental rationale for using metformin as part of combinatorial therapy in a variety of clinical settings, and for reducing the chemotherapy dose in cancer patients.

Local control rate and prognosis after sequential chemoradiation for small cell carcinoma of the bladder

International Nuclear Information System (INIS)

Meijer, Richard P.; Meinhardt, Wim; Poel, Henk G. van der; Rhijn, Bas W. van; Kerst, J. Martijn; Pos, Floris J.; Horenblas, Simon; Bex, Axel

2013-01-01

The objectives of this study were to assess the long-term outcome and the risk for local recurrence of patients with small cell carcinoma of the bladder (SCCB) treated with neoadjuvant chemotherapy followed by external beam radiotherapy (sequential chemoradiation). All consecutive patients with primary small cell carcinoma of the bladder (n=66), treated in our institution between 1993 and 2011 were retrospectively evaluated from an institutional database. Only patients with limited disease (Tx-4N0-1M0) small cell carcinoma of the bladder treated with sequential chemoradiation (n=27) were included in this study. Recurrence rates, overall survival and cancer-specific survival were analyzed using the Kaplan-Meier method. Median time to recurrence was 20 months, median overall survival 26 months, 5-year overall survival 22.2%, median cancer-specific survival 47 months and 5-year cancer-specific survival 39.6%. For complete responders after neoadjuvant chemotherapy (n=19), median cancer-specific survival was 52 months with a 5-year cancer-specific survival 45.9% versus a median cancer-specific survival of 22 months and 5-year cancer-specific survival 0.0% for incomplete responders (n=8; P=0.034). Eight patients (29.6%) underwent transurethral resections (TUR-BT) for local recurrences in the bladder. At the end of follow up, four patients had undergone cystectomy for recurrence of disease resulting in a bladder-preservation rate of 85.2%. Median time to local recurrence was 29 months and median time to distant recurrence was 10 months. Sequential chemoradiation for limited disease small cell carcinoma of the bladder results in a reasonable outcome with a high bladder preservation rate. Response to neoadjuvant chemotherapy represents a significant prognostic factor in this patient population. (author)

Reduced supportive capacity of bone marrow stroma upon chemotherapy is mediated via changes in glycosaminoglycan profile

NARCIS (Netherlands)

Zweegman, Sonja; Kessler, Floortje L.; Kerkhoven, Ron M.; Heimerikx, Mike; Celie, Johanna W. A. M.; Janssen, Jeroen J. W. M.; Huijgens, Peter C.; Drager, Angelika M.; van den Born, Jacob

High dose chemotherapy and radiation have been found to impair the hematopoiesis-supportive capacity of bone marrow stroma. We now provide evidence for an important role of chemotherapy-induced alterations in stromal glycosaminoglycans (GAGs) in reduction of the supportive properties of stromal

Is a reduction in radiation lung volume and dose necessary with paclitaxel chemotherapy for node-positive breast cancer?

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Taghian, Alphonse G; Assaad, Sherif I; Niemierko, Andrzej; Floyd, Scott R; Powell, Simon N

2005-06-01

To evaluate and quantify the effect of irradiated lung volume, radiation dose, and paclitaxel chemotherapy on the development of radiation pneumonitis (RP) in breast cancer patients with positive lymph nodes. We previously reported the incidence of RP among 41 patients with breast cancer treated with radiotherapy (RT) and adjuvant paclitaxel-containing chemotherapy. We recorded the central lung distance, a measure of the extent of lung included in the RT volume, in these patients. We used this measure and the historical and observed rates of RP in our series to model the lung tolerance to RT in patients receiving chemotherapy (CHT) both with and without paclitaxel. To evaluate the risk factors for the development of RP, we performed a case-control study comparing paclitaxel-treated patients who developed RP with those who did not, and a second case-control study comparing patients receiving paclitaxel in addition to standard CHT/RT (n = 41) and controls receiving standard CHT/RT alone (n = 192). The actuarial rate of RP in the paclitaxel-treated group was 15.4% compared with 0.9% among breast cancer patients treated with RT and non-paclitaxel-containing CHT. Our mathematical model found that the effective lung tolerance for patients treated with paclitaxel was reduced by approximately 24%. No statistically significant difference was found with regard to the dose delivered to specific radiation fields, dose per fraction, central lung distance, or percentage of lung irradiated in the case-control study of paclitaxel-treated patients who developed RP compared with those who did not. In the comparison of 41 patients receiving RT and CHT with paclitaxel and 192 matched controls receiving RT and CHT without paclitaxel, the only significant differences identified were the more frequent use of a supraclavicular radiation field and a decrease in the RT lung dose among the paclitaxel-treated patients. This finding indicates that the major factor associated with development

Factors influencing the effectiveness of scalp cooling in the prevention of chemotherapy-induced alopecia.

Science.gov (United States)

Komen, Manon M C; Smorenburg, Carolien H; van den Hurk, Corina J G; Nortier, Johan W R

2013-01-01

The success of scalp cooling in preventing or reducing chemotherapy-induced alopecia (CIA) is highly variable between patients and chemotherapy regimens. The outcome of hair preservation is often unpredictable and depends on various factors. Methods. We performed a structured search of literature published from 1970 to February 2012 for articles that reported on factors influencing the effectiveness of scalp cooling to prevent CIA in patients with cancer. Results. The literature search identified 192 reports, of which 32 studies were considered relevant. Randomized studies on scalp cooling are scarce and there is little information on the determinants of the result. The effectiveness of scalp cooling for hair preservation depends on dose and type of chemotherapy, with less favorable results at higher doses. Temperature seems to be an important determinant. Various studies suggest that a subcutaneous scalp temperature less than 22 °C is required for hair preservation. Conclusions. The effectiveness of scalp cooling for hair preservation varies by chemotherapy type and dose, and probably by the degree and duration of cooling.

Prevalence of menstrual cycles and outcome of 50 pregnancies after high-dose chemotherapy and auto-SCT in non-Hodgkin and Hodgkin lymphoma patients younger than 40 years.

Science.gov (United States)

Akhtar, S; Youssef, I; Soudy, H; Elhassan, T A M; Rauf, S M; Maghfoor, I

2015-12-01

Data are limited regarding the prevalence of menstrual cycles and pregnancies after high-dose chemotherapy (HDC) and auto-stem cell transplantation (SCT). Female patients who underwent HDC auto-SCT for non-Hodgkin and Hodgkin lymphoma (1997-2012) were reviewed. The selection criteria were as follows: (1) alive without disease 12 and 24 months after auto-SCT for menstrual cycles and pregnancy, respectively, (2) age SCT, and (3) no primary infertility. One-hundred and seventy-six females underwent single auto-SCT. Eighty-nine were eligible for menstrual cycles and pregnancy analysis. Median age at auto-SCT was 25 years (14-40 years), at pregnancy 27 years (20-37 years), median follow-up 65 months (range 24-190). Regular menstrual-cycles resumed in 56/89 patients (63%). Increasing age (P=0.02) and number of prior chemotherapy cycles (P=0.02) are associated with higher risk of amenorrhea. Forty patients tried to get pregnant, 26 (65%) became pregnant 50 times: 43 (86%) live birth, 7 (14%) miscarriage and 2/50 had birth defects. Twenty-four patients practiced breastfeeding (median duration 4 months (1-24 months)). Enough breast milk production was reported 62.5% vs 100% in those patients who did or did not receive above the diaphragm radiation therapy, respectively, (P=0.066). Our data highlights significantly higher than perceived incidence of menstrual cycle resumption, successful pregnancies and breastfeeding after HDC auto-SCT.

Dose Escalation of Total Marrow Irradiation With Concurrent Chemotherapy in Patients With Advanced Acute Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

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Wong, Jeffrey Y.C., E-mail: jwong@coh.org [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Forman, Stephen; Somlo, George [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Rosenthal, Joseph [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Department of Pediatrics, City of Hope National Medical Center, Duarte, California (United States); Liu An; Schultheiss, Timothy; Radany, Eric [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Palmer, Joycelynne [Department of Biostatistics, City of Hope National Medical Center, Duarte, California (United States); Stein, Anthony [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States)

2013-01-01

Purpose: We have demonstrated that toxicities are acceptable with total marrow irradiation (TMI) at 16 Gy without chemotherapy or TMI at 12 Gy and the reduced intensity regimen of fludarabine/melphalan in patients undergoing hematopoietic cell transplantation (HCT). This article reports results of a study of TMI combined with higher intensity chemotherapy regimens in 2 phase I trials in patients with advanced acute myelogenous leukemia or acute lymphoblastic leukemia (AML/ALL) who would do poorly on standard intent-to-cure HCT regimens. Methods and Materials: Trial 1 consisted of TMI on Days -10 to -6, etoposide (VP16) on Day -5 (60 mg/kg), and cyclophosphamide (CY) on Day -3 (100 mg/kg). TMI dose was 12 (n=3 patients), 13.5 (n=3 patients), and 15 (n=6 patients) Gy at 1.5 Gy twice daily. Trial 2 consisted of busulfan (BU) on Days -12 to -8 (800 {mu}M min), TMI on Days -8 to -4, and VP16 on Day -3 (30 mg/kg). TMI dose was 12 (n=18) and 13.5 (n=2) Gy at 1.5 Gy twice daily. Results: Trial 1 had 12 patients with a median age of 33 years. Six patients had induction failures (IF), and 6 had first relapses (1RL), 9 with leukemia blast involvement of bone marrow ranging from 10%-98%, 5 with circulating blasts (24%-85%), and 2 with chloromas. No dose-limiting toxicities were observed. Eleven patients achieved complete remission at Day 30. With a median follow-up of 14.75 months, 5 patients remained in complete remission from 13.5-37.7 months. Trial 2 had 20 patients with a median age of 41 years. Thirteen patients had IF, and 5 had 1RL, 2 in second relapse, 19 with marrow blasts (3%-100%) and 13 with peripheral blasts (6%-63%). Grade 4 dose-limiting toxicities were seen at 13.5 Gy (stomatitis and hepatotoxicity). Stomatitis was the most frequent toxicity in both trials. Conclusions: TMI dose escalation to 15 Gy is possible when combined with CY/VP16 and is associated with acceptable toxicities and encouraging outcomes. TMI dose escalation is not possible with BU/VP16 due to

Anemia During Sequential Induction Chemotherapy and Chemoradiation for Head and Neck Cancer: The Impact of Blood Transfusion on Treatment Outcome

International Nuclear Information System (INIS)

Bhide, Shreerang A.; Ahmed, Merina; Rengarajan, Vijayan; Powell, Ceri; Miah, Aisha; Newbold, Kate; Nutting, Christopher M.; Harrington, Kevin J.

2009-01-01

Purpose: Sequential treatment (chemotherapy followed by concomitant chemoradiation; CCRT) is increasingly being used for radical treatment of squamous cell cancer of the head and neck (SCCHN), which results in increased myelosuppression. In this study, we review the incidence of anemia and the effect of a policy of hemoglobin (Hb) maintenance by blood transfusion on disease outcomes in these patients. Methods and Materials: Retrospective review of the records of patients with SCCHN treated with sequential CCRT formed the basis of this study. The incidence of anemia and statistics on blood transfusion were documented. For the purpose of outcome analyses, patients were divided into four categories by (1) transfusion status, (2) nadir Hb concentration, (3) number of transfusion episodes, and (4) number of units of blood transfused (NOUT). Data on 3-year locoregional control (LRC), relapse-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) were analyzed. Results: One hundred and sixty-nine patients were identified. The median follow-up was 23.6 months. The RFS (52% vs. 41%, p = 0.03), DSS (71% vs. 66%, p = 0.02), and OS (58% vs. 42% p = 0.005) were significantly better for patients who did not have a transfusion vs. those who did. The LRC, RFS, DSS, and OS were also significantly better for patients with nadir Hb level >12 vs. 4. Conclusion: Our study seems to suggest that blood transfusion during radical treatment for SCCHN might be detrimental. Further research should be undertaken into the complex interactions among tumor hypoxia, anemia, and the treatment of anemia before making treatment recommendations

Factors Influencing the Effectiveness of Scalp Cooling in the Prevention of Chemotherapy-Induced Alopecia

OpenAIRE

Komen, Manon M.C.; Smorenburg, Carolien H.; van den Hurk, Corina J.G.; Nortier, Johan W.R.

2013-01-01

The success of scalp cooling in preventing or reducing chemotherapy-induced alopecia (CIA) is highly variable. In a review of the literature, this study found that the factors influencing the effectiveness of scalp cooling to prevent CIA in patients with cancer include chemotherapy type and dose, as well as the degree and duration of cooling.

Consolidation whole abdomen irradiation following adjuvant carboplatin-paclitaxel based chemotherapy for advanced uterine epithelial cancer: feasibility, toxicity and outcomes

International Nuclear Information System (INIS)

Rochet, Nathalie; Kahn, Rachel S; Niemierko, Andrzej; Delaney, Thomas F; Russell, Anthony H

2013-01-01

To evaluate feasibility and preliminary outcomes associated with sequential whole abdomen irradiation (WAI) as consolidative treatment following comprehensive surgery and systemic chemotherapy for advanced endometrial cancer. We conducted a retrospective analysis of patients treated at our institution from 2000 to 2011. Inclusion criteria were stage III-IV endometrial cancer patients with histological proof of one or more sites of extra-uterine abdomen-confined disease, treated with WAI as part of multimodal therapy. Endpoints were feasibility, acute toxicity, late effects, recurrence-free survival (RFS) and overall survival (OS). Twenty patients were identified. Chemotherapy consisted of 3 to 6 cycles of a platinum-paclitaxel regimen in 18 patients. WAI was delivered using conventional technique to a median total dose of 27.5 Gy. No grade 4 toxicities occurred during chemotherapy or radiotherapy. No radiation dose reduction was necessary. Three patients developed small bowel obstruction, all in the context of recurrent intraperitoneal disease. Kaplan-Meier estimates and 95% confidence intervals for RFS and OS at one year were 63% (38–80%) and 83% (56-94%) and at 3 years 57% (33-76%) and 62% (34-81%), respectively. On univariate Cox analysis, stage IVB and serous papillary (SP) histology were found to be statistically significantly (at the p = 0.05 level) associated with worse RFS and OS. The peritoneal cavity was the most frequent site of initial failure. Consolidative WAI following chemotherapy is feasible and can be performed without interruption with manageable acute and late toxicity. Patients with endometrioid adenocarcinoma, especially stage FIGO III, had favorable outcomes possibly meriting prospective evaluation of the addition of WAI following chemotherapy in selected patients. Patients with SP do poorly and do not routinely benefit from this approach

Selections of appropriate regimen of high-dose chemotherapy combined with adoptive cellular therapy with dendritic and cytokine-induced killer cells improved progression-free and overall survival in patients with metastatic breast cancer: reargument of such contentious therapeutic preferences.

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Ren, Jun; Di, Lijun; Song, Guohong; Yu, Jing; Jia, Jun; Zhu, Yuling; Yan, Ying; Jiang, Hanfang; Liang, Xu; Che, Li; Zhang, Jie; Wan, Fengling; Wang, Xiaoli; Zhou, Xinna; Lyerly, Herbert Kim

2013-10-01

We hypothesized that combination of dendritic cell (DC) with autologous cytokine-induced killer (CIK) immunotherapy in setting of high-dose chemotherapy (HDC) would be effective for selected metastatic breast cancer (MBC) patients. Our previous work showed thiotepa could eradicate breast cancer stem cells. From 2004 to 2009, 79 patients received standard dose chemotherapy (SDC) of 75 mg/m(2) docetaxel and 75 mg/m(2) thiotepa versus 87 patients of HDC + DC/CIK: 120 mg/m(2) docetaxel to mobilize peripheral CD34(+) progenitor cells, a sequence of HDC (120 mg/m(2) docetaxel, plus 175 mg/m(2) thiotepa) + DC/CIK, with or without 400 mg/m(2) carboplatin depending upon bone marrow function. The endpoints were response rates (RR), progression-free survival (PFS), and overall survival (OS). Compared with SDC, PFS and OS were improved in HDC + DC/CIK (median PFS 10.2 vs. 3.7 months, P < 0.001; median OS 33.1 vs. 15.2 months, P < 0.001). Patients of pre-menopausal, HDC as first-line treatment after metastasis, or with visceral metastasis showed prolonged PFS and OS. SDC group also achieved the similar response as previous reports. Our study demonstrated the novel combination of HDC with DC/CIK to be an effective choice for the selected MBC population, in which choosing appropriate chemo regimens played important roles, and also specific HDC regimen plus DC/CIK immunotherapy showed the clinical benefits compared with chemotherapy alone.

High dose Gd-DTPA-BMA (gadodiamide) for diagnostic imaging and therapy monitoring of malignant bone tumors

International Nuclear Information System (INIS)

Haeussler, M.D.; Rummeny, E.J.; Raufhake, C.; Blasius, S.; Lindner, N.; Daldrup, H.E.; Reimer, P.; Peters, P.E.

1996-01-01

Purpose: To evaluate the efficacy of high-dose Gd-DTPA-BMA (gadodiamide, Omniscan) as a contrast for magnetic resonance imaging of malignant bone tumors and the use of high-dose dynamic studies for predicting the response to preoperative chemotherapy. Materials and methods: Examinations were performed in 22 patients with suspected malignant bone tumor on a 1.5 T system. In 8 cases a follow-up examination was done after preoperative chemotherapy. Static studies included Pd- and T2-weighted spin-echo sequences as well as T1-weighted spin-echo sequences, obtained pre- and post-contrast. Dynamic studies were performed using a FLASH 2D-gradient-echo sequence (TR 40 ms/TE 10 ms, 90 flip angle) every 20 s after intravenous bolus injection of Gd-DTPA-BMA (0.3 mmol/kg body weight). MR images were evaluated qualitatively by visual assessment of conspicuity size, extraosseous delineation and structure of the lesion and quantitatively by measurement of the signal intensities and calculation of the relative increase in signal intensity. Results: Qualitative image analysis showed best demonstration of the lesions on contrast-enhanced T1-weighted images. Comparison of T1-weighted pre- and postcontrast spin-echo sequences revealed significantly better assessment of tumor structure after administration of contrast media. After preoperative chemotherapy, all responders showed a markedly stronger reduction in relative increase in signal intensity in dynamic studies compared to nonresponders. Conclusion: Gd-DTPA-BMA is effective for magnetic resonance imaging of musculoskeletal lesions and improves assessment of the tumor structure. Dynamic studies may help to predict the response to preoperative chemotherapy. (orig.) [de

High dose rate brachytherapy in treatment of high grade astrocytomas

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Garcia-Alejo, R.; Delgado, J.M.; Cerro, E. del; Torres, J.J.; Martinez, R.

1996-01-01

From May 1994 to June 1995, 18 patients with high grade astrocytomas were entered prospectively on a selective protocol combining surgery, external beam radiotherapy, stereotactic interstitial implantation with HDR Iridium 192 and chemotherapy. Only those patients with tumor size 100cc or less average dimension, high grade astrocytoma, Karnofsky 70 or greater, unilateral, circumscribed, unifocal, tumor stable or responding to external radiation and supratentorial were included in the study. Ages ranged from 16 to 69 years. There were 13 males and 5 females. Surgery consisted of biopsy only in 3 patients, subtotal resection in 11, and gross total resection in 4 patients. Focal external beam radiation portals included the contrast enhancing mass on CT scan plus a 3 cm margin. The protocol called for minimum tumor dose of 60 Gy to be given in 2 Gy daily fractions. An interstitial brachytherapy boost was to be performed two weeks after the conclusion of external beam radiation. The dose was 30 Gy in 4 fractions. The authors analyze on basis on their personal experience, the possibilities and the limits offered by this therapeutic procedure in neuro-oncology. Using stereotactic techniques, interstitial brachytherapy of brain tumors was technically possible with negligible acute morbidity and mortality, and appeared to be effective and may provide for an increase in tumor control in selected cases

High reinfection rate after preventive chemotherapy for fishborne zoonotic trematodes in Vietnam

DEFF Research Database (Denmark)

Lier, Tore; Do, Dung Trung; Johansen, Maria Vang

2014-01-01

. The purpose of this study was to investigate the effectiveness of preventive chemotherapy to control FZT in an endemic area in Northern Vietnam. METHODOLOGY AND PRINCIPLE FINDINGS: We followed a cohort of 396 people who fulfilled the criteria for receiving preventive chemotherapy. Stool samples were examined....... CONCLUSIONS: The effectiveness of preventive chemotherapy as a main component in control of FZT is not well documented in most endemic areas. We found a high reinfection rate within the first year after preventive chemotherapy. Since these trematodes are zoonoses, preventive chemotherapy may not have......BACKGROUND: The World Health Organization aims for complete morbidity control of fishborne zoonotic trematodes (FZT) in endemic areas by 2020. The main intervention tool for achieving this goal is regular use of preventive chemotherapy by offering praziquantel to those at risk in endemic areas...

Osteonecrosis in patients with testicular tumours treated with chemotherapy.

NARCIS (Netherlands)

Berkmortel, F.W.P.J. van den; Wit, R. de; Rooy, J.W.J. de; Mulder, P.H.M. de

2004-01-01

The role of antiemetics is invaluable in allowing cancer patients to complete, otherwise possibly intolerable, chemotherapy. In the Perugia Consensus Conference it was decided that the recommended antiemetic regimen in the prevention of acute emesis induced by a single high, low and repeated doses

High-dose radiation-induced meningioma following prophylactic cranial irradiation for acute lymphoblastic leukaemia

International Nuclear Information System (INIS)

Matsuda, Ryosuke; Nikaido, Yuji; Yamada, Tomonori; Mishima, Hideaki; Tamaki, Ryo

2005-01-01

A 12 year-old girl was treated with prophylactic cranial irradiation for acute lymphoblastic leukaemia (ALL). At the age of 39, she was admitted to our hospital for status epilepticus. Computed tomography demonstrated two, enhancing bilateral sided intracranial tumors. After surgery, this patient presented meningiomas which histologically, were of the meningothelial type. The high cure rate in childhood ALL, attributable to aggressive chemotherapy and prophylactic cranial irradiation, is capable of inducing secondary brain tumor. Twelve cases of high-dose radiation-induced meningioma following ALL are also reviewed. (author)

High-dose radiation-induced meningioma following prophylactic cranial irradiation for acute lymphoblastic leukaemia

Energy Technology Data Exchange (ETDEWEB)

Matsuda, Ryosuke; Nikaido, Yuji; Yamada, Tomonori; Mishima, Hideaki; Tamaki, Ryo [National Hospital Organization Osaka Minami Medical Center, Kawachinagano (Japan)

2005-03-01

A 12 year-old girl was treated with prophylactic cranial irradiation for acute lymphoblastic leukaemia (ALL). At the age of 39, she was admitted to our hospital for status epilepticus. Computed tomography demonstrated two, enhancing bilateral sided intracranial tumors. After surgery, this patient presented meningiomas which histologically, were of the meningothelial type. The high cure rate in childhood ALL, attributable to aggressive chemotherapy and prophylactic cranial irradiation, is capable of inducing secondary brain tumor. Twelve cases of high-dose radiation-induced meningioma following ALL are also reviewed. (author)

Profile of netupitant/palonosetron (NEPA fixed dose combination and its potential in the treatment of chemotherapy-induced nausea and vomiting (CINV

Directory of Open Access Journals (Sweden)

Navari RM

2014-12-01

Full Text Available Rudolph M Navari Cancer Care Program, Eastern Europe, World Health Organization, Mishawaka, IN, USA; Indiana University School of Medicine, South Bend, IN, USA; South Bend Medical Services Corporation, IN, USA Abstract: Chemotherapy-induced nausea and vomiting (CINV is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors significantly influence CINV. The use of a combination of a 5-hydroxytryptamine-3 (5-HT3 receptor antagonists, dexamethasone, and a neurokinin-1 (NK-1 receptor antagonist has significantly improved the control of acute and delayed emesis in single-day chemotherapy. Palonosetron, a second generation 5-HT3 receptor antagonist with a different half-life, different binding capacity, and a different mechanism of action than the first generation 5-HT3 receptor antagonists, appears to be the most effective agent in its class. Netupitant, is a new NK-1 receptor antagonist with a high binding affinity, a long half-life of 90 hours, is metabolized by CYP3A4, and is an inhibitor of CYP3A4. NEPA is an oral fixed-dose combination of netupitant and palonosetron which has recently been employed in Phase II and Phase III clinical trials for the prevention of CINV in patients receiving moderately and highly emetogenic chemotherapy (MEC and HEC. The clinical trials demonstrated that NEPA (300 mg of netupitant plus 0.50 mg of palonosetron significantly improved the prevention of CINV compared to the use of palonosetron alone in patients receiving either HEC or MEC. The clinical efficacy was maintained over multiple cycles of chemotherapy. NEPA (Akynzeo® has recently been approved by the Food and Drug Administration (FDA to treat nausea and vomiting in patients undergoing cancer chemotherapy. Keywords: 5-HT3 receptor antagonists, NK-1 receptor antagonists, palonosetron, netupitant, chemotherapy-induced nausea and vomiting

Estimation of the cost of treatment by chemotherapy for early breast cancer in Morocco

Directory of Open Access Journals (Sweden)

Boutayeb Saber

2010-09-01

Full Text Available Abstract Background Breast cancer is the first cancer in women both in incidence and mortality. The treatment of breast cancer benefited from the progress of chemotherapy and targeted therapies, but there was a parallel increase in treatment costs. Despite a relatively high incidence of many sites of cancer, so far, there is no national register for this disease in Morocco. The main goal of this paper is to estimate the total cost of chemotherapy in the early stages of breast cancer due to its frequency and the chances of patients being cured. This study provides health decision-makers with a first estimate of costs and the opportunity to achieve the optimal use of available data to estimate the needs of antimitotics and trastuzumab in Morocco. Method We start by evaluating the individual cost according to the therapeutic sub-groups, namely: 1. Patients needing chemotherapy with only anthracycline-based therapy. 2. Patients needing chemotherapy with both anthracycline and taxane but without trastuzumab. 3. Patients needing trastuzumab in addition to chemotherapy. For each sub-group, the protocol of treatment is described, and the individual costs per unit, and for the whole cycle, are evaluated. Then we estimate the number of women suffering from breast cancer on the basis of two data bases available in Morocco. Finally, we calculate the total annual cost of treatment of breast cancer in Morocco. Results The total cost of breast cancer in Morocco is given in Moroccan dirhams (MAD, the US dollar at the current exchange rate (MAD 10 = USD 1.30 and in international dollars or purchasing power parity (MAD 10 = PPP 1.95. The cost of a therapy with trastuzumab is 8.4 times the cost of a sequential chemotherapy combining anthracycline and taxane, and nearly 60 times the cost of chemotherapy based on anthracycline alone. Globally, between USD 13.3 million and USD 28.6 million need to be devoted every year by the Moroccan health authorities to treat

Dose-response relationship with radiotherapy: an evidence?

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Chauvet, B.; Rauglaudre, G. de; Mineur, L.; Alfonsi, M.; Reboul, F.

2003-01-01

The dose-response relationship is a fundamental basis of radiobiology. Despite many clinical data, difficulties remain to demonstrate a relation between dose and local control: relative role of treatment associated with radiation therapy (surgery, chemotherapy, hormonal therapy), tumor heterogeneity, few prospective randomized studies, uncertainty of local control assessment. Three different situations are discussed: tumors with high local control probabilities for which dose effect is demonstrated by randomized studies (breast cancer) or sound retrospective data (soft tissues sarcomas), tumors with intermediate local control probabilities for which dose effect seems to be important according to retrospective studies and ongoing or published phase III trials (prostate cancer), tumors with low local control probabilities for which dose effect appears to be modest beyond standard doses, and inferior to the benefit of concurrent chemotherapy (lung and oesophageal cancer). For head and neck tumors, the dose-response relationship has been explored through hyperfractionation and accelerated radiation therapy and a dose effect has been demonstrated but must be compared to the benefit of concurrent chemotherapy. Last but not least, the development of conformal radiotherapy allow the exploration of the dose response relationship for tumors such as hepatocellular carcinomas traditionally excluded from the field of conventional radiation therapy. In conclusion, the dose-response relationship remains a sound basis of radiation therapy for many tumors and is a parameter to take into account for further randomized studies. (author)

Escalation to High Dose Defibrotide in Patients with Hepatic Veno-Occlusive Disease

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Triplett, Brandon M.; Kuttab, Hani I.; Kang, Guolian; Leung, Wing

2015-01-01

Hepatic veno-occlusive disease (VOD) is a serious complication of high-dose chemotherapy regimens, such as those utilized in hematopoietic cell transplantation recipients. Defibrotide is considered a safe and effective treatment when dosed at 25 mg/kg/day. However, patients who develop VOD still have increased mortality despite the use of defibrotide. Data are limited on the use of doses above 60 mg/kg/day for persistent VOD. In this prospective clinical trial, 34 patients received escalating doses of defibrotide. For patients with persistent VOD despite doses of 60 mg/kg/day, doses were increased to a maximum of 110 mg/kg/day. There was no observed increase in toxicity until doses rose beyond 100 mg/kg/day. Patients receiving doses between 10–100 mg/kg/day experienced an average of 3 bleeding episodes per 100 days of treatment, while those receiving doses >100 mg/kg/day experienced 13.2 bleeding episodes per 100 days (p=0.008). Moreover, dose reductions due to toxicity were needed at doses of 110 mg/kg/day more often than at lower doses. Defibrotide may be safely escalated to doses well above the current standard without an increase in bleeding risk. However, the efficacy of this dose escalation strategy remains unclear, as outcomes were similar to published cohorts of patients receiving standard doses of defibrotide for VOD. PMID:26278046

Benefit from prolonged dose-intensive chemotherapy for infants with malignant brain tumors is restricted to patients with ependymoma: a report of the Pediatric Oncology Group randomized controlled trial 9233/34.

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Strother, Douglas R; Lafay-Cousin, Lucie; Boyett, James M; Burger, Peter; Aronin, Patricia; Constine, Louis; Duffner, Patricia; Kocak, Mehmet; Kun, Larry E; Horowitz, Marc E; Gajjar, Amar

2014-03-01

The randomized controlled Pediatric Oncology Group study 9233 tested the hypothesis that dose-intensive (DI) chemotherapy would improve event-free survival (EFS) for children chemotherapy (Regimen A, n = 162) or DI chemotherapy (Regimen B, n = 166). Radiation therapy (RT) was recommended for patients with evidence of disease at completion of chemotherapy or who relapsed within 6 months of chemotherapy completion. Distributions of EFS for Regimens A and B were not significantly different (P = 0.32) with 2- and 10-year rates of 22.8% ± 3.3% and 15.4% ± 3.7%, and 27.1% ± 3.4% and 20.8% ± 3.8%, respectively. Thus, the study hypothesis was rejected. While distributions of EFS and OS were not significantly different between Regimens A and B for patients with medulloblastoma and sPNET, DI chemotherapy resulted in significantly improved EFS distribution (P = .0011) (2-year EFS rates of 42.1% vs. 19.6% with SD chemotherapy), but not OS distribution, for patients with centrally confirmed ependymoma. The degree of surgical resection affected EFS, OS or both for most tumor groups. Approximately 20%, 40% and 20% of patients with medulloblastoma, ependymoma treated with DI chemotherapy, and sPNET, respectively appear to have been cured without RT. Of 11 toxic deaths on study, 10 occurred on the DI chemotherapy arm. Prolonged dose-intensive chemotherapy given to infants with malignant brain tumors resulted in increased EFS only for patients with ependymoma.

WE-D-BRE-04: Modeling Optimal Concurrent Chemotherapy Schedules

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Jeong, J; Deasy, J O

2014-01-01

Purpose: Concurrent chemo-radiation therapy (CCRT) has become a more common cancer treatment option with a better tumor control rate for several tumor sites, including head and neck and lung cancer. In this work, possible optimal chemotherapy schedules were investigated by implementing chemotherapy cell-kill into a tumor response model of RT. Methods: The chemotherapy effect has been added into a published model (Jeong et al., PMB (2013) 58:4897), in which the tumor response to RT can be simulated with the effects of hypoxia and proliferation. Based on the two-compartment pharmacokinetic model, the temporal concentration of chemotherapy agent was estimated. Log cell-kill was assumed and the cell-kill constant was estimated from the observed increase in local control due to concurrent chemotherapy. For a simplified two cycle CCRT regime, several different starting times and intervals were simulated with conventional RT regime (2Gy/fx, 5fx/wk). The effectiveness of CCRT was evaluated in terms of reduction in radiation dose required for 50% of control to find the optimal chemotherapy schedule. Results: Assuming the typical slope of dose response curve (γ50=2), the observed 10% increase in local control rate was evaluated to be equivalent to an extra RT dose of about 4 Gy, from which the cell-kill rate of chemotherapy was derived to be about 0.35. Best response was obtained when chemotherapy was started at about 3 weeks after RT began. As the interval between two cycles decreases, the efficacy of chemotherapy increases with broader range of optimal starting times. Conclusion: The effect of chemotherapy has been implemented into the resource-conservation tumor response model to investigate CCRT. The results suggest that the concurrent chemotherapy might be more effective when delayed for about 3 weeks, due to lower tumor burden and a larger fraction of proliferating cells after reoxygenation

Low-dose chemotherapy of hepatocellular carcinoma through triggered-release from bilayer-decorated magnetoliposomes.

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Chen, Yanjing; Chen, Yuan; Xiao, Da; Bose, Arijit; Deng, Ruitang; Bothun, Geoffrey D

2014-04-01

Low-dose (LD) chemotherapy is a promising treatment strategy that may be improved by controlled delivery. Polyethylene glycol-stabilized bilayer-decorated magnetoliposomes (dMLs) have been designed as a stimuli-responsive LD chemotherapy drug delivery system and tested in vitro using Huh-7 hepatocellular carcinoma cell line. The dMLs contained hydrophobic superparamagnetic iron oxide nanoparticles within the lipid bilayer and doxorubicin hydrochloride (DOX, 2 μM) within the aqueous core. Structural analysis by cryogenic transmission electron microscopy and dynamic light scattering showed that the assemblies were approximately 120 nm in diameter. Furthermore, the samples consisted of a mixture of dMLs and bare liposomes (no nanoparticles), which provided dual burst and spontaneous DOX release profiles, respectively. Cell viability results show that the cytotoxicity of DOX-loaded dMLs was similar to that of bare dMLs (∼10%), which indicates that spontaneous DOX leakage had little cytotoxic effect. However, when subjected to a physiologically acceptable radiofrequency (RF) electromagnetic field, cell viability was reduced up to 40% after 8h and significant cell death (>90%) was observed after 24h. The therapeutic mechanism was intracellular RF-triggered DOX release from the dMLs and not intracellular hyperthermia due to nanoparticle heating via magnetic losses. Copyright © 2014 Elsevier B.V. All rights reserved.

Prevention of febrile leucopenia after chemotherapy in high-risk breast cancer patients : no significant difference between granulocyte-colony stimulating growth factor or ciprofloxacin plus amphotericin B

NARCIS (Netherlands)

Schroder, CP; de Vries, EGE; Muder, NH; Willemse, PHB; Sleijfer, DT; Hospers, GAP; van der Graaf, WTA

In a prospective randomized trial, 40 stage IV breast cancer patients undergoing intermediate high-dose chemotherapy (cyclophosphamide, 5-fluorouracil plus epirubicin or methotrexate), received either recombinant human G-CSF (rhG-CSF, group I) or ciprofloxacin and amphotericin B (CAB, group II) for

Does chemotherapy improve survival in high-risk stage I and II Merkel cell carcinoma of the skin?

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Poulsen, Michael G.; Rischin, Danny; Porter, Ian; Walpole, Euan; Harvey, Jennifer; Hamilton, Chris; Keller, Jacqui; Tripcony, Lee

2006-01-01

Purpose: The effectiveness of synchronous carboplatin, etoposide, and radiation therapy in improving survival was evaluated by comparison of a matched set of historic control subjects with patients treated in a prospective Phase II study that used synchronous chemotherapy and radiation and adjuvant chemotherapy. Patients and Methods: Patients were included in the analysis if they had disease localized to the primary site and nodes, and they were required to have at least one of the following high-risk features: recurrence after initial therapy, involved nodes, primary size greater than 1 cm, or gross residual disease after surgery. All patients who received chemotherapy were treated in a standardized fashion as part of a Phase II study (Trans-Tasman Radiation Oncology Group TROG 96:07) from 1997 to 2001. Radiation was delivered to the primary site and nodes to a dose of 50 Gy in 25 fractions over 5 weeks, and synchronous carboplatin (AUC 4.5) and etoposide, 80 mg/m 2 i.v. on Days 1 to 3, were given in Weeks 1, 4, 7, and 10. The historic group represents a single institution's experience from 1988 to 1996 and was treated with surgery and radiation alone, and patients were included if they fulfilled the eligibility criteria of TROG 96:07. Patients with occult cutaneous disease were not included for the purpose of this analysis. Because of imbalances in the prognostic variables between the two treatment groups, comparisons were made by application of Cox's proportional hazard modeling. Overall survival, disease-specific survival, locoregional control, and distant control were used as endpoints for the study. Results: Of the 102 patients who had high-risk Stage I and II disease, 40 were treated with chemotherapy (TROG 96:07) and 62 were treated without chemotherapy (historic control subjects). When Cox's proportional hazards modeling was applied, the only significant factors for overall survival were recurrent disease, age, and the presence of residual disease. For

Can loco-regional irradiation be a routine supplement to high dose chemotherapy with autologous bone marrow transplant in women with poor prognosis breast cancer

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Wobeck, Linda K.; Holland, H. Kent; Landry, Jerome C.; Lynn, Michael J.; Hughes, Lorie L.

1997-01-01

Purpose: High dose chemotherapy followed by bone marrow transplantation (BMT) is currently being performed in many women with localized, poor prognosis breast cancer. The purpose of this study was to examine patterns of care in radiation treatment as well as acute side effects in women who received breast or chest wall and regional nodal irradiation (XRT) post BMT. Methods: The records of 126 consecutive women with localized, poor prognosis breast cancer who received an autologous BMT at Emory University between (3(90)) and (7(96)) were retrospectively reviewed. Results: All 126 women underwent high dose chemotherapy with cyclophosphamide, carboplatinum and thiotepa followed by BMT. Loco - regional XRT after BMT was routinely recommended for patients with 10 or more positive axillary lymph nodes or inflammatory carcinoma. Overall, 90 patients received local +/- regional XRT; 11 patients prior to BMT and 79 patients post BMT. Three of these patients had a local relapse prior to beginning XRT post BMT. Thirty six patients did not receive XRT for the following reasons: major post BMT morbidity or insufficient hematological recovery (15 patients), less than 10 positive axillary lymph nodes (12 patients), or refusal/not referred (9 patients). Therefore, of the 103 patients (excludes those with less than 10 positive nodes) intended to receive post BMT irradiation, 14.5 % (15 patients- 2 with inflammatory carcinoma) were unable to receive it secondary to post BMT morbidity and 9% (9 patients) refused or were not referred. Of these 79 patients irradiated post BMT, 16 had stage IIA, 20 stage IIB, 27 stage IIIA and 16 inflammatory carcinoma (IIIB). The median time from transplant to irradiation was 82 days (range 44 - 641). Average dose to breast or chest wall was 49.5 Gy (range 42-55.8 Gy). Boost dose (mean 12 Gy, range 10-22 Gy) was given in 62% of patients. The median tumor bed/mastectomy scar dose was 60 Gy (range 42-72 Gy). Supraclavicular, posterior axillary and

HIGH-DOSE RATE BRACHYTHERAPY IN CARCINOMA CERVIX STAGE IIIB

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Sathya Maruthavanan

2016-07-01

Full Text Available INTRODUCTION Radiotherapy is the standard treatment in locally advanced (IIB-IVA and early inoperable cases. The current standard of practice with curable intent is concurrent chemoradiation in which intracavitary brachytherapy is an integral component of radiotherapy. This study aims at assessing the efficacy of HDR ICBT (High-dose rate intracavitary brachytherapy in terms local response, normal tissue reactions, and feasibility. METHODS AND MATERIALS A total of 20 patients of stage IIIB cancer of the uterine cervix were enrolled in the study and were planned to receive concurrent chemotherapy weekly along with EBRT (external beam radiotherapy to a dose of 50 Gy/25 Fr. Suitability for ICBT was assessed at 40 Gy/20 Fr. 6/20 patients were suitable at 40 Gy and received HDR ICBT with a dose of 5.5 Gy to point A in 4 sessions (5.5 Gy/4 Fr. The remaining 14/20 patients completed 50 Gy and received HDR ICBT with a dose of 6 Gy to point A in 3 sessions (6 Gy/3 Fr. RESULTS A total of 66 intracavitary applications were done and only one application required dose modification due to high bladder dose, the pelvic control rate was 85% (17/20. 10% (2/20 had stable disease and 5% (1/20 had progressive disease at one year of follow up. When toxicity was considered only 15% developed grade I and grade II rectal complications. Patient compliance and acceptability was 100%. Patients were very comfortable with the short treatment time as compared with patients on LDR ICBT (low-dose rate intracavitary brachytherapy treatment interviewed during the same period. CONCLUSION This study proves that HDR brachytherapy is efficacious and feasible in carcinoma of cervix stage IIIB. It also proves that good dose distribution can be achieved with HDR intracavitary facility by the use of dose optimization. The short treatment time in HDR ICBT makes it possible to maintain this optimised dose distribution throughout the treatment providing a gain in the therapeutic ratio and

Intracranial germinomas: a case for low dose radiation therapy alone

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Harrigan, Patricia M.; Loeffler, Jay S.; Shrieve, Dennis; Tarbell, Nancy J.

1995-01-01

by low dose RT. There were 2 CRs and 1 PR after 3 cycles, and 2 PRs after 1 cycle (chemotherapy was discontinued after 1 cycle due to ototoxicity). Among 18 pts treated with ≤ 3060 cGy WB RT (median follow-up: 35 mos), the most striking toxicity was in (4(5)) pts treated with chemotherapy who developed ototoxicity prior to RT. One pt had worsening of neuropsychological function which was present at diagnosis and 5 pts developed endocrinopathies. Among 20 pts treated with > 3060 cGy WB RT (median follow-up: 72 mos) there were 7 new or worsened neuropsychological outcomes. There were 10 pts who developed endocrinopathies. One female pt who received high dose WB RT was diagnosed with a glioblastoma multiforme within the treatment field 6 yrs after CSI. Conclusions: 1) Germinomas are highly curable with RT alone. 2.) These results suggest that low dose RT alone to the craniospinal axis (2000 cGy) and a boost to the tumor volume (4500 cGy) is effective and associated with few treatment complications. This may be more clearly indicated for pts with MMG or evidence of spinal seeding. Further experience is necessary to confirm this. 3.) The toxicity associated with high dose RT or chemotherapy and low dose RT argues against its use in germinomas

Intracranial germinomas: a case for low dose radiation therapy alone

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Harrigan, Patricia M; Loeffler, Jay S; Shrieve, Dennis; Tarbell, Nancy J

1995-07-01

followed by low dose RT. There were 2 CRs and 1 PR after 3 cycles, and 2 PRs after 1 cycle (chemotherapy was discontinued after 1 cycle due to ototoxicity). Among 18 pts treated with {<=} 3060 cGy WB RT (median follow-up: 35 mos), the most striking toxicity was in (4(5)) pts treated with chemotherapy who developed ototoxicity prior to RT. One pt had worsening of neuropsychological function which was present at diagnosis and 5 pts developed endocrinopathies. Among 20 pts treated with > 3060 cGy WB RT (median follow-up: 72 mos) there were 7 new or worsened neuropsychological outcomes. There were 10 pts who developed endocrinopathies. One female pt who received high dose WB RT was diagnosed with a glioblastoma multiforme within the treatment field 6 yrs after CSI. Conclusions: 1) Germinomas are highly curable with RT alone. 2.) These results suggest that low dose RT alone to the craniospinal axis (2000 cGy) and a boost to the tumor volume (4500 cGy) is effective and associated with few treatment complications. This may be more clearly indicated for pts with MMG or evidence of spinal seeding. Further experience is necessary to confirm this. 3.) The toxicity associated with high dose RT or chemotherapy and low dose RT argues against its use in germinomas.

A phase II clinical trial evaluating the use of two sequential, four-drug combination chemotherapy regimens in ambulatory bronchogenic adenocarcinoma patients.

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Broder, L E; Sridhar, K S; Selawry, O S; Charyulu, K N; Rao, R K; Saldana, M J; Lenz, C

1992-12-01

Forty-three ambulatory patients with locally advanced or metastatic bronchogenic adenocarcinoma were sequentially treated with two potentially mutually non-cross-resistant chemotherapy regimens. A new regimen, MVPF (mitomycin-c, vinblastine, procarbazine, and 5-fluorouracil), was given until progressive disease occurred. Then, a second regimen--MOCC (methotrexate, vincristine [Oncovin], cyclophosphamide, and CCNU)--was initiated. At further progression, regional disease patients received radiotherapy, whereas extensive disease patients received Phase II agents. Of the 43 patients entered on the study, 40 were evaluable. Three patients withdrew early due to poor tolerance of the regimen. The response rate for MVPF was 33% (12 of 40 PR, 1 of 40 CR) compared to a 4% (1 of 23 PR) response for MOCC (difference: p < or = .03), for a total response rate of 35%. Although there was an initial improvement in survival for responders (31.7 weeks) versus nonresponders (15.7 weeks) at the 75th percentile (p < or = .05), there was no significant difference in median survival. The hematologic toxicity was equivalent for both groups, whereas nonhematologic toxicity revealed a high incidence of nausea and vomiting in the MVPF group. It is concluded that this approach lent itself well to ambulatory care, and MVPF could be considered an alternative to cyclophosphamide-based regimens. However, the absence of a meaningful CR rate and lack of influence of response on median survival were factors limiting its effectiveness.

Impact of high-dose chemotherapy and autologous transplantation as first-line therapy on the survival of high-risk diffuse large B cell lymphoma patients: a single-center study in Japan.

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Inano, Shojiro; Iwasaki, Makoto; Iwamoto, Yoshihiro; Sueki, Yuki; Fukunaga, Akiko; Yanagita, Soshi; Arima, Nobuyoshi

2014-02-01

High-dose chemotherapy (HDT), together with autologous stem cell transplantation (ASCT), plays an important role in the treatment of diffuse large B cell lymphoma (DLBCL), especially as second-line therapy. However, its significance in up-front settings remains to be elucidated. In our institute, patients with DLBCL in both the high-intermediate and high international prognostic index (IPI) groups initially underwent CHOP/R-CHOP treatment followed by HDT/ASCT at upfront settings between 2002 and 2011. We retrospectively analyzed 25 patients who were all treated with upfront HDT/ASCT. We excluded one patient who failed to undergo transplantation because of primary refractory disease from the analysis. The median follow-up was 77 months (range 17-110 months). Five-year overall survival (OS) and progression-free survival (PFS) were 91.7 and 79.2 %, respectively, which were higher than the equivalents in previous studies. The OS and PFS in the high-risk group were lower than those in the high-intermediate group. Treatment-related mortalities or fatal complication were not observed. Our results confirm that HDT/ASCT for high-risk aggressive lymphoma is a feasible and promising therapy, but patients with high IPI continued to have poor prognoses; improvements in treatment strategy are clearly needed. Since HDT/ASCT is an aggressive treatment option associated with long-term complications, we need to identify patient groups that will gain the maximum benefit from HDT/ASCT in the upfront setting.

Enhanced therapeutic effect of APAVAC immunotherapy in combination with dose-intense chemotherapy in dogs with advanced indolent B-cell lymphoma.

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Marconato, L; Stefanello, D; Sabattini, S; Comazzi, S; Riondato, F; Laganga, P; Frayssinet, P; Pizzoni, S; Rouquet, N; Aresu, L

2015-09-22

The aim of this non-randomized controlled trial was to compare time to progression (TTP), lymphoma-specific survival (LSS), and safety of an autologous vaccine (consisting of hydroxyapatite ceramic powder and Heat Shock Proteins purified from the dogs' tumors, HSPPCs-HA) plus chemotherapy versus chemotherapy alone in dogs with newly diagnosed, clinically advanced, histologically confirmed, multicentric indolent B-cell lymphoma. The vaccine was prepared from dogs' resected lymph nodes and administered as an intradermal injection. Forty-five client-owned dogs were enrolled: 20 dogs were treated with dose-intense chemotherapy, and 25 received concurrent immunotherapy. Both treatment arms were well tolerated, with no exacerbated toxicity in dogs also receiving the vaccine. TTP was significantly longer for dogs treated with chemo-immunotherapy versus those receiving chemotherapy only (median, 209 versus 85 days, respectively, P=0.015). LSS was not significantly different between groups: dogs treated with chemo-immunotherapy had a median survival of 349 days, and those treated with chemotherapy only had a median survival of 200 days (P=0.173). Among vaccinated dogs, those mounting an immune response had a significantly longer TTP and LSS than those with no detectable response (P=0.012 and P=0.003, respectively). Collectively these results demonstrate that vaccination with HSPPCs-HA may produce clinical benefits with no increased toxicity, thereby providing a strategy for enhancing chemotherapy in dogs with advanced indolent lymphoma. Copyright © 2015 Elsevier Ltd. All rights reserved.

High baseline left ventricular and systolic volume may identify patients at risk of chemotherapy-induced cardiotoxicity

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Atiar Rahman; Alex Gedevanishvili; Seham Ali; Elma G Briscoe; Vani Vijaykumar

2004-01-01

Introduction and Methods: Use of chemotherapeutic drugs in the treatment of cancer may lead to serious cardiotoxicity and to post-treatment heart failure. Various strategies have been developed to minimize the risk of cardiotoxicity including avoiding the total dosage given to each patient above a certain 'threshold' value; and monitoring the patient's cardiac function by means of the 'Multiple Gated Acquisition' (MUGA) scan using Technetium 99m . However, even with all these precautions some patients still develop cardiotoxicity and it is not well known which factors predict deterioration of cardiac functions in patients with optimized chemotherapeutic dosages. In this retrospective study we sought to evaluate the predictive value of seven variables (age, sex, baseline LV ejection fraction, LV end diastolic [LDEDV] and end systolic volumes [LVESV], peak diastolic filling rate, preexisting malignancies requiring chemotherapy) in 172 patients (n=Breast Carcinoma 86, lymphoma 62, Leukemias and others 24) undergoing chemotherapy from 1995 until 2000. There was no cut off for left ventricular ejection fraction prior to chemotherapy. However, patients were excluded from analysis if they had significant cardiac arrhythmias or received doses higher than considered safe for cardiotoxicity at the beginning of the study. Significant cardiotoxicity was defined as a drop in post chemotherapy LVEF by >15%. Results: Logistic regression models were used to predict the probability of developing cardiotoxicity as a function of the seven prognostic covariates. The mean age of all patients was 51+13 years. Significant Cardiac toxicity was noted in 10 percent of patients. The overall risk estimate for subsequent heart failure after chemotherapy, however, climbed to 18 percent in patients with a presenting LVESD >50 mL. Using multivariate logistic regression model, older age was noted to be a weak risk factors for cardiac toxicity (confidence interval 0.8-1.2; p 50 mL) appeared to

Tamoxifen effects on subjective and psychosexual well-being, in a randomised breast cancer study comparing high-dose and standard-dose chemotherapy

NARCIS (Netherlands)

Mourits, MJ; Bockermann, [No Value; de Vries, EG; van der Zee, AG; ten Hoor, KA; van der Graaf, WT; Sluiter, WJ; Willemse, PH

2002-01-01

To evaluate the impact of tamoxifen on subjective and psychosexual well-being in breast cancer patients in relation to type of prior chemotherapy and menopausal status. Longitudinal interview study in breast cancer patients during and after adjuvant tamoxifen use. Menopausal status was defined by

Radiation Therapy to the Primary and Postinduction Chemotherapy MIBG-Avid Sites in High-Risk Neuroblastoma

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Mazloom, Ali; Louis, Chrystal U.; Nuchtern, Jed; Kim, Eugene; Russell, Heidi; Allen-Rhoades, Wendy; Krance, Robert; Paulino, Arnold C., E-mail: apaulino@mdanderson.org

2014-11-15

Purpose: Although it is generally accepted that consolidation therapy for neuroblastoma includes irradiation of the primary site and any remaining metaiodobenzylguanidine (MIBG)-avid metastatic sites, limited information has been published regarding the efficacy of this approach. Methods and Materials: Thirty patients with high-risk neuroblastoma were treated at 1 radiation therapy (RT) department after receiving 5 cycles of induction chemotherapy and resection. All patients had at least a partial response after induction therapy, based upon international neuroblastoma response criteria. The primary sites were treated with 24 to 30 Gy whereas the MIBG-avid metastatic sites were treated with 24 Gy. RT was followed by high-dose chemotherapy with autologous stem cell rescue and 6 months of cis-retinoic acid. Results: The 5-year progression-free survival (PFS) and overall survival (OS) rates were 48% and 59%, respectively. The 5-year locoregional control at the primary site was 84%. There were no differences in locoregional control according to degree of primary surgical resection. The 5-year local control rate for metastatic sites was 74%. The 5-year PFS rates for patients with 0, 1, 2, and >3 postinduction MIBG sites were 66%, 57%, 20%, and 0% (P<.0001), respectively, whereas 5-year OS rates were 80%, 57%, 50%, and 0%, respectively (P<.0001). Conclusions: RT to the primary site and postinduction MIBG-positive metastatic sites was associated with 84% and 74% local control, respectively. The number of MIBG-avid sites present after induction chemotherapy and surgery was predictive of progression-free and overall survival.

Potential risk and benefit of the combination of trastuzumab to chemotherapy and radiation therapy in non-metastatic breast cancer

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Belkacemi, Y.; Laharie-Mineur, H.; Gligorov, J.; Azria, D.

2007-01-01

Trastuzumab (Herceptin) is the first humanized monoclonal antibody targeting the HER2 antigen in breast cancer. HER2 receptor has been individualised 20 years ago. During the past 10 years, trastuzumab administration has radically modified the prognosis of the patients that are treated for HER2 positive breast cancer. Its efficacy has been demonstrated in the metastatic and adjuvant settings. While, trastuzumab based-regimens became the standard of care in the treatment of HER2/neu positive breast cancer, the optimal combination (concurrently or sequentially) to chemotherapy and radiation therapy is still unknown. Indeed, while the concurrent administration of trastuzumab and anthracyclines is not recommended because of a high risk of cardiac toxicity, there is no published data on the best sequence of trastuzumab and radiation therapy administration, particularly when internal mammary chain is involved. The benefit/risk ratio of the concurrent and sequential administration of trastuzumab with chemotherapy and radiation therapy will be discussed in this review. (authors)

Effect of pulsed dose in simultaneous and sequential irradiation of V-79 cells by 14.8 MeV neutrons and 60Co photons

International Nuclear Information System (INIS)

Higgins, P.D.; DeLuca, P.M. Jr.; Gould, M.N.; Schell, M.C.; Pearson, D.W.

1983-01-01

The effect of irradiating V-79 Chinese hamster ovary cells with a mixture of 40% 14.8-MeV neutrons and 60% 60 Co photons with simultaneous or sequential exposures is investigated. Target doses are obtained by irradiating cell samples with 3-minute-long pulses of alternating neutrons and photons (in the sequential case) or with mixed neutrons and photons followed by equal beam-off periods to insure equal total-exposure times for sequenced and simultaneous irradiations. We observe qualitative differences between the survival results under each beam configuration that confirms earlier observations

Preclinical safety, toxicology, and biodistribution study of adenoviral gene therapy with sVEGFR-2 and sVEGFR-3 combined with chemotherapy for ovarian cancer.

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Tuppurainen, Laura; Sallinen, Hanna; Kokki, Emmi; Koponen, Jonna; Anttila, Maarit; Pulkkinen, Kati; Heikura, Tommi; Toivanen, Pyry; Hämäläinen, Kirsi; Kosma, Veli-Matti; Heinonen, Seppo; Alitalo, Kari; Ylä-Herttuala, Seppo

2013-03-01

Abstract Antiangiogenic and antilymphangiogenic gene therapy with soluble vascular endothelial growth factor receptor-2 (VEGFR-2) and soluble VEGFR-3 in combination with chemotherapy is a potential new treatment for ovarian carcinoma. We evaluated the safety, toxicology, and biodistribution of intravenous AdsVEGFR-2 and AdsVEGFR-3 combined with chemotherapy in healthy rats (n=90) before entering a clinical setting. The study groups were: AdLacZ and AdLacZ with chemotherapy as control groups, low dose AdsVEGFR-2 and AdsVEGFR-3, high dose AdsVEGFR-2 and AdsVEGFR-3, combination of low dose AdsVEGFR-2 and AdsVEGFR-3 with chemotherapy, combination of high dose AdsVEGFR-2 and AdVEGFR-3 with chemotherapy, and chemotherapy only. The follow-up time was 4 weeks. Safety and toxicology were assessed by monitoring the clinical status of the animals and by histological, hematological, and clinical chemistry parameters. For the biodistribution studies, quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used. Low dose (2×10(10) vp) AdsVEGFR-2 and AdsVEGFR-3 gene therapy was well tolerated, even when gene therapy was combined with chemotherapy. Notably, only transient elevation of liver enzymes and mild regenerative changes were seen in liver after the gene transfer in the groups that received high doses (2×10(11) vp) of AdsVEGFR-2 and AdsVEGFR-3 with or without chemotherapy. No life-threatening adverse effects were noticed in any of the treatment groups. The highest protein concentration of soluble VEGFR-2 (sVEGFR-2) in circulation was seen 1 week after the gene transfer. The combination of chemotherapy to gene therapy seemed to prolong the time of detectable transgene protein at least 1 week in the circulation. The expression of AdsVEGFR-2 and AdsVEGFR-3 transgenes was mainly seen in the liver and spleen as detected by qRT-PCR. According to these results, AdsVEGFR-2 and AdsVEGFR-3 gene therapy combined with

Primary treatment of acromegaly with high-dose lanreotide: a case series

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Cordes Uwe

2010-03-01

Full Text Available Abstract Introduction The first-line treatment for acromegaly is transsphenoidal surgery. In approximately 50% of patients, however, a cure is not possible with surgery and alternatives are needed. Somatostatin analog therapy is the recommended first-line treatment in patients with such cases. Here we provide the first report of a high-dose lanreotide primary therapy in patients with acromegaly. Case presentation Six patients who were not suitable for surgery were given 60 mg of lanreotide (Autogel® every four weeks. All patients were German nationals and Caucasian. When the response of our patients was unsatisfactory, the dose was increased sequentially to 90 mg every four weeks, 120 mg every four weeks, 120 mg every three weeks and 180 mg every three weeks. Treatment duration was 12 to 24 months. In all cases, the lanreotide dose was 120 mg every 4 weeks or higher. In five of our patients, growth hormone (GH levels were successfully reduced (in three patients GH Tumor shrinkage or degeneration was observed in the five responding patients. No drug-related adverse events were noted. Conclusions These results suggest that lanreotide at high doses of 120 mg every four weeks or more is an effective first-line therapy for patients with acromegaly that surgery alone cannot treat.

MicroRNAs and Metabolites in Serum Change after Chemotherapy: Impact on Hematopoietic Stem and Progenitor Cells.

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Thomas Walenda

Full Text Available Hematopoietic regeneration after high dose chemotherapy necessitates activation of the stem cell pool. There is evidence that serum taken after chemotherapy comprises factors stimulating proliferation and self-renewal of CD34(+ hematopoietic stem and progenitor cells (HSPCs--however, the nature of these feedback signals is yet unclear. Here, we addressed the question if specific microRNAs (miRNAs or metabolites are affected after high dose chemotherapy. Serum taken from the same patients before and after chemotherapy was supplemented for in vitro cultivation of HSPCs. Serum taken after chemotherapy significantly enhanced HSPC proliferation, better maintained a CD34(+ immunophenotype, and stimulated colony forming units. Microarray analysis revealed that 23 miRNAs changed in serum after chemotherapy--particularly, miRNA-320c and miRNA-1275 were down-regulated whereas miRNA-3663-3p was up-regulated. miRNA-320c was exemplarily inhibited by an antagomiR, which seemed to increase proliferation. Metabolomic profiling demonstrated that 44 metabolites were less abundant, whereas three (including 2-hydroxybutyrate and taurocholenate sulphate increased in serum upon chemotherapy. Nine of these metabolites were subsequently tested for effects on HSPCs in vitro, but none of them exerted a clear concentration dependent effect on proliferation, immunophenotype and colony forming unit formation. Taken together, serum profiles of miRNAs and metabolites changed after chemotherapy. Rather than individually, these factors may act in concert to recruit HSPCs into action for hematopoietic regeneration.

Glucocorticosteroids for sepsis : systematic review with meta-analysis and trial sequential analysis

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Volbeda, M.; Wetterslev, J.; Gluud, C.; Zijlstra, J. G.; van der Horst, I. C. C.; Keus, F.

Glucocorticosteroids (steroids) are widely used for sepsis patients. However, the potential benefits and harms of both high and low dose steroids remain unclear. A systematic review of randomised clinical trials with meta-analysis and trial sequential analysis (TSA) might shed light on this

Dose-response effects of systemic anandamide administration in mice sequentially submitted to the open field and elevated plus-maze tests.

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Ribeiro, A; Ferraz-de-Paula, V; Pinheiro, M L; Palermo-Neto, J

2009-06-01

The endocannabinoid system is involved in the control of many physiological functions, including the control of emotional states. In rodents, previous exposure to an open field increases the anxiety-like behavior in the elevated plus-maze. Anxiolytic-like effects of pharmacological compounds that increase endocannabinoid levels have been well documented. However, these effects are more evident in animals with high anxiety levels. Several studies have described characteristic inverted U-shaped dose-response effects of drugs that modulate the endocannabinoid levels. However, there are no studies showing the effects of different doses of exogenous anandamide, an endocannabinoid, in animal models of anxiety. Thus, in the present study, we determined the dose-response effects of exogenous anandamide at doses of 0.01, 0.1, and 1.0 mg/kg in C57BL/6 mice (N = 10/group) sequentially submitted to the open field and elevated plus-maze. Anandamide was diluted in 0.9% saline, ethyl alcohol, Emulphor (18:1:1) and administered ip (0.1 mL/10 g body weight); control animals received the same volume of anandamide vehicle. Anandamide at the dose of 0.1 mg/kg (but not of 0.01 or 1 mg/kg) increased (P open field, as well as the exploration of the open arms of the elevated plus-maze. Thus, exogenous anandamide, like pharmacological compounds that increase endocannabinoid levels, promoted a characteristic inverted U-shaped dose-response effect in animal models of anxiety. Furthermore, anandamide (0.1 mg/kg) induced an anxiolytic-like effect in the elevated plus-maze (P open field test.

Anemia During Sequential Induction Chemotherapy and Chemoradiation for Head and Neck Cancer: The Impact of Blood Transfusion on Treatment Outcome

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Bhide, Shreerang A; Ahmed, Merina [Institute of Cancer Research, Royal Marsden National Health Service Foundation Trust Hospital, London (United Kingdom); Head and Neck Unit, Royal Marsden National Health Service Foundation Trust Hospital, London (United Kingdom); Rengarajan, Vijayan; Powell, Ceri; Miah, Aisha; Newbold, Kate [Head and Neck Unit, Royal Marsden National Health Service Foundation Trust Hospital, London (United Kingdom); Nutting, Christopher M [Institute of Cancer Research, Royal Marsden National Health Service Foundation Trust Hospital, London (United Kingdom); Head and Neck Unit, Royal Marsden National Health Service Foundation Trust Hospital, London (United Kingdom); Harrington, Kevin J [Institute of Cancer Research, Royal Marsden National Health Service Foundation Trust Hospital, London (United Kingdom); Head and Neck Unit, Royal Marsden National Health Service Foundation Trust Hospital, London (United Kingdom)], E-mail: kevinh@icr.ac.uk

2009-02-01

Purpose: Sequential treatment (chemotherapy followed by concomitant chemoradiation; CCRT) is increasingly being used for radical treatment of squamous cell cancer of the head and neck (SCCHN), which results in increased myelosuppression. In this study, we review the incidence of anemia and the effect of a policy of hemoglobin (Hb) maintenance by blood transfusion on disease outcomes in these patients. Methods and Materials: Retrospective review of the records of patients with SCCHN treated with sequential CCRT formed the basis of this study. The incidence of anemia and statistics on blood transfusion were documented. For the purpose of outcome analyses, patients were divided into four categories by (1) transfusion status, (2) nadir Hb concentration, (3) number of transfusion episodes, and (4) number of units of blood transfused (NOUT). Data on 3-year locoregional control (LRC), relapse-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) were analyzed. Results: One hundred and sixty-nine patients were identified. The median follow-up was 23.6 months. The RFS (52% vs. 41%, p = 0.03), DSS (71% vs. 66%, p = 0.02), and OS (58% vs. 42% p = 0.005) were significantly better for patients who did not have a transfusion vs. those who did. The LRC, RFS, DSS, and OS were also significantly better for patients with nadir Hb level >12 vs. <12 g/dL and NOUT 1-4 vs. >4. Conclusion: Our study seems to suggest that blood transfusion during radical treatment for SCCHN might be detrimental. Further research should be undertaken into the complex interactions among tumor hypoxia, anemia, and the treatment of anemia before making treatment recommendations.

Acute emesis: moderately emetogenic chemotherapy

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Herrstedt, Jørn; Rapoport, Bernardo; Warr, David

2011-01-01

This paper is a review of the recommendations for the prophylaxis of acute emesis induced by moderately emetogenic chemotherapy as concluded at the third Perugia Consensus Conference, which took place in June 2009. The review will focus on new studies appearing since the Second consensus conference...... receiving multiple cycles of moderately emetogenic chemotherapy will be reviewed. Consensus statements are given, including optimal dose and schedule of serotonin(3) receptor antagonists, dexamethasone, and neurokinin(1) receptor antagonists. The most significant recommendations (and changes since the 2004...... version of the guidelines) are as follows: the best prophylaxis in patients receiving moderately emetogenic chemotherapy (not including a combination of an anthracycline plus cyclophosphamide) is the combination of palonosetron and dexamethasone on the day of chemotherapy, followed by dexamethasone...

Sequential Monte Carlo with Highly Informative Observations

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Del Moral, Pierre; Murray, Lawrence M.

2014-01-01

We propose sequential Monte Carlo (SMC) methods for sampling the posterior distribution of state-space models under highly informative observation regimes, a situation in which standard SMC methods can perform poorly. A special case is simulating bridges between given initial and final values. The basic idea is to introduce a schedule of intermediate weighting and resampling times between observation times, which guide particles towards the final state. This can always be done for continuous-...

A randomized trial of combined multidrug chemotherapy and radiotherapy in advanced squamous cell carcinoma of the head and neck

International Nuclear Information System (INIS)

1986-01-01

This report concerns the design and results of a randomized prospective trial (SECOG I) in the treatment of advanced Stage III and IV head and neck cancer with radical radiotherapy combined with polychemotherapy. Synchronous administration of chemotherapy and radiotherapy was compared with sequential chemotherapy and radiotherapy and VBM (vincristine, bleomycin and methotrexate) compared with VBM plus 5-fluorouracil in a 2 x 2 standard factorial design. Two-hundred-and-seventy patients were entered and 267 were included in the analysis. Treatment did not present serious problems of toxicity. The addition of 5-fluorouracil to VBM produced a significant improvement in disease-free survival (P=0.04) though not in overall survival. Synchronous chemotherapy was similarly better than sequential chemotherapy, though not significantly so (P=0.1). A new study (SECOG II), based on this was started in February 1984, and one-third of the patients are now being allocated to treatment by radiotherapy as the sole method of treatment. (author)

Chemotherapy followed by low dose radiotherapy in childhood Hodgkin's disease: retrospective analysis of results and prognostic factors

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Pellizzon Cassio A

2006-10-01

Full Text Available Abstract Purpose To report the treatment results and prognostic factors of childhood patients with Hodgkin's disease treated with chemotherapy (CT followed by low dose radiotherapy (RT. Patients and methods This retrospective series analyzed 166 patients under 18 years old, treated from January 1985 to December 2003. Median age was 10 years (range 2–18. The male to female ratio was 2,3 : 1. Lymphonode enlargement was the most frequent clinical manifestation (68%, and the time of symptom duration was less than 6 months in 55% of the patients. In histological analysis Nodular Sclerosis was the most prevalent type (48% followed by Mixed Celularity (34.6%. The staging group according Ann Arbor classification was: I (11.7%, II (36.4%, III (32.1% and IV (19.8%. The standard treatment consisted of chemotherapy multiple drug combination according the period of treatment protocols vigent: ABVD in 39% (n-65 of the cases, by VEEP in 13 %(n-22, MOPP in 13 %(n-22, OPPA-13 %(n-22 and ABVD/OPPA in 22 %(n-33. Radiotherapy was device to all areas of initial presentation of disease. Dose less or equal than 21 Gy was used in 90.2% of patients with most part of them (90% by involved field (IFRT or mantle field. Results The OS and EFS in 10 years were 89% and 87%. Survival according to clinical stage as 94.7%, 91.3%, 82.3% and 71% for stages I to IV(p = 0,005. The OS was in 91.3% of patients who received RT and in 72.6% of patients who did not (p = 0,003. Multivariate analysis showed presence of B symptoms, no radiotherapy and advanced clinical stage to be associated with a worse prognosis. Conclusion This data demonstrating the importance of RT consolidation with low dose and reduced volume, in all clinical stage of childhood HD, producing satisfactory ten years OS and EFS. As the disease is highly curable, any data of long term follow-up should be presented in order to better direct therapy, and to identify groups of patients who would not benefit from radiation

Escalation to High-Dose Defibrotide in Patients with Hepatic Veno-Occlusive Disease.

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Triplett, Brandon M; Kuttab, Hani I; Kang, Guolian; Leung, Wing

2015-12-01

Hepatic veno-occlusive disease (VOD) is a serious complication of high-dose chemotherapy regimens, such as those used in hematopoietic cell transplantation recipients. Defibrotide is considered a safe and effective treatment when dosed at 25 mg/kg/day. However, patients who develop VOD still have increased mortality despite the use of defibrotide. Data are limited on the use of doses above 60 mg/kg/day for persistent VOD. In this prospective clinical trial 34 patients received escalating doses of defibrotide. For patients with persistent VOD despite doses of 60 mg/kg/day, doses were increased to a maximum of 110 mg/kg/day. Increased toxicity was not observed until doses rose beyond 100 mg/kg/day. Patients receiving doses between 10 and 100 mg/kg/day experienced an average of 3 bleeding episodes per 100 days of treatment, whereas those receiving doses >100 mg/kg/day experienced 13.2 bleeding episodes per 100 days (P = .008). Moreover, dose reductions due to toxicity were needed at doses of 110 mg/kg/day more often than at lower doses. Defibrotide may be safely escalated to doses well above the current standard without an increase in bleeding risk. However, the efficacy of this dose-escalation strategy remains unclear, because outcomes were similar to published cohorts of patients receiving standard doses of defibrotide for VOD. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Concurrent radiotherapy and chemotherapy

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Fu, K.K.

1985-01-01

The principal objective of combining chemotherapy with radiotherapy (XRT) for the treatment of advanced head and neck cancer is to improve the therapeutic ratio through the enhancement of local control and reduction of distant metastases without excessively enhancing normal tissue effects. Improved tumour control can result from sole additivity of either therapy or direct interactions between drug and radiation leading to increased tumour cell kill. Chemotherapy may sensitize the cells to radiation, interfere with repair of sublethal or potentially lethal radiation damage, induce cell synchrony, and reduce tumour mass leading to reoxygenation and decreased fraction of resistant hypoxic cells. Radiation may improve drug accessibility to tumour cells and reduce tumour volume leading to increased cell proliferation and chemosensitivity. If the enhanced effects of combined therapy are purely additive, then the two modalities can be administered either sequentially or concurrently with the same results. However, if the enhanced effects result from the direct interaction between drug and radiation, it is necessary that the two modalities be administered concurrently and in close temporal proximity. This review summarizes the results of clinical studies in which chemotherapy was administered concurrently during the course of radiotherapy for patients with previously untreated advanced squamous cell carcinoma in the head and neck

Interaction of 2-Gy Equivalent Dose and Margin Status in Perioperative High-Dose-Rate Brachytherapy

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Martinez-Monge, Rafael; Cambeiro, Mauricio; Moreno, Marta; Gaztanaga, Miren; San Julian, Mikel; Alcalde, Juan; Jurado, Matias

2011-01-01

Purpose: To determine patient, tumor, and treatment factors predictive of local control (LC) in a series of patients treated with either perioperative high-dose-rate brachytherapy (PHDRB) alone (Group 1) or with PHDRB combined with external-beam radiotherapy (EBRT) (Group 2). Patient and Methods: Patients (n = 312) enrolled in several PHDRB prospective Phase I-II studies conducted at the Clinica Universidad de Navarra were analyzed. Treatment with PHDRB alone, mainly because of prior irradiation, was used in 126 patients to total doses of 32 Gy/8 b.i.d. or 40 Gy/10 b.i.d. treatments after R0 or R1 resections. Treatment with PHDRB plus EBRT was used in 186 patients to total doses of 16 Gy/4 b.i.d. or 24 Gy/6 b.i.d. treatments after R0 or R1 resections along with 45 Gy of EBRT with or without concomitant chemotherapy. Results: No dose-margin interaction was observed in Group 1 patients. In Group 2 patients there was a significant interaction between margin status and 2-Gy equivalent (Eq2Gy) dose (p = 0.002): (1) patients with negative margins had 9-year LC of 95.7% at Eq2Gy = 62.9Gy; (2) patients with close margins of >1 mm had 9-year LC of 92.4% at Eq2Gy = 72.2Gy, and (3) patients with positive/close <1-mm margins had 9-year LC of 68.0% at Eq2Gy = 72.2Gy. Conclusions: Two-gray equivalent doses ≥70 Gy may compensate the effect of close margins ≥1 mm but do not counterbalance the detrimental effect of unfavorable (positive/close <1 mm) resection margins. No dose-margin interaction is observed in patients treated at lower Eq2Gy doses ≤50 Gy with PHDRB alone.

BRCA1-like profile predicts benefit of tandem high dose epirubicin-cyclophospamide-thiotepa in high risk breast cancer patients randomized in the WSG-AM01 trial

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Schouten, Philip C.; Gluz, Oleg; Harbeck, Nadia; Mohrmann, Svjetlana; Diallo-Danebrock, Raihana; Pelz, Enrico; Kruizinga, Janneke; Velds, Arno; Nieuwland, Marja; Kerkhoven, Ron M.; Liedtke, Cornelia; Frick, Markus; Kates, Ronald; Linn, Sabine C.; Nitz, Ulrike; Marme, Frederik

2016-01-01

BRCA1 is an important protein in the repair of DNA double strand breaks (DSBs), which are induced by alkylating chemotherapy. A BRCA1-like DNA copy number signature derived from tumors with a BRCA1 mutation is indicative for impaired BRCA1 function and associated with good outcome after high dose

Sequential cisplatin/cyclophosphamide chemotherapy and abdominopelvic radiotherapy in the management of advanced ovarian cancer.

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Green, J A; Warenius, H M; Errington, R D; Myint, S; Spearing, G; Slater, A J

1988-11-01

Forty-six previously untreated patients with advanced ovarian cancer were treated with combination chemotherapy comprising cisplatin 80 mg m-2 i.v. and cyclophosphamide 1 gm-2 i.v. every 28 days for 5 cycles. Eighty-five percent of patients received more than 75% of the calculated doses, and of 43 evaluable patients, a complete response was achieved in 31 (72%), a partial response in 4 (9.3%) and 8 patients had static or progressive disease. The actuarial survival of the whole group is 60% at a median follow-up of 2 years. Twenty-four patients in complete clinical or pathological remission were then treated with whole abdominal radiotherapy 2,500 cGy followed by a pelvic boost of 2,000 cGy. The pelvic boost was omitted in 3 patients, and the overall radiotherapy treatment time extended in a further 4 patients on account of myelosuppression. The actuarial survival of the 24 patients receiving both treatments at a median of 30 months follow-up is 75%. In the 10 patients with negative second-look procedures completing both treatments there have been no tumour related deaths at a median follow-up of 33 months.

Salvage central lymphatic irradiation in follicular lymphomas following failure of chemotherapy: a feasibility study

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Ha, Chul S.; Tucker, Susan L.; Blanco, Angel I.; Cabanillas, Fernando; Cox, James D.

1999-01-01

Purpose: Management of follicular lymphoma after chemotherapy failure has been controversial and has ranged from watchful waiting to high-dose chemotherapy. High-dose chemotherapy with bone marrow reconstitution may produce clinical and molecular complete responses at the risk of serious morbidity and mortality. It has been previously reported that central lymphatic irradiation (CLI) can achieve long-term relapse-free survival in patients with Stage I, II, or III follicular lymphoma. Therefore, we investigated the feasibility of treating patients in whom front-line chemotherapy failed with salvage CLI instead of instituting more intensive chemotherapy. Methods and Materials: Salvage CLI with curative intent for patients with follicular lymphoma was started at The University of Texas M. D. Anderson Cancer Center in 1992. Eleven patients whose disease showed poor response to or relapsed after chemotherapy were managed with this approach. The median age of the patients was 61 years. Criteria for exclusion included bone marrow involvement or other evidence of Ann Arbor Stage IV disease at any time during the course of the disease. Overall survival and relapse-free survival were calculated from the first day of CLI. Results: Ten patients were alive at a median follow-up of 25 months (range 9-73 months). The treatment was well tolerated in general. Two patients could not complete CLI: one 75-year-old patient owing to prolonged platelet count depression and deterioration in general medical condition, and a 66-year-old patient because of exacerbation of preexisting pancytopenia and worsening of heart disease. Everyone who completed CLI remains in remission at the time of this report, except for one patient who had a relapse in the right lacrimal gland at 32 months. This patient was treated with local radiation therapy and is free of disease. Eventual recovery of the blood counts was observed for the patients who completed CLI. Conclusion: These results demonstrate for the

Sequential chemotherapy with dose-dense docetaxel, cisplatin, folinic acid and 5-fluorouracil (TCF-dd) followed by combination of oxaliplatin, folinic acid, 5-fluorouracil and irinotecan (COFFI) in metastatic gastric cancer: results of a phase II trial.

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Dalla Chiesa, Matteo; Tomasello, Gianluca; Buti, Sebastiano; Rovere, Rodrigo Kraft; Brighenti, Matteo; Lazzarelli, Silvia; Donati, Gianvito; Passalacqua, Rodolfo

2011-01-01

To evaluate a new strategy of two sequential, intensified chemotherapy regimens in metastatic gastric cancer. Chemo-naïve patients with metastatic gastric cancer were enrolled to receive 4 cycles of TCF-dd (docetaxel initially 85 mg/m(2) and cisplatin initially 75 mg/m(2) on day 1 [later modified due to toxicity: 70 and 60 mg/m(2) respectively], l-folinic acid 100 mg/m(2) on days 1 and 2, 5-fluorouracil 400 mg/m(2) bolus and then 600 mg/m(2) as a 22 h continuous infusion on day 1 and 2, every 14 days). Subsequently, patients with CR, PR or SD received 4 cycles of COFFI (oxaliplatin 85 mg/m(2), irinotecan 140 mg/m(2), l-folinic acid 200 mg/m(2), 5-fluorouracil bolus 400 mg/m(2) on day 1 followed by 2,400 mg/m(2) as a 48 h continuous infusion, every 14 days). In both regimens pegfilgrastim 6 mg subcutaneously on day 3 was included. Forty consecutive patients were enrolled. TCF-dd regimen achieved an ORR of 55% (95% CI, 40-70). Twenty-three patients proceeded to COFFI. After this regimen the ORR was then increased to 60% (95% CI, 45-75). Among the 21 patients treated with TCF-dd after the protocol amendments, main grade 3-4 toxicities were: neutropenia (29%), thrombocytopenia (19%), asthenia (24%) and diarrhea (14%). COFFI caused grade 3-4 neutropenia (all not febrile) and diarrhea in 35% and 17% of patients respectively. A sequential strategy with TCF-dd followed by COFFI is very active and may be of special interest in selected patients.

High-dose chemoradiotherapy and watchful waiting for distal rectal cancer

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Appelt, Ane L; Pløen, John; Harling, Henrik

2015-01-01

-dose radiotherapy with concomitant chemotherapy followed by observation (watchful waiting) was successful for non-surgical management of low rectal cancer. METHODS: Patients with primary, resectable, T2 or T3, N0-N1 adenocarcinoma in the lower 6 cm of the rectum were given chemoradiotherapy (60 Gy in 30 fractions...

Breast conserving treatment of locally advanced carcinoma T2 and T3 after neoadjuvant chemotherapy followed by quadrantectomy and high dose-rate brachytherapy, as a boost, complementary teletherapy and adjuvant chemotherapy; Tratamento conservador dos carcinomas de mama localmente avancados T2 e T3, apos quimioterapia neoadjuvante, com quadrantectomia e braquiterapia de alta taxa de dose como reforco de dose, teleterapia complementar e quimioterapia adjuvante

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Fristachi, Carlos Elias [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil). Servico de Onco-Ginecologia e Mastologia]. E-mail: cefristachi@uol.com.br; Miziara Filho, Miguel Abrao; Soares, Celia Regina; Fogaroli, Ricardo Cesar; Pelosi, Edilson Lopes; Martins, Homero Lavieri Martins [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil). Servico de Radioterapia; Baracat, Fausto Farah [Hospital do Servidor Publico Estadual de Sao Paulo (HSPE), SP (Brazil). Servico de Ginecologia e Mastologia; Piato, Sebastiao [Irmandade da Santa Casa de Misericordia de Sao Paulo, SP (Brazil). Dept. de Obstetricia e Ginecologia (DOGI)

2005-07-01

Objective: to assess the treatment of breast cancer T2 and T3(T > = 4 cm), through neoadjuvant chemotherapy, quadrantectomy and high-dose-rate (HDR) brachytherapy as a boost, complementary radiotherapy and adjuvant chemotherapy, considering its method problems, its esthetics results, the aspect of local control, overall survival, and disease-free survival. Patients and method: this clinical prospective descriptive study was based on the evaluation of 26 patients ranging from 30 to 70 years old, with infiltrating ductal carcinoma, clinical stage IIB and IIIA, responsive to the neoadjuvant chemotherapy. Early and late radiotherapy complications were evaluated according to the criteria established by the RTOG/EORTC (Radiotherapy and Oncology Group /European Organization for Research and Treatment of Cancer) groups. Esthetics evaluation was done in accordance with the criteria set by a plastic surgeon. Local control was evaluated by clinical method, mammography and ultrasonography. Overall survival (OS) and the disease-free survival (DFS) were assessed according to Kaplan-Meier methodology. All the patients were treated at the Dr. Arnaldo Vieira de Carvalho Cancer Institute, from June/1995 to November/2001, and evaluated in March, 2002, with median follow-up of 28.7 months. Results: early complications were observed in 8 patients (30.6%). Two patients were classified as G3 and G4 (RTOG/EORTC). Six patients had late complications and three of them (11.5%) were classified as G3 and G4. One patient (3.8%) had local recurrence, 64 months after having local treatment. Esthetics results were considered good or regular in 16 patients (60.5%) out of 24 patients who were examined. Overall survival and disease-free survival in 24, 36 and 60 months were 100%, 92.3% and 83.1% respectively. Conclusion: early and late radiotherapy complications were considerate high when compared to literature, but esthetic results were considered acceptable. RL, OS and DFS were comparable to other

Bevacizumab with metronomic chemotherapy of low-dose oral cyclophosphamide in recurrent cervical cancer: Four cases

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Rose Isono-Nakata

2018-05-01

Full Text Available Standard chemotherapy for women with advanced or recurrent cervical cancer involves a combination of paclitaxel, platinum, and bevacizumab. However, for patients who experience anaphylaxis in response to paclitaxel or platinum, have permanent peripheral neuropathy, or develop early recurrence or progressive disease during first-line chemotherapy, the development of a non-taxane non-platinum regimen is mandatory. Clinical trials using anti-angiogenic treatment demonstrated favorable outcomes in cases of highly vascularized cervical cancer. Metronomic chemotherapy has been considered an anti-angiogenic treatment, although its use in combination with bevacizumab has not been studied in cervical cancer. We treated four patients with recurrent cervical cancer with 50 mg of oral cyclophosphamide daily and 15 mg/kg of intravenous bevacizumab every 3 weeks (CFA-BEV. One patient experienced disease progression after 4 months, whereas the other three patients continued the regimen until their last follow-up at 13, 14, and 15 months, respectively. One patient suffered from grade 3 neutropenia; however, no grade 2 or higher non-hematological toxicities were observed. These cases demonstrate the use of CFA-BEV with minimal toxicity and expected anti-cancer activity and indicate that this regimen should be considered for second-line chemotherapy in advanced recurrent cervical cancer. Keywords: Cervical cancer, Metronomic chemotherapy, Bevacizumab

Patterns of failure following high-dose chemotherapy and stem cell rescue for relapsed/refractory non-Hodgkin's lymphoma: implications for the use of adjuvant involved field radiotherapy

International Nuclear Information System (INIS)

Mundt, Arno J.; Williams, Stephanie F.; Hallahan, Dennis; Weichselbaum, Ralph R.

1996-01-01

Purpose: Recent data have suggested a benefit to involved-field radiotherapy (IFRT) in conjunction with high-dose chemotherapy (HDCT) and autologous stem cell rescue (SCR) in patients with metastatic breast cancer, advanced neuroblastoma and relapsed/refractory Hodgkin's disease. The purpose of this study is to determine whether a similar role exists for IFRT in patients with relapsed/refractory Non-Hodgkin's Lymphoma (NHL) undergoing HDCT. Methods/Materials: Forty-nine adult patients with refractory (17) or relapsed (32) NHL underwent HDCT with SCR between 9/90 and 9/95. The most common histology was diffuse large cell (42.8%). Initial stages were I (3), II (23), III (5) and IV (18). All patients had a history of conventional chemotherapy (median regimens 2, range 1-3), 17 (34.7%) had previous RT. Treatment consisted of conventional dose induction chemotherapy followed by high-dose intensification with cytoxan, busulfan and either ara-C or VP-16. Seven patients (14.3%) received IFRT (median dose 34.5 Gy, range 20-45 Gy) to eleven sites of persistent disease following HDCT (HDCT+IFRT). Patients treated with RT to sites of progressive disease following HDCT (salvage RT) were not included in the HDCT+IFRT group. No patient received total body irradiation (TBI). One hundred sixty four sites were identified. Sites were designated as amenable or not to IFRT and divided into those achieving a complete response to induction (IndCR) and those which did not (non-IndCR). An amenable site is defined as disease localized to either an organ or nodal chain and encompassable within a standard RT portal. Relapse sites were designated as in previous (involved) sites (present prior to HDCT) or in new (uninvolved) sites. Median followup was 19.7 months (range, 1-57.3 months). Results: The 4-year actuarial progression-free (PFS), cause-specific (CSS) and overall (OS) survivals of the entire group were 36.4%, 45.9% and 34.9%, respectively. Excluding toxic deaths, 20 (47.6%) patients

Oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis in allogeneic hematopoietic stem cell transplant recipients.

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Aisa, Yoshinobu; Mori, Takehiko; Kudo, Masumi; Yashima, Tomoko; Kondo, Sakiko; Yokoyama, Akihiro; Ikeda, Yasuo; Okamoto, Shinichiro

2005-04-01

The purpose of this study was to evaluate the efficacy of oral cryotherapy to prevent high-dose melphalan-induced stomatitis. Eighteen consecutive recipients of allogeneic hematopoietic stem cell transplant conditioned with high-dose melphalan (140 mg/m2) in combination with fludarabine alone or with fludarabine and additional chemotherapy or radiation were enrolled. The severity of stomatitis was graded according to the National Cancer Institute Common Toxicity Criteria. Patients were kept on oral cryotherapy using ice chips and ice-cold water shortly before, during, and for additional 90 min after completion of melphalan administration. Only two of 18 patients (11.1%) developed grade 2 or 3 stomatitis while six of seven patients in the historical control developed it (85.7%; P=0.001). These results suggested that oral cryotherapy could effectively prevent stomatitis caused by high-dose melphalan, and we recommend that it should be incorporated into the conditioning regimen with high-dose melphalan.

Cavernous angioma after chemotherapy for desmoplastic/nodular medulloblastoma associated with anhidrotic ectodermal dysplasia.

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Yamasaki, Fumiyuki; Takayasu, Takeshi; Nosaka, Ryo; Kawaguchi, Hiroshi; Sugiyama, Kazuhiko; Kobayashi, Masao; Kurisu, Kaoru

2016-02-01

While cavernous angioma (CVA) after cranial irradiation has been documented, its development after high-dose chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT) has not. We present a patient with desmoplastic/nodular medulloblastoma (DNMB) associated with anhidrotic ectodermal dysplasia (AED) who developed CVA 2 years after high-dose chemotherapy and PBSCT. A 1-year-old boy with ingravescent vomiting was admitted to our institute. He presented with a large head, a depressed nasal bridge, low-set ears, thick lips with peg-shaped teeth, hypohidrosis, sparse hair, thin atrophic skin, scaly dermatitis with frontal bossing, and a bulging anterior fontanel. Neuroradiological examination revealed multiple cerebellar masses with heterogeneous enhancement and speckled calcifications and severe obstructive hydrocephalus. The histological diagnosis of surgical specimens was DNMB, and he underwent postoperative multiple-drug chemotherapy with autologous PBSCT. The outcome was favorable and he did not undergo radiotherapy. After 2 years, intracranial hemorrhage was detected at his regular radiological check-up and he again underwent surgery. The histological diagnosis was CVA. To our knowledge, this is the first report of AED-associated DNMB and CVA.

Rolapitant: A Review in Chemotherapy-Induced Nausea and Vomiting.

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Heo, Young-A; Deeks, Emma D

2017-10-01

Oral rolapitant (Varubi™; Varuby ® ), a long-acting neurokinin-1 (NK 1 ) receptor antagonist (RA), is indicated in the USA and EU as part of an antiemetic regimen to prevent delayed chemotherapy-induced nausea and vomiting (CINV) in adults receiving highly or moderately emetogenic chemotherapy (HEC or MEC). In randomized, phase III trials, a single oral dose of rolapitant 180 mg was effective in preventing delayed CINV compared with placebo, when each was used in combination with a 5-HT 3 RA plus dexamethasone, in adults receiving their first course of HEC or MEC. The benefits of rolapitant were maintained over multiple cycles of chemotherapy. The tolerability profile of rolapitant is similar to that of placebo and consistent with that of other NK 1 RAs. However, rolapitant differs from other existing NK 1 RAs in that it does not interact with CYP3A4, thereby negating the need for dexamethasone dose adjustments and potentially making rolapitant a more suitable option for patients receiving CYP3A4 substrates. Thus, oral rolapitant is an effective and well tolerated NK 1 RA that expands the treatment options for preventing delayed CINV in adults receiving HEC or MEC.

Impact of obesity on chemotherapy management and outcomes in women with gynecologic malignancies.

Science.gov (United States)

Horowitz, Neil S; Wright, Alexi A

2015-07-01

To describe the effects of obesity on the pharmacokinetics and dosing of chemotherapies and provide recommendations for chemotherapy management in obese women with gynecologic malignancies. PubMEd and MEDLINE databases were searched for articles published before June 2014. Only English-language articles were considered. 84 manuscripts were reviewed and 66 were included. Search terms included: obesity, overweight, body mass index, body surface area, glomerular filtration rate, chemotherapy, ovarian cancer, endometrial cancer, inflammation, and pharmacokinetics, Obese cancer patients have worse clinical outcomes, compared with non-obese patients. This may be because of differences in pharmacokinetics, metabolic dysregulation, or physicians' decisions to reduce chemotherapy dose-intensity during treatment to minimize toxicities. A 2012 American Society of Clinical Oncology Clinical Practice Guideline recommends using actual body weight for chemotherapy dosing in all patients treated with curative intent, irrespective of obesity, to avoid compromising clinical outcomes, including progression free survival (PFS) and overall survival (OS). In women with gynecologic cancers most studies demonstrate no difference in PFS or OS when obese patients receive the same chemotherapy dose intensity as non-obese patients, except perhaps with bevacizumab. Chemotherapy dose-intensity is a critical determinant of cancer outcomes and should be maintained in all patients, irrespective of obesity. Future studies should prospectively examine the impact of obesity on clinical outcomes (adverse events, survival) to improve the care of this growing population of patients who are at risk for inferior clinical outcomes. Copyright © 2015 Elsevier Inc. All rights reserved.

Intra-individual diagnostic image quality and organ-specific-radiation dose comparison between spiral cCT with iterative image reconstruction and z-axis automated tube current modulation and sequential cCT

Directory of Open Access Journals (Sweden)

Holger Wenz

2016-01-01

Conclusions: Spiral cCT combined with ATCM and IR allows for significant-radiation dose reduction including a reduce eye lens organ-dose when compared to a tilted sequential cCT while improving subjective and objective image quality.

SU-F-SPS-02: Accuracy of the Small Field Dosimetry Using the Monte Carlo and Sequential Dose Calculation Algorithms of Multiplan Treatment Planning System Within and Beyond Heterogeneous Media for Cyberknife M6 Unit

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Serin, E.; Codel, G.; Mabhouti, H.; Cebe, M.; Sanli, E.; Pacaci, P.; Kucuk, N.; Kucukmorkoc, E.; Doyuran, M.; Canoglu, D.; Altinok, A.; Acar, H.; Caglar Ozkok, H. [Medipol University, Istanbul, Istanbul (Turkey)

2016-06-15

Purpose: In small field geometries, the electronic equilibrium can be lost, making it challenging for the dose-calculation algorithm to accurately predict the dose, especially in the presence of tissue heterogeneities. In this study, dosimetric accuracy of Monte Carlo (MC) advanced dose calculation and sequential algorithms of Multiplan treatment planning system were investigated for small radiation fields incident on homogeneous and heterogeneous geometries. Methods: Small open fields of fixed cones of Cyberknife M6 unit 100 to 500 mm2 were used for this study. The fields were incident on in house phantom containing lung, air, and bone inhomogeneities and also homogeneous phantom. Using the same film batch, the net OD to dose calibration curve was obtained using CK with the 60 mm fixed cone by delivering 0- 800 cGy. Films were scanned 48 hours after irradiation using an Epson 1000XL flatbed scanner. The dosimetric accuracy of MC and sequential algorithms in the presence of the inhomogeneities was compared against EBT3 film dosimetry Results: Open field tests in a homogeneous phantom showed good agreement between two algorithms and film measurement For MC algorithm, the minimum gamma analysis passing rates between measured and calculated dose distributions were 99.7% and 98.3% for homogeneous and inhomogeneous fields in the case of lung and bone respectively. For sequential algorithm, the minimum gamma analysis passing rates were 98.9% and 92.5% for for homogeneous and inhomogeneous fields respectively for used all cone sizes. In the case of the air heterogeneity, the differences were larger for both calculation algorithms. Overall, when compared to measurement, the MC had better agreement than sequential algorithm. Conclusion: The Monte Carlo calculation algorithm in the Multiplan treatment planning system is an improvement over the existing sequential algorithm. Dose discrepancies were observed for in the presence of air inhomogeneities.

SU-F-SPS-02: Accuracy of the Small Field Dosimetry Using the Monte Carlo and Sequential Dose Calculation Algorithms of Multiplan Treatment Planning System Within and Beyond Heterogeneous Media for Cyberknife M6 Unit

International Nuclear Information System (INIS)

Serin, E.; Codel, G.; Mabhouti, H.; Cebe, M.; Sanli, E.; Pacaci, P.; Kucuk, N.; Kucukmorkoc, E.; Doyuran, M.; Canoglu, D.; Altinok, A.; Acar, H.; Caglar Ozkok, H.

2016-01-01

Purpose: In small field geometries, the electronic equilibrium can be lost, making it challenging for the dose-calculation algorithm to accurately predict the dose, especially in the presence of tissue heterogeneities. In this study, dosimetric accuracy of Monte Carlo (MC) advanced dose calculation and sequential algorithms of Multiplan treatment planning system were investigated for small radiation fields incident on homogeneous and heterogeneous geometries. Methods: Small open fields of fixed cones of Cyberknife M6 unit 100 to 500 mm2 were used for this study. The fields were incident on in house phantom containing lung, air, and bone inhomogeneities and also homogeneous phantom. Using the same film batch, the net OD to dose calibration curve was obtained using CK with the 60 mm fixed cone by delivering 0- 800 cGy. Films were scanned 48 hours after irradiation using an Epson 1000XL flatbed scanner. The dosimetric accuracy of MC and sequential algorithms in the presence of the inhomogeneities was compared against EBT3 film dosimetry Results: Open field tests in a homogeneous phantom showed good agreement between two algorithms and film measurement For MC algorithm, the minimum gamma analysis passing rates between measured and calculated dose distributions were 99.7% and 98.3% for homogeneous and inhomogeneous fields in the case of lung and bone respectively. For sequential algorithm, the minimum gamma analysis passing rates were 98.9% and 92.5% for for homogeneous and inhomogeneous fields respectively for used all cone sizes. In the case of the air heterogeneity, the differences were larger for both calculation algorithms. Overall, when compared to measurement, the MC had better agreement than sequential algorithm. Conclusion: The Monte Carlo calculation algorithm in the Multiplan treatment planning system is an improvement over the existing sequential algorithm. Dose discrepancies were observed for in the presence of air inhomogeneities.

Multi-Institution Prospective Trial of Reduced-Dose Craniospinal Irradiation (23.4 Gy) Followed by Conformal Posterior Fossa (36 Gy) and Primary Site Irradiation (55.8 Gy) and Dose-Intensive Chemotherapy for Average-Risk Medulloblastoma

International Nuclear Information System (INIS)

Merchant, Thomas E.; Kun, Larry E.; Krasin, Matthew J.; Wallace, Dana; Chintagumpala, Murali M.; Woo, Shiao Y.; Ashley, David M.; Sexton, Maree; Kellie, Stewart J.; Ahern, Verity M.B.B.S.; Gajjar, Amar

2008-01-01

Purpose: Limiting the neurocognitive sequelae of radiotherapy (RT) has been an objective in the treatment of medulloblastoma. Conformal RT to less than the entire posterior fossa (PF) after craniospinal irradiation might reduce neurocognitive sequelae and requires evaluation. Methods and Materials: Between October 1996 and August 2003, 86 patients, 3-21 years of age, with newly diagnosed, average-risk medulloblastoma were treated in a prospective, institutional review board-approved, multi-institution trial of risk-adapted RT and dose-intensive chemotherapy. RT began within 28 days of definitive surgery and consisted of craniospinal irradiation (23.4 Gy), conformal PF RT (36.0 Gy), and primary site RT (55.8 Gy). The planning target volume for the primary site included the postoperative tumor bed surrounded by an anatomically confined margin of 2 cm that was then expanded with a geometric margin of 0.3-0.5 cm. Chemotherapy was initiated 6 weeks after RT and included four cycles of high-dose cyclophosphamide, cisplatin, and vincristine. Results: At a median follow-up of 61.2 months (range, 5.2-115.0 months), the estimated 5-year event-free survival and cumulative incidence of PF failure rate was 83.0% ± 5.3% and 4.9% ± 2.4% (± standard error), respectively. The targeting guidelines used in this study resulted in a mean reduction of 13% in the volume of the PF receiving doses >55 Gy compared with conventionally planned RT. The reductions in the dose to the temporal lobes, cochleae, and hypothalamus were statistically significant. Conclusion: This prospective trial has demonstrated that irradiation of less than the entire PF after 23.4 Gy craniospinal irradiation for average-risk medulloblastoma results in disease control comparable to that after treatment of the entire PF

A Randomized Cross‐over Study of High‐dose Metoclopramide plus Dexamethasone versus Granisetron plus Dexamethasone in Patients Receiving Chemotherapy with High‐dose Cisplatin

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Eguchi, Kenji; Shinkai, Tetsu; Tamura, Tomohide; Ohe, Yuichiro; Nisio, Masato; Kunikane, Hiroshi; Arioka, Hitoshi; Karato, Atsuya; Nakashima, Hajime; Sasaki, Yasutsuna; Tajima, Kinuko; Tada, Noriko; Saijo, Nagahiro

1994-01-01

We carried out a randomized, single‐blind, cross‐over trial to compare the antiemetic effect, for both acute and delayed emesis, of granisetron plus dexamethasone (GRN+Dx) with that of high‐dose metoclopramide plus dexamethasone (HDMP + Dx). Fifty‐four patients with primary or metastatic lung cancer, given single‐dose cisplatin (> 80 mg/m2) chemotherapy more than twice, were enrolled in this study. They were treated with both HDMP+Dx and GRN+Dx in two consecutive chemotherapy courses. On day 1, patients experienced a mean of 2.5 (SD=4.3) and 0,1 (SD = 0.4) episodes of vomiting in the HDMP+Dx and the GRN + Dx groups, respectively (P=0.0008). Complete response rate on day 1 was 45 and 90% in the HDMP+Dx and the GRN+Dx groups, respectively (P= 0.0001). Patients treated with GRN+Dx had a tendency to suffer more episodes of vomiting than the HDMP+Dx group on days 2–5, but it was not statistically significant. Twenty‐four patients (57%) preferred the GRN+Dx treatment and 14 patients (33%), HDMP + Dx. In the HDMP + Dx group, nine patients (21%) had an extrapyramidal reaction, and 5 patients (12%) had constipation that lasted for at least two days. In contrast, no patients had extrapyramidal reactions, and IS patients (43%) had constipation in the GRN+Dx group (P < 0.01). GRN+Dx was more effective than HDMP+Dx only in preventing the acute emesis induced by cisplatin. An effective treatment for delayed emesis is still needed. PMID:7829401

The efficacy and safety of palonosetron compared with granisetron in preventing highly emetogenic chemotherapy-induced vomiting in the Chinese cancer patients: a phase II, multicenter, randomized, double-blind, parallel, comparative clinical trial.

Science.gov (United States)

Yu, Zhaocai; Liu, Wenchao; Wang, Ling; Liang, Houjie; Huang, Ying; Si, Xiaoming; Zhang, Helong; Liu, Duhu; Zhang, Hongmei

2009-01-01

This clinical trial was conducted to evaluate the efficacy and safety of Palonosetron in preventing chemotherapy-induced vomiting (CIV) among the Chinese cancer patients. Two hundred and forty patients were scheduled to be enrolled and randomized to receive a single intravenous dose of palonosetron 0.25 mg, or granisetron 3 mg, 30 min before receiving highly emetogenic chemotherapy. The primary efficacy endpoint was the complete response (CR) rate for acute CIV (during the 0-24-h interval after chemotherapy). Secondary endpoints included the CR rates for delayed CIV (more than 24 h after chemotherapy). Two hundred and eight patients were accrued and received study medication. CR rates for acute CIV were 82.69% for palonosetron and 72.12% for granisetron, which demonstrated that palonosetron was not inferior to granisetron in preventing acute CIV. Comparisons of CR rates for delayed CIV yielded no statistical difference between palonosetron and granisetron groups and did not reveal non-inferiority of palonosetron to granisetron. Adverse events were mostly mild to moderate, with quite low rates among the two groups. A single dose (0.25 mg) of palonosetron is not inferior to a single dose (3 mg) of granisetron in preventing CIV and possesses an acceptable safety profile in the Chinese population.

Germ cell tumors of testis; an update in chemotherapy treatment

International Nuclear Information System (INIS)

Parvez, T.

2002-01-01

Prior to the use of cisplatin, durable complete remission of metastatic testicular cancer were rare. In 1977, a chemotherapy treatment program including cisplatin, vinblastine, and bleomycin (PVB) let to high response rates and acceptable toxicity in patients with disseminated testicular cancer. After that, bleomycin, etoposide, and cisplatin (BEP) chemotherapy regimen was established as a standard therapy for good- and poor-risk disease and further, ifosfamide-based regimens or high-dose chemotherapy with stem cell rescue as the salvage therapy. The results of these prospective, randomized clinical trials that have markedly improved the outlook of patients with this type of cancer have been reviewed in this article. While the present state-of-the-art treatment for metastatic testicular cancer is promising approximately one-third of patients with poor risk disease will not achieve a remission. Trials of new agents and approaches are needed to increase the patient survival. (author)

Treatment of locally advanced breast carcinoma with high-dose external beam supervoltage radiotherapy

International Nuclear Information System (INIS)

Brufman, G.; Weshler, Z.; Prosnitz, L.R.; Fuks, Z.

1981-01-01

Between 1960 and 1978, 87 patients with locally advanced Tsub(3-4)Nsub(0-3)M 0 carcinoma of the breast were treated with 5,000 to 8,000 rad of external beam supervoltage radiotherapy. Initial clinical eradication of the tumour was observed in 76 of 87 cases (87%), but the actuarial probability of local control at 5 yr was only 53%. Furthermore, the actuarial probability of disease-free survival was 25% at 5 yr and 13% at 10 yr. Most of the patients eventually succumbed to metastatic breast carcinoma and the actuarial survival at 5 yr was 43% and at 10 yr, 16%. The addition of adjuvant low-dose chemotherapy, given to 13 patients, did not affect the rates of local control, survival or disease-free survival. The most common long-term complication was extensive and deforming radiation-induced fibrosis of the treated breast. The actuarial probability of 10-yr survival without a local recurrence and without severe fibrosis of the treated breast was only 17.5%. The role of adjuvant high-dose chemotherapy in the treatment of locally advanced breast carcinoma and the possible use of improved radiotherapy techniques to achieve a more effective long-term local control and a more desirable cosmetic end result are discussed. (author)

Sequence-dependent toxicity profile in modified FAMTX (fluorouracil-adriamycin-methotrexate) chemotherapy with lenograstim support for advanced gastric cancer: a feasibility study

NARCIS (Netherlands)

Westermann, A. M.; Taal, B. G.; Swart, M.; Boot, H.; Craanen, M.; Gerritsen, W. R.

2000-01-01

For advanced irresectible gastric cancer, sequential high-dose methotrexate and 5-fluorouracil (both on day 1) combined with adriamycin on day 15 (FAMTX regimen), cycled every 28 days, is a fairly effective but toxic treatment, with a high incidence of neutropenic fever, dose reductions and dose

Relative Contributions of Radiation and Cisplatin-Based Chemotherapy to Sensorineural Hearing Loss in Head-and-Neck Cancer Patients

International Nuclear Information System (INIS)

Hitchcock, Ying J.; Tward, Jonathan D.; Szabo, Aniko; Bentz, Brandon G.; Shrieve, Dennis C.

2009-01-01

Purpose: To investigate the risk of sensorineural hearing loss (SNHL) in patients with head-and-neck cancer and treated with radiation therapy (RT) or concomitant cisplatin-based chemoradiation, the relationship among SNHL and radiation dose to the cochlea, the use of two common cisplatin dose regimens. Methods and Materials: A total of 62 head-and-neck cancer patients treated with curative intent were included in this prospective study. Of the patients, 21 received RT alone, 27 received 40 mg/m 2 weekly cisplatin, 13 received 100 mg/m 2 every 3 weeks during RT, and 1 received RT with weekly epidermal growth factor receptor inhibitor antibody. The effect of chemotherapy and RT dose on hearing was determined using a model that accounted for the age and variability between each ear for each patient. Results: We constructed a model to predict dose-dependent hearing loss for RT or cisplatin-based chemotherapy either alone or in combination. For patients only receiving RT, no significant hearing loss was found at doses to the cochlea of less than 40 Gy. Patients receiving 100 mg/m 2 or 40 mg/m 2 of cisplatin chemotherapy had an estimated +21.5 dB and +9.5 dB hearing loss at 8,000 Hz with low radiation doses (10 Gy), which rose to +38.4 dB and +18.9 dB for high radiation doses (40 Gy). Conclusions: Use of RT alone with doses of less than 40 Gy did not result in clinically significant hearing loss. High-frequency SNHL was profoundly damaged in patients who received concomitant cisplatin when doses of 100 mg/m 2 were used. The threshold cochlear dose for hearing loss with cisplatin-based chemotherapy and RT was predicted to be 10 Gy. The inner ear radiation dose constraints and cisplatin dose intensity should be considered in the treatment of advanced head-and-neck cancer

Role of P53 and BCL-2 in high-risk breast cancer patients treated with adjuvant anthracycline-based chemotherapy.

Science.gov (United States)

Mottolese, M; Benevolo, M; Del Monte, G; Buglioni, S; Papaldo, P; Nisticò, C; Di Filippo, F; Vasselli, S; Vici, P; Botti, C

2000-12-01

Adjuvant therapy has become an integral component of the managment of primary high-risk breast cancer patients. However, a considerable fraction of women receive no benefit from this treatment. This study investigates whether a number of biopathological factors can influence the outcome of patients submitted to adjuvant chemotherapy involving the use of high-dose epirubicin and cyclophosphamide. One hundred and fifty-seven primary breast cancer patients, considered at high risk according to the St. Gallen Meeting Consensus Conference, were evaluated immunohistochemically for estrogen, progesterone receptors, p53, bcl-2, HER-2/neu, and Ki-67, of which the results were correlated with patient outcome. Results obtained demonstrated that p53 is a significant predictor of disease-free survival (DFS P < 0.0001) and overall survival (OS P = 0.0002) both in ductal and lobular carcinomas, whereas bcl-2 expression seems to be of prognostic value only in lobular carcinomas (DFS P = 0.01; OS P = 0.02). This data indicates that in high-risk breast cancer patients the immunohistochemical evaluation of p53 and bcl-2 may be of clinical value in distinguishing different responses to adjuvant anthracycline-based chemotherapy.

Dose accumulation of multiple high dose rate prostate brachytherapy treatments in two commercially available image registration systems.

Science.gov (United States)

Poder, Joel; Yuen, Johnson; Howie, Andrew; Bece, Andrej; Bucci, Joseph

2017-11-01

The purpose of this study was to assess whether deformable image registration (DIR) is required for dose accumulation of multiple high dose rate prostate brachytherapy (HDRPBT) plans treated with the same catheter pattern on two different CT datasets. DIR was applied to 20 HDRPBT patients' planning CT images who received two treatment fractions on sequential days, on two different CT datasets, with the same implant. Quality of DIR in Velocity and MIM image registration systems was assessed by calculating the Dice Similarity Coefficient (DSC) and mean distance to agreement (MDA) for the prostate, urethra and rectum contours. Accumulated doses from each system were then calculated using the same DIR technique and dose volume histogram (DVH) parameters compared to manual addition with no DIR. The average DSC was found to be 0.83 (Velocity) and 0.84 (MIM), 0.80 (Velocity) and 0.80 (MIM), 0.80 (Velocity) and 0.81 (MIM), for the prostate, rectum and urethra contours, respectively. The average difference in calculated DVH parameters between the two systems using dose accumulation was less than 1%, and there was no statistically significant difference found between deformably accumulated doses in the two systems versus manual DVH addition with no DIR. Contour propagation using DIR in velocity and MIM was shown to be at least equivalent to inter-observer contouring variability on CT. The results also indicate that dose accumulation through manual addition of DVH parameters may be sufficient for HDRPBT treatments treated with the same catheter pattern on two different CT datasets. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

A Phase I Trial of High-Dose Lenalidomide and Melphalan as Conditioning for Autologous Stem Cell Transplantation in Relapsed or Refractory Multiple Myeloma.

Science.gov (United States)

Mark, Tomer M; Guarneri, Danielle; Forsberg, Peter; Rossi, Adriana; Pearse, Roger; Perry, Arthur; Pekle, Karen; Tegnestam, Linda; Greenberg, June; Shore, Tsiporah; Gergis, Usama; Mayer, Sebastian; Van Besien, Koen; Ely, Scott; Jayabalan, David; Sherbenou, Daniel; Coleman, Morton; Niesvizky, Ruben

2017-06-01

Autologous stem cell transplantation (ASCT) conditioned with high-dose chemotherapy has long been established as the standard of care for eligible patients with newly diagnosed multiple myeloma. Despite recent therapeutic advances, high-dose melphalan (HDM) remains the chemotherapy regimen of choice in this setting. Lenalidomide (LEN) in combination with low-dose dexamethasone is recognized as a standard of care for patients with relapsed or refractory multiple myeloma (RRMM), and there is growing support for the administration of LEN as maintenance therapy post-ASCT. In view of the above, the present phase I clinical trial was designed to evaluate the safety and tolerability of high-dose LEN (HDLEN) in patients with RRMM, and to determine the maximum tolerated dose of HDLEN when added to HDM before ASCT. Despite administering HDLEN at doses of up to 350 mg/day, the maximum tolerated dose could not be determined, owing to an insufficient number of dose-limiting toxicities in the 21 patients enrolled in the trial. Conditioning with HDLEN plus HDM was associated with a favorable tolerability profile. Adverse events following ASCT were as expected with HDM. Median progression-free and overall survival were 10 months and 22 months, respectively, in this population of heavily pretreated patients. Our findings suggest that HDLEN in combination with HDM may offer significant potential as a conditioning regimen before ASCT in patients with RRMM. These preliminary findings are now being evaluated further in an ongoing phase II clinical trial. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Breast conserving treatment for breast cancer: dosimetric comparison of sequential versus simultaneous integrated photon boost.

Science.gov (United States)

Van Parijs, Hilde; Reynders, Truus; Heuninckx, Karina; Verellen, Dirk; Storme, Guy; De Ridder, Mark

2014-01-01

Breast conserving surgery followed by whole breast irradiation is widely accepted as standard of care for early breast cancer. Addition of a boost dose to the initial tumor area further reduces local recurrences. We investigated the dosimetric benefits of a simultaneously integrated boost (SIB) compared to a sequential boost to hypofractionate the boost volume, while maintaining normofractionation on the breast. For 10 patients 4 treatment plans were deployed, 1 with a sequential photon boost, and 3 with different SIB techniques: on a conventional linear accelerator, helical TomoTherapy, and static TomoDirect. Dosimetric comparison was performed. PTV-coverage was good in all techniques. Conformity was better with all SIB techniques compared to sequential boost (P = 0.0001). There was less dose spilling to the ipsilateral breast outside the PTVboost (P = 0.04). The dose to the organs at risk (OAR) was not influenced by SIB compared to sequential boost. Helical TomoTherapy showed a higher mean dose to the contralateral breast, but less than 5 Gy for each patient. SIB showed less dose spilling within the breast and equal dose to OAR compared to sequential boost. Both helical TomoTherapy and the conventional technique delivered acceptable dosimetry. SIB seems a safe alternative and can be implemented in clinical routine.

A procedure for estimating the dose modifying effect of chemotherapy on radiation response

International Nuclear Information System (INIS)

Hao, Y.; Keane, T.

1994-01-01

A procedure based on a logistic regression model was used to estimate the dose-modifying effect of chemotherapy on the response of normal tissues to radiation. The DEF in the proposed procedure is expressed as a function of logistic regression coefficients, response levels and values of covariates in the model. The proposed procedure is advantageous as it allows consideration of both the response levels and the values of covariates in calculating the DEF. A plot of the DEF against the response or a covariate describes how the DEF varies with the response levels or the covariate values. Confidence intervals of the DEF were obtained based on the normal approximation of the distribution of the estimated DEF and on a non-parametric Bootstrap method. An example is given to illustrate the proposed procedure. (Author)

A randomized, double-blind, multicentre study comparing daily 2 and 5 mg of tropisetron for the control of nausea and vomiting induced by low-dose cisplatin- or non-cisplatin-containing chemotherapy

NARCIS (Netherlands)

Wymenga, ANM; vanderGraaf, WTA; Wils, JA; vanHeukelom, LS; vanderLinden, GHM; DullemondWestland, AC; Nooy, M; vanderHeul, C; deBruijn, KM; deVries, EGE

Background: This study compares efficacy safety and tolerability of 2 and 5 mg tropisetron in prevention of nausea and vomiting induced by low-dose cisplatin- or non-cisplatin-containing chemotherapy. Patients and methods: 152 chemotherapy-naive cancer patients were randomized in a double-blind

128-slice Dual-source Computed Tomography Coronary Angiography in Patients with Atrial Fibrillation: Image Quality and Radiation Dose of Prospectively Electrocardiogram-triggered Sequential Scan Compared with Retrospectively Electrocardiogram-gated Spiral Scan.

Science.gov (United States)

Lin, Lu; Wang, Yi-Ning; Kong, Ling-Yan; Jin, Zheng-Yu; Lu, Guang-Ming; Zhang, Zhao-Qi; Cao, Jian; Li, Shuo; Song, Lan; Wang, Zhi-Wei; Zhou, Kang; Wang, Ming

2013-01-01

Objective To evaluate the image quality (IQ) and radiation dose of 128-slice dual-source computed tomography (DSCT) coronary angiography using prospectively electrocardiogram (ECG)-triggered sequential scan mode compared with ECG-gated spiral scan mode in a population with atrial fibrillation. Methods Thirty-two patients with suspected coronary artery disease and permanent atrial fibrillation referred for a second-generation 128-slice DSCT coronary angiography were included in the prospective study. Of them, 17 patients (sequential group) were randomly selected to use a prospectively ECG-triggered sequential scan, while the other 15 patients (spiral group) used a retrospectively ECG-gated spiral scan. The IQ was assessed by two readers independently, using a four-point grading scale from excel-lent (grade 1) to non-assessable (grade 4), based on the American Heart Association 15-segment model. IQ of each segment and effective dose of each patient were compared between the two groups. Results The mean heart rate (HR) of the sequential group was 96±27 beats per minute (bpm) with a variation range of 73±25 bpm, while the mean HR of the spiral group was 86±22 bpm with a variationrange of 65±24 bpm. Both of the mean HR (t=1.91, P=0.243) and HR variation range (t=0.950, P=0.350) had no significant difference between the two groups. In per-segment analysis, IQ of the sequential group vs. spiral group was rated as excellent (grade 1) in 190/244 (78%) vs. 177/217 (82%) by reader1 and 197/245 (80%) vs. 174/214 (81%) by reader2, as non-assessable (grade 4) in 4/244 (2%) vs. 2/217 (1%) by reader1 and 6/245 (2%) vs. 4/214 (2%) by reader2. Overall averaged IQ per-patient in the sequential and spiral group showed equally good (1.27±0.19 vs. 1.25±0.22, Z=-0.834, P=0.404). The effective radiation dose of the sequential group reduced significantly compared with the spiral group (4.88±1.77 mSv vs. 10.20±3.64 mSv; t=-5.372, P=0.000). Conclusion Compared with retrospectively

Adjuvant chemotherapy for osteosarcoma.

Science.gov (United States)

Eilber, F R; Rosen, G

1989-08-01

From this review of chemotherapy trials, several observations can be made. Osteosarcoma is a complex disease involving multiple histologies, each with a different prognosis. Prognostic factors that have been shown to be important include anatomic location of the primary tumor, stage at presentation (patients with metastatic or local recurrent disease fair far worse than those with primary disease), age at onset (children fair worse than the teenager with osteosarcoma), and location within the extremity (patients with more distal tumors fairing better than patients with more proximal tumors). There is convincing evidence for the efficacy of chemotherapeutic agents such as methotrexate in high doses (at least 8 g/m2 for adults, 12 g/m2 for children), Adriamycin, and cisplatin. The combination of Adriamycin and cisplatin appears to be more beneficial relative to either one of these agents alone. The efficacy of the combination of BCD as a triple-drug regimen, although useful in several different trials, has not been convincingly shown. Finally, from several of the recent randomized trials, it appears, that chemotherapeutic regimens containing an Adriamycin and cisplatin combination appear to be superior to those that do not include this combination. However, these observations are made from a historical perspective and have not been conclusively proven by randomized prospective investigations. The observations concerning the natural history of the disease and the activity of various chemotherapeutic agents suggest certain clinical practice algorithms. Essential staging procedures would include a bone scan looking for multifocal or metastatic disease, and CT scans of the chest looking for metastases to the lung. From all studies, it is apparent that surgery is mandatory for the primary tumor and should be an integral portion of all treatment methods. Chemotherapy should be considered for all patients with osteosarcoma, and the essential drugs in the regimen appear at

[Co-composting high moisture vegetable waste and flower waste in a sequential fed operation].

Science.gov (United States)

Zhang, Xiangfeng; Wang, Hongtao; Nie, Yongfeng

2003-11-01

Co-composting of high moisture vegetable wastes (celery and cabbage) and flower wastes (carnation) were studied in a sequential fed bed. The preliminary materials of composting were celery and carnation wastes. The sequential fed materials of composting were cabbage wastes and were fed every 4 days. Moisture content of mixture materials was between 60% and 70%. Composting was done in an aerobic static bed of composting based temperature feedback and control via aeration rate regulation. Aeration was ended when temperature of the pile was about 40 degrees C. Changes of composting of temperature, aeration rate, water content, organic matter, ash, pH, volume, NH4(+)-N, and NO3(-)-N were studied. Results show that co-composting of high moisture vegetable wastes and flower wastes, in a sequential fed aerobic static bed based temperature feedback and control via aeration rate regulation, can stabilize organic matter and removal water rapidly. The sequential fed operation are effective to overcome the difficult which traditional composting cannot applied successfully where high moisture vegetable wastes in more excess of flower wastes, such as Dianchi coastal.

Low skeletal muscle mass is a predictive factor for chemotherapy dose-limiting toxicity in patients with locally advanced head and neck cancer

NARCIS (Netherlands)

Wendrich, Anne W; Swartz, Justin E; Bril, Sandra I; Wegner, Inge; de Graeff, Alexander; Smid, Ernst J; de Bree, Remco; Pothen, Ajit J

OBJECTIVES: Low skeletal muscle mass (SMM) or sarcopenia is emerging as an adverse prognostic factor for chemotherapy dose-limiting toxicity (CLDT) and survival in cancer patients. Our aim was to determine the impact of low SMM on CDLT in patients with locally advanced head and neck squamous cell

The role of sequential chemoradiation for local advanced oropharyngeal carcinoma

International Nuclear Information System (INIS)

Masterson, Liam; Tanweer, Faiz

2013-01-01

This study aims to assess survival, prognostic indicators, and pattern of failure for advanced oropharyngeal cancer treated by induction chemotherapy followed by concomitant chemoradiation (sequential CRT). A retrospective review of 80 consecutive patients who underwent chemoradiation [doublet cisplatin and 5-fluorouracil (PF)] for local advanced oropharyngeal carcinoma at a tertiary center from March 2003 to July 2008 is reported. Seven studies utilizing a similar protocol were reviewed, and all outcomes are collated. At a median follow-up of 32 months, the 3-year overall survival was 75%. Tumor size (p<0.001), age at presentation (p<0.002), and failure to complete the full course of induction chemotherapy (p<0.01) were all found to be significant factors affecting survival. Induction chemotherapy followed by concomitant chemoradiation utilizing doublet PF is an effective treatment for local advanced oropharyngeal carcinoma. At present, the addition of a taxane to the PF regimen cannot be assumed to provide benefit until further evidence emerges from a representative controlled trial. (author)

Sequential vs alternate chemo-radiotherapy in advanced head and neck tumors

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Corvo', R.; Merlano, M.; Grimaldi, A.; Rosso, R.; Vitale, V.; Scarpati, D.; Santelli, A.; Scasso, F.

1988-01-01

Between 1983 and 1986, a multicenter randomized study was conducted to compare a sequential program of induction chemotherapy (CT) followed by radiotherapy (RT), Arm A, with an alteration of cycles of CT with 3 courses of RT (20 Gy/10 fractions up to a total dose of 60 Gy), Arm B, in advanced head and neck cancer patients. The same CT (VBM: Vinblastine, Bleomycin, Methotrexate) was used on both arms; one hundred and sixteen patients (pts) entered the study, 55 in Arm A, 61 in Arm B. Fourty-five pts had stage III and 71 stage IV cancers. The two arms are fully comparable. Up to October 1987, 116 pts are evaluable for survival, while 112 are evaluable for toxicity and 105 for response. In 21 patients (10 in Arm A, 11 in B) the association CT-RT was followed by surgery. Response analysis shows 14 complete responses in Arm A and 30 in Arm B (p≤0.03). The madian disease-free survival and median overall survival are also statistically different, with an advantage for Arm B (33 vs 22 weeks, p≤0.0007, and 59 vs 38 weeks, p<0.03 respectively). The actual overall survival of complete responders at 50 months id 43% (B) and 21% (A). Toxicity (mainly stage III-IV mucositis) is superior in Arm B (30% vs 4%). This experience demonstrates the advantages of alternate over sequential CT-RT. A comparison of this cyclic assiciation with RT alone is in progress

Single-dose palonosetron for prevention of chemotherapy-induced nausea and vomiting in patients with aggressive non-Hodgkin's lymphoma receiving moderately emetogenic chemotherapy containing steroids: results of a phase II study from the Gruppo Italiano per lo Studio dei Linfomi (GISL).

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Di Renzo, Nicola; Montanini, Antonella; Mannina, Donato; Dondi, Alessandra; Muci, Stefania; Mancuso, Salvatrice; De Paolis, M Rosaria; Plati, Caterina; Stelitano, Caterina; Patti, Catia; Olivieri, Attilio; Liardo, Eliana; Buda, Gabriele; Cantaffa, Renato; Federico, Massimo

2011-10-01

The control of nausea and vomiting induced by chemotherapy is paramount for overall treatment success in cancer patients. Antiemetic therapy during chemotherapy in lymphoma patients generally consists of anti-serotoninergic drugs and dexamethasone. The aim of this trial was to evaluate the efficacy of a single dose of palonosetron, a second-generation serotonin type 3 (5-HT(3)) receptor antagonist, in patients with aggressive non-Hodgkin's lymphoma receiving moderately emetogenic chemotherapy (MEC) containing steroids. Patients received a single intravenous bolus of palonosetron (0.25 mg) before administration of chemotherapy. Complete response (CR) defined as no vomiting and no rescue therapy during overall phase (0-120 h) was the primary endpoint. Complete control (CC) defined as CR and only mild nausea was a secondary endpoint. Eighty-six evaluable patients entered in the study. A CR was observed in 74 patients (86.0%) during the overall phase; the CR during the acute (0-24 h) and delayed (24-120 h) phases was 90.7% and 88.4%, respectively. CC was 89.5% during the acute and 84.9% during the delayed phase; the overall CC was 82.6%. This was the first trial, which demonstrated the efficacy of a single dose of palonosetron in control CINV in patients with aggressive non-Hodgkin's lymphoma receiving MEC regimen containing steroids.

Outcomes in 24 selected patients with stage IVB cervical cancer and excellent performance status treated with radiotherapy and chemotherapy

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Zighelboim, Israel; Taylor, Nicholas P.; Powell, Matthew A.; Gibb, Randall K.; Rader, Janet S.; Mutch, David G.; Grigsby, Perry W.

2006-01-01

We sought to review outcomes in patients with stage IVB carcinoma of the cervix treated with irradiation in combination with chemotherapy. We report outcomes of 24 consecutive patients with good performance status treated from 1998 to 2005. Most of these patients underwent concurrent irradiation with platinum-based chemotherapy. Some patients received subsequent systemic chemotherapy. All patients underwent external beam radiotherapy; 7 patients (29%) had additional high-dose-rate and 12 (50%) low-dose-rate brachytherapy. Two patients (8%) received an intensity modulated radiation therapy (IMRT) boost instead of brachytherapy. The mean dose to point A was variable (73.9±19.2 Gy). Twenty patients (83%) received radio-sensitizing platinum-based chemotherapy, and the remaining had radiotherapy alone. Seven patients (29%) had further combination chemotherapy. Therapy was well tolerated. The overall survival was 44% at 36 months and 22% at 5 years. Patients with stage IVB cervical cancer have mostly been treated with palliative intent. With the advent of concurrent chemoradiation, we have treated many of these cases with aggressive combination therapy. In this series, the use of radiotherapy and multiagent chemotherapy in patients with stage IVB cervical carcinoma and good performance status was well tolerated and resulted in higher survival rates than previously reported. (author)

Randomized phase III trial of APF530 versus palonosetron in the prevention of chemotherapy-induced nausea and vomiting in a subset of patients with breast cancer receiving moderately or highly emetogenic chemotherapy

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Boccia, Ralph; O’Boyle, Erin; Cooper, William

2016-01-01

APF530 provides controlled, sustained-release granisetron for preventing acute (0–24 h) and delayed (24–120 h) chemotherapy-induced nausea and vomiting (CINV). In a phase III trial, APF530 was noninferior to palonosetron in preventing acute CINV following single-dose moderately (MEC) or highly emetogenic chemotherapy (HEC) and delayed CINV in MEC (MEC and HEC defined by Hesketh criteria). This exploratory subanalysis was conducted in the breast cancer subpopulation. Patients were randomized to subcutaneous APF530 250 or 500 mg (granisetron 5 or 10 mg) or intravenous palonosetron 0.25 mg during cycle 1. Palonosetron patients were randomized to APF530 for cycles 2 to 4. The primary efficacy end point was complete response (CR, no emesis or rescue medication) in cycle 1. Among breast cancer patients (n = 423 MEC, n = 185 HEC), > 70 % received anthracycline-containing regimens in each emetogenicity subgroup. There were no significant between-group differences in CRs in cycle 1 for acute (APF530 250 mg: MEC 71 %, HEC 77 %; 500 mg: MEC 73 %, HEC 73 %; palonosetron: MEC 68 %, HEC 66 %) and delayed (APF530 250 mg: MEC 46 %, HEC 58 %; 500 mg: MEC 48 %, HEC 63 %; palonosetron: MEC 52 %, HEC 52 %) CINV. There were no significant differences in within-cycle CRs between APF530 doses for acute and delayed CINV in MEC or HEC in cycles 2 to 4; CRs trended higher in later cycles, with no notable differences in adverse events between breast cancer and overall populations. APF530 effectively prevented acute and delayed CINV over 4 chemotherapy cycles in breast cancer patients receiving MEC or HEC. Clinicaltrials.gov identifier: NCT00343460 (June 22, 2006)

Microdose-Induced Drug-DNA Adducts as Biomarkers of Chemotherapy Resistance in Humans and Mice.

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Zimmermann, Maike; Wang, Si-Si; Zhang, Hongyong; Lin, Tzu-Yin; Malfatti, Michael; Haack, Kurt; Ognibene, Ted; Yang, Hongyuan; Airhart, Susan; Turteltaub, Kenneth W; Cimino, George D; Tepper, Clifford G; Drakaki, Alexandra; Chamie, Karim; de Vere White, Ralph; Pan, Chong-Xian; Henderson, Paul T

2017-02-01

We report progress on predicting tumor response to platinum-based chemotherapy with a novel mass spectrometry approach. Fourteen bladder cancer patients were administered one diagnostic microdose each of [ 14 C]carboplatin (1% of the therapeutic dose). Carboplatin-DNA adducts were quantified by accelerator mass spectrometry in blood and tumor samples collected within 24 hours, and compared with subsequent chemotherapy response. Patients with the highest adduct levels were responders, but not all responders had high adduct levels. Four patient-derived bladder cancer xenograft mouse models were used to test the possibility that another drug in the regimen could cause a response. The mice were dosed with [ 14 C]carboplatin or [ 14 C]gemcitabine and the resulting drug-DNA adduct levels were compared with tumor response to chemotherapy. At least one of the drugs had to induce high drug-DNA adduct levels or create a synergistic increase in overall adducts to prompt a corresponding therapeutic response, demonstrating proof-of-principle for drug-DNA adducts as predictive biomarkers. Mol Cancer Ther; 16(2); 376-87. ©2016 AACR. ©2016 American Association for Cancer Research.

Brachial plexus dose tolerance in head and neck cancer patients treated with sequential intensity modulated radiation therapy

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Thomas, Tarita O; Refaat, Tamer; Choi, Mehee; Bacchus, Ian; Sachdev, Sean; Rademaker, Alfred W; Sathiaseelan, Vythialingam; Karagianis, Achilles; Mittal, Bharat B

2015-01-01

We aimed to study the radiation induced brachial plexopathy in patients with head and neck squamous cell carcinoma (HNSCC) treated with Sequential Intensity Modulated Radiation Therapy (S-IMRT). This IRB approved study included 68 patients with HNSCC treated consecutively. Detailed dose volume histogram data was generated for ipsilateral and contralateral brachial plexus (BP) volumes receiving a specified dose (Vds) i.e. V50-V75 and dose in Gray covering specified percent of BP volume (Dvs) i.e. D5-D30 and maximum point doses (Dmax). To assess BP injury all patients’ charts were reviewed in detail for sign and symptoms of BP damage. Post-hoc comparisons were done using Tukey-Kramer method to account for multiple significance testing. The mean and maximum doses to BP were significantly different (p < .05) based on tumor site, nodal status and tumor stage. The mean volume to the ipsilateral BP for V50, V60, V70, and V75 were 7.01 cc, 4.37 cc, 1.47 cc and 0.24 cc, respectively. The mean dose delivered to ≤5% of ipsilateral BP was 68.70 Gy (median 69.5Gy). None of the patients had acute or late brachial plexopathy or any other significant neurological complications, with a minimum follow up of two years (mean 54 months). In this study cohort, at a minimum of two-years follow up, the mean dose of 68.7Gy, a median dose to 69.5Gy to ≤5% of ipsilateral BP, and a median Dmax of 72.96Gy did not result in BP injury when patients were treated with S-IMRT technique. However, longer follow up is needed

Thalidomide for prevention of chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy

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Geng Song

2017-03-01

Full Text Available Background Antiemetic guidelines recommend co-administration of agents to maximize the prevention of chemotherapyinduced nausea and vomiting (CINV, however, the control of delayed CINV is still not satisfactory. The purpose of this study was to evaluate the effectiveness and safety of thalidomide in the prevention of CINV. Methods Of 89 patients enrolled, 83 chemotherapy-naïve patients receiving highly emetogenic chemotherapy (cisplatin 70mg/m2 were randomized into two groups: standard therapy group (ondansetron on day 1, metoclopramide and dexamethasone on days one to five and thalidomide group (in addition to standard emesis prevention, patients received oral 100mg thalidomide on days one to five. Patients recorded nausea and vomiting episodes in a diary. The primary end point was the efficacy of thalidomide in controlling vomiting and nausea on days one to five post cisplatin, and the secondary end point was the safety of the thalidomide. Results No significant differences of complete response rates (no emesis, no use of rescue therapy and no nausea were observed between the two groups, while the percentages of patients with complete response of delayed vomiting on day four and day five were higher in the thalidomide group, furthermore, the complete response rate of delayed nausea for thalidomide group and standard therapy group showed significant differences. Thalidomide group showed a similar safety profile as standard emesis prevention group. Conclusion Addition of thalidomide was generally well tolerated and improved prevention of CINV in patients receiving cisplatinbased chemotherapy to some degree, especially for delayed nausea.

Sequential transurethral surgery, multiple drug chemotherapy and radiation therapy for invasive bladder carcinoma: Initial report

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Cervek, J.; Cufer, T.; Kragelj, B.; Zakotnik, B.; Stanonik, M.

1993-01-01

Forty-seven patients with muscle-invasive bladder cancer (T2--T4, Nx, MO) were treated by transurethral resection, followed by 3--4 cycles of combination chemotherapy (methothrexate 30 mg/m2 on days 1, 14; cis-platinum 100 mg/m2 on day 2; vinblastine 3 mg/m2 on days 1, 14; repeated every 21 days), and external beam irradiation (64--66 Gy to the bladder and 40 Gy to the pelvic lymphatics). Complete remission after transurethral resection and chemotherapy was achieved in 24 out of 45 patients (53%). Cystectomy was performed in patients without complete response to transurethral resection and chemotherapy. The therapy was completed as planned in 45/47 patients. After transurethral resection, chemotherapy, and radiation therapy, biopsy proven complete response was achieved in 62% (28/45); Stage T2T3 in 67% (23/24), Stage T4 in 45% (5/11) of patients. Among 19 patients with positive biopsy findings after transurethral resection and chemotherapy, 14 underwent cystectomy. After follow-up of 4--55 months (median 23 months) 75% (34/45) are alive, 68% (31/45) have had their bladders preserved, and 53% (24/45) are free of the primary tumor. The actuarial survival of all 45 patients is 73%. Moderate nausea and vomiting during treatment were common; severe leukopenia and mucositis were observed in five patients. Late side effects such as miction disorders and diarrhea were predominantly mild. Although the observation period has been too short to allow a definitive evaluation of treatment results, the authors feel both from the point of bladder preservation and disease-free survival that the presented treatment approach is successful in a majority of T2T3 patients, whereas a large tumor size (T4) renders this treatment less effective. 17 refs., 4 figs., 4 tabs

High-dose simultaneously integrated breast boost using intensity-modulated radiotherapy and inverse optimization

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Hurkmans, Coen W.; Meijer, Gert J.; Vliet-Vroegindeweij, Corine van; Sangen, Maurice J. van der; Cassee, Jorien

2006-01-01

Purpose: Recently a Phase III randomized trial has started comparing a boost of 16 Gy as part of whole-breast irradiation to a high boost of 26 Gy in young women. Our main aim was to develop an efficient simultaneously integrated boost (SIB) technique for the high-dose arm of the trial. Methods and Materials: Treatment planning was performed for 5 left-sided and 5 right-sided tumors. A tangential field intensity-modulated radiotherapy technique added to a sequentially planned 3-field boost (SEQ) was compared with a simultaneously planned technique (SIB) using inverse optimization. Normalized total dose (NTD)-corrected dose volume histogram parameters were calculated and compared. Results: The intended NTD was produced by 31 fractions of 1.66 Gy to the whole breast and 2.38 Gy to the boost volume. The average volume of the PTV-breast and PTV-boost receiving more than 95% of the prescribed dose was 97% or more for both techniques. Also, the mean lung dose and mean heart dose did not differ much between the techniques, with on average 3.5 Gy and 2.6 Gy for the SEQ and 3.8 Gy and 2.6 Gy for the SIB, respectively. However, the SIB resulted in a significantly more conformal irradiation of the PTV-boost. The volume of the PTV-breast, excluding the PTV-boost, receiving a dose higher than 95% of the boost dose could be reduced considerably using the SIB as compared with the SEQ from 129 cc (range, 48-262 cc) to 58 cc (range, 30-102 cc). Conclusions: A high-dose simultaneously integrated breast boost technique has been developed. The unwanted excessive dose to the breast was significantly reduced

A Phase II feasibility study of oral etoposide given concurrently with radiotherapy followed by dose intensive adjuvant chemotherapy for children with newly diagnosed high-risk medulloblastoma (protocol POG 9631): A report from the Children's Oncology Group.

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Esbenshade, Adam J; Kocak, Mehmet; Hershon, Linda; Rousseau, Pierre; Decarie, Jean-Claude; Shaw, Susan; Burger, Peter; Friedman, Henry S; Gajjar, Amar; Moghrabi, Albert

2017-06-01

Children with high-risk medulloblastoma historically have had a poor prognosis. The Children's Oncology Group completed a Phase II study using oral etoposide given with radiotherapy followed by intensive chemotherapy. Patients enrolled in the study had high-risk disease defined as ≥1.5 cm 2 of residual disease postsurgery or definite evidence of central nervous metastasis. All patients underwent surgery followed by radiotherapy. During radiation, the patients received oral etoposide (21 days on, 7 off) at an initial dose of 50 mg/m 2 per day (treatment 1), which was reduced to 35 mg/m 2 per day (treatment 2) due to toxicity. After radiotherapy, the patients received chemotherapy with three cycles of cisplatin and oral etoposide, followed by eight courses of cyclophosphamide and vincristine. Between November 1998 and October 2002, 53 patients were accrued; 15 received treatment 1 and 38 treatment 2. Forty-seven patients (89%) were eligible. Response to radiation was excellent, with 19 (40.4%) showing complete response, 24 (51.1%) partial response, and four (8.5%) no recorded response. The overall 2- and 5-year progression-free survival (PFS) was 76.6 ± 6% and 70.2 ± 7%, respectively. The 2- and 5-year overall survival (OS) was 80.9 ± 6% and 76.6 ± 6%, respectively. Clinical response postradiation and PFS/OS were not significantly different between the treatment groups. There was a trend toward a difference in 5-year PFS between those without and with metastatic disease (P = 0.072). Oral etoposide was tolerable at 35 mg/m 2 (21 days on and 7 days off) when given during full-dose irradiation in patients with high-risk medulloblastoma with encouraging survival data. © 2016 Wiley Periodicals, Inc.

Risk and predictors for early radiation pneumonitis in patients with stage III non-small cell lung cancer treated with concurrent or sequential chemoradiotherapy

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Dang, Jun; Li, Guang; Zang, Shuang; Zhang, Shuo; Yao, Lei

2014-01-01

The rate of radiation pneumonitis (RP) for patients receiving chemoradiotherapy has been various across studies. Whether it is related to different chemotherapy schedules used in combination with radiation therapy were evaluated in this study. New factors associated with RP were also investigated. A total of 369 consecutive patients with Stage III non small cell lung cancer treated with chemoradiotherapy were followed after radiotherapy (RT). Among them 262 patients received concurrent chemoradiotherapy followed by consolidation chemotherapy and 107 patients received only sequential chemotherapy after RT. RP was graded according to Common Terminology Criteria for Adverse Events version 4.0. The rate of grade ≥ 2 were 39.7%, 31% and 33.6% in the concurrent DP (docetaxel/cisplatin), concurrent NP (vinorelbine/cisplatin) and sequential group, and grade ≥ 3 RP were 18.4%, 9.5%, and 11.2% respectively. The rate of grade ≥ 3 RP was significantly higher in concurrent DP group than that in concurrent NP group (p = 0.04). RP occurred earlier in concurrent DP group than that in the other two groups. There were no significant differences in response rate among the three groups. In the multivariate analysis, age (OR = 1.99, p = 0.038 and OR = 8.90, p < 0.001), chemotherapy schedule (OR = 1.45, p = 0.041 and OR = 1.98, p = 0.013), mean lung dose(OR = 1.42, p < 0.001 and OR = 1.64, p < 0.001), and planning target volume(OR = 1.004, p = 0.001 and OR = 1.005, p = 0.021) were predictors for both grade ≥ 2 and grade ≥ 3 RP. Response to treatment was a new predictor for grade ≥ 3 RP only (OR = 4.39, p = 0.034). Response to treatment was found to be a new predictor for grade ≥ 3 RP. Compared to concurrent NP schedule, concurrent DP schedule achieved similar response to treatment but resulted in a higher risk of grade ≥ 3 RP

A model to describe potential effects of chemotherapy on critical radiobiological treatments

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Rodríguez-Pérez, D.; Desco, M. M.; Antoranz, J. C.

2016-08-01

Although chemo- and radiotherapy can annihilate tumors on their own. they are also used in coadjuvancy: improving local effects of radiotherapy using chemotherapy as a radiosensit.izer. The effects of radiotherapy are well described by current radiobiological models. The goal of this work is to describe a discrete radiotherapy model, that has been previously used describe high radiation dose response as well as unusual radio-responses of some types of tumors (e.g. prostate cancer), to obtain a model of chemo+radiotherapy that can describe how the outcome of their combination is a more efficient removal of the tumor. Our hypothesis is that, although both treatments haven different mechanisms, both affect similar key points of cell metabolism and regulation, that lead to cellular death. Hence, we will consider a discrete model where chemotherapy may affect a fraction of the same targets destroyed by radiotherapy. Although radiotherapy reaches all cells equally, chemotherapy diffuses through a tumor attaining lower concentration in its center and higher in its surface. With our simulations we study the enhanced effect of combined therapy treatment and how it depends on the tissue critical parameters (the parameters of the lion-extensive radiobiological model), the number of “targets” aimed at by chemotherapy, and the concentration and diffusion rate of the drug inside the tumor. The results show that an equivalent, cliemo-radio-dose can be computed that allows the prediction of the lower radiation dose that causes the same effect than a radio-only treatment.

Phase I Study of Concurrent High-Dose Three-Dimensional Conformal Radiotherapy With Chemotherapy Using Cisplatin and Vinorelbine for Unresectable Stage III Non-Small-Cell Lung Cancer

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Sekine, Ikuo, E-mail: isekine@ncc.go.jp [Division of Internal Medicine and Thoracic Oncology, National Cancer Center Hospital, Tokyo (Japan); Sumi, Minako; Ito, Yoshinori [Division of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan); Horinouchi, Hidehito; Nokihara, Hiroshi; Yamamoto, Noboru; Kunitoh, Hideo; Ohe, Yuichiro; Kubota, Kaoru; Tamura, Tomohide [Division of Internal Medicine and Thoracic Oncology, National Cancer Center Hospital, Tokyo (Japan)

2012-02-01

Purpose: To determine the maximum tolerated dose in concurrent three-dimensional conformal radiotherapy (3D-CRT) with chemotherapy for unresectable Stage III non-small-cell lung cancer (NSCLC). Patients and Methods: Eligible patients with unresectable Stage III NSCLC, age {>=}20 years, performance status 0-1, percent of volume of normal lung receiving 20 GY or more (V{sub 20}) {<=}30% received three to four cycles of cisplatin (80 mg/m{sup 2} Day 1) and vinorelbine (20 mg/m{sup 2} Days 1 and 8) repeated every 4 weeks. The doses of 3D-CRT were 66 Gy, 72 Gy, and 78 Gy at dose levels 1 to 3, respectively. Results: Of the 17, 16, and 24 patients assessed for eligibility, 13 (76%), 12 (75%), and 6 (25%) were enrolled at dose levels 1 to 3, respectively. The main reasons for exclusion were V{sub 20} >30% (n = 10) and overdose to the esophagus (n = 8) and brachial plexus (n = 2). There were 26 men and 5 women, with a median age of 60 years (range, 41-75). The full planned dose of radiotherapy could be administered to all the patients. Grade 3-4 neutropenia and febrile neutropenia were noted in 24 (77%) and 5 (16%) of the 31 patients, respectively. Grade 4 infection, Grade 3 esophagitis, and Grade 3 pulmonary toxicity were noted in 1 patient, 2 patients, and 1 patient, respectively. The dose-limiting toxicity was noted in 17% of the patients at each dose level. The median survival and 3-year and 4-year survival rates were 41.9 months, 72.3%, and 49.2%, respectively. Conclusions: 72 Gy was the maximum dose that could be achieved in most patients, given the predetermined normal tissue constraints.

High-dose myeloablative versus conventional low-dose radioimmunotherapy (RIT) of mantle cell lymphoma (MCL) with the chimeric anti-CD20 antibody C2B8

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Behr, T.M.; Gotthardt, M.; Schipperm, M.L.; Gratz, S.; Behe, M.P.; Brittinger, G.; Woermann, B.; Becker, W.

2002-01-01

CD20 has been used as target molecule for low-dose as well as high-dose, myeloablative RIT of B-cell NHL. MCL is an especially aggressive, prognostically unfavorable form of B-cell NHL. The aim of this study was to investigate whether high-dose, myeloablative RIT with the 131 I-labeled chimeric anti-CD20 antibody C2B8 (rituxan, Mabthera, Roche) may be therapeutically more effective than conventional low-dose therapy in MCL. A total of twelve patients with chemorefractory or relapsed mantle cell lymphoma were studied so far (all of them having relapsed after high-dose chemotherapy, seven of them combined with 12 Gy TBI). A diagnostic-dosimetric study was performed with 10 mCi of 131 I-C2B8 at a protein dose of 2.5 mg/kg. In case of splenic pooling, the protein dose was increased until a more 'favorable' biodistribution was obtained. Therapy was performed with conventional (30-75 mCi; n=4) or myeloablative activities (261-515 mCi; n=8) of 131 I-C2B8 at the previously optimized protein dose, aiming at whole-body doses of ≤ 0.8 Gy (for low-dose RIT) or lung doses of ≤ 27 Gy (for high-dose RIT). Clinical follow-up was obtained for up to 42 months. Overall, in 11 patients the 2.5 mg/kg protein dose was used, whereas in one patient with marked splenomegaly, 10 mg/kg were necessary to overcome the splenic antigenic sink. In the high-dose patients, non-hematologic toxicity was restricted to mild to moderate nausea, fever, transient bilirubin or liver enzyme elevations. Despite thyroid blocking, 6/8 high-dose (in contrast to 0/4 low-dose) patients developed hypothyroidism, requiring thyroxine substitution at 6-18 months after RIT. The response rate in the low-dose arm was only 1(PR)/4, whereas 7/8 high-dose patients experienced complete and the remainder a partial remission. 6 high-dose patients are still in CR (one of them relapsed locally at 3 months, one systemically at 26 months after RIT), and 7 are still alive for up to 42+ months. In contrast to low-dose therapy

Simultaneous integrated vs. sequential boost in VMAT radiotherapy of high-grade gliomas

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Farzin, Mostafa [Klinikum rechts der Isar, Technische Universitaet Muenchen, Department of Radiation Oncology, Munich (Germany); Tehran University of Medical Science, Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran (Iran, Islamic Republic of); Molls, Michael; Astner, Sabrina; Oechsner, Markus [Klinikum rechts der Isar, Technische Universitaet Muenchen, Department of Radiation Oncology, Munich (Germany); Rondak, Ina-Christine [Klinikum rechts der Isar, Technische Universitaet Muenchen, Institut fuer Medizinische Statistik und Epidemiologie, Munich (Germany)

2015-12-15

In 20 patients with high-grade gliomas, we compared two methods of planning for volumetric-modulated arc therapy (VMAT): simultaneous integrated boost (SIB) vs. sequential boost (SEB). The investigation focused on the analysis of dose distributions in the target volumes and the organs at risk (OARs). After contouring the target volumes [planning target volumes (PTVs) and boost volumes (BVs)] and OARs, SIB planning and SEB planning were performed. The SEB method consisted of two plans: in the first plan the PTV received 50 Gy in 25 fractions with a 2-Gy dose per fraction. In the second plan the BV received 10 Gy in 5 fractions with a dose per fraction of 2 Gy. The doses of both plans were summed up to show the total doses delivered. In the SIB method the PTV received 54 Gy in 30 fractions with a dose per fraction of 1.8 Gy, while the BV received 60 Gy in the same fraction number but with a dose per fraction of 2 Gy. All of the OARs showed higher doses (D{sub max} and D{sub mean}) in the SEB method when compared with the SIB technique. The differences between the two methods were statistically significant in almost all of the OARs. Analysing the total doses of the target volumes we found dose distributions with similar homogeneities and comparable total doses. Our analysis shows that the SIB method offers advantages over the SEB method in terms of sparing OARs. (orig.) [German] Es wurden 2 Arten der Planung fuer die volumetrisch modulierte Rotationsbestrahlung (VMAT) bei 20 Patienten mit hochgradigen Gliomen verglichen: simultan integrierter Boost (SIB) und sequenzieller Boost (SEB). Dazu wurde die Dosisverteilung in den Zielvolumina und den Risikoorganen analysiert. Es wurden Planungsvolumina (PTV), Boostvolumina (BV) und Risikoorgane konturiert sowie SIB- und SEB-Plaene erstellt. Der SEB besteht aus 2 Plaenen. Im ersten Plan erhaelt das PTV 50 Gy in 25 Fraktionen. Im zweiten Plan erhaelt das Boostvolumen 10 Gy in 5 Fraktionen (Einzeldosis jeweils 2 Gy). Die Dosis

Breast Conserving Treatment for Breast Cancer: Dosimetric Comparison of Sequential versus Simultaneous Integrated Photon Boost

Directory of Open Access Journals (Sweden)

Hilde Van Parijs

2014-01-01

Full Text Available Background. Breast conserving surgery followed by whole breast irradiation is widely accepted as standard of care for early breast cancer. Addition of a boost dose to the initial tumor area further reduces local recurrences. We investigated the dosimetric benefits of a simultaneously integrated boost (SIB compared to a sequential boost to hypofractionate the boost volume, while maintaining normofractionation on the breast. Methods. For 10 patients 4 treatment plans were deployed, 1 with a sequential photon boost, and 3 with different SIB techniques: on a conventional linear accelerator, helical TomoTherapy, and static TomoDirect. Dosimetric comparison was performed. Results. PTV-coverage was good in all techniques. Conformity was better with all SIB techniques compared to sequential boost (P = 0.0001. There was less dose spilling to the ipsilateral breast outside the PTVboost (P = 0.04. The dose to the organs at risk (OAR was not influenced by SIB compared to sequential boost. Helical TomoTherapy showed a higher mean dose to the contralateral breast, but less than 5 Gy for each patient. Conclusions. SIB showed less dose spilling within the breast and equal dose to OAR compared to sequential boost. Both helical TomoTherapy and the conventional technique delivered acceptable dosimetry. SIB seems a safe alternative and can be implemented in clinical routine.

The effects of sequence and type of chemotherapy and radiation therapy on cosmesis and complications after breast conservation therapy

International Nuclear Information System (INIS)

Markiewicz, Deborah A.; Schultz, Delray J.; Haas, Jonathan A.; Harris, Eleanor E. R.; Fox, Kevin R.; Glick, John H.; Solin, Lawrence J.

1996-01-01

Purpose: Chemotherapy plays an increasingly important role in the treatment of both node-negative and node-positive breast cancer patients, but the optimal sequencing of chemotherapy and radiation therapy is not well established. The purpose of this study is to evaluate the interaction of sequence and type of chemotherapy and hormonal therapy given with radiation therapy on the cosmetic outcome and the incidence of complications of Stage I and II breast cancer patients treated with breast-conserving therapy. Methods and Materials: The records of 1053 Stage I and II breast cancer patients treated with curative intent with breast-conserving surgery, axillary dissection, and radiation therapy between 1977-1991 were reviewed. Median follow-up after treatment was 6.7 years. Two hundred fourteen patients received chemotherapy alone, 141 patients received hormonal therapy alone, 86 patients received both, and 612 patients received no adjuvant therapy. Patients who received chemotherapy ± hormonal therapy were grouped according to sequence of chemotherapy: (a) concurrent = concurrent chemotherapy with radiation therapy followed by chemotherapy; (b) sequential = radiation followed by chemotherapy or chemotherapy followed by radiation; and (c) sandwich = chemotherapy followed by concurrent chemotherapy and radiation followed by chemotherapy. Compared to node negative patients, node-positive patients more commonly received chemotherapy (77 vs. 9%, p < 0.0001) and/or hormonal therapy (40 vs. 14%, p < 0.0001). Among patients who received chemotherapy, the majority (243 patients) received concurrent chemotherapy and radiation therapy with two cycles of cytoxan and 5-fluorouracil (5-FU) administered during radiation followed by six cycles of chemotherapy with cytoxan, 5-fluorouracil and either methotrexate(CMF) or doxorubicin(CAF). For analysis of cosmesis, patients included were relapse free with 3 years minimum follow-up. Results: The use of chemotherapy had an adverse effect

Esophageal Toxicity From High-Dose, Single-Fraction Paraspinal Stereotactic Radiosurgery

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Cox, Brett W.; Jackson, Andrew; Hunt, Margie; Bilsky, Mark; Yamada, Yoshiya

2012-01-01

Purpose: To report the esophageal toxicity from single-fraction paraspinal stereotactic radiosurgery (SRS) and identify dosimetric and clinical risk factors for toxicity. Methods and Materials: A total of 204 spinal metastases abutting the esophagus (182 patients) were treated with high-dose single-fraction SRS during 2003-2010. Toxicity was scored using the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 4.0. Dose-volume histograms were combined to generate a comprehensive atlas of complication incidence that identifies risk factors for toxicity. Correlation of dose-volume factors with esophageal toxicity was assessed using Fisher’s exact test and logistic regression. Clinical factors were correlated with toxicity. Results: The median dose to the planning treatment volume was 24 Gy. Median follow-up was 12 months (range, 3-81). There were 31 (15%) acute and 24 (12%) late esophageal toxicities. The rate of grade ≥3 acute or late toxicity was 6.8% (14 patients). Fisher’s exact test resulted in significant median splits for grade ≥3 toxicity at V12 = 3.78 cm 3 (relative risk [RR] 3.7, P=.05), V15 = 1.87 cm 3 (RR 13, P=.0013), V20 = 0.11 cm 3 (RR 6, P=0.01), and V22 = 0.0 cm 3 (RR 13, P=.0013). The median split for D2.5 cm 3 (14.02 Gy) was also a significant predictor of toxicity (RR 6; P=.01). A highly significant logistic regression model was generated on the basis of D2.5 cm 3 . One hundred percent (n = 7) of grade ≥4 toxicities were associated with radiation recall reactions after doxorubicin or gemcitabine chemotherapy or iatrogenic manipulation of the irradiated esophagus. Conclusions: High-dose, single-fraction paraspinal SRS has a low rate of grade ≥3 esophageal toxicity. Severe esophageal toxicity is minimized with careful attention to esophageal doses during treatment planning. Iatrogenic manipulation of the irradiated esophagus and systemic agents classically associated with radiation recall reactions are

Methods, safety, and early clinical outcomes of dose escalation using simultaneous integrated and sequential boosts in patients with locally advanced gynecologic malignancies.

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Boyle, John; Craciunescu, Oana; Steffey, Beverly; Cai, Jing; Chino, Junzo

2014-11-01

To evaluate the safety of dose escalated radiotherapy using a simultaneous integrated boost technique in patients with locally advanced gynecological malignancies. Thirty-nine women with locally advanced gynecological malignancies were treated with intensity modulated radiation therapy utilizing a simultaneous integrated boost (SIB) technique for gross disease in the para-aortic and/or pelvic nodal basins, sidewall extension, or residual primary disease. Women were treated to 45Gy in 1.8Gy fractions to elective nodal regions. Gross disease was simultaneously treated to 55Gy in 2.2Gy fractions (n=44 sites). An additional sequential boost of 10Gy in 2Gy fractions was delivered if deemed appropriate (n=29 sites). Acute and late toxicity, local control in the treated volumes (LC), overall survival (OS), and distant metastases (DM) were assessed. All were treated with a SIB to a dose of 55Gy. Twenty-four patients were subsequently treated with a sequential boost to a median dose of 65Gy. Median follow-up was 18months. Rates of acute>grade 2 gastrointestinal (GI), genitourinary (GU), and hematologic (heme) toxicities were 2.5%, 0%, and 30%, respectively. There were no grade 4 acute toxicities. At one year, grade 1-2 late GI toxicities were 24.5%. There were no grade 3 or 4 late GI toxicities. Rates of grade 1-2 late GU toxicities were 12.7%. There were no grade 3 or 4 late GU toxicities. Dose escalated radiotherapy using a SIB results in acceptable rates of acute toxicity. Copyright © 2014 Elsevier Inc. All rights reserved.

Phase I and pharmacokinetic study of preirradiation chemotherapy with BCNU, cisplatin, etoposide, and accelerated radiation therapy in patients with high-grade glioma

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Rajkumar, S. Vincent; Buckner, Jan C.; Schomberg, Paula J.; Reid, Joel M.; Bagniewski, Pamela J.; Ames, Matthew M.; Cascino, Terrence L.; Marks, Randolph S.

1998-01-01

Purpose: We conducted a Phase I study of bischloroethylnitrosourea (BCNU), cisplatin, and oral etoposide administered prior to and during accelerated hyperfractionated radiation therapy in newly diagnosed high-grade glioma. Pharmacokinetic studies of oral etoposide were also done. Methods and Materials: Patients started chemotherapy after surgery but prior to definitive radiation therapy (160 cGy twice daily x 15 days; 4800 cGy total). Initial chemotherapy consisted of BCNU 40 mg/m 2 days 1-3, cisplatin 30 mg/m 2 days 1-3 and 29-31, and etoposide 50 mg orally days 1-14 and 29-42, repeated in 8 weeks concurrent with radiation therapy. BCNU 200 mg/m 2 every 8 weeks x 4 cycles was given after radiation therapy. Results: Sixteen patients, 5 with grade 3 anaplastic astrocytoma and 11 with glioblastoma were studied. Grade 3-4 leukopenia (38%) and thrombocytopenia (31%) were dose-limiting. Other toxicities were anorexia (81%), nausea (94%), emesis (56%), alopecia (88%), and ototoxicity (38%). The maximum tolerated dose was BCNU 40 mg/m 2 days 1-3, cisplatin 20 mg/m 2 days 1-3 and 29-31, and oral etoposide 50 mg days 1-21 and 29-49 prior to radiation therapy and repeated in 8 weeks with the start of radiation therapy followed by BCNU 200 mg/m 2 every 8 weeks for 4 cycles. Median time to progression and survival were 13 and 14 months respectively. Responses occurred in 2 of 9 (22%) patients with evaluable disease. In pharmacokinetic studies, all patients achieved plasma concentrations of >0.1 μg/ml etoposide (the in vitro radiosensitizing threshold), following a 50 mg oral dose. The mean ± SD 2 hr and 6 hr plasma concentrations were 0.92 ± 0.43 μg/ml and 0.36 ± 0.12 μg/ml, respectively. Estimated duration of exposure to >0.1 μg/ml etoposide was 10-17 hr. Conclusions: Preirradiation chemotherapy with BCNU, cisplatin, and oral etoposide with accelerated hyperfractionated radiation therapy in high-grade gliomas is feasible and merits further investigation. Sustained

Effect of Concurrent High-Dose Cisplatin Chemotherapy and Conformal Radiotherapy on Cervical Esophageal Cancer Survival

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Huang Shaohui; Lockwood, Gina; Brierley, James; Cummings, Bernard; Kim, John; Wong, Rebecca; Bayley, Andrew; Ringash, Jolie

2008-01-01

Purpose: To determine whether a change in treatment policy to conformal, elective nodal radiotherapy and concurrent high-dose cisplatin improved survival for cervical esophageal cancer patients. Methods and Materials: All cervical esophageal cancer patients treated between 1997 and 2005 were restaged (1983 American Joint Committee on Cancer criteria). Patients treated before 2001 (previous cohort [PC]) were compared with those treated from 2001 onward (recent cohort [RC]). The PC institutional chemoradiotherapy protocol was 54 Gy in 20 fractions within 4 weeks, with 5-fluorouracil (1,000 mg/m 2 ) on Days 1-4 and either mitomycin C (10 mg/m 2 ) or cisplatin (75 mg/m 2 ) on Day 1. The RC institutional chemoradiotherapy protocol was conformal radiotherapy, 70 Gy in 35 fractions within 7 weeks, to the primary tumor and elective nodes, with high-dose cisplatin (100 mg/m 2 ) on Days 1, 22, and 43. Results: The median follow-up was 3.1 years (PC, 8.1 and RC, 2.3). Of 71 patients (25 women and 46 men), 21 of 29 in the PC and 29 of 42 in the RC were treated curatively (curative subgroup, n = 50). Between the two groups, no differences in overall survival or locoregional relapse-free survival were seen. The overall survival rate at 2 and 5 years was 35% (range, 24-47%) and 21% (range, 12-32%) in the whole group and 46% (range 32-60%) and 28% (range, 15-42%) in the curative group, respectively. In the curative group, no statistically significant prognostic factors were found. Trends toward better locoregional relapse-free survival were seen in women (2-year rate, 73% vs. for men, 36%; p = 0.08) and in patients aged >64 years (2-year rate, 68% vs. age ≤64 years, 34%; p = 0.10). Conclusion: No survival improvement could be demonstrated after changing the treatment policy to high-dose cisplatin-based, conventionally fractionated conformal chemoradiotherapy. Female gender and older age might predict for better outcomes

Use of maintenance endocrine therapy after chemotherapy in metastatic breast cancer.

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Sutherland, S; Miles, D; Makris, A

2016-12-01

For women with oestrogen receptor+ metastatic breast cancer (MBC), the options for systemic treatment include endocrine therapy (ET) and chemotherapy. For women whose disease is also HER2+, anti-HER2 therapies are also routinely used either with chemotherapy or less commonly with ET. Where chemotherapy is used as initial therapy, treatment is often discontinued due to cumulative toxicity in the absence of disease progression. In this setting, there is the option of introducing ET with the aim of prolonging response and delaying relapse. Literature review revealed four trials addressing the question of whether there is a benefit from introducing ET following chemotherapy for MBC. We also sought evidence for alternative approaches, including concurrent chemotherapy and ET and continuing chemotherapy until disease progression. The evidence for the use of ET after chemotherapy in MBC is limited, and the trials done were small. Furthermore, they were performed at a time when both the chemotherapy regimens and ET were different from those used currently. Despite these limitations, there is probably a modest improvement in time to progression for the sequential use of ET after chemotherapy but with no overall survival benefit. An alternative approach, particularly considering agents with relatively low toxicity, such as orally bioavailable fluoropyrimidines, is to continue chemotherapy until disease progression. Where chemotherapy for MBC is discontinued due to toxicity, in the absence of progression, the use of ET, with its relatively low toxicity, is a reasonable approach with the aim of delaying relapse. Copyright © 2016. Published by Elsevier Ltd.

The Results of Radiation Therapy Alone vs Radiation Plus Chemotherapy of Uterine Cervix Cancer

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Lee, Myung Za; Choi, Suk Young; Chun, Ha Jeong

1995-01-01

Purpose : Radiation therapy(RT) is conventionally standard treatment for locally advanced stage for uterine cervix cancer. Recently to improve treatment results, combined chemotherapy and radiation therapy was tried. We retrospectively analysed our experience of 122 patients. Comparison of the results in 45 patients treated with RT alone and 77 patients treated with RT plus chemotherapy was made. Materials and Methods : from January 1985 to December 1991, 122 patients with cervix cancer were treated with whole pelvic external RT and ICR(34 1 ICR, 77 2 ICR, 11 high dose rate ICR) in our department. Forty five patients were treated with RT alone, and 77 patients were treated with combined plus chemotherapy. Mean age was 58 years(range:29-81). Histologic types were 111 squamous cell carcinoma, large cell carcinoma, 3 adenocarcinoma, and 2 adenosquamous cell carcinoma. According to the FIGO stage 6 had stage IA94.9%, 11 had IIA(9.0%), 37 had IIB(30.3%), 3 had IIA(2.5%), 63 had IIB(51.6%), and 2 had stage IV(1.6%). In 77 patients with RT plus chemotherapy, 36 patients were treated with VBP(vinblastin, bleoycin, cisplainum), 39 patients with cisplatinum plus 5-FU and 2 patients with 5-FU. Results : Complete response after external RT(3960cGy-5500cGy)was achieved in 61 patients(50%). He actuarial 5 year and 9 year survival rate was 57.8% and 53.9%, respectively. Five year actuarial survival rate was 63.1% with RT alone(n=45) and 55.9% with RT plus chemotherapy(n=77). Their 5 year survival rate was 35.5% for 1 course of ICR and 67% for 2 courses of ICR. There was statistically significant advantage of survival with RT alone group who were treated with 2 coursed of ICR and dose to the A point≥8000cGy(4/25 died). In RT plus chemotherapy group, dose response was not seen and there was no difference in 5 year survival between 1 course and 2 course of ICR(50% vs 56.8%), and dose to point A less than 8000cGy and more than 8000 cGy(55.6% vs 55.7%). There was no significant

Comparative trial of two intravenous doses of granisetron (1 versus 3 mg) in the prevention of chemotherapy-induced acute emesis: a double-blind, randomized, non-inferiority trial.

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Tsuji, Daiki; Kim, Yong-Il; Taku, Keisei; Nakagaki, Shigeru; Ikematsu, Yoshito; Tsubota, Hiromi; Maeda, Masato; Hashimoto, Naoya; Kimura, Masayuki; Daimon, Takashi

2012-05-01

A single 3 mg or 40 μg/kg intravenous dose of granisetron combined with dexamethasone is routinely used in several countries, although the antiemetic guidelines have recommended granisetron at the dose of 1 mg or 10 μg/kg. A randomized, multicenter trial was conducted to determine the optimal intravenous granisetron dose, 1 or 3 mg, in cancer patients receiving emetogenic chemotherapy. We enrolled 365 patients and randomly assigned them to receive intravenous granisetron 3 mg (3-mg group) or 1 mg (1-mg group), combined with dexamethasone at an adequate dose fixed as per the emetic risk category. The primary end point was the proportion of patients with a complete response during the first 24 h after chemotherapy. The study demonstrated that 1 mg of granisetron was not inferior in effect to 3 mg. For the primary end point, 359 patients were evaluable according to the modified intention-to-treat (ITT) analysis. Complete protection was achieved in the modified ITT population, 90.6% and 88.8% for the 3- and 1-mg groups, respectively (p granisetron is not inferior to 3 mg when both doses are combined with dexamethasone. Therefore, 1-mg dose of intravenous granisetron should be the recommended prophylactic regimen for the prevention of acute emesis.

Application of mathematical models to metronomic chemotherapy: What can be inferred from minimal parameterized models?

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Ledzewicz, Urszula; Schättler, Heinz

2017-08-10

Metronomic chemotherapy refers to the frequent administration of chemotherapy at relatively low, minimally toxic doses without prolonged treatment interruptions. Different from conventional or maximum-tolerated-dose chemotherapy which aims at an eradication of all malignant cells, in a metronomic dosing the goal often lies in the long-term management of the disease when eradication proves elusive. Mathematical modeling and subsequent analysis (theoretical as well as numerical) have become an increasingly more valuable tool (in silico) both for determining conditions under which specific treatment strategies should be preferred and for numerically optimizing treatment regimens. While elaborate, computationally-driven patient specific schemes that would optimize the timing and drug dose levels are still a part of the future, such procedures may become instrumental in making chemotherapy effective in situations where it currently fails. Ideally, mathematical modeling and analysis will develop into an additional decision making tool in the complicated process that is the determination of efficient chemotherapy regimens. In this article, we review some of the results that have been obtained about metronomic chemotherapy from mathematical models and what they infer about the structure of optimal treatment regimens. Copyright © 2017 Elsevier B.V. All rights reserved.

Acute toxicity of postoperative IMRT and chemotherapy for endometrial cancer

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Tierney, R.M.; Powell, M.A.; Mutch, D.G.; Gibb, R.K.; Rader, J.S.; Grigsby, P.W.

2007-01-01

The aim of this study was to determine the acute toxicity of postoperative intensity-modulated radiotherapy (IMRT) with and without chemotherapy in patients with endometrial cancer. A total of 19 patients with stages IB-IVB endometrial cancer who underwent surgery and postoperative IMRT were reviewed. The treatment planning goal was to cover the tissue at risk and minimize the dose to the bladder, bowel, and bone marrow. Median dose was 50.4 Gy (range 49.6-51.2 Gy). Altogether, 14 patients underwent chemotherapy; most were given carboplatin and paclitaxel. Toxicity was scored according to the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE). The prescribed radiation treatment was completed in all patients. The prescribed cycles of chemotherapy were completed in all 14 patients, except one who received five of six cycles limited by prolonged thrombocytopenia. Chemotherapy was delayed in two patients (14%). Three patients required growth factor support during chemotherapy, and one patient required a blood transfusion. Acute grades 3-4 hematological toxicity occurred in 9 of the 14 patients (64%) who underwent chemotherapy. None experienced acute grade 3 or 4 genitourinary or gastrointestinal toxicity. Adjuvant IMRT and chemotherapy following surgery in patients with endometrial cancer is well tolerated and did not lead to treatment modification in most patients. (author)

Chemotherapy followed by low dose radiotherapy in childhood Hodgkin's disease: retrospective analysis of results and prognostic factors

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Viani, Gustavo A; Castilho, Marcus S; Novaes, Paulo E; Antonelli, Celia G; Ferrigno, Robson; Pellizzon, Cassio A; Fogaroli, Ricardo C; Conte, Maria A; Salvajoli, Joao V

2006-01-01

To report the treatment results and prognostic factors of childhood patients with Hodgkin's disease treated with chemotherapy (CT) followed by low dose radiotherapy (RT). This retrospective series analyzed 166 patients under 18 years old, treated from January 1985 to December 2003. Median age was 10 years (range 2–18). The male to female ratio was 2,3 : 1. Lymphonode enlargement was the most frequent clinical manifestation (68%), and the time of symptom duration was less than 6 months in 55% of the patients. In histological analysis Nodular Sclerosis was the most prevalent type (48%) followed by Mixed Celularity (34.6%). The staging group according Ann Arbor classification was: I (11.7%), II (36.4%), III (32.1%) and IV (19.8%). The standard treatment consisted of chemotherapy multiple drug combination according the period of treatment protocols vigent: ABVD in 39% (n-65) of the cases, by VEEP in 13 %(n-22), MOPP in 13 %(n-22), OPPA-13 %(n-22) and ABVD/OPPA in 22 %(n-33). Radiotherapy was device to all areas of initial presentation of disease. Dose less or equal than 21 Gy was used in 90.2% of patients with most part of them (90%) by involved field (IFRT) or mantle field. The OS and EFS in 10 years were 89% and 87%. Survival according to clinical stage as 94.7%, 91.3%, 82.3% and 71% for stages I to IV(p = 0,005). The OS was in 91.3% of patients who received RT and in 72.6% of patients who did not (p = 0,003). Multivariate analysis showed presence of B symptoms, no radiotherapy and advanced clinical stage to be associated with a worse prognosis. This data demonstrating the importance of RT consolidation with low dose and reduced volume, in all clinical stage of childhood HD, producing satisfactory ten years OS and EFS. As the disease is highly curable, any data of long term follow-up should be presented in order to better direct therapy, and to identify groups of patients who would not benefit from radiation treatment

Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy

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Hana Starobova

2017-05-01

Full Text Available Chemotherapy-induced neuropathy is a common, dose-dependent adverse effect of several antineoplastics. It can lead to detrimental dose reductions and discontinuation of treatment, and severely affects the quality of life of cancer survivors. Clinically, chemotherapy-induced peripheral neuropathy presents as deficits in sensory, motor, and autonomic function which develop in a glove and stocking distribution due to preferential effects on longer axons. The pathophysiological processes are multi-factorial and involve oxidative stress, apoptotic mechanisms, altered calcium homeostasis, axon degeneration and membrane remodeling as well as immune processes and neuroinflammation. This review focusses on the commonly used antineoplastic substances oxaliplatin, cisplatin, vincristine, docetaxel, and paclitaxel which interfere with the cancer cell cycle—leading to cell death and tumor degradation—and cause severe acute and chronic peripheral neuropathies. We discuss drug mechanism of action and pharmacokinetic disposition relevant to the development of peripheral neuropathy, the epidemiology and clinical presentation of chemotherapy-induced neuropathy, emerging insight into genetic susceptibilities as well as current understanding of the pathophysiology and treatment approaches.

Comparison of the bronchodilatation produced by inhalation of ipratropium bromide and salbutamol sequentially and in fixed dose combination in stable bronchial asthma patients

Directory of Open Access Journals (Sweden)

Mohan A

2006-01-01

Full Text Available Objectives : The combination of a 43-2 agonist and an anticholinergic agent is of-ten used to manage bronchial asthma. However, it is unclear whether these drugs should be given separately in sequence or in a fixed dose combination for maximum effect. Methods : 27 patients with stable bronchial asthma were given the above two drugs in two separate sessions one week apart. In one session they were given the above two drugs as a fixed dose combination and in the other session, they were given se-quentially with salbutamol following ipratropium after 30 minutes. Spirometry was performed at baseline and 15, 30 and 60 minutes after inhaling the second drug. Results : Both groups showed significant improvement in forced vital capacity (FVC, forced expiratory time in one second (FEV 1 , peak expiratory flow rate (PEFR and forced expiratory flow (FEF 25-75 from baseline upto one hour. FVC increased initially and then stabilized; however, the increase was more sustained in the group getting combination treatment. This group also showed a higher rise in FEV 1 (p=0.02. Both FEV 1 and FEF 25-75 decreased after 30 minutes in the group that received sequential therapy. PEFR increased continuously till 60 minutes in both groups and there was no significant difference between them (p=0.98. Interpretation and Conclusion: Both methods of drug dosing produce equivalent bronchodilation. Fixed dose combinations produced a more sustained rise in FVC and higher increase in FEV 1 . Hence fixed dose combinations are more effective short-term bronchodilators and give an added advantage of reducing the number of inhalers required, thus improv-ing compliance.

Dose-intensive chemotherapy including rituximab is highly effective but toxic in human immunodeficiency virus-infected patients with Burkitt lymphoma/leukemia: parallel study of 81 patients.

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Xicoy, Blanca; Ribera, Josep-Maria; Müller, Markus; García, Olga; Hoffmann, Christian; Oriol, Albert; Hentrich, Marcus; Grande, Carlos; Wasmuth, Jan-Christian; Esteve, Jordi; van Lunzen, Jan; Del Potro, Eloy; Knechten, Heribert; Brunet, Salut; Mayr, Christoph; Escoda, Lourdes; Schommers, Philipp; Alonso, Natalia; Vall-Llovera, Ferran; Pérez, Montserrat; Morgades, Mireia; González, José; Fernández, Angeles; Thoden, Jan; Gökbuget, Nicola; Hoelzer, Dieter; Fätkenheuer, Gerd; Wyen, Christoph

2014-10-01

The results of intensive immunochemotherapy were analyzed in human immunodeficiency virus (HIV)-related Burkitt lymphoma/leukemia (BLL) in two cohorts (Spain and Germany). Alternating cycles of chemotherapy were administered, with dose reductions for patients over 55 years. Eighty percent of patients achieved remission, 11% died during induction, 9% failed and 7% died in remission. Four-year overall survival (OS) and progression-free survival (PFS) probabilities were 72% (95% confidence interval [CI]: 62-82%) and 71% (95% CI: 61-81%). CD4 T-cell count 2 (odds ratio [OR] 11.9 [1.4-99.9]) with induction death. In HIV-related BLL, intensive immunochemotherapy was feasible and effective, but toxic. Prognostic factors were performance status, CD4 T-cell count and bone marrow involvement.

Avascular necrosis of femoral and/or humeral heads in multiple myeloma: results of a prospective study of patients treated with dexamethasone-based regimens and high-dose chemotherapy.

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Talamo, Giampaolo; Angtuaco, Edgardo; Walker, Ronald C; Dong, Li; Miceli, Marisa H; Zangari, Maurizio; Tricot, Guido; Barlogie, Bart; Anaissie, Elias

2005-08-01

To assess the prevalence, time of onset, risk factors, and outcome of avascular necrosis (AVN) of bone in patients with multiple myeloma undergoing antineoplastic therapy. A total of 553 consecutive assessable patients were enrolled onto a treatment protocol consisting of dexamethasone-containing induction chemotherapy, autologous stem-cell transplantation, consolidation chemotherapy, and maintenance with interferon alfa. Patients were randomly assigned to receive thalidomide (269 patients) or no thalidomide (284 patients) throughout the study period. With a median follow-up of 33 months (range, 5 to 114 months), AVN of the femoral head(s) developed in 49 patients (9%). Median time to onset of AVN was 12 months (range, 2 to 41 months). Three risk factors for AVN were identified by multivariate analysis: cumulative dexamethasone dose (odds ratio [OR], 1.028; 95% CI, 1.012 to 1.044; P = .0006 [per 40 mg dexamethasone]), male sex (OR, 0.390; 95% CI, 0.192 to 0.790; P = .009), and younger age (OR, 0.961; 95% CI, 0.934 to 0.991 per year; P = .0122). Thalidomide-treated patients had a prevalence of AVN similar to that of the control group (8% v 10%, respectively; P = .58). AVN-related pain and limited range of motion of the affected joint were present in only nine and four patients, respectively, and four patients underwent hip replacement because of AVN. Fluorine-18 fluorodeoxyglucose positron emission tomography failed to detect abnormal uptake in the AVN-affected bones. AVN is a rare and usually asymptomatic complication during myeloma therapy. Cumulative dexamethasone dose, male sex, and younger age, but not thalidomide, increase the risk of AVN.

Dose-escalated CHOP plus etoposide (MegaCHOEP) followed by repeated stem cell transplantation for primary treatment of aggressive high-risk non-Hodgkin lymphoma

NARCIS (Netherlands)

Glass, B; Kloess, M; Bentz, M; Schlimok, G; Berdel, WE; Feller, A; Trumper, L; Loeffler, M; Pfreundschuh, M; Schmitz, N

2006-01-01

Feasibility, safety, and efficacy of a 4-course high-dose chemotherapy (HDT) protocol including autologous stem cell transplantation (SCT) after courses 2, 3, and 4 was investigated in 110 patients, aged 18 to 60 years, with primary diagnosis of aggressive NHL (aNHL), and lactic dehydrogenase (LDH)

Neoadjuvant chemotherapy for high-grade soft-tissue sarcomas of the limbs

International Nuclear Information System (INIS)

Ramos, Pedro; Gonzalez, Manuel; Perry, Fernando; Cardona, Andres Felipe

2005-01-01

Background: the use of neoadjuvant chemotherapy for high-grade soft-tissue sarcomas of the limbs continues to be an area of controversy; however, the number of clinical studies favoring the use of an anthracycline and iphosphamide-based regimen is increasing steadily. This approach may provide some advantages for facilitating the surgical resection of the tumor and for local disease control. The historical 5-year survival rate of approximately 50% in this high-risk group treated with local therapy alone represents a poor standard of care; thus, there is a need to incorporate systemic therapy early in the management of these patients. Objective: to describe the role of neoadjuvant chemotherapy in the treatment of soft-tissue sarcomas. Materials and methods: the records of 42 patients who attended the national cancer institute of Colombia in search for management of primary soft-tissue sarcomas were retrospectively reviewed. Ten patients with high-grade tumors larger than 8 cm, treated from June 2000 to February 2002 with neoadjuvant chemotherapy based on an anthracycline and iphosphamide regimen, plus vincristin and cisplatinum in selected cases, followed by surgery and adjuvant therapy with chemotherapy combined with local radiotherapy, were included. Evaluations of objective tumor response, survival, and toxicity were carried out. Results: after neoadjuvant therapy, s ix patients underwent conservative and limb-salvage surgery, three required radical interventions, and one refused surgical treatment. Seven experienced an objective response: it was complete in four and partial in three; the disease kept stable in two patients, and the tumor progressed in one case. After an average 46-month follow-up, four patients were permanently free of disease. Hematological and gastrointestinal toxicity was remarkable, and no patient had a long-term morbidity related to the treatment. Conclusions: this limited retrospective review suggests an advantage for the use of

Efficacy and tolerability of concurrent weekly low dose cisplatin during radiation treatment of localised muscle invasive bladder transitional cell carcinoma: A report of two sequential Phase II studies from the Trans Tasman Radiation Oncology Group

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Gogna, Nirdosh Kumar; Matthews, John H.L.; Turner, Sandra L.; Mameghan, Heidi; Duchesne, Gillian M.; Spry, Nigel; Berry, Martin P.; Keller, Jacqui; Tripcony, Lee

2006-01-01

Background and purpose: To determine the feasibility, toxicity, and clinical effectiveness of concurrent weekly cisplatin chemotherapy in conjunction with definitive radiation in the treatment of localised muscle invasive bladder cancer. Patients and methods: In January 1997 the Trans Tasman Radiation Oncology Group embarked on a Phase II study (TROG 97.01) of weekly cisplatin (35 mg/m 2 x 7 doses) plus radiation to a dose of 63 Gy over 7 weeks. Following an interim toxicity analysis, the dose intensity of cisplatin was reduced to 6 cycles and the radiation schedule changed to 64 Gy over 6.5 weeks leading to the second study (TROG 99.06). A total of 113 patients were enrolled. Results: Acute grade 3 urinary toxicity occurred in 23% of the patients. Acute grade 4 pelvic toxicity was not seen. Thirty-eight patients (33%) experienced grade 3 or 4 cisplatin related toxicities with 15 patients (12%) requiring significant dose modification. The reduced dose intensity in Study 99.06 improved tolerability. Incidence of significant late morbidity was low (6%). Seventy-nine patients (70%) achieved complete remission at the 6 month cystoscopic assessment. Local invasive recurrence was seen in 11 of the 79 patients (14%). In 18 patients (16%) isolated superficial TCC/CIS were detected (6 months and beyond).The local control rate was 45% with a functional bladder being retained in 69 of the 113 patients (61%). RFS and DSS at 5 years were 33% and 50%, respectively. Conclusion: Our two sequential Phase II studies have shown that concurrent chemoradiation using weekly cisplatin in the management of localised invasive bladder TCC is feasible and reasonably well tolerated. This approach is currently being investigated further in a randomised study

Is febrile neutropenia prophylaxis with granulocyte-colony stimulating factors economically justified for adjuvant TC chemotherapy in breast cancer?

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Skedgel, Chris; Rayson, Daniel; Younis, Tallal

2016-01-01

Febrile neutropenia (FN) during adjuvant chemotherapy is associated with morbidity, mortality risk, and substantial cost, and subsequent chemotherapy dose reductions may result in poorer outcomes. Patients at high risk of, or who develop FN, often receive prophylaxis with granulocyte colony-stimulating factors (G-CSF). We investigated whether different prophylaxis strategies with G-CSF offered favorable value-for-money. We developed a decision model to estimate the short- and long-term costs and outcomes of a hypothetical cohort of women with breast cancer receiving adjuvant taxotere + cyclophosphamide (TC) chemotherapy. The short-term phase estimated upfront costs and FN risks with adjuvant TC chemotherapy without G-CSF prophylaxis (i.e., chemotherapy dose reductions) as well as with secondary and primary G-CSF prophylaxis strategies. The long-term phase estimated the expected costs and quality-adjusted life years (QALYs) for patients who completed adjuvant TC chemotherapy with or without one or more episodes of FN. Secondary G-CSF was associated with lower costs and greater QALY gains than a no G-CSF strategy. Primary G-CSF appears likely to be cost-effective relative to secondary G-CSF at FN rates greater than 28%, assuming some loss of chemotherapy efficacy at lower dose intensities. The cost-effectiveness of primary vs. secondary G-CSF was sensitive to FN risk and mortality, and loss of chemotherapy efficacy following FN. Secondary G-CSF is more effective and less costly than a no G-CSF strategy. Primary G-CSF may be justified at higher willingness-to-pay thresholds and/or higher FN risks, but this threshold FN risk appears to be higher than the 20% rate recommended by current clinical guidelines.

Definitive intraoperative very high-dose radiotherapy for localized osteosarcoma in the extremities

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Oya, Natsuo; Kokubo, Masaki; Mizowaki, Takashi; Shibamoto, Yuta; Nagata, Yasushi; Sasai, Keisuke; Nishimura, Yasumasa; Tsuboyama, Tadao; Toguchida, Junya; Nakamura, Takashi; Hiraoka, Masahiro

2001-01-01

Purpose: To evaluate the outcome and adverse effects in patients with osteosarcoma treated with very high-dose definitive intraoperative radiotherapy (IORT), with the intention of saving the affected limb. Methods and Materials: Thirty-nine patients with osteosarcoma in their extremities were treated with definitive IORT. The irradiation field included the tumor plus an adequate wide margin and excluded the major vessels and nerves. Forty-five to 80 Gy of electrons or X-rays were delivered. The median follow-up of the surviving patients was 124 months. Results: The cause-specific and relapse-free 5-year survival rate was 50% and 43%, respectively. Distant metastasis developed in 23 patients; 19 died and 4 were alive for >10 years. Nine local recurrences were found 4-29 months after IORT in the affected limb. No radiation-induced skin reaction or nerve palsy was observed in the patients treated with X-rays. Experiments using phantoms also confirmed that the scatter dose was below the toxic level in the IORT setting with X-rays. Conclusions: Very high-dose definitive IORT combined with preventive nailing and chemotherapy appeared to be a promising quality-of-life-oriented alternative to treating patients with osteosarcomas in the extremities, although the problem of recurrences from the surrounding unirradiated soft tissue remains to be solved

Distribution of 99Tcm-rh-Annexin V and its relationship with expression of survivin and Caspase-3 in tumors after a single dose of chemotherapy

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Zhang Xin; Zhang Yanjun; Tao Li; Zhu Yi; Yang Chun; Li Yaming; Zhang Jianying; Zhao Zhenzhen; Ji Xiaopeng; Zhao Ming; Tian Aijuan

2008-01-01

Objective: Recently, molecular imaging for detecting cellular apoptosis is developing rapidly. The aim of the study was to determine the effectiveness of imaging with 99 Tc m labelled recombinant human Annexin V ( 99 Tc m -rh-Annexin V) as a reflection of apoptosis in tumor, and related its distribution with expression of Survivin and Caspase-3 after a single dose of chemotherapy. Methods: Eight days after being inoculated with allogenic hepatoma cells (Hca-F25) into right axillary fossa, the mice (purebred 615) were randomly divided into two groups (control group A, n=9; and treated group B, n=10). Group B was received a single dose of chemotherapy intraperitoneally (cyclophosphamide, 150 mg/kg). Groups A and B were given 99 Tc m -rh-AnnexinV (3.7 MBq·0.5 μg -1 per mouse) intravenously 20 h later. Four hours after 99 Tc m -rh-Annexin V injection, the animals were imaged and sacrificed, and the tumor samples were weighed and the radioactivity was determined in a well-counter. The accumulation of 99 Tc m -rh-Annexin V in tumor was expressed as the percentage activity of injection dose per gram of tissue (% ID/g). Tumor cell apoptosis was examined by terminal deoxynueleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) method, and the expression of Survivin and Caspase-3 in tumor were determined with immunohistochemical method. SPSS 10.0 was used for data analysis. Results: Single dose chemotherapy tsignificantly increased the tumor uptake of 99 Tc m -rh-Annexin V [(0.478 ± 0.123)% ID/g vs (0.332 ± 0.061)% ID/g] and the positive number of TUNEL [(18.030 ± 5.600) cells/field vs (6.744 ± 2.325) cells/field], as well as the expression of Caspase-3 [(3.266 ± 0.482)% vs (2.387 ± 0.387)%, F was 10.502, 31.507, 18.971, respectively, all P 99 Tc m -rh-Annexin V correlated positively well with the expression of Caspase-3 and negatively with the expression of Survivin (P 99 Tc m -rh-Annexin V can not only reflect the extent of apoptosis

Hypofractionated High-Dose Irradiation with Positron Emission Tomography Data for the Treatment of Glioblastoma Multiforme

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Kazuhiro Miwa

2014-01-01

Full Text Available This research paper presents clinical outcomes of hypofractionated high-dose irradiation by intensity-modulated radiation therapy (Hypo-IMRT with 11C-methionine positron emission tomography (MET-PET data for the treatment of glioblastoma multiforme (GBM. A total of 45 patients with GBM were treated with Hypo-IMRT after surgery. Gross tumor volume (GTV was defined as the area of enhanced lesion on MRI, including MET-PET avid region; clinical target volume (CTV was the area with 5 mm margin surrounding the GTV; planning target volume (PTV was the area with 15 mm margin surrounding the CTV, including MET-PET moderate region. Hypo-IMRT was performed in 8 fractions; planning the dose for GTV was escalated to 68 Gy and that for CTV was escalated to 56 Gy, while keeping the dose delivered to the PTV at 40 Gy. Concomitant and adjuvant TMZ chemotherapy was administered. At a median follow-up of 18.7 months, median overall survival (OS was 20.0 months, and median progression-free survival was 13.0 months. The 1- and 2-year OS rates were 71.2% and 26.3%, respectively. Adjuvant TMZ chemotherapy was significantly predictive of OS on multivariate analysis. Late toxicity included 7 cases of Grade 3-4 radiation necrosis. Hypo-IMRT with MET-PET data appeared to result in favorable survival outcomes for patients with GBM.

A model to describe potential effects of chemotherapy on critical radiobiological treatments

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Rodríguez-Pérez, D.; Desco, M.M.; Antoranz, J.C.

2016-01-01

Although chemo- and radiotherapy can annihilate tumors on their own. they are also used in coadjuvancy: improving local effects of radiotherapy using chemotherapy as a radiosensit.izer. The effects of radiotherapy are well described by current radiobiological models. The goal of this work is to describe a discrete radiotherapy model, that has been previously used describe high radiation dose response as well as unusual radio-responses of some types of tumors (e.g. prostate cancer), to obtain a model of chemo+radiotherapy that can describe how the outcome of their combination is a more efficient removal of the tumor. Our hypothesis is that, although both treatments haven different mechanisms, both affect similar key points of cell metabolism and regulation, that lead to cellular death. Hence, we will consider a discrete model where chemotherapy may affect a fraction of the same targets destroyed by radiotherapy. Although radiotherapy reaches all cells equally, chemotherapy diffuses through a tumor attaining lower concentration in its center and higher in its surface. With our simulations we study the enhanced effect of combined therapy treatment and how it depends on the tissue critical parameters (the parameters of the lion-extensive radiobiological model), the number of “targets” aimed at by chemotherapy, and the concentration and diffusion rate of the drug inside the tumor. The results show that an equivalent, cliemo-radio-dose can be computed that allows the prediction of the lower radiation dose that causes the same effect than a radio-only treatment. (paper)

Sequentially administrated of pemetrexed with icotinib/erlotinib in lung adenocarcinoma cell lines in vitro.

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Feng, Xiuli; Zhang, Yan; Li, Tao; Li, Yu

2017-12-26

Combination of chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) had been proved to be a potent anti-drug for the treatment of tumors. However, survival time was not extended for the patients with lung adenocarcinoma (AdC) compared with first-line chemotherapy. In the present study, we attempt to assess the optimal schedule of the combined administration of pemetrexed and icotinib/erlotinib in AdC cell lines. Human lung AdC cell lines with wild-type (A549), EGFR T790M (H1975) and activating EGFR mutation (HCC827) were applied in vitro to assess the differential efficacy of various sequential regimens on cell viability, cell apoptosis and cell cycle distribution. The results suggested that the antiproliferative effect of the sequence of pemetrexed followed by icotinib/erlotinib was more effective than that of icotinib/erlotinib followed by pemetrexed. Additionally, a reduction of G1 phase and increased S phase in sequence of pemetrexed followed by icotinib/erlotinib was also observed, promoting cell apoptosis. Thus, the sequential administration of pemetrexed followed by icotinib/erlotinib exerted a synergistic effect on HCC827 and H1975 cell lines compared with the reverse sequence. The sequential treatment of pemetrexed followed by icotinib/erlotinib has been demonstrated promising results. This treatment strategy warrants further confirmation in patients with advanced lung AdC.

Part of curietherapy at high rate of dose in the treatment of locally advanced esophagus carcinomas: preliminary results

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Maingon, P.; Bidault, F.; Barillot, I.; Bone-Lepinoy, M.C.; Coudert, B.; Horiot, J.C.

1994-01-01

The technology of curietherapy for esophagus shows its feasibility and its interest in advanced tumors of esophagus, by association with external radiotherapy and/or association radio-chemotherapy. It allows to deliver a high dose in the heart of the tumor with a tolerable toxicity. Its efficiency and the analysis of toxicity should be reevaluated at long term. Its place should be discussed in randomized protocols proposed to this selection of patients

Medical visits for chemotherapy and chemotherapy-induced neutropenia: a survey of the impact on patient time and activities

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Moore Kelley

2004-05-01

Full Text Available Abstract Background Patients with cancer must make frequent visits to the clinic not only for chemotherapy but also for the management of treatment-related adverse effects. Neutropenia, the most common dose-limiting toxicity of myelosuppressive chemotherapy, has substantial clinical and economic consequences. Colony-stimulating factors such as filgrastim and pegfilgrastim can reduce the incidence of neutropenia, but the clinic visits for these treatments can disrupt patients' routines and activities. Methods We surveyed patients to assess how clinic visits for treatment with chemotherapy and the management of neutropenia affect their time and activities. Results The mean amounts of time affected by these visits ranged from approximately 109 hours (hospitalization for neutropenia and 8 hours (physician and chemotherapy to less than 3 hours (laboratory and treatment with filgrastim or pegfilgrastim. The visits for filgrastim or pegfilgrastim were comparable in length, but treatment with filgrastim requires several visits per chemotherapy cycle and treatment with pegfilgrastim requires only 1 visit. Conclusions This study provides useful information for future modelling of additional factors such as disease status and chemotherapy schedule and provides information that should be considered in managing chemotherapy-induced neutropenia.

Sequential changes in bone marrow architecture during continuous low dose gamma irradiation

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Seed, T.M.; Chubb, G.T.; Tolle, D.V.

1981-01-01

Beagles continuously exposed to low daily doses (10 R) of whole-body 60Co gamma-radiation are prone to develop either early occurring aplastic anemia or late occurring myeloproliferative disorders (Seed et al., 1977). In this study, we have examined by a combination of light microscopy and scanning and transmission electron microscopy the sequential changes in the morphology of biopsied rib bone marrow of continuously irradiated dogs that developed either aplastic anemia, myelofibrosis, or myelogenous leukemia. Characteristic modification of key elements of marrow architecture have been observed during preclinical and clinical phases of these hemopathological conditions. The more prominent of these changes include the following. (i) In developing aplastic anemia: severe vascular sinus and parenchymal cord compression, and focally degenerate endosteal surfaces. (ii) In developing myelofibrosis: hyperplasia of endosteal and reticular stomal elements. (iii) In developing leukemia: hypertrophy of reticular and endothelial elements in the initial restructuring of the stromal matrix and the subsequent aberrant hemopoietic repopulation of the initially depleted stromal matrix. These architectural changes during preclinical phases appear to be related to the pathological progression to each of the radiation-induced hemopathological end points

Radioimmunotherapy of indolent non-Hodgkin's lymphoma with Yttrium-90 labeled anti-CD20 monoclonal antibody therapy does not preclude subsequent chemotherapy or autologous hematologic stem cell transplantation therapy in most patients

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Wiseman, G.A.; Witzig, T.E.; Ansell, S.M.; Ristow, K.M.

2002-01-01

Introduction: Yttrium-90 (Y-90) labeled anti-CD20 monoclonal antibody (ibritumomab tiuxetan or Zevalin TM ) is a novel therapy for patients with relapsed CD20+ B-cell non-Hodgkin's lymphoma (NHL). Patients treated with Zevalin radioimmunotherapy (RIT) are limited from higher doses due to transient and reversible platelet and neutrophil suppression. Patients with indolent NHL who relapse or are refractory to chemotherapy have a 70-80% overall response rate and a 20-30% complete response rate when treated with Zevalin RIT. Therefore additional treatment is required in a minority of patients shortly after Zevalin therapy and in many others at relapse. Relapsed patients are generally treated with chemotherapy alone or high dose chemotherapy followed by autologous transplantation. We wanted to evaluate the ability of patients to tolerate subsequent therapy given at relapse following Zevalin RIT. Methods: We had 58 patients who relapsed after receiving Zevalin RIT and later received additional therapy. The clinical records and lab results were reviewed and compared with a matched control group of patients treated prior to Zevalin availability who received chemotherapy without prior Zevalin RIT. Results: The toxicity in 58 patients treated with Zevalin RIT and subsequent therapy was not significantly different from the control group who did not receive Zevalin RIT. Patients had a median of two subsequent therapies (range, 1-7) after Zevalin. Twenty eight percent required blood cell growth factor support with subsequent chemotherapy and 2 patients required reductions from the standard chemotherapy doses due to prolonged myelosuppression. Eight patients subsequently had successful autologous hematologic stem cell transplant with cells collected after Zevalin. Thirteen of the 58 patients (28%) treated with standard dose chemotherapy were hospitalized for neutropenic fever or thrombocytopenia. Conclusions: Chemotherapy or high dose chemotherapy with autologous transplantation

Adjuvant chemotherapy and cancer cure

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Bertino, J.R.

1983-01-01

The use of chemotherapy as an adjuvant to surgery and/or radiotherapy is well founded in experimental tumor systems and appears to be effective in patients in some circumstances. It is clear from both clinical and experimental studies that (1) the dose is important, (2) the earlier chemotherapy is started after primary therapy the better, and (3) combination chemotherapy may be more effective than single-agent treatment. The better the estimation of risk of recurrence, the better the assessment of the risk-benefit ratio with adjuvant therapy. Salvage therapy as well as relative risk of recurrence are considerations in the choice of patients to be treated. Finally, some evidence is presented to indicate that alkylating agents may not be necessary in combination regimens for adjuvant therapy if effective antimetabolite combinations are available

Sequential 18F-FDG PET/CT for early prediction of complete pathological response in breast and axilla during neoadjuvant chemotherapy

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Koolen, Bas B.; Pengel, Kenneth E.; Wesseling, Jelle; Vogel, Wouter V.; Valdes Olmos, Renato A.; Vrancken Peeters, Marie-Jeanne T.F.D.; Rutgers, Emiel J.T.; Vincent, Andrew D.; Gilhuijs, Kenneth G.A.; Rodenhuis, Sjoerd

2014-01-01

To investigate the value of response monitoring in both the primary tumour and axillary nodes on sequential PET/CT scans during neoadjuvant chemotherapy (NAC) for predicting complete pathological response (pCR), taking the breast cancer subtype into account. In 107 consecutive patients 290 PET/CT scans were performed at baseline (PET/CT1, 107 patients), after 2 - 3 weeks of chemotherapy (PET/CT2, 85 patients), and after 6 - 8 weeks (PET/CT3, 98 patients). The relative changes in SUVmax (from baseline) of the tumour and the lymph nodes and in both combined (after logistic regression), and the changes in the highest SUVmax between scans (either tumour or lymph node) were determined and their associations with pCR of the tumour and lymph nodes after completion of NAC were assessed using receiver operating characteristic (ROC) analysis. A pCR was seen in 17 HER2-positive tumours (65 %), 1 ER-positive/HER2-negative tumour (2 %), and 16 triple-negative tumours (52 %). The areas under the ROC curves (ROC-AUC) for the prediction of pCR in HER2-positive tumours after 3 weeks were 0.61 for the relative change in tumours, 0.67 for the combined change in tumour and nodes, and 0.72 for the changes in the highest SUVmax between scans. After 8 weeks equivalent values were 0.59, 0.42 and 0.64, respectively. In triple-negative tumours the ROC-AUCs were 0.76, 0.84 and 0.76 after 2 weeks, and 0.87, 0.93 and 0.88 after 6 weeks, respectively. In triple-negative tumours a PET/CT scan after 6 weeks (three cycles) appears to be optimally predictive of pCR. In HER2-positive tumours neither a PET/CT scan after 3 weeks nor after 8 weeks seems to be useful. The changes in SUVmax of both the tumour and axillary nodes combined correlates best with pCR. (orig.)

High-dose-rate intracavitary brachytherapy combined with external beam radiotherapy for stage IIIb adenocarcinoma of the uterine cervix in Japan. A multi-institutional study of Japanese Society of Therapeutic Radiology and Oncology 2006-2007 (Study of JASTRO 2006-2007)

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Niibe, Yuzuru; Kenjo, Masahiro; Onishi, Hiroshi

2010-01-01

The current study was a retrospective questionnaire survey of stage IIIb adenocarcinoma of the uterine cervix treated with high-dose-rate intracavitary brachytherapy combined with external beam radiation therapy in Japan aimed to investigate the optimal dose on the basis of the biological effective dose and prognostic factors. Between 1990 and 2000, 61 patients with stage IIIb adenocarcinoma of the uterine cervix underwent high-dose-rate intracavitary brachytherapy combined with external beam radiation therapy in 19 major hospitals in Japan. This retrospective questionnaire survey was performed by mail including survey charts to be fulfilled by radiation oncologists in these 19 major hospital. Fifty had only adenocarcinoma components and 11 had adenosquamous cell carcinoma components. All patients were treated with high-dose-rate intracavitary brachytherapy combined with external beam radiation therapy. Total biological effective dose (T-BED 10 ) was calculated from the sum of the biological effective doses of the external beam radiation therapy and the intracavitary brachytherapy. Thirty-two patients underwent chemotherapy. The 5-year overall survival rate of all patients was 20.2%. Stratified by total biological effective dose, the 5-year overall survival rate was 0% for T-BED 10 10 between 75 and 100 Gy and 0% for T-BED 10 >110 Gy (P=0.15). Stratified by histopathology, the 5-year overall survival rate was 22.1% for adenocarcinoma and 13.6% for adenosquamous cell carcinoma (P=0.43). Stratified by chemotherapy, the 5-year overall survival rate was 20.3% in patients who received chemotherapy and 20.4% in patients who did not receive chemotherapy (P=0.96). The 5-year overall survival rate of stage IIIb adenocarcinoma of the uterine cervix in this retrospective questionnaire survey was 20.2%. The optimal T-BED 10 and evident prognostic factors were not clear from this questionnaire survey. (author)

Antibody responses to Hepatitis B and measles-mumps-rubella vaccines in children who received chemotherapy for acute lymphoblastic leukemia

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Simone Santana Viana

2012-01-01

Full Text Available OBJECTIVE: To evaluate viral vaccine antibody levels in children with acute lymphoblastic leukemia after chemotherapy and after vaccine booster doses. METHODS: Antibody levels against hepatitis B, rubella, measles and mumps vaccine antigens were evaluated in 33 children after completing chemotherapy (before and after vaccine booster doses and the results were compared to the data of 33 healthy children matched for gender, age and social class. RESULTS: After chemotherapy, 75.9%, 67.9%, 59.3% and 51.7% of the patients showed low antibody titers that would be unlikely to protect against exposure to measles, rubella, hepatitis B and mumps, respectively. After receiving a vaccine booster dose for these antigens the patients had high antibody levels consistent with potential protection against measles, mumps and hepatitis B, but not against rubella. CONCLUSION: Extra doses of measles-mumps-rubella plus hepatitis B vaccines are recommended in acute lymphoblastic leukemia patients submitted to treatment after hematologic recovery. After this, viral vaccine antibody levels should be verified to define the individual's protective status.

Hyperfractionated craniospinal radiotherapy and adjuvant chemotherapy for children with newly diagnosed medulloblastoma and other primitive neuroectodermal tumors

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Allen, Jeffrey C.; Donahue, Bernadine; DaRosso, Robert; Nirenberg, Anita

1996-01-01

Purpose: This single-institution Phase I/II study conducted from 1989 to 1995 evaluates the feasibility of a multi-modality protocol combining hyperfractionated craniospinal radiotherapy (HFRT) followed by adjuvant chemotherapy in 23 patients with newly diagnosed primitive neuroectodermal tumors (PNET) arising in the central nervous system. Methods and Materials: All 23 patients had a histologically confirmed PNET and were over 3 years of age at diagnosis. The eligibility criteria for PNET patients with cerebellar primaries (medulloblastoma) included either a high T stage (T3b or 4) or high M stage (M1-3). All patients with noncerebellar primaries were eligible regardless of T or M stage. The median age of the 23 patients was 9 years (mean 3-25); 11 were female. The primary tumor arose in the cerebellum in 19. Of these medulloblastoma patients, 15 had high T stages (T3b or T4) with large locally invasive tumors and no evidence of metastases (M0), constituting Group 1. Thirteen (86%) of these patients had gross total resections. Four other medulloblastoma patients had both high T and high M stages, constituting Group 2. Group 3 consisted of four other patients with exocerebellar primaries (two brain, one brain stem, and one cauda equina), three of whom were M3. Hyperfractionated radiotherapy was administered within 4 weeks of surgery. Twice-daily 1-Gy fractions were administered separated by 4-6 h. The total dose to the primary intracranial tumor and other areas of measurable intracranial disease was 72 Gy. The prophylactic craniospinal axis dose was 36 Gy, and boosts of 44-56 Gy were administered to metastatic spinal deposits. Following radiotherapy, monthly courses of multiagent chemotherapy were administered sequentially (cyclophosphamide-vincristine followed by cisplatin-etoposide followed by carboplatin-vincristine) for a total of 9 months. Results: All patients completed radiotherapy as planned. Only three patients lost >10% of their body weight. One patient

Uptake and Tolerance of Chemotherapy in Elderly Patients with Small Cell Lung Cancer and Impact on Survival

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Fisher, S.; Winget, M.; Gao, H.; Al Fayea, T. M.; Winget, M.; Butts, C.; Fisher, S.; Winget, M.; Butts, C.

2012-01-01

The treatment of elderly cancer patients is complicated by many factors. We sought to assess the uptake and tolerance of chemotherapy among patients 75 years and older diagnosed with small cell lung cancer (SCLC) in years 2004-2008 in Alberta, Canada, and assess their survival. All patients who met the above criteria and had an oncologist-consult were included. Data were obtained from the Alberta Cancer Registry and chart review. A total of 171 patients were included in the study, 117 (68%) of whom began chemotherapy. Of those, 52% completed all cycles, 66% did not have any dose reductions, and 31% completed all cycles at the recommended dose. The risk of death for patients who did not complete all cycles of chemotherapy was 2.72 (95% CI: 1.52-4.87) and for those who completed all cycles but with a reduced dose was 1.02 (95% CI: 0.57-1.82) relative to those who completed chemotherapy at full dose after adjusting for several demographic/clinical factors. Our results suggest that a significant proportion of elderly patients are able to tolerate chemotherapy and receive a survival benefit from it while those who experience toxicity may receive a survival benefit from a reduction in chemotherapy dose as opposed to stopping treatment.

Neuropsychological function in adults after high dose fractionated radiation therapy of skull base tumors

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Glosser, Guila; McManus, Pat; Munzenrider, John; Austin-Seymour, Mary; Fullerton, Barbara; Adams, Judy; Urie, Marcia M.

1997-01-01

Purpose: To evaluate the long term effects of high dose fractionated radiation therapy on brain functioning prospectively in adults without primary brain tumors. Methods and Materials: Seventeen patients with histologically confirmed chordomas and low grade chondrosarcomas of the skull base were evaluated with neuropsychological measures of intelligence, language, memory, attention, motor function and mood following surgical resection/biopsy of the tumor prior to irradiation, and then at about 6 months, 2 years and 4 years following completion of treatment. None received chemotherapy. Results: In the patients without tumor recurrence or radiation necrosis, there were no indications of adverse effects on cognitive functioning in the post-acute through the late stages after brain irradiation. Even in patients who received doses of radiation up to 66 Cobalt Gy equivalent through nondiseased (temporal lobe) brain tissue, memory and cognitive functioning remained stable for up to 5 years after treatment. A mild decline in psycho-motor speed was seen in more than half of the patients, and motor slowing was related to higher radiation doses in midline and temporal lobe brain structures. Conclusion: Results suggest that in adults, tolerance for focused radiation is relatively high in cortical brain structures

Secondary leukemia associated with a conventional dose of etoposide: review of serial germ cell tumor protocols.

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Nichols, C R; Breeden, E S; Loehrer, P J; Williams, S D; Einhorn, L H

1993-01-06

Case reports have suggested that treatment with high-dose etoposide can result in development of a unique secondary leukemia. This study was designed to estimate the risk of developing leukemia for patients receiving conventional doses of etoposide along with cisplatin and bleomycin. We reviewed the records at Indiana University of all untreated patients entering clinical trials using etoposide at conventional doses (cumulative dose, 2000 mg/m2 or less) for germ cell cancer between 1982 and 1991. The records of all patients who received a chemotherapy regimen containing etoposide, ifosfamide, or cisplatin after failing to respond to primary chemotherapy were also reviewed. Between 1982 and 1991, 538 patients entered serial clinical trials with planned cumulative etoposide doses of 1500-2000 mg/m2 in combination with cisplatin plus either ifosfamide or bleomycin. Of these 538 patients, 348 received an etoposide combination as initial chemotherapy and 190 received etoposide as part of salvage treatment. To date, 315 patients are alive, with median follow-up of 4.9 years, and 337 patients have had follow-up beyond 2 years. Two patients (0.37%) developed leukemia. One developed acute undifferentiated leukemia with a t(4;11) (q21;q23) cytogenetic abnormality 2.0 years after starting etoposide-based therapy, and one developed acute myelomonoblastic leukemia with no chromosome abnormalities 2.3 years after beginning chemotherapy. During this period, several hundred patients were treated with etoposide-based chemotherapy and did not enter clinical trials. Three of these patients are known to have developed hematologic abnormalities, including one patient with acute monoblastic leukemia with a t(11;19)(q13;p13) abnormality. Secondary leukemia after treatment with a conventional dose of etoposide does occur, but the low incidence does not alter the risk-to-benefit ratio of etoposide-based chemotherapy in germ cell cancer. The reports of leukemia associated with high doses of

The dose-volume relationship of acute small bowel toxicity from concurrent 5-FU-based chemotherapy and radiation therapy for rectal cancer

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Baglan, Kathy L.; Frazier, Robert C.; Yan Di; Huang, Raywin R.; Martinez, Alvaro A.; Robertson, John M.

2002-01-01

Purpose: A direct relationship between the volume of small bowel irradiated and the degree of acute small bowel toxicity experienced during concurrent 5-fluorouracil (5-FU)-based chemoradiotherapy for rectal carcinoma is well recognized but poorly quantified. This study uses three-dimensional treatment-planning tools to more precisely quantify this dose-volume relationship. Methods and Materials: Forty patients receiving concurrent 5-FU-based chemotherapy and pelvic irradiation for rectal carcinoma had treatment-planning CT scans with small bowel contrast. A median isocentric dose of 50.4 Gy was delivered using a posterior-anterior and opposed lateral field arrangement. Bowel exclusion techniques were routinely used, including prone treatment position on a vacuum bag cradle to allow anterior displacement of the abdominal contents and bladder distension. Individual loops of small bowel were contoured on each slice of the planning CT scan, and a small bowel dose-volume histogram was generated for the initial pelvis field receiving 45 Gy. The volume of small bowel receiving each dose between 5 and 40 Gy was recorded at 5-Gy intervals. Results: Ten patients (25%) experienced Common Toxicity Criteria Grade 3+ acute small bowel toxicity. A highly statistically significant association between the development of Grade 3+ acute small bowel toxicity and the volume of small bowel irradiated was found at each dose level. Specific dose-volume threshold levels were found, below which no Grade 3+ toxicity occurred and above which 50-60% of patients developed Grade 3+ toxicity. The volume of small bowel receiving at least 15 Gy (V 15 ) was strongly associated with the degree of toxicity. Univariate analysis of patient and treatment-related factors revealed no other significant predictors of severe toxicity. Conclusions: A strong dose-volume relationship exists for the development of Grade 3+ acute small bowel toxicity in patients receiving concurrent 5-FU-based chemoradiotherapy

The interplay of immunotherapy and chemotherapy: harnessing potential synergies.

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Emens, Leisha A; Middleton, Gary

2015-05-01

Although cancer chemotherapy has historically been considered immune suppressive, it is now accepted that certain chemotherapies can augment tumor immunity. The recent success of immune checkpoint inhibitors has renewed interest in immunotherapies, and in combining them with chemotherapy to achieve additive or synergistic clinical activity. Two major ways that chemotherapy promotes tumor immunity are by inducing immunogenic cell death as part of its intended therapeutic effect and by disrupting strategies that tumors use to evade immune recognition. This second strategy, in particular, is dependent on the drug, its dose, and the schedule of chemotherapy administration in relation to antigen exposure or release. In this Cancer Immunology at the Crossroads article, we focus on cancer vaccines and immune checkpoint blockade as a forum for reviewing preclinical and clinical data demonstrating the interplay between immunotherapy and chemotherapy. ©2015 American Association for Cancer Research.

Comparative analyses of the effect of radiotherapy and chemotherapy or chemotherapy alone on patients' electrocardiogram

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Liang Li; Zhang Shulan; Zhang Zhaohui; Wang Junjie; Jia Tingzhen

2005-01-01

Objective: To investigate the change of breast cancer patients' electrocardiogram during combined radiotherapy and chemotherapy or chemotherapy alone for the sake of predicting the cardiotoxicity of combined radiotherapy and chemotherapy. Methods: From January, 1998 to June, 2004, 47 postoperative breast cancer patients were enrolled. Among them 29 patients received chemotherapy combined with radiotherapy (combinative group), and 18 patients received chemotherapy alone (non combinative group). The changes of electrocardiogram were observed and correlation factors were analyzed. Results: Abnormal electrocardiograms were noted in 11 (37.9%) and 2 patients (11.1%) of the combinative group and the non-combinative group respectively(z=-1.977, P=0.048). In the combinative group, heart events were significantly increased in patients above 60 years old (z=- 2.094 P=0.036). The changes of electrocardiogram were not significantly correlative with hypertension history, tumor site, dose of radiotherapy or chemotherapeutic drugs. But the incidence of abnormal electrocardiogram was higher in patients with a hypertension history than in those without it (54.5% vs 27.8%). Conclusion: The abnormalities of electrocardiogram were are more frequent in patients treated with both radiotherapy combined with chemotherapy. Our results suggest that breast cancer patients should be regularly reexamined with electrocardiography during therapy, especially whose age was those have a hypertension history and above 60 years old. (authors)

Updated results of a pilot study of low dose craniospinal irradiation plus chemotherapy for children under five with cerebellar primitive neuroectodermal tumors (medulloblastoma)

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Goldwein, Joel W.; Radcliffe, Jerilynn; Johnson, James; Moshang, Thomas; Packer, Roger J.; Sutton, Leslie N.; Rorke, Lucy B.; D'Angio, Giulio J.

1996-01-01

Purpose: Children under 5 years old with medulloblastoma (MB) have a poor prognosis. They are more susceptible to the deleterious effects of craniospinal irradiation (CSART) and have a higher relapse rate when treated with low-dose CSART alone. We, thus, embarked on a prospective trial testing the usefulness of very low dose CSART and adjuvant chemotherapy. This is an update of a previous report on these patients. Methods and Materials: Between January 1988 and March 1990, 10 patients with medulloblastoma were treated using 18 Gy radiation therapy (RT) to the craniospinal axis, a posterior fossa (PF) boost to 50.4-55.8 Gy and chemotherapy consisting of vincristine (VCR) weekly during RT. This was followed by VCR, cis-diamminedichloroplatinum (CDDP), and lomustine (CCNU) for eight, 6-week cycles. Patients between 18 and 60 months of age without evidence of tumor dissemination were eligible for study. Follow-up was available until September 1994 with a median follow-up for living patients of 6.3 years from diagnosis. Results: Actuarial survival at over 6 years is 70 ± 20%. Three of the 10 patients relapsed and died. In one patient, the relapse developed in the spine and brain outside the posterior fossa, in the second, concurrently in the posterior fossa, brain and spine, and the third, only in the spine. One surviving child developed a brain stem infarct 4.8 years after diagnosis and has since almost fully recovered. A mean intelligence quotient (IQ) score of 103 in six patients surviving at least 1 year is unchanged from the baseline group score of 107. Five children tested at baseline and 2 years following treatment had IQ scores of 101 and 102, respectively. Six children tested at baseline and at 3 years had IQ scores of 106 and 96, respectively. Excluding the child tested shortly after his brain stem infarct, baseline and 3 year IQ scores were 103 and 97, respectively. Five of the seven long-term survivors grew at rates significantly below their expected

VIM-D salvage chemotherapy in Hodgkin's disease.

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Phillips, J K; Spearing, R L; Davies, J M; Hay, C R; Parry, H; Nash, J R; Cawley, J C

1990-01-01

A total of 15 patients with relapsed or resistant Hodgkin's disease were treated with a combination of etoposide (VP16), ifosfamide, mitozantrone and dexamethasone (VIM-D). The regime was well tolerated, the only major toxicity being myelosuppression. Complete remissions (CRs) were obtained in 4 patients and were maintained for 2, 4, 10 and 14 months. 10 subjects subsequently received an autologous bone marrow transplant with high-dose chemotherapy (ABMT). Previous exposure to VIM-D did not appear to predict for or prejudice the response to subsequent ABMT.

Incidence of chemotherapy-induced neutropenia in HIV-infected and uninfected patients with breast cancer receiving neoadjuvant chemotherapy

Directory of Open Access Journals (Sweden)

Sithembile Ngidi

2017-07-01

Full Text Available Background. Chemotherapy-induced neutropenia (CIN can result in poor tolerance of chemotherapy, leading to dose reductions, delays in therapy schedules, morbidity and mortality. Actively identifying predisposing risk factors before treatment is of paramount importance. We hypothesised that chemotherapy is associated with a greater increase in CIN and its complications in HIV-infected patients than in those who are not infected. Objective. To establish the incidence of CIN in HIV-infected and uninfected patients undergoing chemotherapy. Methods. A retrospective chart review and analysis was conducted in the oncology departments at Inkosi Albert Luthuli Central Hospital and Addington Hospital, Durban, South Africa. The study population consisted of 65 previously untreated women of all ages with stage II - IV breast cancer and known HIV status treated with neoadjuvant chemotherapy from January 2012 to December 2015. Results. HIV-infected patients formed 32.3% of the group, and 95.2% of them were on antiretroviral therapy. The mean age (standard deviation (SD of the cohort was 48.5 (13.2 years (40.6 (9.6 years for the HIV-infected group v. 52.0 (13.1 years for the uninfected group; p<0.001. Ninety-five neutropenia episodes were observed (rate 0.85 per 1 year of follow-up time. Following multivariate adjustment, patients with HIV infection were almost two times more likely to develop CIN (hazard ratio (HR 1.76, 95% confidence interval (CI 1.06 - 2.92; p=0.029. A high baseline absolute neutrophil count (ANC (HR 0.80, 95% CI 0.68 - 0.95; p=0.005 remained significantly associated with protection against CIN. Conclusions. HIV-infected patients were younger than those who were not infected, and presented at a more locally advanced stage of disease. HIV infection was an independent predictor for CIN. HIV-infected patients had an almost two-fold increased risk of developing CIN and developed neutropenia at a much faster rate. A high baseline white cell

Is neoadjuvant chemotherapy prior to radio-chemotherapy beneficial in T4 anal carcinoma?

Science.gov (United States)

Moureau-Zabotto, L; Viret, F; Giovaninni, M; Lelong, B; Bories, E; Delpero, J R; Pesenti, C; Caillol, F; de Chaisemartin, C; Minsat, M; Monges, G; Sarran, A; Resbeut, M

2011-07-01

This study retrospectively describes the outcome of a series of 38 patients (pts) with T4 anal carcinoma exclusively treated by radio and chemotherapy. From 1992 to 2007, 38 pts with UST4-N0-2-M0 anal carcinoma were treated with exclusive radiotherapy and chemotherapy. All patients received external beam radiotherapy (EBRT) (median dose 45 Gy) with a concomitant chemotherapy (5-fluorouracil-cisplatin). Eleven patients received neo-adjuvant chemotherapy (5-fluorouracil-cisplatin). After 2-8 weeks, a 15-20 Gy boost was delivered either with EBRT (20 pts) or interstitial (192)Ir brachytherapy (18 pts). Mean follow-up was 66 months. After chemoradiation therapy (CRT), 13 pts (34%) had a complete response, 23 pts (60%) a response >50% (2 pts were not evaluated). The 5-year-disease-free survival was 79.2 ± 6.5%, and the 5-year overall survival was 83.9 ± 6%. Eight patients developed tumor progression (mean delay 8.8 months), six of them requiring a salvage surgery with definitive colostomy for local relapse. Late severe complication requiring colostomy was observed in 2 pts. The 5-year-colostomy-free survival was 78 ± 6.9%. Patients who received primary chemotherapy had a statistically significant better 5-year colostomy-free survival (100% vs. 38 ± 16.4%, P = 0.0006). T4 anal carcinoma can be treated with a curative intent using a sphincter-sparing approach of CRT, and neo-adjuvant chemotherapy should be considered prior to radiotherapy. Copyright © 2011 Wiley-Liss, Inc.

Radiotherapy of esophageal cancer in combination with chemotherapy

International Nuclear Information System (INIS)

Jinnouchi, Shoshi; Koga, Kenji; Nishikawa, Kiyoshi; Kihara, Yasushi; Kusuhara, Toshiyuki; Watanabe, Katuji

1983-01-01

The significance of combination of chemotherapy in radiotherapy for esophageal cancer was evaluated in 32 patients. They were irradiated routinely in 5 times a weeks with a fraction dose of 200 rad by 10MV-X-ray linear accelerator. Combined drugs consist of Bleomycin or Pepleomycin in two-third and 5FU or FT-207 in one-third. There was statistically no significance between the results of radiation alone and combined chemotherapy, and the improvement of survival rate could not be obtained by combining chemotherapy. Some discussion on the causes of this unimprovement were made. (author)

Combination chemotherapy with intermittent erlotinib and pemetrexed for pretreated patients with advanced non-small cell lung cancer: a phase I dose-finding study

International Nuclear Information System (INIS)

Minami, Seigo; Tachibana, Isao; Komuta, Kiyoshi; Kawase, Ichiro; Kijima, Takashi; Takahashi, Ryo; Kida, Hiroshi; Nakatani, Takeshi; Hamaguchi, Masanari; Takeuchi, Yoshiko; Nagatomo, Izumi; Yamamoto, Suguru

2012-01-01

Erlotinib and pemetrexed have been approved for the second-line treatment of non-small cell lung cancer (NSCLC). These two agents have different mechanisms of action. Combined treatment with erlotinib and pemetrexed could potentially augment the antitumor activity of either agent alone. In the present study, we investigated the safety profile of combined administration of the two agents in pretreated NSCLC patients. A phase I dose-finding study (Trial registration: UMIN000002900) was performed in patients with stage III/IV nonsquamous NSCLC whose disease had progressed on or after receiving first-line chemotherapy. Patients received 500 mg/m 2 of pemetrexed intravenously every 21 days and erlotinib (100 mg at Level 1 and 150 mg at Level 2) orally on days 2–16. Twelve patients, nine males and three females, were recruited. Patient characteristics included a median age of 66 years (range, 48–78 years), stage IV disease (nine cases), adenocarcinoma (seven cases) and activating mutation-positives in the epidermal growth factor receptor gene (two cases). Treatment was well-tolerated, and the recommended dose of erlotinib was fixed at 150 mg. Dose-limiting toxicities were experienced in three patients and included: grade 3 elevation of serum alanine aminotransferase, repetitive grade 4 neutropenia that required reduction of the second dose of pemetrexed and grade 3 diarrhea. No patient experienced drug-induced interstitial lung disease. Three patients achieved a partial response and stable disease was maintained in five patients. Combination chemotherapy of intermittent erlotinib with pemetrexed was well-tolerated, with promising efficacy against pretreated advanced nonsquamous NSCLC

Feasibility and preliminary results of intensive chemotherapy and extensive irradiation in selected patients with limited small-cell lung carcinoma--results of three consecutive phase II programs

International Nuclear Information System (INIS)

Tourani, J.M.; Jaillon-Abraham, C.; Coscas, Y.; Dabouis, G.; Andrieu, J.M.

2000-01-01

We report the results of three consecutive programs combining initial intensive chemotherapy and radiotherapy in the treatment of patients with limited small-cell lung cancer (SCLC). The objective was to test the feasibility and the effect of high-dose chemotherapy and three thoracic irradiation programs on survival and patterns of relapse. Forty-two patients with limited SCLC were enrolled. All patients received high-dose chemotherapy (vindesine, etoposide, doxorubicin, cisplatin and cyclophosphamide or ifosfamide). In the SC 84 program, chest and brain radiotherapy was delivered during each course of chemotherapy, with a complementary irradiation after chemotherapy. In the SC 86 and SC 92 programs, patients received chemotherapy followed by thoracic irradiation and prophylactic brain and spinal axis radiotherapy. At the end of treatment, 40 patients (95%) were in complete response. During chemotherapy, high levels of toxicity were noted. All patients had grade IV hematological toxicities. The extra-hematological toxicities were digestive (grade III: 21%; grade IV: 7%) and hepatic (grades III and IV: 14%). During irradiation, patients presented digestive, pulmonary and hematological toxicities. Five patients developed late toxicities and a second malignancy was observed in 4 patients. The 2- and 5-year survival rates for all patients were 51% and 27%, respectively. Despite the marked toxicity of the initial intensive chemotherapy, the treatments are tolerable and effective in the control of extra-thoracic micrometastases, whereas they are less effective for thoracic primary tumor

Assessment of the Radiation-Equivalent of Chemotherapy Contributions in 1-Phase Radio-chemotherapy Treatment of Muscle-Invasive Bladder Cancer

International Nuclear Information System (INIS)

Plataniotis, George A.; Dale, Roger G.

2014-01-01

Purpose: To estimate the radiation equivalent of the chemotherapy contribution to observed complete response rates in published results of 1-phase radio-chemotherapy of muscle-invasive bladder cancer. Methods and Materials: A standard logistic dose–response curve was fitted to data from radiation therapy-alone trials and then used as the platform from which to quantify the chemotherapy contribution in 1-phase radio-chemotherapy trials. Two possible mechanisms of chemotherapy effect were assumed (1) a fixed radiation-independent contribution to local control; or (2) a fixed degree of chemotherapy-induced radiosensitization. A combination of both mechanisms was also considered. Results: The respective best-fit values of the independent chemotherapy-induced complete response (CCR) and radiosensitization (s) coefficients were 0.40 (95% confidence interval −0.07 to 0.87) and 1.30 (95% confidence interval 0.86-1.70). Independent chemotherapy effect was slightly favored by the analysis, and the derived CCR value was consistent with reports of pathologic complete response rates seen in neoadjuvant chemotherapy-alone treatments of muscle-invasive bladder cancer. The radiation equivalent of the CCR was 36.3 Gy. Conclusion: Although the data points in the analyzed radio-chemotherapy studies are widely dispersed (largely on account of the diverse range of chemotherapy schedules used), it is nonetheless possible to fit plausible-looking response curves. The methodology used here is based on a standard technique for analyzing dose-response in radiation therapy-alone studies and is capable of application to other mixed-modality treatment combinations involving radiation therapy

MR-guided simultaneous integrated boost in preoperative radiotherapy of locally advanced rectal cancer following neoadjuvant chemotherapy

International Nuclear Information System (INIS)

Seierstad, Therese; Hole, Knut Hakon; Saelen, Erik; Ree, Anne Hansen; Flatmark, Kjersti; Malinen, Eirik

2009-01-01

Purpose: To evaluate a simultaneous integrated boost (SIB) strategy in preoperative radiotherapy of rectal cancer patients following neoadjuvant chemotherapy using pre- and post-chemotherapy tumor volumes assessed by MRI. Materials and methods: Ten patients with locally advanced rectal cancer, receiving chemotherapy prior to radiotherapy, were included in this study. Pre- and post-chemotherapy MR tumor images were co-registered with CT images for IMRT planning. Three planning target volumes were defined: PTV risk , PTV pre c hemo and PTV post c hemo . For SIB, prescribed mean doses to the PTVs were 46, 50 and 58 Gy, respectively, given in 25 fractions. Organs at risk (OARs) were bladder and intestine. The novel three-volume SIB strategy was compared to a conventional two-volume SIB plan, in which PTV post c hemo was ignored, using dose-volume histograms (DVHs) and the generalized equivalent uniform dose (gEUD). Results: All patients showed tumor shrinkage following chemotherapy. For the novel SIB, population-based mean doses given to PTV risk , PTV pre c hemo and PTV post c hemo were 46.8 ± 0.3, 50.6 ± 0.4 and 58.1 ± 0.4 Gy, respectively. DVHs and gEUDs for PTV risk , PTV pre c hemo , bladder and intestine revealed minimal differences between the two SIB strategies. Conclusions: Tumor volume reduction for rectal cancer patients following neoadjuvant chemotherapy allows for increased tumor dose using a SIB strategy without increased OAR toxicity.

Radiation and chemotherapy from the viewpoint of radiochemist

International Nuclear Information System (INIS)

Moebius, S.

1989-01-01

Fundamentals of radiation and chemotherapy in cancer treatment are presented from the viewpoint of radiochemistry. Properties and mechanism of chemotherapy, especially of platinum compounds are explained. The present state of radiation therapy is shown and possibilities for future reduction of the patients dose burden are discussed. Promising ways are the radiation sensitization of tumor cells by oxygen or the use of particle radiation instead of γ-quants. (orig.) [de

Sequential {sup 18}F-FDG PET/CT for early prediction of complete pathological response in breast and axilla during neoadjuvant chemotherapy

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Koolen, Bas B. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Surgical Oncology, Amsterdam (Netherlands); Pengel, Kenneth E. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Radiology, Amsterdam (Netherlands); Wesseling, Jelle [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Pathology, Amsterdam (Netherlands); Vogel, Wouter V.; Valdes Olmos, Renato A. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Vrancken Peeters, Marie-Jeanne T.F.D.; Rutgers, Emiel J.T. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Surgical Oncology, Amsterdam (Netherlands); Vincent, Andrew D. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Biometrics, Amsterdam (Netherlands); Gilhuijs, Kenneth G.A. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Radiology, Amsterdam (Netherlands); University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Rodenhuis, Sjoerd [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Medical Oncology, Amsterdam (Netherlands)

2014-01-15

To investigate the value of response monitoring in both the primary tumour and axillary nodes on sequential PET/CT scans during neoadjuvant chemotherapy (NAC) for predicting complete pathological response (pCR), taking the breast cancer subtype into account. In 107 consecutive patients 290 PET/CT scans were performed at baseline (PET/CT1, 107 patients), after 2 - 3 weeks of chemotherapy (PET/CT2, 85 patients), and after 6 - 8 weeks (PET/CT3, 98 patients). The relative changes in SUVmax (from baseline) of the tumour and the lymph nodes and in both combined (after logistic regression), and the changes in the highest SUVmax between scans (either tumour or lymph node) were determined and their associations with pCR of the tumour and lymph nodes after completion of NAC were assessed using receiver operating characteristic (ROC) analysis. A pCR was seen in 17 HER2-positive tumours (65 %), 1 ER-positive/HER2-negative tumour (2 %), and 16 triple-negative tumours (52 %). The areas under the ROC curves (ROC-AUC) for the prediction of pCR in HER2-positive tumours after 3 weeks were 0.61 for the relative change in tumours, 0.67 for the combined change in tumour and nodes, and 0.72 for the changes in the highest SUVmax between scans. After 8 weeks equivalent values were 0.59, 0.42 and 0.64, respectively. In triple-negative tumours the ROC-AUCs were 0.76, 0.84 and 0.76 after 2 weeks, and 0.87, 0.93 and 0.88 after 6 weeks, respectively. In triple-negative tumours a PET/CT scan after 6 weeks (three cycles) appears to be optimally predictive of pCR. In HER2-positive tumours neither a PET/CT scan after 3 weeks nor after 8 weeks seems to be useful. The changes in SUVmax of both the tumour and axillary nodes combined correlates best with pCR. (orig.)

Enhanced response rates in pancreatic cancer with concurrent continuous infusion(CI) low dose chemotherapy and hyperfractionated radiotherapy

International Nuclear Information System (INIS)

Bronn, Donald G.; Franklin, Roman; Krishnan, Rajan S.; Richardson, Ralph W.; Conlin, Christopher

1996-01-01

Objective: Many patients with a diagnosis of pancreatic cancer are not offered any therapeutic intervention other than surgical bypass due to very poor prognosis, poor patient tolerance to current therapeutic regimens, and a dismal tumor response to therapy. In view of these circumstances, an acceptable treatment regimen for pancreatic cancer must first demonstrate an ability to obtain a rapid tumor response with a regimen that will be well tolerated enabling the patient to maintain a good quality of life with full ambulatory status. Materials and Methods: Nine unresectable pancreatic cancer patients ((4(9)) had liver metastases) with an average age of 62 (range: 41-79) were treated with a concurrent regimen consisting of 5-Fluorouracil (CI 200-250 mg/m 2 /24 hrs) and Cisplatin (CI 5mg/24 hrs: 2 weeks on, 1 week off) given simultaneously with 3-D planned BID hyperfractionated radiotherapy to the pancreas (5940 cGy/66 fractions/6.5 weeks), and whole liver (1980 cGy/22 fractions/2 weeks), plus additional dose to the partial liver in metastatic disease. Continuous infusion combination chemotherapy was continued alone after radiotherapy for a total of six months. Chemotherapy was delivered by dual light weight portable external pumps. Hyperalimentation was used as needed to maintain nutritional status and warfarin thromboembolic prophylaxis was also utilized. Tumor response was monitored by monthly abdominal CAT scans, serum markers (CEA, CA 19-9), weight gain, and symptomatology. Full radiographic resolution of tumor mass was considered to be a complete response (CR), whereas 50% or greater radiographic decrease in size was considered a partial response (PR). Evaluation was done by independent diagnostic radiologists. Results: CR and PR of the pancreatic mass was achieved in 88% of all patients ((8(9))). CR was achieved in 44% of all patients ((4(9))). Patients with liver metastases exhibited 75% ((3(4))) PR in liver masses and either CR or PR in the primary site. All

CD34-positive cells as stem cell support after high dose therapy

International Nuclear Information System (INIS)

Kvalheim, G.; Pharo, A.; Holte, H.

1996-01-01

Six patients, five with breast cancer and one with non-Hodgkin's lymphoma, were mobilized by chemotherapy and G-CSF. CD34-positive cells were isolated by means of immunomagnetic beads and Isolex 300 Cell Separator. Mean purity of isolated CD34-positive cells was 97% and mean yield was 54%. Three patients were treated with high dose therapy followed by reinfusion of CD34-positive cells as stem cell support. Recovery of neutrophils occurred at day 8, 11 and 13 and of platelets at day 9, 14 and 32. It is concluded that immunomagnetic isolated CD34-positive cells give high purity and yield. Although use of CD34-positive cells reduces the content of contaminating tumours cells in the graft, breast cancer cells were still detectable in two out of five CD34-positive cell products. 20 refs., 2 figs., 1 tab

Late effects of adjuvant chemotherapy on cognitive function: a follow-up study in breast cancer patients

NARCIS (Netherlands)

Schagen, S. B.; Muller, M. J.; Boogerd, W.; Rosenbrand, R. M.; van Rhijn, D.; Rodenhuis, S.; van Dam, F. S. A. M.

2002-01-01

BACKGROUND: Neuropsychological examinations have shown an elevated risk for cognitive impairment 2 years after therapy in breast cancer patients randomized to receive adjuvant high-dose cyclophosphamide, thiotepa, carboplatin (CTC) chemotherapy compared with a non-treated control group of stage I

A phase II study evaluating neo-/adjuvant EIA chemotherapy, surgical resection and radiotherapy in high-risk soft tissue sarcoma.

Science.gov (United States)

Schmitt, Thomas; Lehner, Burkhard; Kasper, Bernd; Bischof, Marc; Roeder, Falk; Dietrich, Sascha; Dimitrakopoulou-Strauss, Antonia; Strauss, Ludwig G; Mechtersheimer, Gunhild; Wuchter, Patrick; Ho, Anthony D; Egerer, Gerlinde

2011-12-07

The role of chemotherapy in high-risk soft tissue sarcoma is controversial. Though many patients undergo initial curative resection, distant metastasis is a frequent event, resulting in 5-year overall survival rates of only 50-60%. Neo-adjuvant and adjuvant chemotherapy (CTX) has been applied to achieve pre-operative cytoreduction, assess chemosensitivity, and to eliminate occult metastasis. Here we report on the results of our non-randomized phase II study on neo-adjuvant treatment for high-risk STS. Patients with potentially curative high-risk STS (size ≥ 5 cm, deep/extracompartimental localization, tumor grades II-III [FNCLCC]) were included. The protocol comprised 4 cycles of neo-adjuvant chemotherapy (EIA, etoposide 125 mg/m(2) iv days 1 and 4, ifosfamide 1500 mg/m2 iv days 1 - 4, doxorubicin 50 mg/m(2) day 1, pegfilgrastim 6 mg sc day 5), definitive surgery with intra-operative radiotherapy, adjuvant radiotherapy and 4 adjuvant cycles of EIA. Between 06/2005 and 03/2010 a total of 50 subjects (male = 33, female = 17, median age 50.1 years) were enrolled. Median follow-up was 30.5 months. The majority of primary tumors were located in the extremities or trunk (92%), 6% originated in the abdomen/retroperitoneum. Response by RECIST criteria to neo-adjuvant CTX was 6% CR (n = 3), 24% PR (n = 12), 62% SD (n = 31) and 8% PD (n = 4). Local recurrence occurred in 3 subjects (6%). Distant metastasis was observed in 12 patients (24%). Overall survival (OS) and disease-free survival (DFS) at 2 years was 83% and 68%, respectively. Multivariate analysis failed to prove influence of resection status or grade of histological necrosis on OS or DFS. Severe toxicities included neutropenic fever (4/50), cardiac toxicity (2/50), and CNS toxicity (4/50) leading to CTX dose reductions in 4 subjects. No cases of secondary leukemias were observed so far. The current protocol is feasible for achieving local control rates, as well as OS and DFS comparable to previously published

A phase II study evaluating neo-/adjuvant EIA chemotherapy, surgical resection and radiotherapy in high-risk soft tissue sarcoma

Directory of Open Access Journals (Sweden)

Schmitt Thomas

2011-12-01

Full Text Available Abstract Background The role of chemotherapy in high-risk soft tissue sarcoma is controversial. Though many patients undergo initial curative resection, distant metastasis is a frequent event, resulting in 5-year overall survival rates of only 50-60%. Neo-adjuvant and adjuvant chemotherapy (CTX has been applied to achieve pre-operative cytoreduction, assess chemosensitivity, and to eliminate occult metastasis. Here we report on the results of our non-randomized phase II study on neo-adjuvant treatment for high-risk STS. Method Patients with potentially curative high-risk STS (size ≥ 5 cm, deep/extracompartimental localization, tumor grades II-III [FNCLCC] were included. The protocol comprised 4 cycles of neo-adjuvant chemotherapy (EIA, etoposide 125 mg/m2 iv days 1 and 4, ifosfamide 1500 mg/m2 iv days 1 - 4, doxorubicin 50 mg/m2 day 1, pegfilgrastim 6 mg sc day 5, definitive surgery with intra-operative radiotherapy, adjuvant radiotherapy and 4 adjuvant cycles of EIA. Result Between 06/2005 and 03/2010 a total of 50 subjects (male = 33, female = 17, median age 50.1 years were enrolled. Median follow-up was 30.5 months. The majority of primary tumors were located in the extremities or trunk (92%, 6% originated in the abdomen/retroperitoneum. Response by RECIST criteria to neo-adjuvant CTX was 6% CR (n = 3, 24% PR (n = 12, 62% SD (n = 31 and 8% PD (n = 4. Local recurrence occurred in 3 subjects (6%. Distant metastasis was observed in 12 patients (24%. Overall survival (OS and disease-free survival (DFS at 2 years was 83% and 68%, respectively. Multivariate analysis failed to prove influence of resection status or grade of histological necrosis on OS or DFS. Severe toxicities included neutropenic fever (4/50, cardiac toxicity (2/50, and CNS toxicity (4/50 leading to CTX dose reductions in 4 subjects. No cases of secondary leukemias were observed so far. Conclusion The current protocol is feasible for achieving local control rates, as well as OS

Improved Tumor-Specific Drug Accumulation by Polymer Therapeutics with pH-Sensitive Drug Release Overcomes Chemotherapy Resistance.

Science.gov (United States)

Heinrich, Anne-Kathrin; Lucas, Henrike; Schindler, Lucie; Chytil, Petr; Etrych, Tomáš; Mäder, Karsten; Mueller, Thomas

2016-05-01

The success of chemotherapy is limited by poor selectivity of active drugs combined with occurrence of tumor resistance. New star-like structured N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based drug delivery systems containing doxorubicin attached via a pH-sensitive hydrazone bond were designed and investigated for their ability to overcome chemotherapy resistance. These conjugates combine two strategies to achieve a high drug concentration selectively at the tumor site: (I) high accumulation by passive tumor targeting based on enhanced permeability and retention effect and (II) pH-sensitive site-specific drug release due to an acidic tumor microenvironment. Mice bearing doxorubicin-resistant xenograft tumors were treated with doxorubicin, PBS, poly HPMA (pHPMA) precursor or pHPMA-doxorubicin conjugate at different equivalent doses of 5 mg/kg bodyweight doxorubicin up to a 7-fold total dose using different treatment schedules. Intratumoral drug accumulation was analyzed by fluorescence imaging utilizing intrinsic fluorescence of doxorubicin. Free doxorubicin induced significant toxicity but hardly any tumor-inhibiting effects. Administering at least a 3-fold dose of pHPMA-doxorubicin conjugate was necessary to induce a transient response, whereas doses of about 5- to 6-fold induced strong regressions. Tumors completely disappeared in some cases. The onset of response was differential delayed depending on the tumor model, which could be ascribed to distinct characteristics of the microenvironment. Further fluorescence imaging-based analyses regarding underlying mechanisms of the delayed response revealed a related switch to a more supporting intratumoral microenvironment for effective drug release. In conclusion, the current study demonstrates that the concept of tumor site-restricted high-dose chemotherapy is able to overcome therapy resistance. Mol Cancer Ther; 15(5); 998-1007. ©2016 AACR. ©2016 American Association for Cancer Research.

Palonosetron for the prevention of nausea and vomiting in children with acute lymphoblastic leukemia treated with high dose methotrexate

DEFF Research Database (Denmark)

Nadaraja, Sambavy; Mamoudou, Aissata Diop; Thomassen, Harald

2012-01-01

High dose methotrexate (HD-MTX), used in the treatment of children with acute lymphoblastic leukemia (ALL), is moderately emetogenic. First generation 5-HT(3) receptor antagonists are effective prophylactic agents but require multiple administrations. Palonosetron has a half life of 36-42 hours...... of palonosetron (5 µg/kg) for the prevention of chemotherapy-induced nausea and vomiting in children 18 years of age with ALL treated with HD-MTX, 5 g/m(2)....

Gamma dosimetry of high doses

International Nuclear Information System (INIS)

Martinez C, T.; Galvan G, A.; Canizal, G.

1991-01-01

The gamma dosimetry of high doses is problematic in almost all the classic dosemeters either based on the thermoluminescence, electric, chemical properties, etc., because they are saturated to very high dose and they are no longer useful. This work carries out an investigation in the interval of high doses. The solid system of heptahydrate ferrous sulfate, can be used as solid dosemeter of routine for high doses of radiation. The proposed method is simple, cheap and it doesn't require sophisticated spectrophotometers or spectrometers but expensive and not common in some laboratories

Image Quality of 3rd Generation Spiral Cranial Dual-Source CT in Combination with an Advanced Model Iterative Reconstruction Technique: A Prospective Intra-Individual Comparison Study to Standard Sequential Cranial CT Using Identical Radiation Dose.

Science.gov (United States)

Wenz, Holger; Maros, Máté E; Meyer, Mathias; Förster, Alex; Haubenreisser, Holger; Kurth, Stefan; Schoenberg, Stefan O; Flohr, Thomas; Leidecker, Christianne; Groden, Christoph; Scharf, Johann; Henzler, Thomas

2015-01-01

To prospectively intra-individually compare image quality of a 3rd generation Dual-Source-CT (DSCT) spiral cranial CT (cCT) to a sequential 4-slice Multi-Slice-CT (MSCT) while maintaining identical intra-individual radiation dose levels. 35 patients, who had a non-contrast enhanced sequential cCT examination on a 4-slice MDCT within the past 12 months, underwent a spiral cCT scan on a 3rd generation DSCT. CTDIvol identical to initial 4-slice MDCT was applied. Data was reconstructed using filtered backward projection (FBP) and 3rd-generation iterative reconstruction (IR) algorithm at 5 different IR strength levels. Two neuroradiologists independently evaluated subjective image quality using a 4-point Likert-scale and objective image quality was assessed in white matter and nucleus caudatus with signal-to-noise ratios (SNR) being subsequently calculated. Subjective image quality of all spiral cCT datasets was rated significantly higher compared to the 4-slice MDCT sequential acquisitions (pspiral compared to sequential cCT datasets with mean SNR improvement of 61.65% (p*Bonferroni0.05spiral cCT with an advanced model IR technique significantly improves subjective and objective image quality compared to a standard sequential cCT acquisition acquired at identical dose levels.

Mechanisms of chemotherapy-induced behavioral toxicities

Directory of Open Access Journals (Sweden)

Elisabeth G Vichaya

2015-04-01

Full Text Available While chemotherapeutic agents have yielded relative success in the treatment of cancer, patients are often plagued with unwanted and even debilitating side-effects from the treatment which can lead to dose reduction or even cessation of treatment. Common side effects (symptoms of chemotherapy include (i cognitive deficiencies such as problems with attention, memory and executive functioning; (ii fatigue and motivational deficit; and (iii neuropathy. These symptoms often develop during treatment but can remain even after cessation of chemotherapy, severely impacting long-term quality of life. Little is known about the underlying mechanisms responsible for the development of these behavioral toxicities, however, neuroinflammation is widely considered to be one of the major mechanisms responsible for chemotherapy-induced symptoms. Here, we critically assess what is known in regards to the role of neuroinflammation in chemotherapy-induced symptoms. We also argue that, based on the available evidence neuroinflammation is unlikely the only mechanism involved in the pathogenesis of chemotherapy-induced behavioral toxicities. We evaluate two other putative candidate mechanisms. To this end we discuss the mediating role of damage-associated molecular patterns (DAMPs activated in response to chemotherapy-induced cellular damage. We also review the literature with respect to possible alternative mechanisms such as a chemotherapy-induced change in the bioenergetic status of the tissue involving changes in mitochondrial function in relation to chemotherapy-induced behavioral toxicities. Understanding the mechanisms that underlie the emergence of fatigue, neuropathy, and cognitive difficulties is vital to better treatment and long-term survival of cancer patients.

Understanding the antiangiogenic effect of metronomic chemotherapy through a simple mathematical model

Science.gov (United States)

Rodrigues, Diego S.; Mancera, Paulo F. A.; Pinho, Suani T. R.

2016-12-01

Despite the current and increasingly successful fight against cancer, there are some important questions concerning the efficiency of its treatment - in particular, the design of oncology chemotherapy protocols. Seeking efficiency, schedules based on more frequent, low-doses of drugs, known as metronomic chemotherapy, have been proposed as an alternative to the classical standard protocol of chemotherapy administration. The in silico approach may be very useful for providing a comparative analysis of these two kinds of protocols. In so doing, we found that metronomic schedules are more effective in eliminating tumour cells mainly due to their chemotherapeutic action on endothelial cells and that more frequent, low drug doses also entail outcomes in which the survival time of patient is increased.

Granulocyte colony stimulating factor priming chemotherapy is more effective than standard chemotherapy as salvage therapy in relapsed acute myeloid leukemia.

Science.gov (United States)

Shen, Ying; He, Aili; Wang, Fangxia; Bai, Ju; Wang, Jianli; Zhao, Wanhong; Zhang, Wanggang; Cao, Xingmei; Chen, Yinxia; Liu, Jie; Ma, Xiaorong; Chen, Hongli; Feng, Yuandong; Yang, Yun

2017-12-29

To improve the complete remission (CR) rate of newly diagnosed acute myeloid leukemia (AML) patients and alleviate the severe side effects of double induction chemotherapy, we combined a standard regimen with granulocyte colony-stimulating factor (G-CSF) priming chemotherapy to compose a new double induction regimen for AML patients who failed to achieve CR after the first course. Ninety-seven patients with AML who did not achieve CR after the first course of standard chemotherapy were enrolled. Among them, 45 patients received G-CSF priming combined with low-dose chemotherapy during days 20-22 of the first course of chemotherapy, serving as priming group, 52 patients were administered standard chemotherapy again, serving as control group. Between the two groups there were no differences in the French-American-British (FAB) classification, risk status, the first course of chemotherapy, blood cell count or blasts percentage of bone marrow before the second course. But the CR rate was significantly higher and the adverse effect was much lower in the priming group than the control group. Cox multivariate regression analysis showed that WBC level before the second course and the selection of the second chemotherapy regimen were two independent factors for long survival of patients. These results elucidate that standard chemotherapy followed by G-CSF priming new double induction chemotherapy is an effective method for AML patients to improve CR rate and reduce adverse effects. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Chemotherapy in patients with hepatic failure

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Roldán, G.; Sosa, A.

2004-01-01

The toxicity of chemotherapy in the liver may manifest as hepatocyte dysfunction with chemical hepatitis, veno-occlusive disease or chronic fibrosis. The hepatocyte dysfunction is caused by direct effect of the drug or its metabolites evidencing by increased bilirubin and liver enzymes (Sgot, SGPT). Prolonged effect leads to cholestasis and fatty infiltration. This dysfunction is concomitant enhanced by viral infection, liver metastases and other drugs as antiemetics. The vast majority of the indicated drugs in a cancer patient, cytostatics, antiemetics, analgésios, anticonvulsants, etc, are metabolized in the liver. The evidence of abnormal hepatocyte function in a patient in which involves chemotherapy raises the need for dose modification indicated and / or discontinuation. The aim of this paper is to review existing information on the use of cytostatics in cancer patients with hepatic impairment, classifying drugs according to their potential hepato toxicity and recommended dose modification in patients with hepatic dysfunction

Intercalated radio-chemotherapy in small cell lung cancer

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Hoskin, P.J.; Parton, D.; Yarnold, J.R.; Cherryman, G.; Smith, I.E.

1991-01-01

36 patients with small cell lung cancer have been treated using chemotherapy comprising carboplatin, ifosphamide and etoposide. A total of 6 cycles of chemotherapy was given. In 15 patients with limited disease intercalated radio-chemotherapy was used in which two 5-day courses of hyperfractionated radiotherapy were given to the thorax after the 1st and 2nd cycles of chemotherapy. Each course of thoracic radiotherapy delivered 15 Gy in 15 fractions over 5 days. Oesophagitis occurred in 7 patients (40 percent), in 5 of whom this was severe (WHO grade 3). Radiological pneumonitis developed in 6 patients (40 percent) with subsequent fibrosis in 2 patients. These effects are greater than would be expected with this dose of radiation alone and reflect marked enhancement of normal tissue toxicity. (author). 11 refs.; 1 fig.; 1 tab

Combination radiotherapy and chemotherapy for primary lung cancer

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Nishikawa, Kiyoshi; Koga, Kenji; Kusuhara, Toshiyuki; Kodama, Takao; Takeuchi, Midori; Watanabe, Katsushi

1984-01-01

Fifty-six patients with carcinoma of the lung treated with radiotherapy alone or combination of chemotherapy were reviewed. Radiation was given with a 10MV photon beam by a linear accelerator. A fraction dose of 2Gy (200 rad) was given routinely 5 times a week. Combined durgs consist of 5FU or FT-207 in monochemotherapy and METT, MFC, or METVFC in combination chemotherapy. 5 year survival rate of all patients was 3.8%. As for the stage classification, 5 year survival rate is 30% in Stage I and II cancer, but there was no 3 year survivor in Stage III cancer and 2 year survivor in Stage IV cancer. As for the cell types, cases of adenocarcinoma had worse prognosis than them of squamous cell carcinoma and small cell carcinoma. The prognosis of patients treated with combination of radiotherapy and chemotherapy was similar to that of patients treated with radiotherapy alone. These results suggest that combined chemotherapy did not influence tumor control. Some discussion on the treatment modality of chemotherapy are made, emphasizing untoward effect of chemotherapy on immunopotency. (author)

Experimental study on combination of chemotherapy and radiotherapy

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Tanaka, Juichi

1986-01-01

Recently, by applying multidrug therapy using cisplatin and bleomycin to the treatment of head and neck cancer, the response rate of chemotherapy has been markedly increased and thus, chemotherapy has taken an important part in the treatment of head and neck cancer. In this paper a clinical application of chemotherapy in combination with radiotherapy was evaluated from the point of the cure rate and also preservation of the structures and the functions of the head and neck region. In order to test the advantage or usefulness of initial chemotherapy followed by radiotherapy (= pre-radiation chemotherapy), the experimental study on combination of chemotherapy and radiotherapy was designed by using ICR mice and Ehrlich solid carcinoma. Cisplatin and peplomycin, a newly developed derivative of bleomycin, were used as chemotherapeutic agents. Tumor growth delay rate was chosen as a parameter to indicate the effectiveness. Results obtained are as follows. 1. Combination chemotherapy of cisplatin and peplomycin was more effective than each single agent on Ehrlich solid carcinoma. Synergistic effect was obtained by higher dose. So, the combination of cisplatin and peplomycin was proved to be eligible for pre-radiation chemotherapy. 2. Synergistic effect of chemotherapy and radiotherapy was observed when chemotherapy was used prior to radiotherapy on Ehrlich solid carcinoma. 3. Even their additional effect was not recognized when radiotherapy preceded to chemotherapy on Ehrlich solid carcinoma. 4. No severe toxic effect was seen in the mice. The experimental results made it clear that pre-radiation chemotherapy is beneficial to the treatment of head and neck cancer. (author)

An open-label, sequential, dose-finding study of peginesatide for the maintenance treatment of anemia in chronic hemodialysis patients

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Besarab Anatole

2012-08-01

Full Text Available Abstract Background Peginesatide is a peptide-based erythropoiesis-stimulating agent that was designed and engineered to stimulate specifically the erythropoietin receptor dimer that governs erythropoiesis. The primary objective of this phase 2 dose-finding study was to determine the once-monthly peginesatide dosing strategy that would maintain hemoglobin within ±1.0 g/dL of baseline values after conversion from epoetin alfa; the safety of peginesatide was evaluated concurrently. Methods Chronic hemodialysis patients on stable regimens of epoetin alfa were sequentially assigned to cohorts that differed on (1 how the peginesatide starting dose was determined (using a single epoetin alfa–to-peginesatide dose conversion ratio or a tiered, weight-based or absolute-dose conversion table and on (2 whether or not a 1-week erythropoiesis-stimulating agent-free interval was used. Peginesatide doses were titrated to maintain hemoglobin levels within ±1.0 g/dL from baseline. Results A total of 164 patients were enrolled and received intravenous peginesatide every 4 weeks for up to 6 doses; the duration of the study including follow-up was ≤29 weeks. Overall, the proportion of patients with hemoglobin levels within ±1.0 g/dL of baseline increased over the course of the study from 39% (Weeks 2–13 to 54% (Weeks 18–25. Cohorts that used tiered dose conversion tables trended towards having more stable peginesatide doses than did those cohorts that used a single dose conversion ratio. Moreover, cohorts that used an erythropoiesis-stimulating agent-free interval did not have the substantial initial increase in hemoglobin levels that was seen in those cohorts that did not use such an interval. In this study, the safety profile of peginesatide was consistent with those of marketed erythropoiesis-stimulating agents. Conclusions The results of this study were used to guide the dosing regimens used subsequently in phase 3 studies. Once

Efficacy and toxicity of adjuvant chemotherapy in elderly patients with colorectal cancer

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Lund, C M; Nielsen, D; Dehlendorff, Christian

2016-01-01

BACKGROUND: Elderly patients with primary colorectal cancer (CRC) are less frequently treated with adjuvant chemotherapy than younger patients due to concerns regarding toxicity and efficiency. We investigated how age, performance status (PS) and comorbidity influence treatment outcomes. PATIENTS...... AND METHODS: A retrospective single-centre study of 529 patients with stages II-III CRC treated with adjuvant chemotherapy (5-fluorouracil/capecitabine+/÷oxaliplatin) from 2001 to 2011 at Herlev Hospital, Denmark. Baseline characteristics, chemotherapy and outcome were analysed with respect to age after......-dependent difference in 3-year disease-free survival (DFS; HR 1.09, 95% CI 0.80 to 1.47, p=0.59), in grade 3-5 toxicity (29% vs 28%, p=0.86) or in 10-year CRC mortality (28%, HR 1.07, p=0.71). In elderly patients, a reduction in chemotherapy dose intensity compared with full dose had no impact on DFS or CRC mortality...

Study on delineation of tumor volume of primary locally advanced nasopharyngeal carcinoma after induction chemotherapy

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Long Jinhua; Dong Shi; Jin Feng; Wu Weili; Gan Jiaying; Chen Haixia; Li Yuanyuan; Gong Xiuyun