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Sample records for weekly carboplatin reduces

  1. Tolerance of weekly paclitaxel and carboplatin as neoadjuvant chemotherapy in advanced ovarian cancer patients who are unlikely to tolerate 3 weekly paclitaxel and carboplatin.

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    Dessai, S B; Chakraborty, S; Babu, Tvs; Nayanar, S; Bhattacharjee, A; Jones, J; Balasubramanian, S; Patil, V M

    2016-01-01

    There are little data regarding safety and effectiveness of neoadjuvant chemotherapy (NACT) in patients who are considered unfit for receiving 3 weekly paclitaxel and carboplatin. The aim of this study was to study the toxicity and response rates of weekly paclitaxel and carboplatin as NACT in such cohort of patients. Study population included advanced ovarian cancer patients who were unlikely to tolerate 3 weekly paclitaxel and carboplatin and hence received weekly paclitaxel (80 mg/m2) and carboplatin AUC-2 as NACT. The data regarding the baseline characteristics, chemotherapy tolerance, completion rates, toxicity (CTCAE version 4.02), and radiological response rates are presented. SPSS version 16 was used for analysis. Descriptive statistics is presented. Eleven patients received this schedule. Nine patients completed nine cycles of NACT. Except one, all patients completed NACT with an average relative dose intensity of >0.8. There was no chemotherapy-related mortality. Grade 3-4 life-threatening complications were seen in two patients. The post NACT response rate was 100%. Weekly paclitaxel and carboplatin chemotherapy is safe and efficacious in patients who are unsuitable for 3 weekly paclitaxel and carboplatin chemotherapy schedules.

  2. Tolerance of weekly metronomic paclitaxel and carboplatin as neoadjuvant chemotherapy in advanced ovarian cancer patients who are unlikely to tolerate 3 weekly paclitaxel and carboplatin

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    S B Dessai

    2016-01-01

    Full Text Available Objective: There are little data regarding safety and effectiveness of neoadjuvant chemotherapy (NACT in patients who are considered unfit for receiving 3 weekly paclitaxel and carboplatin. The aim of this study was to examine the toxicity and response rates of weekly paclitaxel and carboplatin as NACT in such cohort of patients. Methods: Study population included advanced ovarian cancer patients who were unlikely to tolerate 3 weekly paclitaxel and carboplatin and hence received weekly paclitaxel (80 mg/m 2 and carboplatin AUC-2 as NACT. The data regarding the baseline characteristics, chemotherapy tolerance, completion rates, toxicity (Common Terminology Criteria for Adverse Events version 4.02, and radiological response rates are presented. SPSS version 16 was used for analysis. Descriptive statistics is presented. Results: Eleven patients received this schedule. Nine patients completed nine cycles of NACT. Except one, all patients completed NACT with an average relative dose intensity of >0.8. There was no chemotherapy-related mortality. Grade 3-4 life-threatening complications were seen in two patients. The post NACT response rate was 100%. Conclusions: Weekly paclitaxel and carboplatin chemotherapy is safe and efficacious in patients who are unsuitable for 3 weekly paclitaxel and carboplatin chemotherapy schedules.

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

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    Hala Mohamed El-Shenshawy

    2012-10-01

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

  4. A phase I and pharmacokinetic study of weekly paclitaxel and carboplatin in patients with metastatic esophageal cancer

    NARCIS (Netherlands)

    M.B. Polee; A. Sparreboom (Alex); F.A.L.M. Eskens (Ferry); R. Hoekstra (Rosa); J. van de Schaaf; J. Verweij (Jaap); G. Stoter (Gerrit); A. van der Gaast (Ate)

    2004-01-01

    textabstractPURPOSE: To determine the maximum-tolerated dose, toxicity profile, and pharmacokinetics of a fixed dose of paclitaxel followed by increasing doses of carboplatin, given weekly to patients with advanced esophageal or gastric junction cancer. EXPERIMENTAL DESIGN:

  5. Phase 1 study of veliparib with carboplatin and weekly paclitaxel in Japanese patients with newly diagnosed ovarian cancer.

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    Nishio, Shin; Takekuma, Munetaka; Takeuchi, Satoshi; Kawano, Kouichirou; Tsuda, Naotake; Tasaki, Kazuto; Takahashi, Nobutaka; Abe, Masakazu; Tanaka, Aki; Nagasawa, Takayuki; Shoji, Tadahiro; Xiong, Hao; Nuthalapati, Silpa; Leahy, Terri; Hashiba, Hideyuki; Kiriyama, Tsukasa; Komarnitsky, Philip; Hirashima, Yasuyuki; Ushijima, Kimio

    2017-11-01

    This phase 1, open-label, dose-escalation study was conducted to determine the safety, tolerability, pharmacokinetics and preliminary efficacy of veliparib with carboplatin and weekly paclitaxel in Japanese women with newly diagnosed, advanced ovarian cancer. Patients received veliparib at 100 or 150 mg b.i.d. on days 1-21 with carboplatin (area under the concentration-time curve 6 mg/mL•min) on day 1 and paclitaxel 80 mg/m2 on days 1, 8 and 15 every 3 weeks for up to 6 21-day cycles. Dose escalation followed a 3 + 3 design to determine dose-limiting toxicities, maximum tolerated dose and the recommended phase 2 dose. Nine patients (median age 62 [range 27-72] years) received a median of 5 (range 3-6) cycles of treatment (3 at 100 mg, 6 at 150 mg). There were no dose-limiting toxicities. The most common adverse events of any grade were neutropenia (100%), alopecia (89%), peripheral sensory neuropathy (78%), and anemia, nausea and malaise (67% each). Grade 3 or 4 adverse events were associated with myelosuppression. Pharmacokinetics of carboplatin/paclitaxel were similar at both veliparib doses. Response, assessed in five patients, was partial in four and complete in one (objective response rate 100%). The response could not be assessed in four patients who had no measurable disease at baseline. The recommended phase 2 dose of veliparib, when combined with carboplatin/paclitaxel, is 150 mg b.i.d. Findings from this phase 1 trial demonstrate the tolerability and safety of veliparib with carboplatin/paclitaxel, a regimen with potential clinical benefit in Japanese women with ovarian cancer. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

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

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    Zhi-Yong Wang

    2016-01-01

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

  7. Sustained platelet-sparing effect of weekly low dose paclitaxel allows effective, tolerable delivery of extended dose dense weekly carboplatin in platinum resistant/refractory epithelial ovarian cancer

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    2011-01-01

    Background Platinum agents have shown demonstrable activity in the treatment of patients with platinum resistant, recurrent ovarian cancer when delivered in a "dose-dense" fashion. However, the development of thrombocytopenia limits the weekly administration of carboplatin to no greater than AUC 2. Paclitaxel has a well-described platelet sparing effect however its use to explicitly provide thromboprotection in the context of dose dense carboplatin has not been explored. Methods We treated seven patients with platinum resistant ovarian cancer who had previously received paclitaxel or who had developed significant peripheral neuropathy precluding the use of further full dose weekly paclitaxel. Results We were able to deliver carboplatin AUC 3 and paclitaxel 20 mg/m2 with no thrombocytopenia or worsening of neuropathic side-effects, and with good activity. Conclusions We conclude that this regimen may be feasible and active, and could be formally developed as a "platinum-focussed dose-dense scaffold" into which targeted therapies that reverse platinum resistance can be incorporated, and merits further evaluation. PMID:21745358

  8. Trastuzumab in combination with weekly paclitaxel and carboplatin as neo-adjuvant treatment for HER2-positive breast cancer : The TRAIN-study

    NARCIS (Netherlands)

    van Ramshorst, Mette S.; van Werkhoven, Erik; Mandjes, Ingrid A.M.; Schot, Margaret; Wesseling, Jelle; Vrancken Peeters, Marie Jeanne T.F.D.; Meerum Terwogt, Jetske M.; Bos, Monique M E M; Oosterkamp, Hendrika M; Rodenhuis, Sjoerd; Linn, Sabine C.|info:eu-repo/dai/nl/166275549; Sonke, Gabe S

    2017-01-01

    Aim To determine the efficacy and safety of an anthracycline-free neo-adjuvant regimen consisting of weekly paclitaxel, carboplatin and trastuzumab in HER2-positive breast cancer. Patients and methods Patients with stage II or III HER2-positive breast cancer received weekly paclitaxel ([P],

  9. Carboplatin Injection

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    Carboplatin is used alone or in combination with other medications to treat cancer of the ovaries (cancer ... after treatment with other medications or radiation therapy. Carboplatin is in a class of medications known as ...

  10. Trastuzumab in combination with weekly paclitaxel and carboplatin as neo-adjuvant treatment for HER2-positive breast cancer: The TRAIN-study.

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    van Ramshorst, Mette S; van Werkhoven, Erik; Mandjes, Ingrid A M; Schot, Margaret; Wesseling, Jelle; Vrancken Peeters, Marie-Jeanne T F D; Meerum Terwogt, Jetske M; Bos, Monique E M; Oosterkamp, Hendrika M; Rodenhuis, Sjoerd; Linn, Sabine C; Sonke, Gabe S

    2017-03-01

    To determine the efficacy and safety of an anthracycline-free neo-adjuvant regimen consisting of weekly paclitaxel, carboplatin and trastuzumab in HER2-positive breast cancer. Patients with stage II or III HER2-positive breast cancer received weekly paclitaxel ([P], 70 mg/m(2)), trastuzumab ([T], 2 mg/kg, loading dose 4 mg/kg) and carboplatin ([C], AUC = 3 mg ml(-1) min) for 24 weeks. In weeks 7, 8, 15, 16, 23 and 24, trastuzumab was administered without chemotherapy. The primary end-point was pathologic complete response in the surgical resection specimen, defined as the absence of invasive tumour cells in breast and axilla. One hundred and eleven patients were included in the study, and 108 were evaluable for the primary end-point. The pathologic complete response rate was 43% (95% confidence interval [CI]: 33-52). Median follow-up was 52 months, and the 3-year event-free survival was 88% (95% CI: 82-94), and the 3-year overall survival was 92% (95% CI: 88-98). The most common grade 3-4 adverse events were neutropenia (67%) and thrombocytopenia (43%). Less than five percent of patients experienced febrile neutropenia. No symptomatic left ventricular systolic dysfunction was observed during neo-adjuvant treatment. An anthracycline-free neo-adjuvant regimen of weekly paclitaxel, trastuzumab and carboplatin is highly effective in HER2-positive breast cancer with manageable toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Results of paclitaxel (day 1 and 8 and carboplatin given on every three weeks in advanced (stage III-IV non-small cell lung cancer

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    Salepci Taflan

    2005-01-01

    Full Text Available Abstract Background Both paclitaxel (P and carboplatin (C have significant activity in non-small cell lung cancer (NSCLC. The weekly administration of P is active, dose intense, and has a favorable toxicity profile. We retrospectively reviewed the data of 51 consecutive patients receiving C and day 1 and 8 P chemotherapy (CT regimen in advanced stage NSCLC to evaluate the efficacy and toxicity. Methods Patients treated in our institutions having pathologically proven NSCLC, no CNS metastases, adequate organ function and performance status (PS ECOG 0–2 were given P 112.5 mg/m2 intravenously (IV over 1 hour on day 1 and 8, followed by C AUC 5 IV over 1 hour, repeated in every three weeks. PC was given for maximum of 6 cycles. Results Median age was 58 (age range 39–77 and 41 patients (80% were male. PS was 0/1/2 in 29/17/5 patients and stage was IIIA/IIIB/IV in 3/14/34 patients respectively. The median number of cycles administered was 3 (1–6. Seven patients (14% did not complete the first 3 cycles either due to death, progression, grade 3 hypersensitivity reactions to P or lost to follow up. Best evaluable response was partial response (PR in 45% and stable disease (SD in 18%. Twelve patients (24% received local RT. Thirteen patients (25% received 2nd line CT at progression. At a median follow-up of 7 months (range, 1–20, 25 (49% patients died and 35 patients (69% progressed. Median overall survival (OS was 11 ± 2 months (95% CI; 6 to 16, 1-year OS ratio was 44%. Median time to progression (TTP was 6 ± 1 months (95% CI; 4 to 8, 1-year progression free survival (PFS ratio was 20%. We observed following grade 3 toxicities: asthenia (10%, neuropathy (4%, anorexia (4%, anemia (4%, hypersensitivity to P (2%, nausea/vomiting (2%, diarrhea (2% and neutropenia (2%. Two patients (4% died of febrile neutropenia. Doses of CT were reduced or delayed in 12 patients (24%. Conclusions P on day 1 and 8 and C every three weeks is practical and fairly

  12. Phase II trial of weekly nab-paclitaxel and carboplatin treatment with or without trastuzumab as nonanthracycline neoadjuvant chemotherapy for locally advanced breast cancer.

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    Huang, Liang; Chen, Sheng; Yao, Ling; Liu, Guangyu; Wu, Jiong; Shao, Zhiming

    2015-01-01

    Neoadjuvant chemotherapy has become standard treatment for women with locally advanced breast cancer. The aim of this study was to compare the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) versus paclitaxel combined with carboplatin. Thirty patients were treated with neoadjuvant nab-paclitaxel (125 mg/m(2), days 1, 8, and 15) and carboplatin (area under the curve =2; days 1, 8, and 15) every 21 days for four cycles. Ninety matched patients received paclitaxel (80 mg/m(2), days 1, 8, and 15) and carboplatin every 21 days for four cycles. Weekly trastuzumab is recommended for overexpression of human epidermal receptor-2. The primary endpoint was pathologic complete response (defined as ypT0/is ypN0). Matching was conducted according to six variables: body mass index, clinical tumor stage, clinical lymph node status, estrogen receptor status, HER2 status, and trastuzumab receiving rate. Ninety percent of patients in the nab-paclitaxel group and 80% of patients in the paclitaxel group experienced a clinical objective response (complete response or partial response; P=0.450). Eight patients in the nab-paclitaxel group and 23 patients in the paclitaxel group had a pathologic complete response in the breast and axillary nodes (26.7% versus 25.6%; P=0.904). Nab-paclitaxel showed a beneficial effective trend on clinical tumor stage II (36.8% versus 15.8%; P=0.051). When trastuzumab was added to nab-paclitaxel, the pathologic complete response rate was not significantly improved more than with trastuzumab and paclitaxel (43.6% versus 39.6%; P=0.769). Carboplatin plus nab-paclitaxel or paclitaxel had similarly low pathologic complete response rates (7.7% versus 10.5%) for the luminal molecular subtype. One (50%) triple-negative patient achieved a pathologic complete response. The nab-paclitaxel regimen caused more grade 4 neutropenia than the paclitaxel regimen (56.7% versus 21.1%; Pcarboplatin with or without trastuzumab resulted in a

  13. Safety of a 3-weekly schedule of carboplatin plus pegylated liposomal doxorubicin as first line chemotherapy in patients with ovarian cancer: preliminary results of the MITO-2 randomized trial

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    D'Arco Alfonso

    2006-08-01

    Full Text Available Abstract Background The MITO-2 (Multicentre Italian Trials in Ovarian cancer study is a randomized phase III trial comparing carboplatin plus paclitaxel to carboplatin plus pegylated liposomal doxorubicin in first-line chemotherapy of patients with ovarian cancer. Due to the paucity of published phase I data on the 3-weekly experimental schedule used, an early safety analysis was planned. Methods Patients with ovarian cancer (stage Ic-IV, aged 2, every 3 weeks or to carboplatin AUC 5 plus pegylated liposomal doxorubicin 30 mg/m2, every 3 weeks. Treatment was planned for 6 cycles. Toxicity was coded according to the NCI-CTC version 2.0. Results The pre-planned safety analysis was performed in July 2004. Data from the first 50 patients treated with carboplatin plus pegylated liposomal doxorubicin were evaluated. Median age was 60 years (range 34–75. Forty-three patients (86% completed 6 cycles. Two thirds of the patients had at least one cycle delayed due to toxicity, but 63% of the cycles were administered on time. In most cases the reason for chemotherapy delay was neutropenia or other hematological toxicity. No delay due to palmar-plantar erythrodysesthesia (PPE was recorded. No toxic death was recorded. Reported hematological toxicities were: grade (G 3 anemia 16%, G3/G4 neutropenia 36% and 10% respectively, G3/4 thrombocytopenia 22% and 4% respectively. Non-haematological toxicity was infrequent: pulmonary G1 6%, heart rhythm G1 4%, liver toxicity G1 6%, G2 4% and G3 2%. Complete hair loss was reported in 6% of patients, and G1 neuropathy in 2%. PPE was recorded in 14% of the cases (G1 10%, G2 2%, G3 2%. Conclusion This safety analysis shows that the adopted schedule of carboplatin plus pegylated liposomal doxorubicin given every 3 weeks is feasible as first line treatment in ovarian cancer patients, although 37% of the cycles were delayed due to haematological toxicity. Toxicities that are common with standard combination of carboplatin

  14. Targeted concurrent chemoradiotherapy, by using improved microcapsules that release carboplatin in response to radiation, improves detectability by computed tomography as well as antitumor activity while reducing adverse effect in vivo.

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    Harada, Satoshi; Ehara, Shigeru; Ishii, Keizo; Sato, Takahiro; Koka, Masashi; Kamiya, Tomihiro; Sera, Koichiro; Goto, Shyoko

    2015-03-01

    The effect of alginate-hyaluronate microcapsules that release carboplatin in response to radiation was improved by adding ascorbic acid (AA). Four measures of the effectiveness of the microcapsules were evaluated: 1) release of carboplatin in response to radiation in vitro and in vivo; 2) detectability of their accumulation by computed tomography (CT) in vivo; 3) enhancement of antitumor effects in vivo; and 4) reduction of adverse effects in vivo. There were significant increases in the rupture of microcapsules by adding AA in vitro. Subcutaneously injected microcapsules around the tumor could be detected by using CT and the alteration of CT-values correlated with the accumulation of the microcapsules. Those microcapsules released carboplatin and resulted in synergistic antitumor effect with concomitant radiation. With the encapsulation of carboplatin, chemotherapeutic effects were still observed two weeks after treatment. However, addition of AA did not result in increased antitumor effect in vivo. A reduction in adverse effects was observed with the encapsulation of carboplatin, through localization of carboplatin around the tumor. Addition of AA to the materials of microcapsules did not result in increasing antitumor effect. However encapsulation of carboplatin will be useful as a clinical cancer-therapy option. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  15. Health-related quality of life during sequential chemotherapy with carboplatin followed by weekly paclitaxel in advanced ovarian cancer: a multicenter phase ii study of the North Eastern German Society of Gynecological Oncology.

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    Richter, Rolf; Oskay-Oezcelik, Guelten; Chekerov, Radoslav; Pilger, Adak; Hindenburg, Hans-Joachim; Sommer, Harald; Camara, Oumar; Keil, Elke; Einenkel, Jens; Sehouli, Jalid

    2012-09-01

    We describe the impact of a sequential dose-dense schedule of carboplatin and paclitaxel on the quality of life (QoL) of patients with ovarian cancer. In this multicenter phase II trial, four cycles of carboplatin followed by 12 cycles of weekly paclitaxel were applied after cytoreductive surgery. QoL was assessed using the QoL questionnaires EORTC QLQ-C30 and QLQ-OV28 before chemotherapy (baseline), after four cycles of carboplatin, at the end of treatment (EOT), and after 6, 12, and 24 months. Out of 104 eligible patients 87 (84%) participated in at least one QoL assessment. At baseline, all QLQ-C30 scales and symptoms were significantly worse than age-adjusted values for the general population. Subsequently QoL improved in general. During chemotherapy with paclitaxel, most functioning scales and symptoms worsened slightly (not significantly). However, peripheral neuropathy and chemotherapy-related side-effects increased to clinically important levels. At the end of treatment, most QoL scores were similar to those of the general population, but physical functioning and fatigue were worse. Sexual functioning and peripheral neuropathy remained problematic. QoL was affected mainly by the weekly paclitaxel schedule, but effects were in most cases only temporary. A dose-dense regimen using a sequential protocol may be favourable in terms of QoL.

  16. Safety of a 3-weekly schedule of carboplatin plus pegylated liposomal doxorubicin as first line chemotherapy in patients with ovarian cancer: preliminary results of the MITO-2 randomized trial.

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    Pignata, Sandro; Scambia, Giovanni; Savarese, Antonella; Breda, Enrico; Scollo, Paolo; De Vivo, Rocco; Rossi, Emanuela; Gebbia, Vittorio; Natale, Donato; Del Gaizo, Filomena; Naglieri, Emanuele; Ferro, Antonella; Musso, Pietro; D'Arco, Alfonso Maria; Sorio, Roberto; Pisano, Carmela; Di Maio, Massimo; Signoriello, Giuseppe; Annunziata, Annalisa; Perrone, Francesco

    2006-08-01

    The MITO-2 (Multicentre Italian Trials in Ovarian cancer) study is a randomized phase III trial comparing carboplatin plus paclitaxel to carboplatin plus pegylated liposomal doxorubicin in first-line chemotherapy of patients with ovarian cancer. Due to the paucity of published phase I data on the 3-weekly experimental schedule used, an early safety analysis was planned. Patients with ovarian cancer (stage Ic-IV), aged liposomal doxorubicin 30 mg/m2, every 3 weeks. Treatment was planned for 6 cycles. Toxicity was coded according to the NCI-CTC version 2.0. The pre-planned safety analysis was performed in July 2004. Data from the first 50 patients treated with carboplatin plus pegylated liposomal doxorubicin were evaluated. Median age was 60 years (range 34-75). Forty-three patients (86%) completed 6 cycles. Two thirds of the patients had at least one cycle delayed due to toxicity, but 63% of the cycles were administered on time. In most cases the reason for chemotherapy delay was neutropenia or other hematological toxicity. No delay due to palmar-plantar erythrodysesthesia (PPE) was recorded. No toxic death was recorded. Reported hematological toxicities were: grade (G) 3 anemia 16%, G3/G4 neutropenia 36% and 10% respectively, G3/4 thrombocytopenia 22% and 4% respectively. Non-haematological toxicity was infrequent: pulmonary G1 6%, heart rhythm G1 4%, liver toxicity G1 6%, G2 4% and G3 2%. Complete hair loss was reported in 6% of patients, and G1 neuropathy in 2%. PPE was recorded in 14% of the cases (G1 10%, G2 2%, G3 2%). This safety analysis shows that the adopted schedule of carboplatin plus pegylated liposomal doxorubicin given every 3 weeks is feasible as first line treatment in ovarian cancer patients, although 37% of the cycles were delayed due to haematological toxicity. Toxicities that are common with standard combination of carboplatin plus paclitaxel (neurotoxicity and hair loss) are infrequent with this experimental schedule, and skin toxicity appears

  17. Carboplatin plus weekly nanoparticle albumin-bound paclitaxel in elderly patients with previously untreated advanced squamous non-small-cell lung cancer selected based on Mini Nutritional Assessment short-form scores: a multicenter phase 2 study.

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    Shiroyama, Takayuki; Tamiya, Motohiro; Minami, Seigo; Takata, So; Masuhiro, Kentaro; Futami-Nishijima, Yu; Uenami, Takeshi; Mori, Masahide; Koba, Taro; Matsuki, Takanori; Takimoto, Takayuki; Suzuki, Hidekazu; Okamoto, Norio; Komuta, Kiyoshi; Hirashima, Tomonori; Kumanogoh, Atsushi; Kijima, Takashi

    2017-09-01

    This multicenter, single-arm, open-label, phase 2 study assessed the efficacy and safety of carboplatin plus weekly nanoparticle albumin-bound paclitaxel in elderly patients with previously untreated advanced squamous non-small-cell lung cancer, selected based on the Mini Nutritional Assessment short-form scores (MNA-SF). Patients received carboplatin (area under the curve: 6) on Day 1, and nanoparticle albumin-bound paclitaxel (100 mg/m2) on Days 1, 8, and 15, every 28 days for ≤4 cycles. Eligibility criteria included an MNA-SF score of ≥8 points. The primary endpoint was the objective response rate. Thirty patients with a median age of 76 (range 70-83) years were enrolled. The objective response rate was 50.0% (95% confidence interval: 31.3-68.7%), which met the primary objective of this study. The disease control rate was 73.3% (95% CI: 54.1-87.7%). At a median follow-up of 15.0 months, the median progression-free and overall survival was 7.1 and 19.1 months, respectively. The most common treatment-related adverse event of Grade ≥3 was neutropenia (66.7%). Non-hematological adverse events of Grade ≥3 were minor. Well-nourished patients, based on the MNA-SF, experienced fewer adverse events of Grade ≥3 compared to patients at risk of malnutrition. All treatment-related adverse events were tolerable and reversible. There were no treatment-related deaths. Carboplatin plus weekly nanoparticle albumin-bound paclitaxel is effective and well tolerated as a first-line treatment for elderly patients with advanced squamous non-small-cell lung cancer. Eligibility based on MNA-SF screening may be useful in determining acceptable toxicity.

  18. Carboplatin binding to histidine

    NARCIS (Netherlands)

    Tanley, Simon W M; Diederichs, Kay; Kroon - Batenburg, Louise|info:eu-repo/dai/nl/070944172; Levy, Colin; Schreurs, Antoine M M|info:eu-repo/dai/nl/304847453; Helliwell, John R.

    2014-01-01

    Carboplatin is a second-generation platinum anticancer agent used for the treatment of a variety of cancers. Previous X-ray crystallographic studies of carboplatin binding to histidine (in hen egg-white lysozyme; HEWL) showed the partial conversion of carboplatin to cisplatin owing to the high NaCl

  19. Carboplatin binding to histidine

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

    2014-08-29

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

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

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

    2016-01-01

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

  1. Concurrent Chemoradiotherapy Followed by Consolidation Chemotherapy With Bi-Weekly Docetaxel and Carboplatin for Stage III Unresectable, Non-Small-Cell Lung Cancer: Clinical Application of a Protocol Used in a Previous Phase II Study

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    Saitoh, Jun-Ichi, E-mail: junsaito@sannet.ne.jp [Division of Radiation Oncology, Saitama Cancer Center, Saitama (Japan); Saito, Yoshihiro; Kazumoto, Tomoko; Kudo, Shigehiro; Yoshida, Daisaku; Ichikawa, Akihiro [Division of Radiation Oncology, Saitama Cancer Center, Saitama (Japan); Sakai, Hiroshi; Kurimoto, Futoshi [Division of Respiratory Disease, Saitama Cancer Center, Saitama (Japan); Kato, Shingo [Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Shibuya, Kei [Department of Radiation Oncology, Gunma University Graduate School of Medicine, Gunma (Japan)

    2012-04-01

    Purpose: To assess the clinical applicability of a protocol evaluated in a previously reported phase II study of concurrent chemoradiotherapy followed by consolidation chemotherapy with bi-weekly docetaxel and carboplatin in patients with stage III, unresectable, non-small-cell lung cancer (NSCLC). Methods and Materials: Between January 2000 and March 2006, 116 previously untreated patients with histologically proven, stage III NSCLC were treated with concurrent chemoradiotherapy. Radiation therapy was administered in 2-Gy daily fractions to a total dose of 60 Gy in combination with docetaxel, 30 mg/m{sup 2}, and carboplatin at an area under the curve value of 3 every 2 weeks during and after radiation therapy. Results: The median survival time for the entire group was 25.5 months. The actuarial 2-year and 5-year overall survival rates were 53% and 31%, respectively. The 3-year cause-specific survival rate was 60% in patients with stage IIIA disease, whereas it was 35% in patients with stage IIIB disease (p = 0.007). The actuarial 2-year and 5-year local control rates were 62% and 55%, respectively. Acute hematologic toxicities of Grade {>=}3 severity were observed in 20.7% of patients, while radiation pneumonitis and esophagitis of Grade {>=}3 severity were observed in 2.6% and 1.7% of patients, respectively. Conclusions: The feasibility of the protocol used in the previous phase II study was reconfirmed in this series, and excellent treatment results were achieved.

  2. Carboplatin binding to histidine

    Science.gov (United States)

    Tanley, Simon W. M.; Diederichs, Kay; Kroon-Batenburg, Loes M. J.; Levy, Colin; Schreurs, Antoine M. M.; Helliwell, John R.

    2014-01-01

    Carboplatin is a second-generation platinum anticancer agent used for the treatment of a variety of cancers. Previous X-ray crystallographic studies of carboplatin binding to histidine (in hen egg-white lysozyme; HEWL) showed the partial conversion of carboplatin to cisplatin owing to the high NaCl concentration used in the crystallization conditions. HEWL co-crystallizations with carboplatin in NaBr conditions have now been carried out to confirm whether carboplatin converts to the bromine form and whether this takes place in a similar way to the partial conversion of carboplatin to cisplatin observed previously in NaCl conditions. Here, it is reported that a partial chemical transformation takes place but to a transplatin form. Thus, to attempt to resolve purely carboplatin binding at histidine, this study utilized co-crystallization of HEWL with carboplatin without NaCl to eliminate the partial chemical conversion of carboplatin. Tetragonal HEWL crystals co-crystallized with carboplatin were successfully obtained in four different conditions, each at a different pH value. The structural results obtained show carboplatin bound to either one or both of the N atoms of His15 of HEWL, and this particular variation was dependent on the concentration of anions in the crystallization mixture and the elapsed time, as well as the pH used. The structural details of the bound carboplatin molecule also differed between them. Overall, the most detailed crystal structure showed the majority of the carboplatin atoms bound to the platinum centre; however, the four-carbon ring structure of the cyclobutanedicarboxylate moiety (CBDC) remained elusive. The potential impact of the results for the administration of carboplatin as an anticancer agent are described. PMID:25195881

  3. Phase II Study Evaluating the Addition of Cetuximab to the Concurrent Delivery of Weekly Carboplatin, Paclitaxel, and Daily Radiotherapy for Patients With Locally Advanced Squamous Cell Carcinomas of the Head and Neck

    Energy Technology Data Exchange (ETDEWEB)

    Suntharalingam, Mohan, E-mail: msuntha@umm.edu [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); Kwok, Young [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); Goloubeva, Olga [University of Maryland Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD (United States); Parekh, Arti [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); Taylor, Rodney; Wolf, Jeffrey [Department of Otorhinolaryngology, University of Maryland School of Medicine, Baltimore, MD (United States); Zimrin, Ann [University of Maryland Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD (United States); Strome, Scott [Department of Otorhinolaryngology, University of Maryland School of Medicine, Baltimore, MD (United States); Ord, Robert [Department of Oral-Maxillo Facial Surgery, University of Maryland School of Medicine, Baltimore, MD (United States); Cullen, Kevin J. [University of Maryland Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD (United States)

    2012-04-01

    Purpose: To report the mature data of a prospective Phase II trial designed to evaluate the efficacy of an epidermal growth factor receptor inhibitor cetuximab (CTX) added to the concurrent therapy of weekly paclitaxel/carboplatin (PC) and daily radiation therapy (RT). Methods and Materials: From 2005 to 2009, a total of 43 patients were enrolled in the study. The median follow-up was 31 months (range, 9-59 months). All patients had Stage III/IV disease at presentation, and 67% had oropharyngeal primaries. The weekly IV dose schedules were CTX 250 mg/m{sup 2} (400 mg/m{sup 2} IV loading dose 1 week before RT), paclitaxel 40 mg/m{sup 2}, and carboplatin AUC 2. RT was given at 1.8 Gy per day to 70.2 Gy. Intensity-modulated RTwas used in 70% of cases. Results: All patients completed the planned RT dose, 74% without any treatment breaks. The planned CTX and PC cycles were completed in 70% (91% with at least seven of planned nine cycles) and 56% (93% with at least seven of planned eight cycles) of patients, respectively. Toxicity included Grade 3 mucositis (79%), rash (9%), leucopenia (19%), neutropenia (19%), and RT dermatitis (16%). The complete response (CR) rate at the completion of therapy was 84%. The estimated 3-year local regional control rate was 72%. Six patients with an initial CR subsequently experienced a local recurrence, 10 patients experienced distant progression. The median overall survival and disease-free survivals have not been reached. The 3-year actuarial overall survival and disease-free survival were 59% and 58%, respectively. Conclusions: The addition of CTX to weekly PC and daily RT was well tolerated and resulted in encouraging local control and survival rates.

  4. [Outcomes and Toxicity of Concurrent Radiotherapy with Carboplatin/Paclitaxel 
Administrated Every Three Weeks in Inoperable Advanced 
Non-small Cell Lung Cancer: 
A Retrospective Study from A Single Center].

    Science.gov (United States)

    Zhao, Jing; Zhang, Xiaotong; Hu, Ke; Wang, Hanping; Xu, Yan; Si, Xiaoyan; Zhong, Wei; Huang, Xia; Zhang, Li; Wang, Mengzhao

    2016-11-20

    Standard care for patients with inoperable advanced non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy. The ideal concurrent chemotherapy regimen has not been determined. The aim of this study is to retrospectively analyze the efficacy and safety of concurrent radiotherapy with carboplatin/paclitaxel administrated every three weeks (PC three-week regimen) in inoperable advanced NSCLC and compare them with the results of cisplatin/etoposide. The 43 patients with inoperable advanced NSCLC receiving concurrent chemotherapy in Peking Union Medical College Hospital from January 2012 to June 2014 were enrolled and analyzed. Of them, 15 patients received carboplatin/paclitaxel with concurrent thoracic radiotherapy; the other 28 patients received cisplatin/etoposide. Clinical characteristic, efficacy and toxicity data were compared in these two groups. For the overall population, the objective response rate (ORR) and disease control rate (DCR) were 41.9% and 90.7% respectively. The median progression free survival (PFS) was 10.6 months (95%CI: 7.4-13.8). And the median overall survival (OS) was 19.2 months (95%CI: 15.3-23.1). There were no significant differences in response rates (ORR: 33.3% vs 46.4%; DCR: 86.7% vs 92.9%, P=0.638), PFS (6.6 months vs 12.2 months, P=0.389), or OS (16.1 months vs 22.1 months, P=0.555) in either group. The adverse events were generally manageable and no treatment-related deaths occurred. Compared with PE, PC three-week regimen concurrent thoracic radiotherapy for inoperable advanced NSCLC has the similar efficacy and acceptable toxicity profile, which can be used in clinical setting.

  5. Outcomes and Toxicity of Concurrent Radiotherapy with Carboplatin/Paclitaxel 
Administrated Every Three Weeks in Inoperable Advanced 
Non-small Cell Lung Cancer: 
A Retrospective Study from A Single Center

    Directory of Open Access Journals (Sweden)

    Jing ZHAO

    2016-11-01

    Full Text Available Background and objective Standard care for patients with inoperable advanced non-small cell lung cancer (NSCLC is concurrent chemoradiotherapy. The ideal concurrent chemotherapy regimen has not been determined. The aim of this study is to retrospectively analyze the efficacy and safety of concurrent radiotherapy with carboplatin/paclitaxel administrated every three weeks (PC three-week regimen in inoperable advanced NSCLC and compare them with the results of cisplatin/etoposide. Methods The 43 patients with inoperable advanced NSCLC receiving concurrent chemotherapy in Peking Union Medical College Hospital from January 2012 to June 2014 were enrolled and analyzed. Of them, 15 patients received carboplatin/paclitaxel with concurrent thoracic radiotherapy; the other 28 patients received cisplatin/etoposide. Clinical characteristic, efficacy and toxicity data were compared in these two groups. Results For the overall population, the objective response rate (ORR and disease control rate (DCR were 41.9% and 90.7% respectively. The median progression free survival (PFS was 10.6 months (95%CI: 7.4-13.8. And the median overall survival (OS was 19.2 months (95%CI: 15.3-23.1. There were no significant differences in response rates (ORR: 33.3% vs 46.4%; DCR: 86.7% vs 92.9%, P=0.638, PFS (6.6 months vs 12.2 months, P=0.389, or OS (16.1 months vs 22.1 months, P=0.555 in either group. The adverse events were generally manageable and no treatment-related deaths occurred. Conclusion Compared with PE, PC three-week regimen concurrent thoracic radiotherapy for inoperable advanced NSCLC has the similar efficacy and acceptable toxicity profile, which can be used in clinical setting.

  6. Single agent carboplatin for pediatric low-grade glioma: A retrospective analysis shows equivalent efficacy to multiagent chemotherapy.

    Science.gov (United States)

    Dodgshun, Andrew J; Maixner, Wirginia J; Heath, John A; Sullivan, Michael J; Hansford, Jordan R

    2016-01-15

    Pediatric low-grade gliomas (LGG) that are unresectable often require adjuvant chemotherapy such as carboplatin/vincristine. Small Phase II studies have suggested equivalent efficacy of single agent 4-weekly carboplatin. A single-institution retrospective review captured all patients aged 0 to 18 years diagnosed with LGG between 1996 and 2013 and treated with carboplatin monotherapy. The response and survival according to tumor site was compared to published results for multiagent chemotherapy. Of 268 children diagnosed with LGG diagnosed in this period, 117 received chemotherapy and 104 children received single agent carboplatin as first line chemotherapy. All patients received carboplatin at 560 mg/m(2), four-weekly for a median of 12 courses. The mean age at diagnosis was 5.8 years (range 3m-16y) and 32% had neurofibromatosis type 1. With a mean followup of 54 months, 86% of patients achieved stabilisation or better (SD/PR/CR). 3-year progression free survival (PFS) 66% (95% CI 57-76%), and 5-year PFS was 51% (95% CI 41-63%). 5-year overall survival was 97%. Multivariate analysis showed poorer PFS for those with chiasmatic/hypothalamic tumors. In this retrospective analysis single agent carboplatin shows comparable efficacy to historical multiagent chemotherapy for the treatment of patients with unresectable LGG. Equivalent outcomes are achieved with less chemotherapy, reduced side effects and fewer hospital visits. Further research is required to establish the place of this simplified regimen in the up-front treatment of unresectable LGG. © 2015 UICC.

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    This randomised phase III study in advanced non-small cell lung cancer (NSCLC) patients was conducted to compare vinorelbine/carboplatin (VC) and gemcitabine/carboplatin (GC) regarding efficacy, health-related quality of life (HRQOL) and toxicity. Chemonaive patients with NSCLC stage IIIB....../IV and WHO performance status 0-2 were eligible. No upper age limit was defined. Patients received vinorelbine 25 mg m(-2) or gemcitabine 1000 mg m(-2) on days 1 and 8 and carboplatin AUC4 on day 1 and three courses with 3-week cycles. HRQOL questionnaires were completed at baseline, before chemotherapy...

  8. Iontophoretic delivery of carboplatin in a murine model of retinoblastoma.

    Science.gov (United States)

    Hayden, Brandy; Jockovich, Maria-Elena; Murray, Timothy G; Kralinger, Martina T; Voigt, Monika; Hernandez, Eleut; Feuer, William; Parel, Jean-Marie

    2006-09-01

    To evaluate the efficacy and dose-response of transcorneoscleral Coulomb controlled iontophoresis (CCI) of carboplatin in the treatment of retinal tumors of a murine model of retinoblastoma. Thirty 6-week-old LHBETATAG mice underwent a total of six, serial iontophoretic treatments administered two times per week using a current density of 2.57 mA/cm2 for 5 minutes. Fourteen animals received carboplatin treatments at concentrations of 1.4, 7.0, 10.0, or 14.0 mg/mL without current. Ten control mice underwent treatment with balanced saline solution. A dose-dependent inhibition of intraocular tumor was observed after repetitive iontophoretic treatment. At carboplatin concentrations of 7 mg/mL, 50% of the treated eyes (4/8) exhibited tumor control. No corneal toxicity was observed in eyes treated at carboplatin concentrations under 10 mg/mL. CCI delivery of carboplatin safely and effectively controls intraocular tumors in a dose-dependent manner in this murine model of retinoblastoma. CCI is a noninvasive, painless option for the focal delivery of carboplatin. However, further clinical and laboratory research is needed before this method of drug delivery is available for children with retinoblastoma.

  9. Role of the DNA Base Excision Repair Protein, APE1 in Cisplatin, Oxaliplatin, or Carboplatin Induced Sensory Neuropathy

    Science.gov (United States)

    Kelley, Mark R.; Jiang, Yanlin; Guo, Chunlu; Reed, April; Meng, Hongdi; Vasko, Michael R.

    2014-01-01

    Although chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect of platinum drugs, the mechanisms of this toxicity remain unknown. Previous work in our laboratory suggests that cisplatin-induced CIPN is secondary to DNA damage which is susceptible to base excision repair (BER). To further examine this hypothesis, we studied the effects of cisplatin, oxaliplatin, and carboplatin on cell survival, DNA damage, ROS production, and functional endpoints in rat sensory neurons in culture in the absence or presence of reduced expression of the BER protein AP endonuclease/redox factor-1 (APE1). Using an in situ model of peptidergic sensory neuron function, we examined the effects of the platinum drugs on hind limb capsaicin-evoked vasodilatation. Exposing sensory neurons in culture to the three platinum drugs caused a concentration-dependent increase in apoptosis and cell death, although the concentrations of carboplatin were 10 fold higher than cisplatin. As previously observed with cisplatin, oxaliplatin and carboplatin also increased DNA damage as indicated by an increase in phospho-H2AX and reduced the capsaicin-evoked release of CGRP from neuronal cultures. Both cisplatin and oxaliplatin increased the production of ROS as well as 8-oxoguanine DNA adduct levels, whereas carboplatin did not. Reducing levels of APE1 in neuronal cultures augmented the cisplatin and oxaliplatin induced toxicity, but did not alter the effects of carboplatin. Using an in vivo model, systemic injection of cisplatin (3 mg/kg), oxaliplatin (3 mg/kg), or carboplatin (30 mg/kg) once a week for three weeks caused a decrease in capsaicin-evoked vasodilatation, which was delayed in onset. The effects of cisplatin on capsaicin-evoked vasodilatation were attenuated by chronic administration of E3330, a redox inhibitor of APE1 that serendipitously enhances APE1 DNA repair activity in sensory neurons. These outcomes support the importance of the BER pathway, and particularly APE

  10. Phase II/III weekly nab-paclitaxel plus gemcitabine or carboplatin versus gemcitabine/carboplatin as first-line treatment of patients with metastatic triple-negative breast cancer (the tnAcity study): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Yardley, Denise A; Brufsky, Adam; Coleman, Robert E; Conte, Pierfranco F; Cortes, Javier; Glück, Stefan; Nabholtz, Jean-Mark A; O'Shaughnessy, Joyce; Beck, Robert M; Ko, Amy; Renschler, Markus F; Barton, Debora; Harbeck, Nadia

    2015-12-16

    Triple-negative breast cancer is an aggressive disease with unmet clinical needs. In a phase III study of patients with metastatic triple-negative breast cancer, first-line gemcitabine/carboplatin resulted in a median progression-free survival of 4.6 months. nab-paclitaxel-based regimens (with gemcitabine or carboplatin±bevacizumab) also demonstrated efficacy and safety in first-line phase II trials of human epidermal growth factor receptor 2-negative metastatic breast cancer. In this international, multicenter, open-label, randomized phase II/III trial, the efficacy and safety of first-line nab-paclitaxel with gemcitabine or with carboplatin will be compared with gemcitabine/carboplatin (control arm) for metastatic triple-negative breast cancer. In the phase II portion, 240 patients with measurable metastatic triple-negative breast cancer and treatment-naive for metastatic disease will be randomized 1:1:1 (stratified by disease-free interval: ≤1 versus>1 year) to nab-paclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2, nab-paclitaxel 125 mg/m2 plus carboplatin area under the curve 2 mg×min/mL, or gemcitabine 1000 mg/m2 plus carboplatin area under the curve 2 mg×min/mL, all given on days 1 and 8 of a 21-day cycle. Investigator-assessed progression-free survival (primary endpoint), overall response rate, overall survival, and safety will be assessed. A ranking algorithm of five efficacy and safety parameters will be used to pick the "winner" of the nab-paclitaxel regimens. In the phase III portion, 550 patients will be randomized 1:1 (stratified by disease-free interval: ≤1 versus >1 year, and prior adjuvant/neoadjuvant taxane use) to the nab-paclitaxel combination arm selected from the phase II portion or to the control arm. Patients in phase II will not be part of the phase III population. The phase III primary endpoint is blinded, independently-assessed progression-free survival; secondary endpoints include blinded, independently-assessed overall response

  11. Convection-Enhanced Delivery of Carboplatin PLGA Nanoparticles for the Treatment of Glioblastoma

    Science.gov (United States)

    Arshad, Azeem; Yang, Bin; Bienemann, Alison S.; Barua, Neil U.; Wyatt, Marcella J.; Woolley, Max; Johnson, Dave E.; Edler, Karen J.; Gill, Steven S.

    2015-01-01

    We currently use Convection-Enhanced Delivery (CED) of the platinum-based drug, carboplatin as a novel treatment strategy for high grade glioblastoma in adults and children. Although initial results show promise, carboplatin is not specifically toxic to tumour cells and has been associated with neurotoxicity at high infused concentrations in pre-clinical studies. Our treatment strategy requires intermittent infusions due to rapid clearance of carboplatin from the brain. In this study, carboplatin was encapsulated in lactic acid-glycolic acid copolymer (PLGA) to develop a novel drug delivery system. Neuronal and tumour cytotoxicity were assessed in primary neuronal and glioblastoma cell cultures. Distribution, tissue clearance and toxicity of carboplatin nanoparticles following CED was assessed in rat and porcine models. Carboplatin nanoparticles conferred greater tumour cytotoxicity, reduced neuronal toxicity and prolonged tissue half-life. In conclusion, this drug delivery system has the potential to improve the prognosis for patients with glioblastomas. PMID:26186224

  12. Convection-Enhanced Delivery of Carboplatin PLGA Nanoparticles for the Treatment of Glioblastoma.

    Science.gov (United States)

    Arshad, Azeem; Yang, Bin; Bienemann, Alison S; Barua, Neil U; Wyatt, Marcella J; Woolley, Max; Johnson, Dave E; Edler, Karen J; Gill, Steven S

    2015-01-01

    We currently use Convection-Enhanced Delivery (CED) of the platinum-based drug, carboplatin as a novel treatment strategy for high grade glioblastoma in adults and children. Although initial results show promise, carboplatin is not specifically toxic to tumour cells and has been associated with neurotoxicity at high infused concentrations in pre-clinical studies. Our treatment strategy requires intermittent infusions due to rapid clearance of carboplatin from the brain. In this study, carboplatin was encapsulated in lactic acid-glycolic acid copolymer (PLGA) to develop a novel drug delivery system. Neuronal and tumour cytotoxicity were assessed in primary neuronal and glioblastoma cell cultures. Distribution, tissue clearance and toxicity of carboplatin nanoparticles following CED was assessed in rat and porcine models. Carboplatin nanoparticles conferred greater tumour cytotoxicity, reduced neuronal toxicity and prolonged tissue half-life. In conclusion, this drug delivery system has the potential to improve the prognosis for patients with glioblastomas.

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

    Directory of Open Access Journals (Sweden)

    Denisa Darsová

    2011-01-01

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

  14. Interaction of carboplatin with SWCNT (10, 10): A first principles study

    Science.gov (United States)

    Surya, V. J.; Iyakutti, K.; Mizuseki, H.; Kawazoe, Y.

    2013-02-01

    The present work deals with interaction of an anti-cancer drug, carboplatin with single walled carbon nanotube (10, 10). The binding of carboplatin is more stable when it is inside the nanotube. The effect of water molecules on the whole system (single walled carbon nanotube with carboplatin) is examined. The presence of water molecules reduces the binding of carboplatin from the nanotube. This property enables the delivery of this anti-cancer drug from the nanotube at the targeted sites. Overall, this study projects that the single walled carbon nanotubes can be employed as efficient boats for targeted drug delivery.

  15. A randomised study of carboplatin vs sequential ifosfamide/carboplatin for patients with FIGO stage III epithelial ovarian carcinoma. The London Gynaecologic Oncology Group.

    OpenAIRE

    Perren, T. J.; Wiltshaw, E.; Harper, P.; Slevin, M.; Stein, R.; Tan, S.; Gore, M.; Fryatt, I. J.; Blake, P. R.

    1993-01-01

    In a study designed to compare response rates of patients with stage III epithelial ovarian carcinoma to ifosfamide and carboplatin, 152 patients were randomised to receive either sequential therapy with three cycles of ifosfamide followed by three cycles of carboplatin, or to six cycles of single agent carboplatin. Ifosfamide was given every 3 weeks in a dose of 5 gm m-2 as a 24 h infusion with mesna, 1 gm m-2 by i.v. bolus prior to ifosfamide, 3 gm m-2 with ifosfamide, and 1 gm m-2 as an 8 ...

  16. Transscleral diffusion of carboplatin: an in vitro and in vivo study.

    Science.gov (United States)

    Simpson, Amanda E; Gilbert, Jake A; Rudnick, David E; Geroski, Dayle H; Aaberg, Thomas M; Edelhauser, Henry F

    2002-08-01

    To compare the in vitro scleral permeability of carboplatin using either a fibrin sealant or a balanced salt solution (BSS) vehicle and to measure in vivo ocular tissue levels following subconjunctival injection of carboplatin in fibrin sealant or BSS. The permeability of carboplatin in fibrin sealant or BSS through human eye bank sclera was tested using an in vitro perfusion apparatus. Levels of carboplatin permeating the sclera were measured every hour for 24 hours using atomic absorption spectrometry. In vivo studies were performed in Dutch Belted rabbits injected subconjunctivally with carboplatin in either fibrin sealant or BSS; eyes were enucleated at 1(1/2) hours, 48 hours, and 2 weeks after injection, and levels of carboplatin were measured in various tissues. In vitro carboplatin in fibrin sealant had a peak permeability constant of 13.7 +/- 2.3 x 10(-6) cm/s; carboplatin in BSS, 27.0 +/- 1.7 x 10(-6) cm/s. After 24 hours, 33.2% +/- 1.8% of the carboplatin was retained in the fibrin sealant, while 5.5% +/- 1.0% was retained in the BSS. In vivo subconjunctival injection of carboplatin in fibrin sealant vehicle achieved 11.83 +/- 5.16 microg/mL in the vitreous at 1(1/2) hours and 0.03 +/- 0.06 microg/mL in the vitreous at 2 weeks. The fibrin sealant also attained 396.59 +/- 177.84 microg/mg in the choroid and retina at 1(1/2) hours and 3.38 +/- 1.97 microg/mg in the choroid and retina at 2 weeks. (Data are given as mean +/- SEM.) Fibrin sealant provided a more controlled and localized release of carboplatin and delivered carboplatin to the ocular tissues for up to 2 weeks. This study reports the use of fibrin sealant as a subconjunctival delivery vehicle for carboplatin, and quantifies ocular drug levels achieved in an animal model.

  17. Compound list: carboplatin [Open TG-GATEs

    Lifescience Database Archive (English)

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

  18. Quality of life, geriatric assessment and survival in elderly patients with non-small-cell lung cancer treated with carboplatin-gemcitabine or carboplatin-paclitaxel : NVALT-3 a phase III study

    NARCIS (Netherlands)

    Biesma, B.; Wymenga, A. N. M.; Vincent, A.; Dalesio, O.; Smit, H. J. M.; Stigt, J. A.; Smit, E. F.; van Felius, C. L.; van Putten, J. W. G.; Slaets, J. P. J.; Groen, H. J. M.

    Patients and methods: A total of 181 chemotherapy-naive patients [>= 70 years, performance score (PS) of 0-2] with stage III-IV NSCLC received carboplatin and gemcitabine (CG) (n = 90) or carboplatin and paclitaxel (CP) (n = 91) every 3 weeks for up to four cycles. Primary end point was change in

  19. Carboplatin plus paclitaxel versus carboplatin plus pegylated liposomal doxorubicin as first-line treatment for patients with ovarian cancer: the MITO-2 randomized phase III trial.

    Science.gov (United States)

    Pignata, Sandro; Scambia, Giovanni; Ferrandina, Gabriella; Savarese, Antonella; Sorio, Roberto; Breda, Enrico; Gebbia, Vittorio; Musso, Pietro; Frigerio, Luigi; Del Medico, Pietro; Lombardi, Alessandra Vernaglia; Febbraro, Antonio; Scollo, Paolo; Ferro, Antonella; Tamberi, Stefano; Brandes, Alba; Ravaioli, Alberto; Valerio, Maria Rosaria; Aitini, Enrico; Natale, Donato; Scaltriti, Laura; Greggi, Stefano; Pisano, Carmela; Lorusso, Domenica; Salutari, Vanda; Legge, Francesco; Di Maio, Massimo; Morabito, Alessandro; Gallo, Ciro; Perrone, Francesco

    2011-09-20

    Carboplatin/paclitaxel is the standard first-line chemotherapy for patients with advanced ovarian cancer. Multicentre Italian Trials in Ovarian Cancer-2 (MITO-2), an academic multicenter phase III trial, tested whether carboplatin/pegylated liposomal doxorubicin (PLD) was more effective than standard chemotherapy. Chemotherapy-naive patients with stage IC to IV ovarian cancer (age ≤ 75 years; Eastern Cooperative Oncology Group performance status ≤ 2) were randomly assigned to carboplatin area under the curve (AUC) 5 plus paclitaxel 175 mg/m(2) or to carboplatin AUC 5 plus PLD 30 mg/m(2), every 3 weeks for six cycles. Primary end point was progression-free survival (PFS). With 632 events in 820 enrolled patients, the study would have 80% power to detect a 0.80 hazard ratio (HR) of PFS. Eight hundred twenty patients were randomly assigned. Disease stages III and IV were prevalent. Occurrence of PFS events substantially slowed before obtaining the planned number. Therefore, in concert with the Independent Data Monitoring Committee, final analysis was performed with 556 events, after a median follow-up of 40 months. Median PFS times were 19.0 and 16.8 months with carboplatin/PLD and carboplatin/paclitaxel, respectively (HR, 0.95; 95% CI, 0.81 to 1.13; P = .58). Median overall survival times were 61.6 and 53.2 months with carboplatin/PLD and carboplatin/paclitaxel, respectively (HR, 0.89; 95% CI, 0.72 to 1.12; P = .32). Carboplatin/PLD produced a similar response rate but different toxicity (less neurotoxicity and alopecia but more hematologic adverse effects). There was no relevant difference in global quality of life after three and six cycles. Carboplatin/PLD was not superior to carboplatin/paclitaxel, which remains the standard first-line chemotherapy for advanced ovarian cancer. However, given the observed CIs and the different toxicity, carboplatin/PLD could be considered an alternative to standard therapy.

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

    Directory of Open Access Journals (Sweden)

    Yu-Hsiao Tai

    2017-11-01

    Full Text Available We evaluated the prevalence of and risk factors for hypersensitivity reactions related to carboplatin, which is commonly used to treat gynecological malignancies. All women with pathologically documented ovarian, fallopian tube, or primary peritoneal cancer treated with carboplatin alone or a carboplatin-based combination chemotherapy regimen at a single hospital between January 2006 and December 2013 were retrospectively recruited. We analyzed the incidence, characteristics, risk factors, management, and outcomes of carboplatin-related hypersensitivity reactions among these patients. Among 735 eligible women, 75 (10.2% experienced a total of 215 carboplatin-related hypersensitivity reaction events. The annual incidence of carboplatin-related hypersensitivity reactions gradually increased from 0.88% in 2006 to 5.42% in 2013. The incidence of carboplatin-related hypersensitivity was higher in patients with advanced stage disease (P < 0.001, Kruskal-Wallis test, serous and mixed histological types (P = 0.003, Kruskal-Wallis test, malignant ascites (P = 0.009, chi-square test, and history of other drug allergy (P < 0.001, chi-square test. Compared to women without hypersensitivity reactions, women who experienced hypersensitivity reactions had a significantly greater median cycle number (12 vs. 6, P < 0.001, independent sample t-test and dose (6,816 vs. 3,844 mg, P < 0.001, independent sample t-test. The cumulative incidence of carboplatin-related hypersensitivity reactions dramatically increased with >8 cycles or dose >3,500 mg. Therefore, disease severity, histological type, malignant ascites, past drug allergies, and cumulative carboplatin dose are risk factors for carboplatin-related hypersensitivity reactions. Such reactions could potentially be reduced or prevented by slowing the infusion rate and using a desensitization protocol involving anti-allergy medications.

  1. Carboplatin loaded polymethylmethacrylate nano-particles in an adjunctive role in retinoblastoma: An animal trial

    Science.gov (United States)

    Shome, Debraj; Kalita, Dhrubajyoti; Jain, Viral; Sarin, Rajiv; Maru, Girish B.; Bellare, Jayesh R.

    2014-01-01

    Purpose: The purpose of the study is to compare the intra-vitreal concentrations of carboplatin, post peri-ocular injections of commercially available carboplatin (CAC) and a novel carboplatin loaded polymethylmethacrylate nanoparticulate carboplatin (NPC), in either eye, as a model system for treatment of advanced intra-ocular retinoblastoma (RB). Design: Experimental, comparative, animal study. Materials and Methods: Polymethylmethacrylate nanoparticles were prepared by free radical emulsion polymerization of methyl methacrylate in aqueous solution of carboplatin in the presence of surfactant sodium dodecyl sulfate and thermal initiator ammonium persulfate. 21 Sprague-Dawley rats, aged between 6 weeks and 3 months were enrolled. The right eye of each rat was injected peri-ocularly with CAC formulation (1 ml of 10 mg/ml) and the left eye with NPC (1 ml of 10 mg/ml), post-anesthesia, by an ophthalmologist trained in ocular oncology. Three rats each were euthanized on days 1, 3, 5, 7, 14, 28 and 42, post-injection and both eyes were carefully enucleated. Intra-vitreal concentrations of CAC and NPC were determined with Inductively Coupled Plasma Atomic Emission Spectroscopy. Analysis of data was done with paired t-test. Results: The intra-vitreal concentration of carboplatin with NPC was ~3-4 times higher than with CAC in all animals, on all the days (P carboplatin in the vitreous. Peri-ocular injection of NPC could thus have an adjuvant efficacy in the treatment for advanced clinical RB, specifically those with vitreous seeds. PMID:24881606

  2. Carboplatin therapeutic monitoring in preterm and full-term neonates.

    Science.gov (United States)

    Veal, Gareth J; Errington, Julie; Hayden, James; Hobin, David; Murphy, Dermot; Dommett, Rachel M; Tweddle, Deborah A; Jenkinson, Helen; Picton, Susan

    2015-09-01

    Administration of the most appropriate dose of chemotherapy to neonates is particularly challenging and frequently not standardised based on any scientific rationale. We report the clinical utility of carboplatin therapeutic drug monitoring in preterm and full-term neonates within the first month of life. Carboplatin therapeutic monitoring was performed to achieve target drug exposures area under the plasma concentration-time curve (AUC values) in nine preterm and full-term neonates diagnosed with retinoblastoma or neuroblastoma treated over an 8 year period. Carboplatin was administered over 3 days with therapeutic drug monitoring utilised to target cumulative AUC values of 5.2-7.8 mg/ml min. AUC values achieved were within 15% of target values for the individual courses of treatment in all but one patient (12/13 courses of treatment), with dose modifications of up to 215% required to achieve target AUC values, based on initial mg/kg dosing schedules. Carboplatin clearance determined across three consecutive chemotherapy courses in two patients increased from 3.4 to 7.1 ml/min and from 7.2 to 16.5 ml/min, representing increases of 210-230% over several weeks of treatment. Complete remission was observed in 8/9 patients, with no renal toxicity reported and only one patient experiencing ototoxicity. The study highlights the benefits of utilising therapeutic drug monitoring to achieve target carboplatin AUC values in preterm and full-term neonates treated within the first few weeks of life, particularly in view of marked increases in drug clearance observed over consecutive chemotherapy courses. In the absence of therapeutic drug monitoring, body-weight based dosing is recommended, with dosing guidance provided for both approaches to inform future treatment. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. A Brief Orientation Week Ecological Momentary Intervention to Reduce University Student Alcohol Consumption.

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    Riordan, Benjamin C; Conner, Tamlin S; Flett, Jayde A M; Scarf, Damian

    2015-07-01

    Orientation Week is a series of events at the beginning of the university year that introduces incoming students to university life. It is also the period of the academic year when students consume more alcohol than at any other time. Recently, we demonstrated that alcohol consumption during Orientation Week was related to alcohol consumption during the academic year. The aim of the present study was to determine whether a brief Ecological Momentary Intervention (EMI) implemented during Orientation Week could reduce alcohol consumption during Orientation Week and throughout the academic year. Participants were 130 freshman-year university students (72 women, 58 men) randomly assigned to either an Ecological Momentary Assessment (EMA) condition or an EMA-EMI condition. In both conditions, participants reported pre-university, Orientation Week, and academic year weekend alcohol consumption. Those in the EMA-EMI condition also received EMI text messages promoting moderation every night during Orientation Week. Although the EMI did not reduce men's drinking, women in the EMA-EMI condition, compared with women in the EMA condition, consumed significantly fewer drinks during Orientation Week, M = 17.1, SD = 13.3, vs. M = 26.4, SD = 22.5, respectively, t(70) = -1.927, p EMIs during Orientation Week.

  4. Four Weeks of IV Iron Supplementation Reduces Perceived Fatigue and Mood Disturbance in Distance Runners

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    Woods, Amy; Garvican-Lewis, Laura A.; Saunders, Philo U.; Lovell, Greg; Hughes, David; Fazakerley, Ruth; Anderson, Bev; Gore, Christopher J.; Thompson, Kevin G.

    2014-01-01

    Purpose To determine the effect of intravenous iron supplementation on performance, fatigue and overall mood in runners without clinical iron deficiency. Methods Fourteen distance runners with serum ferritin 30–100 µg·L−1 were randomly assigned to receive three blinded injections of intravenous ferric-carboxymaltose (2 ml, 100 mg, IRON) or normal saline (PLACEBO) over four weeks (weeks 0, 2, 4). Athletes performed a 3,000 m time trial and 10×400 m monitored training session on consecutive days at week 0 and again following each injection. Hemoglobin mass (Hbmass) was assessed via carbon monoxide rebreathing at weeks 0 and 6. Fatigue and mood were determined bi-weekly until week 6 via Total Fatigue Score (TFS) and Total Mood Disturbance (TMD) using the Brief Fatigue Inventory and Brunel Mood Scale. Data were analyzed using magnitude-based inferences, based on the unequal variances t-statistic and Cohen's Effect sizes (ES). Results Serum ferritin increased in IRON only (Week 0: 62.8±21.9, Week 4: 128.1±46.6 µg·L−1; p = 0.002) and remained elevated two weeks after the final injection (127.0±66.3 µg·L−1, p = 0.01), without significant changes in Hbmass. Supplementation had a moderate effect on TMD of IRON (ES -0.77) with scores at week 6 lower than PLACEBO (ES -1.58, p = 0.02). Similarly, at week 6, TFS was significantly improved in IRON vs. PLACEBO (ES –1.54, p = 0.05). There were no significant improvements in 3,000 m time in either group (Week 0 vs. Week 4; Iron: 625.6±55.5 s vs. 625.4±52.7 s; PLACEBO: 624.8±47.2 s vs. 639.1±59.7 s); but IRON reduced their average time for the 10×400 m training session at week 2 (Week 0: 78.0±6.6 s, Week 2: 77.2±6.3; ES–0.20, p = 0.004). Conclusion During 6 weeks of training, intravenous iron supplementation improved perceived fatigue and mood of trained athletes with no clinical iron deficiency, without concurrent improvements in oxygen transport capacity or performance. PMID

  5. Four weeks of IV iron supplementation reduces perceived fatigue and mood disturbance in distance runners.

    Directory of Open Access Journals (Sweden)

    Amy Woods

    Full Text Available To determine the effect of intravenous iron supplementation on performance, fatigue and overall mood in runners without clinical iron deficiency.Fourteen distance runners with serum ferritin 30-100 µg · L(-1 were randomly assigned to receive three blinded injections of intravenous ferric-carboxymaltose (2 ml, 100 mg, IRON or normal saline (PLACEBO over four weeks (weeks 0, 2, 4. Athletes performed a 3,000 m time trial and 10 × 400 m monitored training session on consecutive days at week 0 and again following each injection. Hemoglobin mass (Hbmass was assessed via carbon monoxide rebreathing at weeks 0 and 6. Fatigue and mood were determined bi-weekly until week 6 via Total Fatigue Score (TFS and Total Mood Disturbance (TMD using the Brief Fatigue Inventory and Brunel Mood Scale. Data were analyzed using magnitude-based inferences, based on the unequal variances t-statistic and Cohen's Effect sizes (ES.Serum ferritin increased in IRON only (Week 0: 62.8 ± 21.9, Week 4: 128.1 ± 46.6 µg · L(-1; p = 0.002 and remained elevated two weeks after the final injection (127.0 ± 66.3 µg · L(-1, p = 0.01, without significant changes in Hbmass. Supplementation had a moderate effect on TMD of IRON (ES -0.77 with scores at week 6 lower than PLACEBO (ES -1.58, p = 0.02. Similarly, at week 6, TFS was significantly improved in IRON vs. PLACEBO (ES -1.54, p = 0.05. There were no significant improvements in 3,000 m time in either group (Week 0 vs. Week 4; Iron: 625.6 ± 55.5 s vs. 625.4 ± 52.7 s; PLACEBO: 624.8 ± 47.2 s vs. 639.1 ± 59.7 s; but IRON reduced their average time for the 10 × 400 m training session at week 2 (Week 0: 78.0 ± 6.6 s, Week 2: 77.2 ± 6.3; ES-0.20, p = 0.004.During 6 weeks of training, intravenous iron supplementation improved perceived fatigue and mood of trained athletes with no clinical iron deficiency, without concurrent improvements in oxygen transport capacity or performance.

  6. Sequence-Specific Pharmacokinetic and Pharmacodynamic Phase I/Ib Study of Olaparib Tablets and Carboplatin in Women's Cancer.

    Science.gov (United States)

    Lee, Jung-Min; Peer, Cody J; Yu, Minshu; Amable, Lauren; Gordon, Nicolas; Annunziata, Christina M; Houston, Nicole; Goey, Andrew K L; Sissung, Tristan M; Parker, Bernard; Minasian, Lori; Chiou, Victoria L; Murphy, Robert F; Widemann, Brigitte C; Figg, William D; Kohn, Elise C

    2017-03-15

    Purpose: Our preclinical studies showed that the PARP inhibitor, olaparib, prior to carboplatin attenuated carboplatin cytotoxicity. We evaluated sequence-specific pharmacokinetic and pharmacodynamic effects, safety, and activity of the combination.Experimental Design: Eligible patients had metastatic or recurrent women's cancer. Olaparib tablets were introduced (100 or 200 mg twice daily, days 1-7) in a 3 + 3 dose escalation with carboplatin AUC4 or 5 every 21 days, up to eight cycles, followed by olaparib 300 mg twice daily maintenance. Patients were randomly assigned to starting schedule: cohort A (olaparib days 1-7, carboplatin on day 8) or B (carboplatin on day 1, olaparib days 2-8) during cycle 1. Patients received the reversed scheme in cycle 2. Blood was collected for olaparib pharmacokinetics, platinum-DNA adducts, comet assay, and PAR concentrations. The primary objectives were to examine schedule-dependent effects on olaparib pharmacokinetics and platinum-DNA adducts.Results: A total of 77 (60 ovarian, 14 breast, and 3 uterine cancer) patients were treated. Dose-limiting toxicity was thrombocytopenia and neutropenia, defining olaparib 200 mg twice daily + carboplatin AUC4 as the MTD. Olaparib clearance was increased approximately 50% when carboplatin was given 24 hours before olaparib. In vitro experiments demonstrated carboplatin preexposure increased olaparib clearance due to intracellular olaparib uptake. Quantities of platinum-DNA adducts were not different as a function of the order of drug administration. Responses included 2 CRs and 31 PRs (46%) with a higher RR in BRCA mutation carriers compared with nonmutation carriers (68% vs. 19%).Conclusions: Tablet olaparib with carboplatin is a safe and active combination. Carboplatin preexposure causes intracellular olaparib accumulation reducing bioavailable olaparib, suggesting carboplatin should be administered prior to olaparib. Clin Cancer Res; 23(6); 1397-406. ©2016 AACR. ©2016 American

  7. A 12-week aerobic training programme reduced plasmatic allantoin in adolescents with Down syndrome.

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    Rosety-Rodriguez, M; Rosety, I; Fornieles-Gonzalez, G; Diaz, A; Rosety, M; Ordonez, F J

    2010-07-01

    To assess the influence of a 12-week training programme on plasmatic levels of allantoin, an in vivo marker for oxidative stress, in adolescents with Down syndrome. This finding would be of great interest, since oxidative damage has been proposed as a pathogenic mechanism of several pathologies in this population. To reach this goal, 31 male adolescents with Down syndrome (16.3 (1.1) years; 155.2 (5.7) cm; 70.8 (4.5) kg) performed a 12-week training programme, three sessions per week, consisting of warm-up (15 min) followed by a main part (20-35 min (increasing 5 min each 3 weeks)) at a work intensity of 60-75% of peak heart rate (increasing by 5% each 3 weeks) and then a cool-down period (10 min). According to previous studies, it should be emphasised that the maximal heart rate for individuals with Down syndrome was predicted by the equation HRmax = 194.5-(0.56 age). The control group included seven age-, sex- and BMI-matched adolescents with trisomy 21 that did not perform any training programme. The levels uric acid and allantoin were assayed in plasma by HPLC. This protocol was approved by an institutional ethics committee. When compared with baseline, plasmatic levels of allantoin were decreased significantly (22.09 (1.62) vs 18.74 (1.38) micromol/l; p<0.001) after being exercised. Furthermore, the allantoin/uric acid ratio was decreased significantly (0.071 (0.006) vs 0.059 (0.004); p<0.05). On the contrary, no changes were reported in controls. A 12-week aerobic programme significantly reduced oxidative damage expressed in terms of plasmatic allantoin content in adolescents with Down syndrome. Further studies on this topic are required.

  8. Cisplatin can be safely administered to ovarian cancer patients with hypersensitivity to carboplatin.

    Science.gov (United States)

    Bergamini, A; Pisano, C; Di Napoli, M; Arenare, L; Della Pepa, C; Tambaro, R; Facchini, G; Gargiulo, P; Rossetti, S; Mangili, G; Pignata, S; Cecere, S C

    2017-01-01

    Hypersensitivity reactions (HSR) are frequently reported in patients rechallenged with carboplatin for recurrent ovarian cancer (ROC) and represent a critical issue, since discontinuation of the platinum-based therapy could affect prognosis. Several strategies to allow platinum rechallenge have been described, with controversial outcomes. The aim of this study is to illustrate a 10-year experience with cisplatin in patients with a previous HSR to carboplatin or at risk for allergy. A retrospective review of all patients with platinum sensitive ROC retreated with carboplatin was performed between January 2007 and May 2016 at the Istituto Nazionale Tumori, Fondazione "G. Pascale", Naples. Among 183 patients, 49 (26.8%) presented HSR to carboplatin, mainly during second line therapy. Mean number of cycles before HSR was 8 (range 3-17). G2, G3 and G4 reaction were detected in 83%, 15% and 2% of patients, respectively. In a multivariate analysis including age, hystotype, BRCA status, previous known HSR, and combination drug administered, only the type of carboplatin-based doublet used as 2nd line therapy was found to significantly affect HSR development, with a protective effect of PLD (pegylated liposomal doxorubicin) (p = 0.014, OR = 0.027). Thirty seven patients (77%) with a previous HSR to carboplatin were rechallenged with cisplatin. Treatment was generally well tolerated. 5 patients (13.1%) experienced mild HSR to cisplatin, successfully managed in all cases. 14 patients were treated with cisplatin even without a carboplatin-related HSR due to other allergies. Among these, only one developed HSR (7.1%). Cisplatin rechallenge is a feasible approach in patients experiencing HSR to carboplatin to maintain the beneficial effect of platinum while reducing hypersensitivity-related risks. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. The Effect of Two Weeks Preoperative Finasteride Therapy in Reducing Prostate Vascularity.

    Science.gov (United States)

    Khwaja, Muhammad Athar; Nawaz, Gul; Muhammad, Shujah; Jamil, Muhammad Imran; Faisal, Muhammad; Akhter, Saeed

    2016-03-01

    To determine the effect of two weeks preoperative finasteride therapy in reducing prostate vascularity in terms of mean microvessel density (MVD) and expression of VEGF in prostate urothelium among patients of BPH by comparing with controls. Randomized controlled trial. Shifa International Hospital, Islamabad, from January 2013 to January 2014. A total of 80 patients of Benign Prostatic Hyperplasia (BPH) planned for Trans-Urethral Resection of Prostate (TURP) having prostate size of more than 40 grams on trans-abdominal ultrasonography was randomized into two groups, each group having 40 patients. The finasteride group (Group A) was prescribed oral 5 mg of finasteride daily for 2 weeks before surgery. The control group (Group B) did not receive any agent. After 2 weeks, TURP was performed and prostate samples were sent for histopathological determination of MVD and expression of VEGF. The mean age of patients was 66.21 ±10.08 years, ranging from 48 to 86 years. The mean prostate gland size was comparable in both groups (55 ±10.7 vs. 58.1 ±10.8 grams, p=0.21). Mean MVD in finasteride group (20.25 ±10.3) was significantly lower as compared to control group (48.9 ±22.6, p finasteride group (30%) as compared to control group (65%) [p= 0.0017]. Mean MVD had a significant weak correlation with the size of prostate gland on Pearson correlation test (2-tailed) with r = 0.222. Finasteride reduces microvessel density and hence prostate vascularity with only 2-week therapy and the mean MVD is clearly correlated with size of prostate.

  10. Phase 2 trial of everolimus and carboplatin combination in patients with triple negative metastatic breast cancer

    Science.gov (United States)

    2014-01-01

    Introduction Rapamycin acts synergistically with platinum agents to induce apoptosis and inhibit proliferation in breast cancer cell lines. Combination of everolimus also known as RAD001 (oral mammalian target of rapamycin (mTOR) inhibitor) and carboplatin may have activity in metastatic triple-negative breast cancer (TNBC). Methods The primary objective of this study was to determine clinical benefit rate (CBR), that is (complete remission (CR) + partial remission (PR) + stable disease (SD) lasting ≥6 months) and the toxicity of everolimus/carboplatin in women with metastatic TNBC. Prior carboplatin was allowed. Treatment consisted of intravenous carboplatin area under the curve (AUC) 6 (later decreased to AUC 5 and subsequently to AUC 4) every 3 weeks with daily 5 mg everolimus. Results We enrolled 25 patients in this study. Median age was 58 years. There were one CR, six PRs, seven SDs and eight PDs (progression of disease). CBR was 36% (95% confidence interval (CI) 21.1 to 57.4%). One SD was achieved in a patient progressing on single agent carboplatin. The median progression free survival (PFS) was 3 months (95% CI 1.6 to 4.6 months) and overall survival (OS) was 16.6 months (95% CI 7.3 months to not reached). There were seven patients (28%) with ≥ grade 3 thrombocytopenia; three (12%) with grade 3 neutropenia (no bleeding/febrile neutropenia) and one (4%) with grade 3 anemia. Greater hematological toxicity was seen in the first seven patients treated with carboplatin AUC5/6. After the amendment for starting dose of carboplatin to AUC 4, the regimen was well tolerated with only one out of 18 patients with grade 3 neutropenia and two patients with grade 3 thrombocytopenia. There was only one case of mucositis. Conclusion Everolimus-carboplatin was efficacious in metastatic TNBC. Dose limiting hematological toxicity was observed when AUC5/6 of carboplatin was combined with everolimus. However, carboplatin AUC 4 was well tolerated in

  11. Effects of reduced food intake for 4 weeks on physiological parameters in toxicity studies in dogs.

    Science.gov (United States)

    Morita, Junya; Izumi, Tomoko; Ogawa, Bunichiro; Ban, Yoshiki; Takagi, Hironori; Sasaki, Minoru; Tsutsumi, Shunsuke

    2017-01-01

    This study sought to clarify the effects of reduced feeding on physiological parameters in dogs to enable appropriate evaluations of the safety and toxicity of test compounds. We measured alkaline phosphatase isozymes and the circulating blood volume, as well as clinical signs, body weight, hematology, blood chemistry, electrocardiography, organ weight, and histopathology, in male beagle dogs fed a diet consisting of 300 g/day or 150 g/day for 4 weeks. There were no abnormal clinical signs in any of the dogs. In the 150-g/day feeding group, a decreased alkaline phosphatase 3 suggesting effects on the bone and a decreased circulating blood volume associated with body weight loss were observed. Additionally, the following changes were also observed in the 150-g/day group: a decrease in body weight; hematologic changes including decreases in white blood cells, neutrophils, red blood cells, hemoglobin, hematocrit and reticulocytes; blood chemical changes including decreases in aspartate aminotransferase, lactate dehydrogenase and calcium and an increase in the creatinine at week 1 or thereafter; electrocardiographic changes including a decrease in the heart rate, a prolonged QRS duration and the occurrence of a second-degree atrioventricular block at week 3 or thereafter; and pathological changes including decreases in the weights of the liver and thymus, a decrease in hepatocyte rarefaction, and thymic atrophy. These results provide useful information for assessing the safety of compounds in toxicological studies, enabling direct treatment effects and secondary changes caused by decreased food intake to be distinguished.

  12. First-Line Treatment with Carboplatin plus nab-Paclitaxel and Maintenance Monotherapy with nab-Paclitaxel for a Thymic Carcinoma: A Case Report

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    Kunihiko Funaishi

    2017-06-01

    Full Text Available Thymic carcinomas are rare malignant tumors, located in the anterior mediastinum. For the treatment of these carcinomas, several chemotherapy regimens have been suggested, including carboplatin plus paclitaxel. However, because of the rarity of these tumors, the standard chemotherapy regimen has not yet been established. Here, we report a case of thymic carcinoma that responded to first-line carboplatin plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel therapy with continuation maintenance nab-paclitaxel monotherapy. A 78-year-old male presented to a hospital with the chief complaint of dyspnea. Cardiomegaly was detected on chest X-ray scans, and marked pericardial effusion was observed by echocardiography. Chest computed tomography scans revealed the presence of a mediastinal mass, pericardial thickening, and pericardial effusion. The serum levels of the tumor marker CYFRA 21-1 (cytokeratin-19 fragment were elevated. Eventually, he was diagnosed with squamous cell carcinoma of the thymus, which was staged as cT4N3M0 or stage IV (according to the tumor-node-metastasis classification. Chemotherapy with carboplatin on day 1 and nab-paclitaxel on days 1, 8, and 15, every 4 weeks was initiated. After the administration of 4 cycles of this regimen, the tumor diameter appeared reduced, and the serum CYFRA 21-1 levels were normalized. After a 1-month interval, the serum CYFRA 21-1 levels increased again; therefore, maintenance nab-paclitaxel monotherapy was initiated. At the end of the treatment, the patient experienced a progression-free survival of 10.3 months. Carboplatin plus nab-paclitaxel may be an appropriate alternative first-line treatment for thymic carcinomas. Additionally, maintenance nab-paclitaxel monotherapy may prolong the progression-free survivals of patients with thymic carcinomas.

  13. L-Carnitine Protects against Carboplatin-Mediated Renal Injury: AMPK- and PPARα-Dependent Inactivation of NFAT3

    Science.gov (United States)

    Chang, Chih-Cheng; Yang, Nian-Jie; Chou, Ying; Juan, Shu-Hui

    2014-01-01

    We have previously shown that carboplatin induces inflammation and apoptosis in renal tubular cells (RTCs) through the activation of the nuclear factor of activated T cells-3 (NFAT3) protein by reactive oxygen species (ROS), and that the ROS-mediated activation of NFAT3 is prevented by N-acetyl cysteine and heme oxygenase-1 treatment. In the current study, we investigated the underlying molecular mechanisms of the protective effect of L-carnitine on carboplatin-mediated renal injury. Balb/c mice and RTCs were used as model systems. Carboplatin-induced apoptosis in RTCs was examined using terminal-deoxynucleotidyl-transferase-mediated dUTP nick end labeling. We evaluated the effects of the overexpression of the peroxisome-proliferator-activated receptor alpha (PPARα) protein, the knockdown of PPARα gene, and the blockade of AMPK activation and PPARα to investigate the underlying mechanisms of the protective effect of L-carnitine on carboplatin-mediated renal injury. Carboplatin reduced the nuclear translocation, phosphorylation, and peroxisome proliferator responsive element transactivational activity of PPARα. These carboplatin-mediated effects were prevented by L-carnitine through a mechanism dependent on AMPK phosphorylation and subsequent PPARα activation. The activation of PPARα induced cyclooxygenase 2 (COX-2) and prostacyclin (PGI2) synthase expression that formed a positive feedback loop to further activate PPARα. The coimmunoprecipitation of the nuclear factor (NF) κB proteins increased following the induction of PPARα by L-carnitine, which reduced NFκB transactivational activity and cytokine expression. The in vivo study showed that the inactivation of AMPK suppressed the protective effect of L-carnitine in carboplatin-treated mice, indicating that AMPK phosphorylation is required for PPARα activation in the L-carnitine-mediated protection of RTC apoptosis caused by carboplatin. The results of our study provide molecular evidence that L

  14. Potent therapeutic activity of folate receptor-targeted liposomal carboplatin in the localized treatment of intraperitoneally grown human ovarian tumor xenograft

    Science.gov (United States)

    Chaudhury, Anumita; Das, Surajit; Bunte, Ralph M; Chiu, Gigi NC

    2012-01-01

    Intraperitoneal (IP) therapy with platinum (Pt)-based drugs has shown promising results clinically; however, high locoregional concentration of the drug could lead to adverse side effects. In this study, IP administration was coupled with a folate receptor-targeted (FRT) liposomal system, in an attempt to achieve intracellular delivery of the Pt-based drug carboplatin in order to increase therapeutic efficacy and to minimize toxicity. In vitro and in vivo activity of FRT carboplatin liposomes was compared with the activity of free drug and nontargeted (NT) carboplatin liposomes using FR-overexpressing IGROV-1 ovarian cancer cells as the model. Significant reduction in cell viability was observed with FRT liposomes, which, compared with the free drug, provided an approximately twofold increase in carboplatin potency. The increase in drug potency was correlated with significantly higher cellular accumulation of Pt resulting from FRT liposomal delivery. Further evaluation was conducted in mice bearing intraperitoneally inoculated IGROV-1 ovarian tumor xenografts. A superior survival rate (five out of six animals) was achieved in animals treated with FRT carboplatin liposomes, injected intraperitoneally with a dose of 15 mg/kg and following a schedule of twice-weekly administration for 3 weeks. In contrast, no survivors were observed in the free drug or NT carboplatin liposome groups. The presence of cancer cells in lung and liver tissues was observed in the saline, free carboplatin, and NT carboplatin liposome groups. However, there was no sign of cancer cells or drug-related toxicity detected in tissues from the animals treated with FRT carboplatin liposomes. The results of this study have demonstrated for the first time that the approach of coupling IP administration with FRT liposomal delivery could provide significantly improved therapeutic efficacy of carboplatin in the treatment of metastatic ovarian cancer. PMID:22359453

  15. Potent therapeutic activity of folate receptor-targeted liposomal carboplatin in the localized treatment of intraperitoneally grown human ovarian tumor xenograft.

    Science.gov (United States)

    Chaudhury, Anumita; Das, Surajit; Bunte, Ralph M; Chiu, Gigi N C

    2012-01-01

    Intraperitoneal (IP) therapy with platinum (Pt)-based drugs has shown promising results clinically; however, high locoregional concentration of the drug could lead to adverse side effects. In this study, IP administration was coupled with a folate receptor-targeted (FRT) liposomal system, in an attempt to achieve intracellular delivery of the Pt-based drug carboplatin in order to increase therapeutic efficacy and to minimize toxicity. In vitro and in vivo activity of FRT carboplatin liposomes was compared with the activity of free drug and nontargeted (NT) carboplatin liposomes using FR-overexpressing IGROV-1 ovarian cancer cells as the model. Significant reduction in cell viability was observed with FRT liposomes, which, compared with the free drug, provided an approximately twofold increase in carboplatin potency. The increase in drug potency was correlated with significantly higher cellular accumulation of Pt resulting from FRT liposomal delivery. Further evaluation was conducted in mice bearing intraperitoneally inoculated IGROV-1 ovarian tumor xenografts. A superior survival rate (five out of six animals) was achieved in animals treated with FRT carboplatin liposomes, injected intraperitoneally with a dose of 15 mg/kg and following a schedule of twice-weekly administration for 3 weeks. In contrast, no survivors were observed in the free drug or NT carboplatin liposome groups. The presence of cancer cells in lung and liver tissues was observed in the saline, free carboplatin, and NT carboplatin liposome groups. However, there was no sign of cancer cells or drug-related toxicity detected in tissues from the animals treated with FRT carboplatin liposomes. The results of this study have demonstrated for the first time that the approach of coupling IP administration with FRT liposomal delivery could provide significantly improved therapeutic efficacy of carboplatin in the treatment of metastatic ovarian cancer.

  16. Reduced Pro-Inflammatory Cytokines after Eight Weeks of Low-Dose Naltrexone for Fibromyalgia

    Directory of Open Access Journals (Sweden)

    Luke Parkitny

    2017-04-01

    Full Text Available Fibromyalgia (FM is a complex, multi-symptom condition that predominantly affects women. The majority of those affected are unlikely to gain significant symptomatic control from the few treatments that are approved for FM. In this 10-week, single-blind, crossover trial we tested the immune effects of eight weeks of oral administration of low-dose naltrexone (LDN. We enrolled eight women with an average age of 46 years, symptom severity of 62 out of 100, and symptom duration of 14 years. We found that LDN was associated with reduced plasma concentrations of interleukin (IL-1β, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-15, IL-17A, IL-27, interferon (IFN-α, transforming growth factor (TGF-α, TGF-β, tumor necrosis factor (TNF-α, and granulocyte-colony stimulating factor (G-CSF. We also found a 15% reduction of FM-associated pain and an 18% reduction in overall symptoms. The findings of this pilot trial suggest that LDN treatment in fibromyalgia is associated with a reduction of several key pro-inflammatory cytokines and symptoms. The potential role of LDN as an atypical anti-inflammatory medication should be explored further.

  17. A Two-Week Psychosocial Intervention Reduces Future Aggression and Incarceration in Clinically Aggressive Juvenile Offenders.

    Science.gov (United States)

    Kendall, Ashley D; Emerson, Erin M; Hartmann, William E; Zinbarg, Richard E; Donenberg, Geri R

    2017-12-01

    There is a largely unmet need for evidence-based interventions that reduce future aggression and incarceration in clinically aggressive juvenile offenders serving probation. We addressed this gap using a group randomized controlled trial. Offenders both with and without clinical aggression were included, enabling comparison of intervention effects. Juveniles 13 to 17 years old (N = 310, mean = 16 years, 90% African-American, 66% male) on probation were assigned to a 2-week intervention targeting psychosocial factors implicated in risky behavior (e.g., learning strategies to manage "hot" emotions that prompt risk taking) or to an equally intensive health promotion control. Participants completed aggression measures at baseline, 6-, and 12-month follow-up and reported on incarceration at 12 months. Spline regression tested symptom change. Among clinically aggressive offenders (n = 71), the intervention arm showed significantly greater reductions in aggression over the first 6 months compared with controls. Juveniles from the intervention no longer met clinical criteria, on average, but clinically significant symptoms persisted in the control group. By 12 months, participants from the intervention appeared to maintain treatment gains, but their symptom levels no longer differed significantly from those in the control. However, the intervention group was nearly 4 times less likely than controls to report incarceration. Intervention effects were significantly stronger for offenders with clinical than with nonclinical (n = 239) baseline aggression. A 2-week intervention expedited improvements in aggression and reduced incarceration in clinically aggressive juvenile offenders. The findings underscore the importance of directing intervention resources to the most aggressive youth. Clinical trial registration information-PHAT Life: Preventing HIV/AIDS Among Teens in Juvenile Justice (PHAT Life); http://clinicaltrials.gov/; NCT02647710. Copyright © 2017 American

  18. Curcumin sensitizes human lung cancer cells to apoptosis and metastasis synergistically combined with carboplatin.

    Science.gov (United States)

    Kang, Ji Ho; Kang, Hye Seon; Kim, In Kyoung; Lee, Hwa Young; Ha, Jick Hwan; Yeo, Chang Dong; Kang, Hyun Hui; Moon, Hwa Sik; Lee, Sang Haak

    2015-11-01

    Although carboplatin is one of the standard chemotherapeutic agents for non-small cell lung cancer (NSCLC), it has limited therapeutic efficacy due to activation of a survival signaling pathway and the induction of multidrug resistance. Curcumin, a natural compound isolated from the plant Curcuma longa, is known to sensitize tumors to different chemotherapeutic agents. The aim of this study is to evaluate whether curcumin can chemosensitize lung cancer cells to carboplatin and to analyze the signaling pathway underlying this synergism. We investigated the synergistic effect of both agents on cell proliferation, apoptosis, invasion, migration, and expression of related signaling proteins using the human NSCLC cell line, A549. A549 cell was treated with different concentrations of curcumin and carboplatin alone and in combination. Combined treatment with curcumin and carboplatin inhibited tumor cell growth, migration, and invasion compared with either drug alone. Matrix metalloproteinase (MMP)-2 and MMP-9 were more efficiently downregulated by co-treatment than by each treatment alone. mRNA and protein expression of caspase-3 and caspase-9 and proapoptotic genes was increased in cells treated with a combination of curcumin and carboplatin, whereas expression of the antiapoptotic Bcl-2 gene was suppressed. Co-treatment of both agents substantially suppressed NF-κB activation and increased expression of p53. Phosphorylation of Akt, a protein upstream of NF-κB, was reduced, resulting in inhibition of the degradation of inhibitor of κB(IκBα), whereas the activity of extracellular signal-regulated kinase (ERK1/2) was enhanced. Our study demonstrated that the synergistic antitumor activity of curcumin combined with carboplatin is mediated by multiple mechanisms involving suppression of NF-κB via inhibition of the Akt/IKKα pathway and enhanced ERK1/2 activity. Based on this mechanism, curcumin has potential as a chemosensitizer for carboplatin in the treatment of

  19. Carboplatin-Induced Bilateral Papilledema: A Case Report

    Directory of Open Access Journals (Sweden)

    N. Fischer

    2009-04-01

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

  20. Subconjunctival carboplatin in fibrin sealant in the treatment of transgenic murine retinoblastoma.

    Science.gov (United States)

    Van Quill, Kurtis R; Dioguardi, Phyllis K; Tong, Candice T; Gilbert, Jake A; Aaberg, Thomas M; Grossniklaus, Hans E; Edelhauser, Henry F; O'Brien, Joan M

    2005-06-01

    To evaluate the efficacy of subconjunctival carboplatin in fibrin sealant in the treatment of transgenic murine retinoblastoma. Experimental study using LHbeta-Tag transgenic mice in a randomized controlled trial. Thirty-three 10-week-old LHbeta-Tag transgenic mice: 22 carboplatin-treated animals and 11 control animals. Three groups of 11 mice were treated with a single, 30 microl injection of fibrin sealant in the subconjunctival space of 1 eye; the opposite eye was left untreated as an internal control. Group 1 (low-dose group) received 37.5 mg/ml calculated concentration of carboplatin in fibrin sealant (0.66 mg measured total dose). Group 2 (high-dose group) received 75 mg/ml calculated concentration of carboplatin in fibrin sealant (1.23 mg measured total dose). Group 3 (control group) received fibrin sealant only. Mice were killed on day 22 after treatment. Eyes were serially sectioned, and retinal tumor burden was quantified by histopathologic analysis. For statistical analysis of treatment effects, eyes were divided into 6 groups: low-dose group, sealant-treated eyes; low-dose group, untreated eyes; high-dose group, sealant-treated eyes; high-dose group, untreated eyes; control group, sealant-treated eyes; and control group, untreated eyes. Main outcome measure was mean tumor burden per level per eye in each experimental group. The best therapeutic results were obtained in eyes treated with low-dose carboplatin in fibrin sealant, where no histopathologic evidence of toxicity was observed, and 6 of 11 eyes had zero tumor burden. Tumor burden in the remaining 5 eyes in this group was minimal (4 eyes) or moderate (1 eye) compared with mean control values. Mean tumor burden in this group was significantly smaller than mean tumor burden in untreated eyes from the same mice (P<0.004), sealant-treated eyes in the control group (P<0.004), and untreated eyes in the control group (P<0.002). Although a similar reduction in mean tumor burden was observed in eyes

  1. Fulminant Clostridium difficile colitis associated with paclitaxel and carboplatin chemotherapy.

    Science.gov (United States)

    Resnik, E.; Lefevre, C. A.

    1999-11-01

    Resnik E, LeFevre CA. Fulminant Clostridium difficile colitis associated with paclitaxel and carboplatin chemotherapy. Pseudomembranous colitis is commonly associated with the use of antibiotics. Some antineoplastic agents even without associated antibiotic use can predispose patients to developing infection with Clostridium difficile. The infection is usually mild; however, in rare cases severe forms of pseudomembranous colitis may be encountered. A 66 year-old female with stage IIIC suboptimally debulked epithelial ovarian cancer was treated with paclitaxel and carboplatin. the patient developed fulminant C. difficile colitis three weeks after the second cycle of chemotherapy. Severe symptoms began 24 h prior to admission; however, mild nausea and diarrhea had been present for a week despite self-treatment with over-the-counter Imodium and Pepto-Bismol. Her last antibiotic use was seven weeks previously. The patient was hospitalized immediately for aggressive treatment. Notwithstanding all the efforts, her condition continued to deteriorate and she expired. Severe C. difficile colitis can be life threatening. Patients undergoing chemotherapy who develop significant diarrhea should be evaluated for C. difficile. Prompt diagnosis and intervention prior to onset of severe symptoms can potentially improve the outcome.

  2. Encapsulation in Nanoparticles Improves Anti-cancer Efficacy of Carboplatin

    OpenAIRE

    Sadhukha, Tanmoy; Prabha, Swayam

    2014-01-01

    Poor cellular uptake contributes to high dose requirement and limited therapeutic efficacy of the platinum-based anticancer drug carboplatin. Delivery systems that can improve the cellular accumulation of carboplatin will, therefore, likely improve its therapeutic potential. The objective of this study was to evaluate nanoparticles composed of the biodegradable polymer, poly(d, l-lactide-co-glycolide), for carboplatin delivery to tumor cells. Carboplatin-loaded nanoparticles were formulated b...

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

    KAUST Repository

    Jain, Harsh Vardhan

    2014-01-06

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

  4. Topotecan plus carboplatin versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabine plus carboplatin (GC) or pegylated liposomal doxorubicin plus carboplatin (PLDC): a randomized phase III trial of the NOGGO-AGO-Study Group-AGO Austria and GEICO-ENGOT-GCIG intergroup study (HECTOR).

    Science.gov (United States)

    Sehouli, J; Chekerov, R; Reinthaller, A; Richter, R; Gonzalez-Martin, A; Harter, P; Woopen, H; Petru, E; Hanker, L C; Keil, E; Wimberger, P; Klare, P; Kurzeder, C; Hilpert, F; Belau, A K; Zeimet, A; Bover-Barcelo, I; Canzler, U; Mahner, S; Meier, W

    2016-12-01

    Randomized, phase III trial to evaluate safety and efficacy of topotecan and carboplatin (TC) compared with standard platinum-based combinations in platinum-sensitive recurrent ovarian cancer (ROC). Patients were randomly assigned in a 1:1 ratio to the experimental TC arm (topotecan 0.75 mg/m2/ days 1-3 and carboplatin AUC 5 on day 3 every 3 weeks) or to one of the standard regimes [(PC) paclitaxel plus carboplatin; (GC) gemcitabine plus carboplatin; (PLDC) pegylated liposomal doxorubicin and carboplatin] which could be chosen by individual preference but before randomization. The primary end point was progression-free survival (PFS) after 12 months. Overall survival (OS), response rate, toxicity, quality of life and treatment preference regarding standard treatment were defined as secondary end points. A total of 550 patients were recruited. The PFS rate after 12 months was 37.0% for TC compared with 40.2% in the standard combinations (P = 0.470). The overall response rate was 73.1% for TC versus 75.1% for standard combinations (P = 0.149). After a median follow-up of 20 months, the median PFS was 10 months [95% confidence interval (CI) 9.4-10.6] and did not differ between both arms (P = 0.414). The median OS was 25 months in the TC arm versus 31 months in the standard arm (95% CI: 22.4-27.6 resp. 26.0-36.0; P = 0.163). Severe hematologic toxicities (grade 3/4) were rare in the experimental arm (P carboplatin and topotecan was well tolerated with significant lower rates of severe hematological toxicities but did not improve PFS or OS in platinum-sensitive relapsed ovarian cancer compared with established standard regimens. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  5. Exploiting the Synergy between Carboplatin and ABT-737 in the Treatment of Ovarian Carcinomas

    Science.gov (United States)

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

    2014-01-01

    Platinum drug-resistance in ovarian cancers mediated by anti-apoptotic proteins such as Bcl-xL is a major factor contributing to the chemotherapeutic resistance of recurrent disease. Consequently, concurrent inhibition of Bcl-xL in combination with chemotherapy may improve treatment outcomes for patients. Here, we develop a mathematical model to investigate the potential of combination therapy with ABT-737, a small molecule inhibitor of Bcl-xL, and carboplatin, a platinum-based drug, on a simulated tumor xenograft. The model is calibrated against in vivo experimental data, wherein xenografts established in mice were treated with ABT-737 and/or carboplatin on a fixed periodic schedule. The validated model is used to predict the minimum drug load that will achieve a predetermined level of tumor growth inhibition, thereby maximizing the synergy between the two drugs. Our simulations suggest that the infusion-duration of each carboplatin dose is a critical parameter, with an 8-hour infusion of carboplatin given weekly combined with a daily bolus dose of ABT-737 predicted to minimize residual disease. The potential of combination therapy to prevent or delay the onset of carboplatin-resistance is also investigated. When resistance is acquired as a result of aberrant DNA-damage repair in cells treated with carboplatin, drug delivery schedules that induce tumor remission with even low doses of combination therapy can be identified. Intrinsic resistance due to pre-existing cohorts of resistant cells precludes tumor regression, but dosing strategies that extend disease-free survival periods can still be identified. These results highlight the potential of our model to accelerate the development of novel therapeutics such as BH3 mimetics. PMID:24400068

  6. Phase 1b safety study of farletuzumab, carboplatin and pegylated liposomal doxorubicin in patients with platinum-sensitive epithelial ovarian cancer.

    Science.gov (United States)

    Kim, Kenneth H; Jelovac, Danijela; Armstrong, Deborah K; Schwartz, Benjamin; Weil, Susan C; Schweizer, Charles; Alvarez, Ronald D

    2016-02-01

    Farletuzumab is a humanized monoclonal antibody that binds to folate receptor alpha, over-expressed in epithelial ovarian cancer (EOC) but largely absent in normal tissue. Previously, carboplatin plus pegylated liposomal doxorubicin showed superior progression-free survival and an improved therapeutic index compared with carboplatin/paclitaxel in relapsed platinum-sensitive EOC. This study assessed safety of farletuzumab/carboplatin/pegylated liposomal doxorubicin in women with platinum-sensitive recurrent EOC. This multicenter, single-arm study enrolled patients with platinum-sensitive EOC in first or second relapse for treatment with weekly farletuzumab 2.5mg/kg plus carboplatin AUC5-6 and pegylated liposomal doxorubicin 30mg/m(2) every 4weeks for 6cycles. Subsequently, maintenance with single-agent farletuzumab 2.5mg/kg once weekly or farletuzumab 7.5mg/kg once every three weeks continued until progression. The primary objective was to assess the safety of farletuzumab/carboplatin/pegylated liposomal doxorubicin. Fifteen patients received a median of 12.0cycles (range, 3-26) of farletuzumab as combination therapy or maintenance, for a median of 45.0weeks (range 9-95). Farletuzumab/carboplatin/pegylated liposomal doxorubicin was generally well tolerated, with no farletuzumab-related grades 3-4 adverse events. The most commonly reported adverse events were associated with combination chemotherapy: fatigue (73.3%), nausea (46.7%), and neutropenia (40%). Ten patients had grade ≥3 adverse events, most frequently neutropenia and fatigue. No cardiac toxicity was seen. Best overall responses (RECIST) were a complete response for one patient, partial responses for 10 patients, and stable disease for four patients. Farletuzumab plus carboplatin/pegylated liposomal doxorubicin in women with platinum-sensitive EOC demonstrated a safety profile consistent with that of carboplatin plus pegylated liposomal doxorubicin. Copyright © 2015 The Authors. Published by Elsevier Inc

  7. Effects of 12 weeks high-intensity & reduced-volume training in elite athletes

    DEFF Research Database (Denmark)

    Kilen, Anders; Larsson, Tanja Hultengren; Jørgensen, Majke

    2014-01-01

    It was investigated if high-intensity interval training (HIT) at the expense of total training volume improves performance, maximal oxygen uptake and swimming economy. 41 elite swimmers were randomly allocated to a control (CON) or HIT group. For 12 weeks both groups trained ∼12 h per week. HIT...

  8. Adjuvant Carboplatin Treatment in 115 Patients With Stage I Seminoma: Retrospective Multicenter Survey.

    Science.gov (United States)

    Diminutto, Alberto; Basso, Umberto; Maruzzo, Marco; Morelli, Franco; De Giorgi, Ugo; Perin, Alessandra; Fraccon, Anna Paola; Lo Re, Giovanni; Rizzi, Anna; Sava, Teodoro; Fornarini, Giuseppe; Valcamonico, Francesca; Zustovich, Fable; Massari, Francesco; Zanardi, Elisa; Roma, Anna; Zattoni, Filiberto; Zagonel, Vittorina

    2016-04-01

    The administration of carboplatin AUC 7 has become a standard adjuvant option for patients undergoing orchiectomy for stage I seminoma, in alternative to radiotherapy on retroperitoneal lymphnodes or surveillance. The toxicity of AUC 7 carboplatin appeared manageable in the pivotal trial of Oliver et al, but dose ranges were not reported. Fear of toxicity may induce arbitrary dose reductions, which may potentially compromise patients' outcome. We reviewed adjuvant carboplatin administration in 115 stage I seminoma patients followed in 11 Italian medical oncology centers since 2005. Clinical and pathological data, modality of carboplatin dose calculation, dose reductions, toxicities, and relapses were recorded. Median age was 35 years (range, 18-65 years), adverse prognostic factors were either T ≥ 4 cm (17.4%) or rete testis invasion (28.7%), both of them (35.7%), none or unspecified (18.3%). GFR was estimated mainly by Cockroft-Gault formula (55.7%) or Jeliffe formula (26.1%), with a median of 105 mL/min (range, 75-209 mL/min). The median dose of carboplatin was 900 mg (range, 690-1535 mg). A dose reduction > 10% was applied to 14 patients. Toxicities were mild fatigue, moderate nausea/vomiting, 5.2% of grade 3 to 4 thrombocytopenia. After a median follow-up of 22.1 months, 5.2% of patients have relapsed in the retroperitoneal lymph nodes. None of the patients that relapsed were treated with reduced dose. All but one achieved complete remission with salvage chemotherapy. Adjuvant AUC 7 carboplatin reduce relapses of stage I seminoma patients to 5.2%, with manageable toxicities. Dose reductions should be proscribed. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2015-06-01

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

  10. Pregabalin reduces postoperative opioid consumption and pain for 1 week after hospital discharge, but does not affect function at 6 weeks or 3 months after total hip arthroplasty.

    Science.gov (United States)

    Clarke, H; Pagé, G M; McCartney, C J L; Huang, A; Stratford, P; Andrion, J; Kennedy, D; Awad, I T; Gollish, J; Kay, J; Katz, J

    2015-12-01

    This study examined whether a perioperative regimen of pregabalin added to celecoxib improved pain scores and functional outcomes postdischarge up to 3 months after total hip arthroplasty (primary outcome) and acute postoperative pain and adverse effects (secondary outcomes). One hundred and eighty-four patients were enrolled in a randomized, double-blind, placebo-controlled study. Two hours before receiving a spinal anaesthetic and undergoing surgery, patients received celecoxib 400 mg p.o. and were randomly assigned to receive either pregabalin 150 mg p.o. or placebo p.o. After surgery, patients received pregabalin 75 mg or placebo twice daily in hospital and for 7 days after discharge. Patients also received celecoxib 200 mg every 12 h for 72 h and morphine i.v. patient-controlled analgesia for 24 h. Pain and function were assessed at baseline, 6 weeks, and 3 months after surgery. There was no difference between groups in physical function or incidence and intensity of chronic pain 3 months after total hip arthroplasty. The pregabalin group used less morphine [mean (sd): 39.85 (28.1) mg] than the placebo group [54.01 (31.2) mg] in the first 24 h after surgery (Ppregabalin group vs the placebo group on days 1-7 after hospital discharge, and the pregabalin group required less adjunctive opioid medication (Percocet) 1 week after hospital discharge (Ppregabalin did not improve pain or physical function at 6 weeks or 3 months after total hip arthroplasty. Perioperative administration of pregabalin decreased opioid consumption in hospital and reduced daily pain scores and adjunct opioid consumption for 1 week after discharge. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Pregnancy week by week

    Science.gov (United States)

    ... Global Map Premature Birth Report Cards Careers Archives Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal ... Home > Pregnancy > Prenatal care > Pregnancy week by week Pregnancy week by week Week by week Videos Infographics ...

  12. Effects of 12 weeks high-intensity & reduced-volume training in elite athletes.

    Directory of Open Access Journals (Sweden)

    Anders Kilen

    Full Text Available It was investigated if high-intensity interval training (HIT at the expense of total training volume improves performance, maximal oxygen uptake and swimming economy. 41 elite swimmers were randomly allocated to a control (CON or HIT group. For 12 weeks both groups trained ∼12 h per week. HIT comprised ∼5 h vs. 1 h and total distance was ∼17 km vs. 35 km per week for HIT and CON, respectively. HIT was performed as 6-10×10-30 s maximal effort interspersed by 2-4 minutes of rest. Performance of 100 m all-out freestyle and 200 m freestyle was similar before and after the intervention in both HIT (60.4±4.0 vs. 60.3±4.0 s; n = 13 and 133.2±6.4 vs. 132.6±7.7 s; n = 14 and CON (60.2±3.7 vs. 60.6±3.8 s; n = 15 and 133.5±7.0 vs. 133.3±7.6 s; n = 15. Maximal oxygen uptake during swimming was similar before and after the intervention in both the HIT (4.0±0.9 vs. 3.8±1.0 l O2×min-1; n = 14 and CON (3.8±0.7 vs. 3.8±0.7 l O2×min-1; n = 11 group. Oxygen uptake determined at fixed submaximal speed was not significantly affected in either group by the intervention. Body fat % tended to increase (P = 0.09 in the HIT group (15.4±1.6% vs. 16.3±1.6%; P = 0.09; n = 16 and increased (P<0.05 in the CON group (13.9±1.5% vs. 14.9±1.5%; n = 17. A distance reduction of 50% and a more than doubled HIT amount for 12 weeks did neither improve nor compromise performance or physiological capacity in elite swimmers.

  13. Carboplatin and paclitaxel as first-line treatment of unresectable or metastatic esophageal or gastric cancer.

    Science.gov (United States)

    Prithviraj, G K; Baksh, K; Fulp, W; Meredith, K; Hoffe, S; Shridhar, R; Almhanna, K

    2015-01-01

    Survival in patients with metastatic esophageal and gastric cancer is dismal. No standard treatment has been established. Carboplatin/paclitaxel is active in both advanced gastric and esophageal cancer. Here we retrospectively present our single center experience. Between 1998 and 2013, a total of 134 patients with metastatic esophageal and gastric adenocarcinoma treated with carboplatin/paclitaxel (carboplatin predominantly area under the curve 5 and paclitaxel predominantly 175 mg/m(2)) every 3 weeks as first-line therapy were identified. Baseline characteristics, response to therapy, toxicities, and survival in this patient population were evaluated. Overall survival was defined as date from diagnosis to death or last follow up, and progression-free survival was defined at time from cycle 1 to, progression or last follow up. Kaplan-Meier curves were fit to estimate overall and progression-free survival. Of the 134 patients evaluated, the median age at diagnosis was 65 years. Disease control rate was 62.6% (complete response: 11%, partial response: 28%, stable disease: 33%). Median overall survival from date of initial diagnosis was 15.5 months (95% confidence interval [CI] 1.06-1.5). Median progression-free survival from date of initiation of carboplatin and paclitaxel was 5.3 months (95% CI 0.34-0.5). Grade III or greater toxicity occurred in 26.1% of patients. The most common grade III toxicities were neutropenia and neuropathy, present in 14.2% and 3.7% of the total study population, respectively. In patients with metastatic or unresectable esophageal or gastric cancer, the combination of carboplatin and paclitaxel is well tolerated with comparable overall survival and progression-free survival to existing regimens in this population. © 2014 International Society for Diseases of the Esophagus.

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

    Science.gov (United States)

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

    2005-05-01

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

  15. High frequency of radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with concurrent radiotherapy and gemcitabine after induction with gemcitabine and carboplatin.

    Science.gov (United States)

    Arrieta, Oscar; Gallardo-Rincón, Dolores; Villarreal-Garza, Cynthia; Michel, Rosa M; Astorga-Ramos, Alma M; Martínez-Barrera, Luis; de la Garza, Jaime

    2009-07-01

    The combination of chemotherapy and thoracic radiation is the standard treatment for locally advanced non-small cell lung cancer (NSCLC). However, most favorable chemotherapy regimen, timing of full-dose chemotherapy, and optimal combination of chemotherapy with radiation remain to be determined. Our primary objective was to evaluate the efficacy and safety of gemcitabine concurrent with radiotherapy after induction chemotherapy with gemcitabine plus carboplatin for locally advanced NSCLC. Patients with histologically proven NSCLC stage IIIA and -B received carboplatin (area under the curve of 2.5) and gemcitabine (800 mg/m) on days 1 and 8, every 21 days for two cycles, followed by conventional fractioned thoracic radiotherapy and concomitant weekly gemcitabine 200 mg/m, and finally, consolidation chemotherapy. Inclusion was discontinued because of high-grade 3 to 5 radiation-pneumonitis events (6 of 19 patients, 31.6%), including one treatment-related death associated with radiation pneumonitis. Median follow-up was 11.9 months. Most common grades 3/4 hematological side effects comprised anemia, neutropenia 3 of 19 patients, each (15.8%), and thrombocytopenia (4 of 19, 21.1%) during induction. Partial response was observed in 10 patients (52.6%) following induction chemotherapy. After concurrent chemo-radiotherapy, overall response was 68.4%. Four patients (21.1%) underwent surgical resection. Median progression-free survival and overall survival were 12 +/- 1 month (95% confidence interval [CI], 9.8-14.1) and 21 +/- 3.5 months (95% CI, 14-27.9 months), respectively. Concurrent radiotherapy with gemcitabine after induction with gemcitabine and carboplatin showed a high-response rate; however, it is associated with excessive pulmonary toxicity. Adjustments in gemcitabine dosage during radiotherapy or changes in radiotherapy planning could reduce toxicity.

  16. Dexamethasone as a chemoprotectant in cancer chemotherapy: hematoprotective effects and altered pharmacokinetics and tissue distribution of carboplatin and gemcitabine.

    Science.gov (United States)

    Wang, Hui; Li, Mao; Rinehart, John J; Zhang, Ruiwen

    2004-06-01

    Hematoprotective strategies may offer new approaches to prevent chemotherapy-induced hematotoxicity. The present study was undertaken to investigate the chemoprotective effects of dexamethasone and its optimal dose and the underlying mechanisms. Lethal toxicity and hematotoxicity of carboplatin were compared in CD-1 mice with or without dexamethasone pretreatment. Plasma and tissue pharmacokinetics of carboplatin were determined in CD-1 mice. Carboplatin was quantified by HPLC. Gemcitabine was analyzed by radioactivity counting. Pretreatment with dexamethasone prevented lethal toxicity of carboplatin in a dose- and schedule-dependent manner. The best protective effects of dexamethasone pretreatment as measured by survival were observed at the dose level of 0.1 mg/mouse per day for 5 days (80% vs 10% in controls). In contrast, posttreatment with dexamethasone had no protective effects. Pretreatment with dexamethasone significantly prevented the decrease in granulocyte counts. To elucidate the mechanisms by which dexamethasone pretreatment reduces hematotoxicity, we examined the effects of dexamethasone pretreatment on the pharmacokinetics of carboplatin and gemcitabine in CD-1 mice. No significant differences in plasma pharmacokinetics of carboplatin or gemcitabine were observed between control and mice pretreated with dexamethasone. However, dexamethasone pretreatment significantly decreased carboplatin and gemcitabine uptake in spleen and bone marrow with significant decreases in AUC, T(1/2), and C(max), and an increase in CL. To our knowledge, this is the first time that dexamethasone has been shown to significantly decrease host tissue uptake of chemotherapeutic agents, suggesting a mechanism responsible for the chemoprotective effects of dexamethasone. This study provides a basis for future study to evaluate dexamethasone as a chemoprotectant in cancer patients.

  17. A five-week exercise program can reduce falls and improve obstacle avoidance in the elderly

    NARCIS (Netherlands)

    Weerdesteyn, [No Value; Rijken, H; Smits-Engelsman, BCM; Mulder, T; Duysens, J

    2006-01-01

    Background: Falls in the elderly are a major health problem. Although exercise programs have been shown to reduce the risk of falls, the optimal exercise components, as well as the working mechanisms that underlie the effectiveness of these programs, have not yet been established. Objective: To test

  18. A five-week exercise program can reduce falls and improve obstacle avoidance in the elderly.

    NARCIS (Netherlands)

    Weerdesteijn, V.G.M.; Rijken, H.A.F.M.; Geurts, A.C.H.; Smits-Engelsman, B.C.M.; Mulder, T.; Duysens, J.E.J.

    2006-01-01

    BACKGROUND: Falls in the elderly are a major health problem. Although exercise programs have been shown to reduce the risk of falls, the optimal exercise components, as well as the working mechanisms that underlie the effectiveness of these programs, have not yet been established. OBJECTIVE: To test

  19. Paclitaxel Enhances Carboplatin-DNA Adduct Formation and Cytotoxicity.

    Science.gov (United States)

    Jiang, Shuai; Pan, Amy W; Lin, Tzu-yin; Zhang, Hongyong; Malfatti, Michael; Turteltaub, Kenneth; Henderson, Paul T; Pan, Chong-xian

    2015-12-21

    This rapid report focuses on the pharmacodynamic mechanism of the carboplatin/paclitaxel combination and correlates it with its cytotoxicity. Consistent with the synergistic to additive antitumor activity (the combination index ranging from 0.53 to 0.94), cells exposed to this combination had significantly increased carboplatin-DNA adduct formation when compared to that of carboplatin alone (450 ± 30 versus 320 ± 120 adducts per 10(8) nucleotides at 2 h, p = 0.004). Removal of paclitaxel increased the repair of carboplatin-DNA adducts: 39.4 versus 33.1 adducts per 10(8) nucleotides per hour in carboplatin alone (p = 0.021). This rapid report provides the first pharmacodynamics data to support the use of carboplatin/paclitaxel combination in the clinic.

  20. Carboplatin Induced Fatal Autoimmune Hemolytic Anemia: First Reported Case

    OpenAIRE

    Dacha, Sunil; Reddivari, Anil K; Latta, Shadi; Devidi, Manjari; Iroegbu, Nkemakolam

    2010-01-01

    Carboplatin is an alkylating anti-neoplastic drug used in various cancers especially ovarian cancer, germ cell tumors, endometrial cancer besides others. We present a case of acute autoimmune hemolytic anemia during Carboplatin infusion in a patient previously exposed to the drug, resulting in the death of the patient. Published reports of Carboplatin induced autoimmune hemolytic anemia suggest these are usually nonfatal and improve after discontinuation of the drug. Fatal autoimmune hemolysi...

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-03-01

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

  3. Radiation therapy combined with intracerebral administration of carboplatin for the treatment of brain tumors

    Science.gov (United States)

    2014-01-01

    Background In this study we determined if treatment combining radiation therapy (RT) with intracerebral (i.c.) administration of carboplatin to F98 glioma bearing rats could improve survival over that previously reported by us with a 15 Gy dose (5 Gy × 3) of 6 MV photons. Methods First, in order to reduce tumor interstitial pressure, a biodistribution study was carried out to determine if pretreatment with dexamethasone alone or in combination with mannitol and furosemide (DMF) would increase carboplatin uptake following convection enhanced delivery (CED). Next, therapy studies were carried out in rats that had received carboplatin either by CED over 30 min (20 μg) or by Alzet pumps over 7 d (84 μg), followed by RT using a LINAC to deliver either 20 Gy (5 Gy × 4) or 15 Gy (7.5 Gy × 2) dose at 6 or 24 hrs after drug administration. Finally, a study was carried out to determine if efficacy could be improved by decreasing the time interval between drug administration and RT. Results Tumor carboplatin values for D and DMF-treated rats were 9.4 ±4.4 and 12.4 ±3.2 μg/g, respectively, which were not significantly different (P = 0.14). The best survival data were obtained by combining pump delivery with 5 Gy × 4 of X-irradiation with a mean survival time (MST) of 107.7 d and a 43% cure rate vs. 83.6 d with CED vs. 30-35 d for RT alone and 24.6 d for untreated controls. Treatment-related mortality was observed when RT was initiated 6 h after CED of carboplatin and RT was started 7 d after tumor implantation. Dividing carboplatin into two 10 μg doses and RT into two 7.5 Gy fractions, administered 24 hrs later, yielded survival data (MST 82.1 d with a 25% cure rate) equivalent to that previously reported with 5 Gy × 3 and 20 μg of carboplatin. Conclusions Although the best survival data were obtained by pump delivery, CED was highly effective in combination with 20 Gy, or as previously reported, 15 Gy, and the latter would be preferable since it would produce less

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

    Science.gov (United States)

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

    2017-03-10

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

  5. Eight weeks of exercise training increases aerobic capacity and muscle mass and reduces fatigue in patients with cirrhosis.

    Science.gov (United States)

    Zenith, Laura; Meena, Neha; Ramadi, Ailar; Yavari, Milad; Harvey, Andrea; Carbonneau, Michelle; Ma, Mang; Abraldes, Juan G; Paterson, Ian; Haykowsky, Mark J; Tandon, Puneeta

    2014-11-01

    Patients with cirrhosis have reduced exercise tolerance, measured objectively as decreased peak exercise oxygen uptake (peak VO2). Reduced peak VO2 is associated with decreased survival time. The effect of aerobic exercise training on peak VO2 has not been well studied in patients with cirrhosis. We evaluated the safety and efficacy of 8 weeks of supervised exercise on peak VO2, quadriceps muscle thickness, and quality of life. In a prospective pilot study, stable patients (79% male, 57.6 ± 6.7 years old) with Child-Pugh class A or B cirrhosis (mean Model for End-Stage Liver Disease score, 10 ± 2.2) were randomly assigned to groups that received exercise training (n = 9) or usual care (controls, n = 10) at the University of Alberta Hospital in Canada from February through June 2013. Supervised exercise was performed on a cycle ergometer 3 days/week for 8 weeks at 60%-80% of baseline peak VO2. Peak VO2, quadriceps muscle thickness (measured by ultrasound), thigh circumference, answers from Chronic Liver Disease Questionnaires, EQ-visual analogue scales, 6-minute walk distance, and Model for End-Stage Liver Disease scores were evaluated at baseline and at week 8. Analysis of covariance was used to compare variables. At week 8, peak VO2 was 5.3 mL/kg/min higher in the exercise group compared with controls (95% confidence interval, 2.9-7.8; P = .001). Thigh circumference (P = .001), thigh muscle thickness (P = .01), and EQ-visual analogue scale determined self-perceived health status (P = .01) was also significantly higher in the exercise group compared with controls at week 8; fatigue subscores of the Chronic Liver Disease Questionnaires were lower in the exercise group compared with controls (P = .01). No adverse events occurred during cardiopulmonary exercise testing or training. In a controlled prospective pilot trial, 8 weeks of supervised aerobic exercise training increased peak VO2 and muscle mass and reduced fatigue in patients with cirrhosis. No

  6. Effects of 6-Week Use of Reduced-Nicotine Content Cigarettes in Smokers With and Without Elevated Depressive Symptoms.

    Science.gov (United States)

    Tidey, Jennifer W; Pacek, Lauren R; Koopmeiners, Joseph S; Vandrey, Ryan; Nardone, Natalie; Drobes, David J; Benowitz, Neal L; Dermody, Sarah S; Lemieux, Andrine; Denlinger, Rachel L; Cassidy, Rachel; al'Absi, Mustafa; Hatsukami, Dorothy K; Donny, Eric C

    2017-01-01

    The FDA recently acquired regulatory authority over tobacco products, leading to renewed interest in whether reducing the nicotine content of cigarettes would reduce tobacco dependence in the United States. Given the association between depressive symptoms and cigarette smoking, it is important to consider whether smokers with elevated depressive symptoms experience unique benefits or negative consequences of nicotine reduction. In this secondary analysis of a randomized clinical trial that examined the effects of cigarettes varying in nicotine content over a 6-week period in non-treatment-seeking smokers, we used linear regression to examine whether baseline depressive symptom severity (scores on the Center for Epidemiologic Studies Depression Scale [CES-D]) moderated the effects of reduced-nicotine content (RNC) cigarettes, relative to normal-nicotine content (NNC) cigarettes, on smoking rates, depressive symptom severity, and related subjective and physiological measures. Of the 717 participants included in this analysis, 109 (15.2%) had CES-D scores ≥ 16, indicative of possible clinical depression. Relative to NNC cigarettes, RNC cigarettes reduced smoking rates, nicotine dependence, and cigarette craving, and these effects were not significantly moderated by baseline CES-D score. A significant interaction between baseline CES-D score and cigarette condition on week 6 CES-D score was observed (p nicotine content conditions, biochemically confirmed compliance with the RNC cigarettes was associated with an increase in CES-D score for those with baseline CES-D scores nicotine standard for cigarettes may reduce smoking, without worsening depressive symptoms, among smokers with elevated depressive symptoms. This secondary analysis of a recent clinical trial examined whether depressive symptom severity moderated the effects of reduced-nicotine cigarettes on smoking and depressive symptoms. Results indicate that, regardless of baseline depressive symptoms

  7. Definitive radiochemotherapy of advanced head and neck cancer with carboplatin and paclitaxel. A phase II study

    Energy Technology Data Exchange (ETDEWEB)

    Semrau, Robert; Temming, Susanne; Mueller, Rolf-Peter [Cologne Univ., Koeln (Germany). Dept. of Radiation Oncology; Preuss, Simon Florian [Cologne Univ., Koeln (Germany). Dept. of Otorhinolaryngology, Head and Neck Surgery; Klussmann, Jens Peter [Giessen Univ. (Germany). Dept. of Otorhinolaryngology and Head and Neck Surgery; Guntinas-Lichius, Orlando [Friedrich-Schiller Univ. Jena (Germany). Dept. of Otorhinolaryngology and Head and Neck Surgery

    2011-10-15

    To report outcome and toxicity of concurrent radiochemotherapy with carboplatin and paclitaxel in advanced squamous cell carcinomas of the oropharynx and hypopharynx. Advanced inoperable carcinomas of the oropharynx and hypopharynx were treated with either hyper-fractionated, accelerated radiotherapy (50.0 Gy/2.0 with concomitant boost to 69.2 Gy/1.6) or conventional fractionated radiotherapy (70.2-72 Gy/1.8) concurrent with paclitaxel 40 mg/m{sup 2} and carboplatin AUC 1 weekly for 6 weeks. Acute and long-term toxicity was measured according to WHO- and CTC-criteria. A total of 84 patients were included between 2000 and 2008. Median follow-up time of patients alive was 36 months. Conventionally fractionated radiotherapy was given to 16 patients, while 68 patients were treated with concomitant boost. Finally, 88.1% of patients received full dose paclitaxel. Acute mucositis {>=} grade 3 was present in 51.2% of patients, while 6% of patients experienced {>=} grade 3 leucopenia and thrombopenia. A supportive gastric feeding tube was implanted in 89.1% of patients. Overall survival after 2 years was 46.3%, progression-free survival after 2 years was 41.0%. There was no significant survival difference between the different radiotherapy protocols. Concomitant carboplatin and paclitaxel is feasible and effective in advanced carcinomas of the head and neck.

  8. Biomodulation of capecitabine by paclitaxel and carboplatin in advanced solid tumors and adenocarcinoma of unknown primary.

    Science.gov (United States)

    Mikhail, Sameh; Lustberg, Maryam B; Ruppert, Amy S; Mortazavi, Amir; Monk, Paul; Kleiber, Barbara; Villalona-Calero, Miguel; Bekaii-Saab, Tanios

    2015-11-01

    Paclitaxel and carboplatin upregulate thymidine phosphorylase and thus may provide synergistic antitumor activity in combination with capecitabine (CTX). We, therefore, performed a phase I/II study of CTX. In the phase I study, patients with advanced solid tumors received carboplatin on day 1, paclitaxel on days 1, 8, 15 and capecitabine orally twice a day on days 8-21, every 4 weeks. Phase II patients with advanced adenocarcinoma of unknown primary (ACUP) were treated at the maximal tolerable dose. The phase I study enrolled 29 patients evaluable for dose limiting toxicity. The recommended phase II dose was capecitabine 750 mg/m(2) bid, paclitaxel 60 mg/m(2)/week and carboplatin AUC of 6. There were 9 confirmed responses, 5 partial responses and disease stabilization >3 months in 14 patients. The phase II study was prematurely terminated at 25 patients due to cessation of funding. The objective response rate was 32 % (95 % CI 0.15-0.54), the median progression-free survival 5.5 months (95 % CI 2.8-10.8 months) and the median overall survival 10.8 months (95 % CI 6.0-32.0 months). CTX demonstrated acceptable tolerability and antitumor activity. At the recommended dose level in patients with ACUP, this regimen showed encouraging preliminary activity.

  9. Isoleucine and valine supplementation of crude protein-reduced diets for pigs aged 5-8 weeks

    DEFF Research Database (Denmark)

    Nørgaard, Jan Værum; Fernández, José Adalberto

    2009-01-01

    The present experiment had two purposes: (i) to study crystalline amino acid supplementation to crude protein-reduced diets, and (ii) to study the effect of different isoleucine (Ile) to lysine (Lys) and valine (Val) to Lys ratios in diets for young pigs. A total of 145 pigs were weaned at 28 days...... the PRD diet. These results indicate that Val is limiting before Ile, when reduced relative to Lys. By supplying crystalline amino acids, dietary crude protein can be reduced without negative effects on animal performance....... and fed one of 5 diets for a total of 4 weeks. Two basal diets were formulated to provide crude protein in levels either as recommended (positive reference diet, PRD), or below recommendations (negative reference diet, NRD). The basal diets contained 95% of recommended Lys, and all other essential amino...

  10. Weekly iron and folic acid supplementation as a tool to reduce anemia among primary school children in Cambodia.

    Science.gov (United States)

    Longfils, Philippe; Heang, Ung Kim; Soeng, Hay; Sinuon, Muth

    2005-12-01

    The prevalence of anemia decreased from 62% to 12% and from 57% to 26% in children 5 to 11 years of age in two rural primary schools in Kampot Province, Cambodia, after oral weekly supplementation with iron-folic acid tablets for 20 weeks and with vitamin A and mebendazole twice per year. In 12- to 15-year-old children, success was less marked. The prevalence of hookworm infestation did not change, but the number of eggs in the stool decreased drastically. The intervention had no significant influence on stunting and wasting. An integrated community approach including mass deworming, health education, and multi-micronutrient supplementation was very effective in reducing anemia in Cambodian schoolchildren and should be adopted on a larger scale.

  11. Ten weeks of physical-cognitive-mindfulness training reduces fear-avoidance beliefs about work-related activity

    DEFF Research Database (Denmark)

    Jay, Kenneth; Brandt, Mikkel; Jakobsen, Markus Due

    2016-01-01

    on physical exercise, mindfulness, and education on pain and behavior, can decrease work-related fear-avoidance beliefs.As part of a large scale 10-week worksite randomized controlled intervention trial focusing on company initiatives to combat work-related musculoskeletal pain and stress, we evaluated fear......, as assessed by the Fear-avoidance Beliefs Questionnaire, can be significantly reduced by 10 weeks of physical-cognitive-mindfulness training in female laboratory technicians with chronic pain.......People with chronic musculoskeletal pain often experience pain-related fear of movement and avoidance behavior. The Fear-Avoidance model proposes a possible mechanism at least partly explaining the development and maintenance of chronic pain. People who interpret pain during movement as being...

  12. Clinical pharmacology of carboplatin administered in combination with paclitaxel

    NARCIS (Netherlands)

    van Warmerdam, L. J.; Huizing, M. T.; Giaccone, G.; Postmus, P. E.; ten Bokkel Huinink, W. W.; van Zandwijk, N.; Koolen, M. G.; Helmerhorst, T. J.; van der Vijgh, W. J.; Veenhof, C. H.; Beijnen, J. H.

    1997-01-01

    The clinical pharmacology of carboplatin (C) administered with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (P) was investigated in two phase I studies undertaken in 83 previously untreated patients with either non-small cell lung cancer or ovarian cancer. Carboplatin was

  13. 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

  14. Survival and Toxicity After Cisplatin Plus Etoposide Versus Carboplatin Plus Etoposide for Extensive-Stage Small-Cell Lung Cancer in Elderly Patients.

    Science.gov (United States)

    Hatfield, Laura A; Huskamp, Haiden A; Lamont, Elizabeth B

    2016-07-01

    Elderly patients with cancer are under-represented in clinical trials and risk greater toxicity from chemotherapy. These patients and their physicians need better evidence to decide among guideline-recommended regimens. We test whether patients with extensive-stage small-cell lung cancer (ES SCLC) have noninferior survival and less hospital-based health care after carboplatin/etoposide compared with cisplatin/etoposide. We analyzed SEER-Medicare data for beneficiaries with ES SCLC diagnosed at age 67 years and older between 1995 and 2009. Among patients treated with first-line chemotherapy in the ambulatory setting, 831 received cisplatin/etoposide and 2,846 received carboplatin/etoposide. Propensity score matching (2:1 ratio) yielded 778 cisplatin/etoposide and 1,502 carboplatin/etoposide patients. Survival was nearly identical in the two groups: 35.7 weeks for cisplatin/etoposide and 35.9 weeks for carboplatin/etoposide. The hazard ratio of 1 (95% CI, 0.91 to 1.09) excluded our prespecified threshold, indicating noninferiority. Mortality at 6 months was indistinguishable: 35% for cisplatin/etoposide and 34% for carboplatin/etoposide. After carboplatin/etoposide, patients were less likely to be admitted to a hospital (80% v 86%, P < .001) and had fewer hospitalizations (median 1 v 2, odds ratio 0.76, 95% CI, 0.65 to 0.9), ED visits (median 1 v 2, odds ratio 0.82, 95% CI, 0.7 to 0.96), and ICU stays (median 0 v 0, odds ratio 0.82, 95% CI, 0.69 to 0.99). First-line carboplatin/etoposide is associated with similar survival and less subsequent hospital-based health care use than cisplatin/etoposide among elderly patients with ES SCLC treated in ambulatory settings. Copyright © 2016 by American Society of Clinical Oncology.

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

    Directory of Open Access Journals (Sweden)

    Go Makimoto

    2014-01-01

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

  16. Unilateral Optic Disc Papilloedema following Administration of Carboplatin Chemotherapy for Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    Philippa Lewis

    2014-01-01

    Full Text Available A 48-year-old woman with a positive BRCA1 gene mutation was diagnosed with stage 3b high-grade ovarian endometrioid carcinoma. She was treated with adjuvant carboplatin at a dose of 740 mg (AUC 6 in 3-weekly cycles. Five days after her fifth cycle of carboplatin, she awoke with new-onset blurred vision in her left eye. An ophthalmology review showed left-sided disc oedema with normal optic nerve function tests and 6/24 visual acuity. A CT scan of the head and orbits was performed which showed no evidence of metastasis or raised intracranial pressure. An autoimmune screen was performed which did not reveal any explanation for her visual symptoms. Fundus fluorescein angiography showed bilateral intense late disc leakage with no evidence of vasculitis. Her chemotherapy was stopped in view of a radiological and biochemical remission and her visual symptoms were monitored. She was also started on a tapering dose of prednisolone 40 mg daily. Five months after the initial review, she has developed left optic disc atrophy with 6/18 visual acuity, while the right eye remains asymptomatic. The diagnosis was felt to be that of carboplatin-induced unilateral disc oedema, a very rare side effect of this chemotherapy.

  17. 18F-Labeled Carboplatin Derivative for PET Imaging of Platinum Drug Distribution.

    Science.gov (United States)

    Lamichhane, Narottam; Dewkar, Gajanan K; Sundaresan, Gobalakrishnan; Wang, Li; Jose, Purnima; Otabashi, Muhammad; Morelle, Jean-Luc; Farrell, Nicholas; Zweit, Jamal

    2017-12-01

    Increasing evidence indicates that reduced intracellular drug accumulation is the parameter most consistently associated with platinum drug resistance, emphasizing the need to directly measure the intratumor drug concentration. In the era of precision medicine and with the advent of powerful imaging and proteomics technologies, there is an opportunity to better understand drug resistance by exploiting these techniques to provide new knowledge on drug-target interactions. Here, we contribute to this endeavor by reporting on the development of an 18F-labeled carboplatin derivative (18F-FCP) that has the potential to image drug uptake and retention, including intratumoral distribution, by PET. Methods: Fluorinated carboplatin (19F-FCP) was synthesized using 19F-labeled 2-(5-fluoro-pentyl)-2-methyl malonic acid (19F-FPMA) as the labeling agent to coordinate with the cisplatin-aqua complex. It was then used to treat cell lines and compared with cisplatin and carboplatin at different concentrations. Manual radiosynthesis and characterization of 18F-FCP were performed using 18F-FPMA for coordination with the cisplatin-aqua complex. Automated radiosynthesis of 18F-FCP was optimized on the basis of manual synthesis procedures. The stability of 18F-FCP was verified using high-performance liquid chromatography. 18F-FCP was evaluated using ex vivo biodistribution and in vivo PET imaging in non-tumor-bearing animals as well as in KB-3-1 and COLO-205 tumor xenograft-bearing nude mice. Results: In vitro cytotoxicity studies demonstrated that 19F-FCP has an antitumor activity profile similar to that of the parent drug carboplatin. In vivo plasma and urine stability analysis showed intact 18F-FCP at 24 h after injection. PET imaging and biodistribution studies showed fast clearance from blood and major accumulation in the kidneys, indicating substantial renal clearance of 18F-FCP. Using 18F-FCP PET, we could image and identify the intratumor drug profile. Conclusion: Our results

  18. Carboplatin +/− Topotecan Ophthalmic Artery Chemosurgery for Intraocular Retinoblastoma

    Science.gov (United States)

    Francis, Jasmine H.; Gobin, Y. Pierre; Dunkel, Ira J.; Marr, Brian P.; Brodie, Scott E.; Jonna, Gowtham; Abramson, David H.

    2013-01-01

    Purpose Carboplatin administered systemically or periocularly can result in dramatic and prompt regression of retinoblastoma. However, both routes are rarely curative alone and have undesirable side effects. We aimed to assess the efficacy and toxicity of carboplatin +/− topotecan delivered by ophthalmic artery chemosurgery whereby chemotherapy is infused into the eye via the ophthalmic artery. Methods This retrospective, IRB-approved study investigated retinoblastoma patients whom received carboplatin +/− topotecan ophthalmic artery chemosurgery. Patient survival, ocular survival, hematologic toxicity, ocular toxicity, second cancer development and electroretinogram response were all evaluated. Results 57 carboplatin +/− topotecan infusions (of 111 total) were performed in 31 eyes of 24 patients. The remaining infusions were melphalan-containing. All patients were alive and no patient developed a second malignancy at a median follow up of 25 months. The Kaplan-Meier estimate of ocular survival at two years was 89.9% (95% confidence interval [CI], 82.1–97.9%) for all eyes. Grade 3 or 4 neutropenia developed in two patients and one patient developed metastatic disease. By univariate analysis, neither increasing maximum carboplatin/topotecan dose nor cumulative carboplatin/topotecan dose was associated with statistically significant reduction in the electroretinogram responses. Conclusion Carboplatin +/− topotecan infusions are effective for ophthalmic artery chemosurgery in retinoblastoma: they demonstrate low hematologic and ocular toxicity and no statistically significant influence on electroretinogram responses, and used in conjunction with melphalan-containing OAC, demonstrate excellent patient survival and satisfactory ocular survival. PMID:23991112

  19. Carboplatin +/- topotecan ophthalmic artery chemosurgery for intraocular retinoblastoma.

    Directory of Open Access Journals (Sweden)

    Jasmine H Francis

    Full Text Available PURPOSE: Carboplatin administered systemically or periocularly can result in dramatic and prompt regression of retinoblastoma. However, both routes are rarely curative alone and have undesirable side effects. We aimed to assess the efficacy and toxicity of carboplatin +/- topotecan delivered by ophthalmic artery chemosurgery whereby chemotherapy is infused into the eye via the ophthalmic artery. METHODS: This retrospective, IRB-approved study investigated retinoblastoma patients whom received carboplatin +/- topotecan ophthalmic artery chemosurgery. Patient survival, ocular survival, hematologic toxicity, ocular toxicity, second cancer development and electroretinogram response were all evaluated. RESULTS: 57 carboplatin +/- topotecan infusions (of 111 total were performed in 31 eyes of 24 patients. The remaining infusions were melphalan-containing. All patients were alive and no patient developed a second malignancy at a median follow up of 25 months. The Kaplan-Meier estimate of ocular survival at two years was 89.9% (95% confidence interval [CI], 82.1-97.9% for all eyes. Grade 3 or 4 neutropenia developed in two patients and one patient developed metastatic disease. By univariate analysis, neither increasing maximum carboplatin/topotecan dose nor cumulative carboplatin/topotecan dose was associated with statistically significant reduction in the electroretinogram responses. CONCLUSION: Carboplatin +/- topotecan infusions are effective for ophthalmic artery chemosurgery in retinoblastoma: they demonstrate low hematologic and ocular toxicity and no statistically significant influence on electroretinogram responses, and used in conjunction with melphalan-containing OAC, demonstrate excellent patient survival and satisfactory ocular survival.

  20. Concurrent carboplatin with radiotherapy in T2 laryngeal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Hitoshi; Suzuki, Mamoru; Yoshida, Tomoyuki [Tokyo Medical Coll. (Japan); Kida, Akinori; Endo, Sohei [Nihon Univ., Tokyo (Japan). Itabashi Hospital; Furusaka, Tohru; Nakai, Takahisa [Nihon Univ., Tokyo (Japan). Surugadai Hospital

    2002-03-01

    A combination of carboplatin (CBDCA) therapy and radiotherapy was used in T2 laryngeal cancer. The subjects were 34 untreated patients with T2 laryngeal cancer, who were enrolled during the period from May 1998 to April 2000. All the patients were male, and their average age was 64.4 years. The dose of CBDCA was properly adjusted so that the AUC would be either 1.5 or 2.0. CBDCA therapy was conducted once a week for four weeks. As a rule, radiotherapy was administered at a dose of 2 Gy, with a total of 60 Gy to be given to each patient. Of the 34 patients, 29 were eligible for evaluation. Twenty-five of the 29 patients demonstrated complete response (CR) (86.2%). The larynx was preserved in 25 of these 29 patients (86.2%). The complete response rate was 81.8% in those who were placed on CBDCA therapy with an AUC of 1.5, and 88.9% in those with an AUC of 2.0. Regarding hematological toxicity, grade 3 leukocytopenia was recognized in three patients, while symptoms of thrombocytopenia severer than grade 3 were rarely observed. Accordingly, CBDCA therapy with an AUC of 2.0 reflects the optimum dose of CBDCA. The combination of CBDCA therapy and radiology is considered to be an effective treatment for T2 laryngeal cancer. (author)

  1. Six physical education lessons a week can reduce cardiovascular risk in school children aged 6-13 years

    DEFF Research Database (Denmark)

    Christensen, Heidi Klakk; Andersen, Lars B; Heidemann, Malene Søborg

    2014-01-01

    -up measures were anthropometrics, cardiorespiratory fitness, blood pressure and blood samples providing lipids and measures for insulin resistance. Based on these variables, a composite risk score was calculated and used for further analysis. Multivariate multilevel mixed effect regression models were used...... to estimate effect of intervention taking the hierarchical structure of data into account. Individual, class and school were considered random effects. Intra class correlation (ICC) was calculated. Results: Intervention significantly lowered mean of composite risk score with 0.17 SD (95% CI: -0.34 to -0.......01). Six PE lessons per week had a beneficial effect on triglycerides (TG) levels (-0.18 SD, 95% CI: -0.36 to 0.00), systolic blood pressure (SBP) (-0.22 SD, 95% CI: -0.42 to -0.02) and insulin resistance (HOMA-IR) (-0.17 SD, 95% CI: -0.34 to 0.01). Conclusions: Six PE lessons at school can reduce children...

  2. A comparison study on RNase A oligomerization induced by cisplatin, carboplatin and oxaliplatin.

    Science.gov (United States)

    Picone, Delia; Donnarumma, Federica; Ferraro, Giarita; Gotte, Giovanni; Fagagnini, Andrea; Butera, Giovanna; Donadelli, Massimo; Merlino, Antonello

    2017-08-01

    Cisplatin (CDDP) can form interprotein cross-links, leading to the formation of platinated oligomers. A dimer, a trimer and higher oligomers of bovine pancreatic ribonuclease (RNase A) obtained upon reaction with CDDP in 1:10 protein to metal ratio at 37°C have been previously characterized. Here, we verify the ability of carboplatin and oxaliplatin to induce RNase A oligomerization under the same experimental conditions. The amount of formed RNase A oligomers was compared with that obtained in the reaction of the protein with CDDP. Among the three anticancer agents, CDDP is the most reactive and the most effective in inhibiting the ribonucleolytic activity of the protein. Oxaliplatin is the least potent oligomerization agent. Biophysical characterizations of structure and stability of platinated dimers formed in the presence of carboplatin and oxaliplatin suggest that they have a similar thermal stability and are more prone to dissociation than the corresponding dimer obtained with CDDP. Oligomers obtained in the presence of carboplatin are the most active. X-ray structures of the monomeric adducts that RNase A forms with the three drugs provide a rational basis to explain the different effects of the three anticancer agents on enzymatic activity and protein aggregation. Although platinated oligomers of RNase A formed upon reaction with CDDP, carboplatin and oxaliplatin retain a residual ribonuclease activity, they do not show cytotoxic action, suggesting that protein aggregation processes induced by Pt-based drugs can represent a collateral drawback, which affects the functional state of protein targets and reduces the efficacy of Pt-based drug treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. A novel implantable catheter system with transcutaneous port for intermittent convection-enhanced delivery of carboplatin for recurrent glioblastoma.

    Science.gov (United States)

    Barua, Neil U; Hopkins, Kirsten; Woolley, Max; O'Sullivan, Stephen; Harrison, Rob; Edwards, Richard J; Bienemann, Alison S; Wyatt, Marcella J; Arshad, Azeem; Gill, Steven S

    2016-01-01

    Inadequate penetration of the blood-brain barrier (BBB) by systemically administered chemotherapies including carboplatin is implicated in their failure to improve prognosis for patients with glioblastoma. Convection-enhanced delivery (CED) of carboplatin has the potential to improve outcomes by facilitating bypass of the BBB. We report the first use of an implantable CED system incorporating a novel transcutaneous bone-anchored port (TBAP) for intermittent CED of carboplatin in a patient with recurrent glioblastoma. The CED catheter system was implanted using a robot-assisted surgical method. Catheter targeting accuracy was verified by performing intra-operative O-arm imaging. The TBAP was implanted using a skin-flap dermatome technique modeled on bone-anchored hearing aid surgery. Repeated infusions were performed by attaching a needle administration set to the TBAP. Drug distribution was monitored with serial real-time T2-weighted magnetic resonance imaging (MRI). All catheters were implanted to within 1.5 mm of their planned target. Intermittent infusions of carboplatin were performed on three consecutive days and repeated after one month without the need for further surgical intervention. Infused volumes of 27.9 ml per day were well tolerated, with the exception of a single seizure episode. Follow-up MRI at eight weeks demonstrated a significant reduction in the volume of tumor enhancement from 42.6 ml to 24.6 ml, and was associated with stability of the patient's clinical condition. Reduction in the volume of tumor enhancement indicates that intermittent CED of carboplatin has the potential to improve outcomes in glioblastoma. The novel technology described in this report make intermittent CED infusion regimes an achievable treatment strategy.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-01-15

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

  5. Carboplatin treatment of antiestrogen-resistant breast cancer cells

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Tugce Kazgan

    2016-12-01

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

  7. Quantification and clinical application of carboplatin in plasma ultrafiltrate.

    Science.gov (United States)

    Downing, Kim; Jensen, Berit Packert; Grant, Sue; Strother, Matthew; George, Peter

    2017-05-10

    Carboplatin is a chemotherapy drug used in a variety of cancers with the primary toxicity being exposure-dependant myelosuppression. We present the development and validation of a simple, robust inductively coupled plasma mass spectrometry (ICP-MS) method to measure carboplatin in plasma ultrafiltrate. Plasma ultrafiltrates samples were prepared using Amicon Ultra 30,000da cut-off filters and then diluted with ammonia EDTA before ICP-MS analysis. The assay was validated in the range 0.19-47.5mg/L carboplatin in ultrafiltrate. The assay was linear (r 2 >0.9999), accurate (plasma ultrafiltrate and aqueous platinum calibrators and recovery was complete. The assay was applied to 10 clinical samples from patients receiving carboplatin. Incurred sample reanalysis showed reproducible values over 3 analysis days (plasma stability prior to ultrafiltration has been a major concern in previous clinical studies this was studied extensively at room temperature (22°C) over 24h. Carboplatin was found to be stable in both spiked plasma (n=3) and real patient samples (n=10) at room temperature for up to 8h before ultrafiltration. This makes routine measurement of carboplatin concentrations in clinical settings feasible. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Positive performance and health effects of a football training program over 12 weeks can be maintained over a 1-year period with reduced training frequency

    DEFF Research Database (Denmark)

    Randers, Morten Bredsgaard; Nielsen, Jens Jung; Krustrup, Birgitte Rejkjær

    2010-01-01

    We examined whether improvements in the performance and health profile of an intensive 12-week football intervention could be maintained with a reduced training frequency. Seventeen healthy untrained males completed the study. Ten subjects trained 2.4 times/week for 12 weeks and another 52 weeks...... with 1.3 sessions/week [football group (FG)] and seven subjects acted as controls [control group (CG)]. For FG, fat mass (3.2 kg) and systolic blood pressure (8 mmHg) were lower (Pintermittent endurance level 2 test performance (49%) were higher...... unaltered for CG. In conclusion, positive adaptations in cardiovascular fitness obtained over 12 weeks of regular recreational football training can be maintained over a 1-year period with a reduced training frequency, with further development in musculo-skeletal fitness....

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

    Directory of Open Access Journals (Sweden)

    Derick Lau

    2009-01-01

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

  10. Pharmacokinetics of carboplatin with and without amifostine in patients with solid tumors

    NARCIS (Netherlands)

    Korst, A.E.C.; Sterre, M.L.T. van der; Eeltink, C.M.; Fichtinger-Schepman, A.M.J.; Vermorken, J.B.; Vijgh, W.J.F. van der

    1997-01-01

    We showed previously that amifostine (WR 2721; Ethyol), a protector against carboplatin-induced toxicities, changed the pharmacokinetics of carboplatin in tumor-bearing nude mice. In the present study, the influence of amifostine on the pharmacokinetics of carboplatin was studied in patients when

  11. Reduced wave amplitudes of brainstem auditory response in high-risk babies born at 28-32week gestation.

    Science.gov (United States)

    Jiang, Ze Dong; Ping, Li Li

    2016-11-01

    To examine brainstem auditory electrophysiology in high-risk babies born at 28-32week gestation by analysing the amplitudes of wave components in maximum length sequence brainstem auditory evoked response (MLS BAER). 94 preterm babies, ranging in gestation 28-32weeks, with perinatal problems (high-risk) were recruited. The amplitudes of MLS BAER wave components were studied at term age (37-42weeks postconceptional age). Compared with normal term controls, the amplitude in the high-risk preterm babies was significantly smaller at the highest click rate 910/s for wave I (pauditory neuron in such babies is depressed, mainly attributed to or related to the associated perinatal problems. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  12. Long-term Smoking Mediated Down-regulation of Smad3 Induces Resistance to Carboplatin in Non-Small Cell Lung Cancer12

    Science.gov (United States)

    Samanta, Debangshu; Kaufman, Jacob; Carbone, David P; Datta, Pran K

    2012-01-01

    While numerous cell signaling pathways are known to play decisive roles in chemotherapeutic response, relatively little is known about the impact of the Smad-dependent transforming growth factor β pathway on the therapeutic outcome. Previous reports suggested that patients with lung cancer who continue to smoke while receiving chemotherapy have a poorer outcome than their nonsmoking counterparts do. In our previous study, we showed that long-term cigarette smoke condensate (CSC)-mediated down-regulation of Smad3 induces tumorigenesis. The objective of this study was to determine the mechanism of function of Smad3 in chemoresistance induced by CSC in human lung cell lines, namely, A549 and HPL1A. Long-term CSC treatment increases the half-maximal inhibitory concentration (IC50) of carboplatin and makes cells resistant to carboplatin. The increase in IC50 of long-term CSC-treated cells is due to the reduced induction in apoptosis by carboplatin. The increase in IC50 and decrease in apoptosis in long-term CSC-treated cells is correlated with the expression of Bcl2. We have determined that Bcl2 is both necessary and sufficient to make the cells resistant to carboplatin. We have also shown that Smad3 acts upstream to regulate the expression of Bcl2 specifically and, thus, sensitivity of the cells to carboplatin. This is supported by the inverse correlation between the expressions of Smad3 and Bcl2 in human lung tumors. Collectively, these data suggest that loss of Smad3 expression in CSC-treated cells induces resistance to carboplatin by upregulating the expression of Bcl2. This study explains, at least in part, the higher chemoresistance rate observed in smokers. PMID:22904681

  13. Ten weeks of physical-cognitive-mindfulness training reduces fear-avoidance beliefs about work-related activity

    DEFF Research Database (Denmark)

    Jay, Kenneth; Brandt, Mikkel; Jakobsen, Markus Due

    2016-01-01

    on physical exercise, mindfulness, and education on pain and behavior, can decrease work-related fear-avoidance beliefs.As part of a large scale 10-week worksite randomized controlled intervention trial focusing on company initiatives to combat work-related musculoskeletal pain and stress, we evaluated fear......-avoidance behavior in 112 female laboratory technicians with chronic neck, shoulder, upper back, lower back, elbow, and hand/wrist pain using the Fear-Avoidance Beliefs Questionnaire at baseline, before group allocation, and again at the post intervention follow-up 10 weeks later.A significant group by time......People with chronic musculoskeletal pain often experience pain-related fear of movement and avoidance behavior. The Fear-Avoidance model proposes a possible mechanism at least partly explaining the development and maintenance of chronic pain. People who interpret pain during movement as being...

  14. Preclinical Assessment of Carboplatin Treatment Efficacy in Lung Cancer by 18F-ICMT-11-Positron Emission Tomography

    Science.gov (United States)

    Witney, Timothy H.; Fortt, Robin R.; Aboagye, Eric O.

    2014-01-01

    Tumour response to therapy is assessed primarily in the clinic by monitoring reductions in tumour size. However, this approach lacks sensitivity since in many cases several weeks may elapse before there is evidence of tumour shrinkage. There is therefore a need to develop non-invasive imaging techniques for monitoring tumour treatment response in the clinic. Here, we assessed the pre-clinical utility of 18F-ICMT-11 positron emission tomography - a method for detecting caspase 3/7 activation - in non-small cell lung cancer (NSCLC). 18F-ICMT-11 uptake was compared to molecular biochemical measures of cell death in PC9 and A549 NSCLC cells following treatment with carboplatin in vitro and in vivo. Carboplatin-induced apoptosis in the ERCC1 low/mutant EGFR PC9 cells was characterised by time and dose-related increased caspase-3/7 activation, poly-ADP-ribose polymerase cleavage and Annexin V staining. 18F-ICMT-11 uptake was consequently increased up to 14-fold at 200 µM carboplatin compared to vehicle treated cells (Pcarboplatin therapy. Average PET-derived tumour 18F-ICMT-11 uptake was insensitive to changes in apoptosis in the presence of substantial pre-existing necrosis. PET-based voxel intensity sorting however, identified intra-tumoural regions of high 18F-ICMT-11 uptake, enabling accurate assessment of apoptosis and therefore therapy response. In A549 tumours that lacked high pre-therapy necrosis, carboplatin induced growth inhibition that was only minimally associated with apoptosis and thus not detectable by 18F-ICMT-11 PET. PMID:24618809

  15. Phase I study of flavopiridol in combination with Paclitaxel and Carboplatin in patients with non-small-cell lung cancer.

    Science.gov (United States)

    George, Saby; Kasimis, Basil S; Cogswell, Janet; Schwarzenberger, Paul; Shapiro, Geoffrey I; Fidias, Panos; Bukowski, Ronald M

    2008-05-01

    The aim of this study was to evaluate the safety and tolerability of escalating doses of flavopiridol/ paclitaxel/carboplatin in patients with advanced-stage non-small-cell lung cancer (NSCLC) as well as the pharmacokinetics and activity of flavopiridol when used in combination with paclitaxel/carboplatin. Eligible patients aged 18-75 years with previously untreated stage IIIB/IV NSCLC received paclitaxel 175 mg/m2 over 3 hours followed by carboplatin area under the curve (AUC) 5 over 1 hour and flavopiridol 30-85 mg/m2 over 24 hours every 3 weeks for 3 cycles. Eighteen patients were enrolled at 4 sites in the United States and received flavopiridol 30 mg/m2 (n = 3), 50 mg/m2 (n = 6), 70 mg/m2 (n = 3), or 85 mg/m2 (n = 6). No dose-limiting toxicities (DLTs) occurred at the 50-mg/m2 or 70-mg/m2 dose levels. Two patients treated at the 85-mg/m2 dose level experienced cardiovascular events that did not meet the criteria for DLT but were fatal in 1 case, prompting no further flavopiridol dose escalations and establishment of 70 mg/m2 as the maximum tolerated dose. The most frequently reported adverse events across all dose levels combined were nausea (89%), asthenia (67%), and diarrhea (56%). Flavopiridol concentrations increased rapidly, reached a plateau, and showed a multiphasic decline after the 24-hour infusion. Of 12 patients evaluable for efficacy, 8 achieved a partial response, and 4 had stable disease. Flavopiridol in doses carboplatin AUC 5.

  16. Feasibility of adjuvant chemotherapy with S-1 plus carboplatin followed by single-agent maintenance therapy with S-1 for completely resected non-small-cell lung cancer: results of the Setouchi Lung Cancer Group Study 1001.

    Science.gov (United States)

    Okumura, Norihito; Sonobe, Makoto; Okabe, Kazunori; Nakamura, Hiroshige; Kataoka, Masafumi; Yamashita, Motohiro; Nakata, Masao; Kataoka, Kazuhiko; Yamashita, Yoshinori; Soh, Junichi; Yoshioka, Hiroshige; Hotta, Katsuyuki; Matsuo, Keitaro; Sakamoto, Junichi; Toyooka, Shinichi; Date, Hiroshi

    2017-04-01

    This multicenter study evaluated the feasibility of novel adjuvant chemotherapy with S-1 plus carboplatin followed by single-agent, long-term maintenance with S-1 in patients with completely resected stage II-IIIA non-small-cell lung cancer (NSCLC). Patients received four cycles of S-1 (80 mg/m2/day for 2 weeks, followed by 2 weeks rest) plus carboplatin (area under the curve 5, day 1) followed by S-1 (80 mg/m2/day for 2 weeks, followed by a 1-week rest). Patients unable to continue S-1 plus carboplatin because of severe toxicity converted to single-agent S-1 maintenance. The duration of adjuvant chemotherapy was 10 months in both situations. The primary endpoint was feasibility, defined as the proportion of patients who completed four cycles of S-1 plus carboplatin and single-agent S-1 maintenance for 10 months. The treatment completion rate was determined; treatment was considered feasible if the lower 90% confidence interval (CI) was ≥50%. Eighty-nine patients were enrolled, of whom 87 were eligible and assessable. Seventy-eight patients (89.7%) completed four cycles of S-1 plus carboplatin and 55 (63.2%) completed the following S-1 maintenance therapy for a total of 10 months. The treatment completion rate was 63.2% (90% CI, 54.4-71.2%), indicating feasibility. There were no treatment-related deaths. Grade 3/4 toxicities included neutropenia (13.8%), thrombocytopenia (11.5%), and anorexia (4.6%). The 2-year relapse-free survival rate was 59.8%. We concluded that adjuvant chemotherapy with S-1 plus carboplatin followed by single-agent maintenance therapy with S-1 is feasible and tolerable in patients with completely resected NSCLC. UMIN000005041.

  17. Safety and efficacy of concurrent carboplatin plus radiotherapy for locally advanced head and neck cancer patients ineligible for treatment with cisplatin.

    Science.gov (United States)

    Hamauchi, Satoshi; Yokota, Tomoya; Onozawa, Yusuke; Ogawa, Hirofumi; Onoe, Tsuyoshi; Kamijo, Tomoyuki; Iida, Yoshiyuki; Nishimura, Tetsuo; Onitsuka, Tetsuro; Yasui, Hirofumi

    2015-12-01

    Cisplatin-based chemoradiotherapy is the standard treatment for patients with locally advanced squamous cell carcinoma of the head and neck. However, patients with advanced age, renal, cardiac or neurogenic dysfunction seem ineligible for cisplatin treatment. We evaluated the safety and efficacy of concurrent carboplatin plus radiotherapy in patients ineligible for cisplatin usage. We retrospectively analyzed the records of 25 consecutive locally advanced squamous cell carcinoma of the head and neck patients who received concurrent carboplatin plus radiotherapy at Shizuoka Cancer Center between August 2006 and March 2014. Carboplatin was administered tri-weekly or weekly. Patient characteristics were analyzed. The median age was 75 years (range, 54-82), male:female ratio, 24:1; performance status, 0-1 (23) or 2 (2); primary tumor site, oropharynx (10), hypopharynx (12), larynx (1) or oral cavity (2); Stage III (3), IVa (19) or IVb (3); induction chemotherapy, with (2) or without (23); and a median creatinine clearance of 62 ml/min (range, 37-117). The main reasons for choosing carboplatin were age (40%), renal impairment (36%) and cardiac dysfunction (20%). All patients received a planned irradiation dose of 70 Gy. Median follow-up was 30.9 months. Complete response was observed 70% patients. Median progression-free survival duration was 42.7 months. Median overall survival could not be analyzed. The 2-year progression-free and overall survival rates were 68 and 74%, respectively. The main toxicity Grade 3 or 4 was oral mucositis (56%), thrombocytopenia (34%), neutropenia (28%) and infection (24%). Concurrent carboplatin plus radiotherapy is tolerated and may be an option in treating locally advanced squamous cell carcinoma of the head and neck patients ineligible for treatment with cisplatin. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Safety and efficacy of carboplatin plus nab-paclitaxel for treating advanced non-small-cell lung cancer with interstitial lung disease.

    Science.gov (United States)

    Niwa, Hideyuki; Nakahara, Yoshiro; Yokoba, Masanori; Mitsufuji, Hisashi; Sasaki, Jiichiro; Masuda, Noriyuki

    2017-10-01

    There are few established treatments for patients with non-small-cell lung cancer (NSCLC) with interstitial lung disease (ILD). The safety and efficacy of albumin-bound paclitaxel (nab-paclitaxel) in combination with carboplatin is uncertain, although the combination of carboplatin and paclitaxel is the most common regimen for treating NSCLC patients with ILD. A total of 9 NSCLC patients with ILD, treated between April 2013 and March 2016, were retrospectively investigated. Carboplatin (AUC 5-6) was administered on day 1 and nab-paclitaxel on days 1, 8 and 15, every 4-6 weeks. The median age of the patients upon initiating chemotherapy was 67 years. The pathological examination revealed 6 patients with squamous cell carcinoma, and 6 patients exhibited the typical pattern of ILD. The response rate was 55.6%, and the median progression-free and overall survival time was 174 and 344 days, respectively. Acute exacerbation of ILD was not observed in any of the patients, and febrile neutropenia developed in 3 patients (3/9, 33.3%). Thus, treatment with carboplatin plus nab-paclitaxel was found to be safe and effective for NSCLC patients with ILD, although management of hematological adverse events, such as febrile neutropenia, was required. However, these encouraging results require confirmation by a large-scale clinical trial.

  19. Efficacy of carboplatin alone and in combination with ABT888 in intracranial murine models of BRCA-mutated and BRCA-wild-type triple negative breast cancer

    Science.gov (United States)

    Karginova, Olga; Siegel, Marni B.; Van Swearingen, Amanda E. D.; Deal, Allison M.; Adamo, Barbara; Sambade, Maria J.; Bazyar, Soha; Nikolaishvili-Feinberg, Nana; Bash, Ryan; O’Neal, Sara; Sandison, Katie; Parker, Joel S.; Santos, Charlene; Darr, David; Zamboni, William; Lee, Yueh Z.; Miller, C. Ryan; Anders, Carey K.

    2015-01-01

    Patients with breast cancer brain metastases have extremely limited survival and no approved systemic therapeutics. Triple negative breast cancer (TNBC) commonly metastasizes to the brain and predicts poor prognosis. TNBC frequently harbors BRCA mutations translating to platinum sensitivity potentially augmented by additional suppression of DNA repair mechanisms through poly(ADP-ribose)polymerase (PARP) inhibition. We evaluated brain penetrance and efficacy of Carboplatin +/− the PARP inhibitor ABT888, and investigated gene expression changes in murine intracranial (IC) TNBC models stratified by BRCA and molecular subtype status. Athymic mice were inoculated intra-cerebrally with BRCA-mutant: SUM149 (basal), MDA-MB-436 (claudin-low), or BRCA-wild-type: MDA-MB-468 (basal), MDA-MB-231BR (claudin-low) TNBC cells and treated with PBS control (IP, weekly), Carboplatin (50mg/kg/week, IP), ABT888 (25mg/kg/day, OG), or their combination. DNA-damage (γ-H2AX), apoptosis (cleaved-Caspase-3(cC3)) and gene expression were measured in IC tumors. Carboplatin+/−ABT888 significantly improved survival in BRCA-mutant IC models compared to control, but did not improve survival in BRCA-wild-type IC models. Carboplatin+ABT888 revealed a modest survival advantage versus Carboplatin in BRCA-mutant models. ABT888 yielded a marginal survival benefit in the MDA-MB-436, but not in the SUM149 model. BRCA-mutant SUM149 expression of γ-H2AX and cC3 proteins was elevated in all treatment groups compared to Control, while BRCA-wild-type MDA-MB-468 cC3 expression did not increase with treatment. Carboplatin treatment induced common gene expression changes in BRCA-mutant models. Carboplatin+/−ABT888 penetrates the brain and improves survival in BRCA-mutant IC TNBC models with corresponding DNA damage and gene expression changes. Combination therapy represents a potential promising treatment strategy for patients with TNBC brain metastases warranting further clinical investigation. PMID

  20. Twelve weeks of nightly stretch does not reduce thumb web-space contractures in people with a neurological condition: a randomised controlled trial.

    Science.gov (United States)

    Harvey, Lisa; de Jong, Inge; Goehl, Gerlinde; Mardwedel, Samantha

    2006-01-01

    What is the effectiveness of 12 weeks of nightly stretch in reducing thumb web-space contracture in people with neurological conditions? Assessor-blinded, randomised controlled trial. Forty-four (one dropout)community-dwelling patients with a neurological condition (14 stroke, 7 traumatic brain injury, 23 spinal cord injury) who had uni or bilateral thumb web-space contractures (60 thumbs). The experimental thumbs were splinted into a stretched,abducted position each night for 12 weeks. The control thumbs were not splinted. Thumb web-space was measured as the carpometacarpal angle during the application of a 0.9 Nm abduction torque before and after intervention. The mean increase in thumb web-space after 12 weeks was 1 deg (95% CI, -1 to 2). Intensive stretch administered regularly over three months does not reduce thumb web-space contractures in neurological conditions.

  1. Hyperthermic isolated regional perfusion of the limb with carboplatin

    NARCIS (Netherlands)

    Daryanani, D; de Vries, EGE; Guchelaar, HJ; van Weerden, TW; Hoekstra, HJ

    2000-01-01

    Aims: To investigate the feasibility of hyperthermic isolated regional perfusion (HIRP) with carboplatin in the management of locally recurrent and/or intransit metastases of melanoma or locally advanced soft tissue sarcoma. Methods: Three patients, two with locally advanced melanoma and one with a

  2. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma.

    Science.gov (United States)

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

    2009-09-03

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

  3. A phase II trial of thymidine and carboplatin for recurrent malignant glioma: a North American Brain Tumor Consortium Study.

    Science.gov (United States)

    Robins, H. Ian; Chang, Susan M.; Prados, Michael D.; Yung, W. K. Alfred; Hess, Kenneth; Schiff, David; Greenberg, Harry; Fink, Karen; Nicolas, Kelly; Kuhn, John G.; Cloughesy, Timothy; Junck, Larry; Mehta, Minesh

    2002-01-01

    This phase II study in recurrent high-grade glioma evaluated the response rate, toxicities, and time to treatment failure of high-dose carboplatin modulated by a 24-h infusion of thymidine (75 g/m(2)). The trial was based on preclinical data and a prior phase I study ( J. Clin. Oncol. 17, 2922-2931, 1999); a phase II recurrent high-grade glioma study was initiated in July of 1998. Thymidine was given over 24 h; carboplatin was given over 20 min at hour 20 of the thymidine infusion. The starting dose of carboplatin had a value of 7 for the area under the curve (AUC), with allowance for dose escalation of 1 AUC unit per cycle if grade 2 toxicity was observed. Treatment cycles were repeated every 4 weeks. Accrual as of September 1999 was 45 patients [4 were unevaluable]: 76% with glioblastoma multiforme (GBM), 20% with anaplastic oligodendroglioma, 2% with mixed type, and 2% with anaplastic astrocytoma. Most patients had prior chemotherapy (78%). As observed in the earlier phase I study (in which carboplatin pharmacokinetics were unaltered by thymidine or antiseizure medications), thymidine was myeloprotective, resulting in a minimal need for dose reduction for patients having a >2 grade toxicity (in only 4% of the courses of treatment). Of 101 total courses, the number of courses (at the AUCs) was 3 (5), 4 (6), 58 (7), 20 (8), 11 (9), and 5 (10). Grade 3 nonhematologic toxicities included headache (4%), altered consciousness (3%), fatigue (1%), and nausea (3%). Responses included 2 partial (1 oligodendroglioma, 1 GBM; 5%); 3 minor (1 anaplastic astrocytoma, 2 GBM; 7.3%); 6 stable disease (14.6%); and 30 progressive disease (73.2%). For GBM patients, median survival was 23 weeks (with a 95% confidence interval of 20 to 50 weeks), and progression-free survival was 8 weeks (with a 95% confidence interval of 7-16 weeks). These results in GBM were comparable to other phase II GBM trials and thus do not represent a therapeutic advance in the treatment of GBM. Taken

  4. Increased serum triglycerides and reduced HDL cholesterol in male rats after intake of ammonium chloride for 3 weeks

    Science.gov (United States)

    2013-01-01

    Background Previous data suggested that intake of sodas and other acid beverages might be associated with increased levels of serum triglycerides, lowered HDL cholesterol, and increased formation of mono unsaturated fatty acids, which are the preferred ones for triglyceride synthesis. The present work is an extension of these studies. Methods Thirty male rats were divided into 3 groups. All groups were given the same food, but various beverages: water (W), ammonium chloride, 200 mmol/L (AC), or sodium bicarbonate, 200 mmol/L (SB). Serum triglycerides, HDL cholesterol, and the fatty acid distribution in total serum lipids were determined. Delta9-desaturase in serum lipids was estimated by the ratio of palmitoleic to palmitic acid, and by the oleic/stearic acid ratio. Correlation and ANOVA were used to study associations and group differences. Results After 3 weeks, the AC group had higher triglyceride concentration and higher Delta9 desaturase indexes, but lower serum HDL and body weight as compared with the SB and W groups. In each of the groups, the oleic acid/stearic acid ratio correlated positively with serum triglycerides; in the pooled group the correlation coefficient was r = 0.963, ptriglycerides, and lowered HDL cholesterol concentration, thereby possibly contributing to explain the increased triglyceride concentration previously observed in subjects with a frequent intake of acid beverages, such as sodas containing carbonic acid, citric acid, and phosphoric acid. PMID:23800210

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

    Directory of Open Access Journals (Sweden)

    Bikul Das

    2008-10-01

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

  6. A short 2 week dose titration regimen reduces the severity of flu-like symptoms with initial interferon gamma-1b treatment.

    Science.gov (United States)

    Devane, John G; Martin, Mary L; Matson, Mark A

    2014-06-01

    during week 1 treatment, indicating an early peak in FLS severity during the No Titration treatment and subsequent development of tolerance. In contrast, titration results in near baseline severity scores throughout the treatment period. Similar trends were seen for 4 and 12 hour FLS severity scores. Of the individual FLS, difference in fever severity was most marked. Safety profiles for both regimens were consistent with the approved prescribing information for interferon gamma-1b. Study limitations included the use of healthy subjects rather than disease subjects, the lack of a validated assessment tool for evaluating FLS and the relatively high discontinuation rate. A short 2 week, dose-titration regimen reduces FLS severity following interferon gamma-1b treatment initiation in normal subjects.

  7. Efficacy of a combined in-office/home-use desensitizing system containing 8% arginine and calcium carbonate in reducing dentin hypersensitivity: an 8-week randomized clinical study.

    Science.gov (United States)

    França, Isabela Lima; Sallum, Enilson Antonio; Do Vale, Hugo Felipe; Casati, Márcio Zaffalon; Sallum, Antonio Wilson; Stewart, Bernal

    2015-02-01

    To determine the efficacy in reducing dentin hypersensitivity (DHS) of a combined in-office and home-use desensitizing system, each product containing 8% arginine and calcium carbonate (Test), following a dental scaling procedure, compared to the combination of a conventional prophylactic paste and a potassium nitrate dentifrice (Control), in a group of patients with known dentin hypersensitivity. An 8-week clinical study, with 50 subjects, was conducted in Piracicaba, São Paulo, Brazil, using a double-blind/two treatment design. Air blast sensitivity assessments were used to compare the efficacy of the two approaches using both the Schiff scale as well as a Visual Analogue Scale (VAS). Immediately after prophylaxis, the Test treatment provided significant reduction in DHS when compared to baseline values (VAS = 26.2% and Schiff = 29.1%), while for Control treatment this difference was not statistically significant (VAS = 8.1% and Schiff = 6.6%). The comparison between groups after prophylaxis showed a greater DHS reduction for the Test treatment (P < 0.05). The reductions in DHS after 2, 4 and 8 weeks were significant for both groups, however, when considering Schiff scale, the Test treatment provided greater DHS reduction after 2 weeks (44.5% for Test versus 27.7% for Control) and 4 weeks (55.2% for Test and 40.5% for Control), while after 8 weeks there was no significant difference between groups (71.1% for Test versus 61.1% for Control).

  8. Gemcitabine causes minimal modulation of carboplatin-DNA monoadduct formation and repair in bladder cancer cells

    OpenAIRE

    Wang, Sisi; Zhang, Hongyong; Malfatti, Michael; de Vere White, Ralph; Lara, Primo N.; Turteltaub, Kenneth; Henderson, Paul; Pan, Chong-xian

    2010-01-01

    We are developing a method to identify cellular resistance to carboplatin by using accelerator mass spectrometry to measure carboplatin-DNA adducts formed from drug microdoses (~1/100th the therapeutic dose). Such an approach would be particularly useful if it is still valid in combination chemotherapy. We examined whether the addition of gemcitabine, another chemotherapeutic drug, could influence carboplatin-DNA adduct levels. There were no substantial differences in the levels of carboplati...

  9. P56CONVECTION-ENHANCED DELIVERY (CED) OF CARBOPLATIN NANOSPHERES FOR THE TREATMENT OF GLIOBLASTOMA

    OpenAIRE

    Arshad, Azeem; Yang, Bin; Bienemann, Ali; Barua, Neil; Gill, Steve

    2014-01-01

    INTRODUCTION: We are currently investigating CED of the platinum-based drug, carboplatin as a novel treatment strategy for high grade glioma in adults and children. Although initial results show significant promise, our current treatment strategy requires intermittent infusions due to rapid clearance of carboplatin from the brain. Furthermore, carboplatin is not specifically toxic to tumour cells and has been associated with neurotoxicity at high infused concentrations. We sought to encapsula...

  10. Quality of life, geriatric assessment and survival in elderly patients with non-small-cell lung cancer treated with carboplatin-gemcitabine or carboplatin-paclitaxel: NVALT-3 a phase III study.

    Science.gov (United States)

    Biesma, B; Wymenga, A N M; Vincent, A; Dalesio, O; Smit, H J M; Stigt, J A; Smit, E F; van Felius, C L; van Putten, J W G; Slaets, J P J; Groen, H J M

    2011-07-01

    Elderly patients with advanced non-small-cell lung cancer (NSCLC) may derive similar benefit from platinum-based chemotherapy as younger patients. Quality of life (QoL) and comprehensive geriatric assessment (CGA) is often advocated to assess benefits and risks. A total of 181 chemotherapy-naive patients [≥70 years, performance score (PS) of 0-2] with stage III-IV NSCLC received carboplatin and gemcitabine (CG) (n = 90) or carboplatin and paclitaxel (CP) (n = 91) every 3 weeks for up to four cycles. Primary end point was change in global QoL from baseline compared with week 18. Pretreatment CGA and mini geriatric assessment during and after treatment were undertaken. A principal component (PC) analysis was carried out to determine the underlying dimensions of CGA and QoL and subsequently related to survival. There were no changes in QoL after treatment. The number of QoL responders (CG arm, 12%; CP arm, 5%) was not significantly different. CGA items were only associated with neuropsychiatric toxicity. Quality-adjusted survival was not different between treatment arms. The PC analysis derived from nine CGA, six QoL and one PS score indicated only one dominant dimension. This dimension was strongly prognostic, and physical and role functioning, Groningen Frailty Indicator and Geriatric Depression Scale were its largest contributors. Paclitaxel or gemcitabine added to carboplatin did not have a differential effect on global QoL. CGA was associated with toxic effects in a very limited manner. CGA and QoL items measure one underlying dimension, which is highly prognostic.

  11. Deleterious BRCA1/2 mutation is an independent risk factor for carboplatin hypersensitivity reactions

    Science.gov (United States)

    Moon, D H; Lee, J-M; Noonan, A M; Annunziata, C M; Minasian, L; Houston, N; Hays, J L; Kohn, E C

    2013-01-01

    Background: We tested the hypothesis that BRCA1/2 mutation carriers with ovarian cancer are at higher risk of carboplatin hypersensitivity reactions (HSRs). Methods: Medical records of women enrolled in two carboplatin+olaparib clinical trials (NCT01237067/NCT01445418) were reviewed. A maximum of eight cycles containing carboplatin were administered. Results: All women (N=87) had good performance status and end-organ function. Incidences of carboplatin HSR before enrolment and on study were 17% and 21%, respectively. Most patients who developed carboplatin HSR had a deleterious BRCA1/2 mutation (93%) vs 50% in patients without HSR (Pcarboplatin cycles confirmed deleterious BRCA1/2 mutation as an independent risk factor for carboplatin HSR (odds ratio 13.1 (95% confidence interval 2.6–65.4), P=0.0017). Mutation carriers had onset of carboplatin HSR at lower cumulative exposure (P=0.003). No significant difference in outcome was observed on our study between patients with and without a history of HSR. Conclusion: Deleterious BRCA1/2 mutation increased susceptibility and shortened time to carboplatin HSR, independently of other reported factors. These data suggest that at-risk women should be counselled regarding likelihood, symptoms, and potential earlier onset of carboplatin HSRs. PMID:23867999

  12. Phase 2 trial of neoadjuvant bevacizumab plus pemetrexed and carboplatin in patients with unresectable stage III lung adenocarcinoma (GASTO 1001).

    Science.gov (United States)

    Ou, Wei; Li, Ning; Wang, Si-Yu; Li, Jian; Liu, Qian-Wen; Huang, Qun-Ai; Wang, Bao-Xiao

    2016-03-01

    The objective of this phase 2 trial was to assess the efficacy and safety of induction bevacizumab plus chemotherapy followed by surgery in patients with unresectable stage III lung adenocarcinoma. The authors investigated induction bevacizumab (7.5 mg/kg) plus pemetrexed (500 mg/m(2) and carboplatin (area under the receiver operating characteristic curve = 5) followed by surgery for patients with unresectable stage III lung adenocarcinoma ages 18 to 65 years. The patients received neoadjuvant therapy every 3 weeks for 4 cycles. Surgery was scheduled 3 to 4 weeks after the last neoadjuvant therapy; then, the medical team assessed each patient's resectability status. The primary endpoint was the resectability rate. From April 2012 to April 2014, 42 patients were enrolled and received bevacizumab plus pemetrexed and carboplatin. Grade 3 or 4 induction-related AEs included fatigue in 5 patients, neutropenia in 4 patients, hypertension in 1 patient, anemia in 1 patient, and thrombocytopenia in 1 patient. One patient achieved a complete response, 22 achieved a partial response, 17 had stable disease, and 2 had progressive disease. After neoadjuvant therapy, 31 patients (73.8%) underwent surgery, including 11 who underwent pneumonectomy. Complete (R0) resection was achieved in 22 patients (52.4%). Reoperation was required in 1 patient because of a bleeding intercostal artery. No perioperative thromboembolic events or wound-healing problems were observed. The median event-free survival was 15.4 months, and the 1-year event-free survival rate was 56.1%. Treatment with neoadjuvant bevacizumab in combination with pemetrexed and carboplatin followed by surgery appears to be feasible and safe in patients with unresectable stage III lung adenocarcinoma. Cancer 2016;122:740-747. © 2015 American Cancer Society. © 2015 American Cancer Society.

  13. A phase I study of bortezomib, etoposide and carboplatin in patients with advanced solid tumors refractory to standard therapy

    NARCIS (Netherlands)

    Lieu, Christopher; Chow, Laura; Pierson, A. Scott; Eckhardt, S. Gail; O'Bryant, Cindy L.; Morrow, Mark; Tran, Zung Vu; Wright, John J.; Gore, Lia

    Purpose: To evaluate the toxicity, pharmacological, and biological properties of the combination of bortezomib, etoposide, and carboplatin in adults with advanced solid malignancies. Patients and methods: Patients received escalating doses of bortezomib, etoposide, and carboplatin every 21 days.

  14. Streaming weekly soap opera video episodes to smartphones in a randomized controlled trial to reduce HIV risk in young urban African American/black women.

    Science.gov (United States)

    Jones, Rachel; Lacroix, Lorraine J

    2012-07-01

    Love, Sex, and Choices is a 12-episode soap opera video series created as an intervention to reduce HIV sex risk. The effect on women's HIV risk behavior was evaluated in a randomized controlled trial in 238 high risk, predominately African American young adult women in the urban Northeast. To facilitate on-demand access and privacy, the episodes were streamed to study-provided smartphones. Here, we discuss the development of a mobile platform to deliver the 12-weekly video episodes or weekly HIV risk reduction written messages to smartphones, including; the technical requirements, development, and evaluation. Popularity of the smartphone and use of the Internet for multimedia offer a new channel to address health disparities in traditionally underserved populations. This is the first study to report on streaming a serialized video-based intervention to a smartphone. The approach described here may provide useful insights in assessing advantages and disadvantages of smartphones to implement a video-based intervention.

  15. Self-rating level of perceived exertion for guiding exercise intensity during a 12-week cardiac rehabilitation programme and the influence of heart rate reducing medication

    DEFF Research Database (Denmark)

    Tang, Lars; Zwisler, Ann-Dorthe; Taylor, Rod S.

    2016-01-01

    OBJECTIVES: To investigate whether self-rating level of perceived exertion can adequately guide exercise intensity during a 12-week cardiac rehabilitation programme. DESIGN: Linear regression analysis using rehabilitation data from two randomised controlled trials. METHODS: Patients undergoing ra......-led and self-regulated model using rating of perceived exertion can help guide exercise intensity in everyday clinical practice among patients with heart disease, irrespective if they are taking heart rate-reducing medication.......OBJECTIVES: To investigate whether self-rating level of perceived exertion can adequately guide exercise intensity during a 12-week cardiac rehabilitation programme. DESIGN: Linear regression analysis using rehabilitation data from two randomised controlled trials. METHODS: Patients undergoing...

  16. Carboplatin: molecular mechanisms of action associated with chemoresistance

    Directory of Open Access Journals (Sweden)

    Graziele Fonseca de Sousa

    2014-12-01

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

  17. Carboplatin-induced severe hypersensitivity reaction: Role of IgE-dependent basophil activation and FcεRI

    OpenAIRE

    Iwamoto, Takuya; Hirai, Hiroyuki; Yamaguchi, Nozomi; Kobayashi, Natsuki; Sugimoto, Hiroko; Tabata, Tsutomu; Okuda, Masahiro

    2014-01-01

    Basophil activation was observed in patients with a history of carboplatin-induced severe hypersensitivity reaction (HR). However, the precise mechanism by which carboplatin induces basophil activation and the associated surrogate markers remains to be elucidated. To investigate whether IgE-dependent mechanisms, including the overexpression of FcεRI, participate in carboplatin-induced basophil activation, 13 ovarian cancer patients were enrolled: 5 with a history of carboplatin-induced severe...

  18. A four-week clinical study to evaluate and compare the effectiveness of a baking soda dentifrice and an antimicrobial dentifrice in reducing plaque.

    Science.gov (United States)

    Ghassemi, Annahita; Vorwerk, Linda M; Hooper, William J; Putt, Mark S; Milleman, Kimberly R

    2008-01-01

    To evaluate and compare the effectiveness in reducing plaque of a fluoride dentifrice containing baking soda and a non-baking soda fluoride dentifrice containing an antimicrobial (triclosan/copolymer) system after a single brushing and over a four-week period of daily brushing. A total of 207 subjects completed this randomized, blinded, parallel-group clinical study. Twenty-four hour plaque buildup was scored at baseline and after two and four weeks of twice-daily use of the products. Additionally, controlled single brushing with the assigned dentifrice, followed by post-brushing plaque assessment, was performed at the start (baseline visit) and end (Week-4 visit) of the study. Plaque was scored using the Turesky, et al. modification of Quigley-Hein Index at six sites per tooth, according to Soparkar's modification. Mean baseline whole mouth plaque scores for the baking soda and triclosan dentifrice groups were 2.90 +/- 0.40 and 2.90 +/- 0.39, respectively, and the difference was not statistically significant. Within-group analysis showed that both products significantly reduced the amount of plaque over the four-week period (p baking soda dentifrice exhibited significantly greater reduction in plaque scores (p baking soda dentifrice group (0.34 +/- 0.32) was 2.22-fold greater than that observed for the triclosan dentifrice group (0.15 +/- 0.24). Similarly, single brushing with the baking soda dentifrice showed a 1.88- to 2.08-fold greater pre- to post-brushing plaque difference as compared to the triclosan dentifrice at the baseline visit (mean plaque reduction: baking soda 0.54 +/- 0.26; triclosan 0.28 +/- 0.18; ratio 1.88X) and Week-4 visit (baking soda 0.47 +/- 0.21; triclosan 0.23 +/- 0.15; ratio 2.08X). Similar to the whole mouth scores, evaluation of various tooth sites (facial, lingual, proximal, and gingival) showed a significantly greater reduction in plaque scores for brushing with the baking soda dentifrice as compared to brushing with the triclosan

  19. A first-in-human phase I dose-escalation, pharmacokinetic, and pharmacodynamic evaluation of intravenous LY2090314, a glycogen synthase kinase 3 inhibitor, administered in combination with pemetrexed and carboplatin.

    Science.gov (United States)

    Gray, Jhanelle E; Infante, Jeffrey R; Brail, Les H; Simon, George R; Cooksey, Jennifer F; Jones, Suzanne F; Farrington, Daphne L; Yeo, Adeline; Jackson, Kimberley A; Chow, Kay H; Zamek-Gliszczynski, Maciej J; Burris, Howard A

    2015-12-01

    LY2090314 (LY) is a glycogen synthase kinase 3 inhibitor with preclinical efficacy in xenograft models when combined with platinum regimens. A first-in-human phase 1 dose-escalation study evaluated the combination of LY with pemetrexed/carboplatin. Forty-one patients with advanced solid tumors received single-dose LY monotherapy lead-in and 37 patients received LY (10-120 mg) plus pemetrexed/carboplatin (500 mg/m(2) and 5-6 AUC, respectively) across 8 dose levels every 21 days. Primary objective was maximum tolerated dose (MTD) determination; secondary endpoints included safety, antitumor activity, pharmacokinetics, and beta-catenin pharmacodynamics. MTD of LY with pemetrexed/carboplatin was 40 mg. Eleven dose-limiting toxicities (DLTs) occurred in ten patients. DLTs during LY monotherapy occurred at ≥ 40 mg: grade 2 visual disturbance (n = 1) and grade 3/4 peri-infusional thoracic pain during or shortly post infusion (n = 4; chest, upper abdominal, and back pain). Ranitidine was added after de-escalation to 80 mg LY to minimize peri-infusional thoracic pain. Following LY with pemetrexed/carboplatin therapy, DLTs included grade 3/4 thrombocytopenia (n = 4) and grade 4 neutropenia (n = 1). Best overall response by RECIST included 5 confirmed partial responses (non-small cell lung cancer [n = 3], mesothelioma, and breast cancer) and 19 patients having stable disease. Systemic LY exposure was approximately linear over dose range studied. Transient upregulation of beta-catenin measured in peripheral blood mononuclear cells (PBMCs) occurred at 40 mg LY. The initial safety profile of LY2090314 was established. MTD LY dose with pemetrexed/carboplatin is 40 mg IV every 3 weeks plus ranitidine. Efficacy of LY plus pemetrexed/carboplatin requires confirmation in randomized trials.

  20. A comparison of carboplatin and paclitaxel with cisplatinum and 5-fluorouracil in definitive chemoradiation in esophageal cancer patients

    NARCIS (Netherlands)

    Honing, J; Smit, J.K.; Muijs, C T; Burgerhof, J G M; de Groot, J W; Paardekooper, G; Muller, K; Woutersen, D; Legdeur, M J C; Fiets, W E; Slot, A; Beukema, Janet; Plukker, John; Hospers, G A P

    We compared retrospectively carboplatin/paclitaxel to cisplatinum/5-FU as dCRT treatment in esophageal cancer patients. We found comparable outcome, but lower toxicity rates and higher treatment compliance in the carboplatin/paclitaxel group. Therefore, we suggest carboplatin/paclitaxel as an

  1. Periocular carboplatin for retinoblastoma: long-term report (12 years) on efficacy and toxicity.

    Science.gov (United States)

    Marr, Brian P; Dunkel, Ira J; Linker, Anne; Abramson, David H

    2012-06-01

    To report the experience of the authors with efficacy and toxicity of periocular chemotherapy over a 12-year period. 102 periocular injections of 2 cc (10 mg of carboplatin/1 cc) were given every 4-6 weeks in 33 eyes of 29 patients. Patient's data were reviewed retrospectively. Thirty-three eyes were followed for 7-148 months following initiation of periocular injections, and 13 (39%) have avoided enucleation. There were two cases of second malignancy resulting in one death and one survivor, two survivors of metastatic disease, and two survivors of orbital recurrence. Twenty eyes were enucleated for disease progression at a mean time of 15 months postinitiation of periocular carboplatin (POC). The Kaplan-Meier estimate of eye survival at 36 months is 36%. Eleven of the 13 salvaged eyes received concurrent treatment with chemotherapy (n=4, 30%), external beam radiation and chemotherapy in (n=6, 46%), or brachytherapy (n=1, 8%). Two of the salvaged eyes (16%) were treated with POC alone. Orbital swelling occurred in 14/33 (42%) eyes. There were no symptomatic motility disorders. One severe toxicity reaction resulted in acute loss of vision, down to light perception, which failed to recover and one eye had progression of optic nerve pallor. This paper demonstrates that POC has limited short-term and long-term systemic toxicity and most of the ocular complications were acute, not delayed. Only two select cases showed long-term complete responses to POC alone and the data do not support the use as monotherapy, although where it was used in combination with other modalities, 39% of the eyes were saved.

  2. Eight weeks of a combination of high intensity interval training and conventional training reduce visceral adiposity and improve physical fitness: a group-based intervention.

    Science.gov (United States)

    Giannaki, Christoforos D; Aphamis, George; Sakkis, Panikos; Hadjicharalambous, Marios

    2016-04-01

    High intensity interval training (HIIT) has been recently promoted as an effective, low volume and time-efficient training method for improving fitness and health related parameters. The aim of the current study was to examine the effect of a combination of a group-based HIIT and conventional gym training on physical fitness and body composition parameters in healthy adults. Thirty nine healthy adults volunteered to participate in this eight-week intervention study. Twenty three participants performed regular gym training 4 days a week (C group), whereas the remaining 16 participants engaged twice a week in HIIT and twice in regular gym training (HIIT-C group) as the other group. Total body fat and visceral adiposity levels were calculated using bioelectrical impedance analysis. Physical fitness parameters such as cardiorespiratory fitness, speed, lower limb explosiveness, flexibility and isometric arm strength were assessed through a battery of field tests. Both exercise programs were effective in reducing total body fat and visceral adiposity (Pflexibility (Pgyms and craving to acquire significant fitness benefits in relatively short period of time.

  3. Validation of techniques for the prediction of carboplatin exposure: application of Bayesian methods

    NARCIS (Netherlands)

    Huitema, A. D.; Mathôt, R. A.; Tibben, M. M.; Schellens, J. H.; Rodenhuis, S.; Beijnen, J. H.

    2000-01-01

    Several methods have been developed for the prediction of carboplatin exposure to facilitate pharmacokinetic guided dosing. The aim of this study was to develop and validate sparse data Bayesian methods for the estimation of carboplatin exposure and to validate other commonly applied techniques,

  4. Effectiveness of twice weekly iron supplementation compared with daily regimen in reducing anemia and iron deficiency during pregnancy: a randomized trial in Iran

    Directory of Open Access Journals (Sweden)

    Ahmadreza Zamani

    2008-10-01

    Full Text Available

    • BACKGROUND: Over 40 millions pregnant women are suffering from iron deficiency (ID and it’s consequences in developing countries presently. If the effects of twice weekly iron supplementation on hemoglobin (Hb and serum ferritin (SF to be shown comparable to daily iron supplementation in pregnancy, it will reduce the cost, will diminish the side effects, will increase the compliance and will prevent the potential harmful effects of extra iron supplement.
    • METHODS: A total of 152 pregnant women were enrolled in the study in two different clinics in Isfahan, Iran. The inclusion criteria were 2nd trimester pregnant women aged between 18-38 years with the initial Hb >= 110 g/L. They were randomized into two treatment groups, either the twice weekly (TW taking iron group (two 45-mg ferrous sulfate tablets per week or daily taking iron group (45 mg ferrous sulfate tablet. The age, weight, education and employment status of pregnant women along with their parity distributions and gestational age at onset of treatment in the two groups were comparable. Sixty nine and fifty three pregnant women of daily group and TW group, respectively, could be followed up regularly at 4 weekly intervals until 16 weeks of supplementation. Side effects, compliance and the number of tablets consumed were noted for each group. Blood was sampled at 15-16 and 37-39 weeks of pregnancy and blood indices were evaluated to see the effect of iron supplementation.
    • RESULTS: The mean initial Hb concentrations were 133 ± 11 g/L and 130 ± 12 g/L in daily and TW groups, respectively, which were not significant. The mean final Hb concentrations were 127 ± 15 g/L in daily group and 120 ± 13 g/L in TW group (p < 0.05. The decrease of Hb from the start to the end of therapy was significant in both groups and the decrements significantly were less in daily group. The SF increased non-significantly in daily

    • 12 min/week of high-intensity interval training reduces aortic reservoir pressure in individuals with metabolic syndrome: a randomized trial.

      Science.gov (United States)

      Ramos, Joyce S; Dalleck, Lance C; Ramos, Maximiano V; Borrani, Fabio; Roberts, Llion; Gomersall, Sjaan; Beetham, Kassia S; Dias, Katrin A; Keating, Shelley E; Fassett, Robert G; Sharman, James E; Coombes, Jeff S

      2016-10-01

      Decreased aortic reservoir function leads to a rise in aortic reservoir pressure that is an independent predictor of cardiovascular events. Although there is evidence that high-intensity interval training (HIIT) would be useful to improve aortic reservoir pressure, the optimal dose of high-intensity exercise to improve aortic reservoir function has yet to be investigated. Therefore, this study compared the effect of different volumes of HIIT and moderate-intensity continuous training (MICT) on aortic reservoir pressure in participants with the metabolic syndrome (MetS). Fifty individuals with MetS were randomized into one of the following 16-week training programs: MICT [n = 17, 30 min at 60-70% peak heart rate (HRpeak), five times/week]; 4 × 4-min high-intensity interval training (4HIIT) (n = 15, 4 × 4 min bouts at 85-95% HRpeak, interspersed with 3 min of active recovery at 50-70% HRpeak, three times/week); and 1 × 4-min high-intensity interval training (1HIIT) (n = 18, 1 × 4 min bout at 85-95% HRpeak, three times/week). Aortic reservoir pressure was calculated from radial applanation tonometry. Although not statistically significant, there was a trend for a small-to-medium group × time interaction effect on aortic reservoir pressure, indicating a positive adaptation following 1HIIT compared with 4HIIT and MICT [F (2,46) = 2.9, P = 0.07, η = 0.06]. This is supported by our within-group analysis wherein only 1HIIT significantly decreased aortic reservoir pressure from pre to postintervention (pre-post: 1HIIT 33 ± 16 to 31 ± 13, P = 0.03; MICT 29 ± 9-28 ± 8, P = 0.78; 4HIIT 28 ± 10-30 ± 9 mmHg, P = 0.10). Three sessions of 4 min of high-intensity exercise per week (12 min/week) was sufficient to improve aortic reservoir pressure, and thus may be a time-efficient exercise modality for reducing cardiovascular risk in individuals with MetS.

    • Reduced right ventrolateral prefrontal cortex activity while inhibiting positive affect is associated with improvement in hedonic capacity after 8 weeks of antidepressant treatment in major depressive disorder.

      Science.gov (United States)

      Light, Sharee N; Heller, Aaron S; Johnstone, Tom; Kolden, Gregory G; Peterson, Michael J; Kalin, Ned H; Davidson, Richard J

      2011-11-15

      Anhedonia, a reduced ability to experience pleasure, is a chief symptom of major depressive disorder and is related to reduced frontostriatal connectivity when attempting to upregulate positive emotion. The present study examined another facet of positive emotion regulation associated with anhedonia-namely, the downregulation of positive affect-and its relation to prefrontal cortex (PFC) activity. Neuroimaging data were collected from 27 individuals meeting criteria for major depressive disorder as they attempted to suppress positive emotion during a positive emotion regulation task. Their PFC activation pattern was compared with the PFC activation pattern exhibited by 19 healthy control subjects during the same task. Anhedonia scores were collected at three time points: at baseline (time 1), 8 weeks after time 1 (i.e., time 2), and 6 months after time 1 (i.e., time 3). Prefrontal cortex activity at time 1 was used to predict change in anhedonia over time. Analyses were conducted utilizing hierarchical linear modeling software. Depressed individuals who could not inhibit positive emotion-evinced by reduced right ventrolateral prefrontal cortex activity during attempts to dampen their experience of positive emotion in response to positive visual stimuli-exhibited a steeper anhedonia reduction slope between baseline and 8 weeks of treatment with antidepressant medication (p < .05). Control subjects showed a similar trend between baseline and time 3. To reduce anhedonia, it may be necessary to teach individuals how to counteract the functioning of an overactive pleasure-dampening prefrontal inhibitory system. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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

      Science.gov (United States)

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

      2010-10-20

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

    • Skin Testing in the Evaluation and Management of Carboplatin-Related Hypersensitivity Reactions.

      Science.gov (United States)

      Lax, Timothy; Long, Aidan; Banerji, Aleena

      2015-01-01

      Carboplatin-induced hypersensitivity reactions (HSRs) are a frequent occurrence in patients being retreated for malignancy. The most common and severe reactions are thought to be IgE mediated. Currently, skin testing is the only method used clinically to identify individuals sensitized to carboplatin. Despite almost 20 years of clinical use, a standardized approach to skin testing and its use in the management of carboplatin HSRs has not been well established. We review the utility of carboplatin skin testing and discuss factors that influence the interpretation of skin testing results. A risk stratification strategy using skin testing and desensitization to manage patients with carboplatin HSRs is proposed. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

    • [A 65-year-old man with liver metastases after lung cancer resection that responded to concomitant use of gemcitabine and carboplatin].

      Science.gov (United States)

      Kawabe, Masakazu; Sasaki, Masato; Hirai, Seiya; Ikeda, Takeshi; Sasaki, Hisashi; Yoshida, Makoto; Amaya, Hirokazu; Aotake, Toshiharu; Uchinami, Masaru; Ihaya, Akio; Tanaka, Kuniyoshi

      2006-01-01

      A 65-year-old male with liver metastases after lung cancer resection was treated with five courses of chemotherapy consisting of gemcitabine (GEM) 1,000 mg/m2 (day 1, 8, every 4 weeks) plus carboplatin (CBDCA) AUC 6 (day 1, every 4 weeks). A partial response (PR) was achieved, his symptoms abated and his quality of life(QOL) improved. Although bone marrow suppression was observed as a side effect, it was within the tolerable range and did not interfere with therapy. This approach may be worth considering as a first-line anti-cancer chemotherapy for recurrence lung cancer.

    • Sequential Therapy with Gemcitabine and Carboplatin Followed by Paclitaxel as First Line Treatment for Advanced Urothelial Cancer

      Directory of Open Access Journals (Sweden)

      Joseph G Kattan, Celine Y Boutros, Fadi S Farhat, Georges Y Chahine, Khaled M Musallam, Marwan G Ghosn

      2012-01-01

      Full Text Available Objective: Gemcitabine and platinum-based compounds represent the new standard combination therapy for bladder cancer. In this study, we evaluate the efficacy and safety of gemcitabine and carboplatin followed sequentially by paclitaxel in 27 patients with advanced transitional cell carcinoma.Methods: This phase II multicentre study was based on the doublet gemcitabine 800 mg/m2 and carboplatin area under the concentration-time curve 2 on days 1 and 8 every 21 days for 4 cycles, followed sequentially by paclitaxel 60 mg/m2/w for 12 consecutive weeks. The disease was assessed after each sequence.Results: Primary tumor was localized in the bladder and renal pelvis in 25 and 2 patients, respectively. Twenty patients completed all 4 cycles of the gemcitabine and carboplatin sequence. Mean number of cycles was 3.5 (range 1 to 4. Toxicities were mainly hematologic, including Grade 3 neutropenia and anemia in 3 patients. Objective response was noted in 11 pts (40.7%, including 1 complete response (CR and 10 partial responses (PR. Three patients had stable disease and 11 progressed. Among the 20 patients, 14 received the second sequence. Mean number of paclitaxel injections was 7 (range 2 to 12. Toxicities were limited to diarrhea and neurotoxicity in 1 patient each. Objective response was documented in 6 patients (30% (3 CR and 3 PR, including the improvement of PR into CR in 2 patients. Median duration of response was 6 months. After a median follow-up of 7 months, 21 patients died and 6 remained alive, including 2 who maintained CR and 1 PR.Sixteen patients had locally advanced disease and 11 had metastatic disease, better prognostic was noticed with patients with locally advanced disease.Conclusion: the sequential approach of treatment for advanced urothelial cancer using gemcitabine and carboplatine followed by paclitaxel seems to be a safer alternative to the combined triplet, but due to the limited number of patients this study failed to improve

    • Metformin enhancing the antitumor efficacy of carboplatin against Ehrlich solid carcinoma grown in diabetic mice: Effect on IGF-1 and tumoral expression of IGF-1 receptors.

      Science.gov (United States)

      Abo-Elmatty, Dina M; Ahmed, Eman A; Tawfik, Mona K; Helmy, Seham A

      2017-03-01

      Diabetes has been listed as a risk factor for various types of cancer. Cancer cell development can be promoted by increased levels of IGF-1 and hyperinsulinemia that are associated with diabetes type II. Metformin is an anti-diabetic agent and its potential antitumor impact has become the objective of numerous studies. In this vein, we hypothesize that using metformin in diabetes type II mice may synergistic with carboplatin for reducing the risk of cancer. Therefore, the study aimed to evaluate the in vivo antitumor activity of metformin against solid EAC tumor growth in female diabetic mice and its potential pro-apoptotic and anti-proliferative effects with clarification of its inconclusive biological mechanisms. Mice were assigned into nine groups; normal control, diabetic control, diabetic plus EAC control, EAC control, and treated groups received carboplatin and/or metformin (100, 200mg/kg). Metformin administration especially with high dose potentiated the antitumor activity of carboplatin displayed by increased pro-apoptotic activators "caspase-3 and bax" and reduced anti-apoptotic protein bcl-2. This was confirmed by the histopathological scores. Moreover, the combination therapy was effective in attenuating the expression of the pro-angiogenic mediator "VEGF" and the microvessel density as revealed by the CD34. Additionally, this combination down-regulated the high levels of the mutagenic element "IGF-1" and its receptor expression, and attenuated the intensity of inflammatory mediators. In conclusion, it was found that metformin therapy could enhance apoptotic marker, and suppress the neovascularization and proliferation process. This clarified the ability of metformin to support carboplatin activity in reducing tumor progression in type II diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

    • Early Non-anticoagulant Desulfated Heparin After TBI: Reduced Brain Edema and Leukocyte Mobilization is Associated with Improved Watermaze Learning Ability Weeks After Injury.

      Science.gov (United States)

      Nagata, Katsuhiro; Suto, Yujin; Cognetti, John; Browne, Kevin D; Kumasaka, Kenichiro; Johnson, Victoria E; Kaplan, Lewis; Marks, Joshua; Smith, Douglas H; Pascual, Jose L

      2018-01-26

      Unfractionated heparin (UFH) administered immediately after TBI reduces brain leukocyte (LEU) accumulation, and enhances early cognitive recovery, but may increase bleeding after injury. It is unknown how non-anticoagulant heparins such as 2,3-O desulfated heparin (ODSH), impact post-TBI cerebral inflammation and long term recovery. We hypothesized that ODSH after TBI reduces LEU-mediated brain inflammation and improves long term neurological recovery. CD1 male mice (n=66) underwent either TBI (controlled cortical impact; CCI) or sham craniotomy. ODSH [25mg/kg (25ODSH) or 50mg/kg (50ODSH)] or saline was administered for 48h after TBI in 46 animals. At 48h, intravital microscopy visualized rolling LEUs and fluorescent albumin leakage in the pial circulation, and the Garcia Neurological Test (GNT) assessed neurologic function. Brain edema (wet/dry ratio) was evaluated post-mortem. In a separate group of animals (n=20), learning/memory ability (% time swimming in the Probe platform quadrant) was assessed by the Morris Water Maze (MWM) 17 days after TBI. ANOVA with Bonferroni correction determined significance (pLearning/memory ability (% time swimming in target quadrant) was lowest in CCI (5.9±6.4%) and significantly improved in the 25ODSH group (27.5±8.2% p=0.025). ODSH after TBI reduces cerebral LEU recruitment, microvascular permeability and edema. ODSH may also improve acute neurological recovery leading to improved learning/memory ability weeks after injury. 1 STUDY TYPE: Therapeutic Trial.

    • 12 Weeks of Combined Endurance and Resistance Training Reduces Innate Markers of Inflammation in a Randomized Controlled Clinical Trial in Patients with Multiple Sclerosis

      Directory of Open Access Journals (Sweden)

      Nathalie Deckx

      2016-01-01

      Full Text Available Previously, we reported that patients with multiple sclerosis (MS demonstrate improved muscle strength, exercise tolerance, and lean tissue mass following a combined endurance and resistance exercise program. However, the effect of exercise on the underlying disease pathogenesis remains elusive. Since recent evidence supports a crucial role of dendritic cells (DC in the pathogenesis of MS, we investigated the effect of a 12-week combined exercise program in MS patients on the number and function of DC. We demonstrate an increased number of plasmacytoid DC (pDC following the exercise program. These pDC display an activated phenotype, as evidenced by increased numbers of circulating CD62L+ and CD80+ pDC. Interestingly, the number of CD80+ pDC positively correlates with the presence of IL-10-producing regulatory type 1 cells (Tr1, an important cell type for maintaining peripheral tolerance to self-antigens. In addition, decreased production of the inflammatory mediators, TNF-α and MMP-9, upon Toll-like receptor (TLR stimulation was found at the end of the exercise program. Overall, our findings suggest that the 12-week exercise program reduces the secretion of inflammatory mediators upon TLR stimulation and promotes the immunoregulatory function of circulating pDC, suggestive for a favorable impact of exercise on the underlying immunopathogenesis of MS.

    • Reduced-Sodium Lunches Are Well-Accepted by Uninformed Consumers Over a 3-Week Period and Result in Decreased Daily Dietary Sodium Intakes: A Randomized Controlled Trial.

      Science.gov (United States)

      Janssen, Anke M; Kremer, Stefanie; van Stipriaan, Willeke L; Noort, Martijn W J; de Vries, Jeanne H M; Temme, Elisabeth H M

      2015-10-01

      -sodium foods over a 3-week period was well accepted by the uninformed participants in an experimental real-life canteen setting. The reduced-sodium foods did not trigger compensation behavior during the remainder of the day in the intervention group compared with the control group, as reflected by 24-hour urinary sodium excretion. Therefore, offering reduced-sodium foods without explicitly informing consumers of the sodium reduction can contribute to daily sodium intake reduction. Copyright © 2015 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

    • Removing inactive NRTIs in a salvage regimen is safe, maintains virological suppression and reduces treatment costs: 96 weeks post VERITAS study

      Directory of Open Access Journals (Sweden)

      Benoit Trottier

      2014-11-01

      deaths or serious adverse events were observed. One or two ARV removals translated to a mean annual saving of $3319 CDN (11% and $8630 (24% respectively. Conclusions: Final results indicate that removing one or two inactive NRTIs from a regimen in patients taking four or more ARVs with controlled VL appears to be safe, maintains virological suppression through 144 weeks and significantly reduces treatment costs.

    • Carboplatin Rechallenge After Hypersensitivity Reactions in Pediatric Patients With Low-Grade Glioma.

      Science.gov (United States)

      Shah, Amish C; Minturn, Jane E; Li, Yimei; Belasco, Jean B; Phillips, Peter C; Kang, Tammy I; Cole, Kristina A; Waanders, Angela J; Pollack, Rosanna; Didomenico, Concetta; Wildes, Cynthia; Fisher, Michael J

      2016-01-01

      The high prevalence of carboplatin hypersensitivity reactions (HSR) significantly affects the treatment of pediatric patients with low-grade glioma (LGG). Rechallenging patients is an option that must balance the risks of repeat allergic reaction to the benefits of retaining an effective anti-tumor regimen. We performed a retrospective review of children with LGG treated with carboplatin and vincristine between October 2000 and April 2013, who had a documented HSR to carboplatin. Patients were re-exposed to carboplatin using either precautionary measures (prolonged infusion time and premedication with H1 antagonists, H2 antagonists, and corticosteroids), a desensitization protocol, or both. We report the results of our institutional experience of carboplatin re-exposure using both premedication with a prolonged infusion time and a desensitization protocol. Overall, 40 of 55 (73%) patients were successfully rechallenged with carboplatin, including 19 of 25 (76%) patients who underwent desensitization. Our results demonstrate re-exposure to be a safe alternative to abandoning carboplatin for patients with a hypersensitivity reaction. We propose a clinical algorithm for treatment. © 2015 Wiley Periodicals, Inc.

    • Carboplatin interaction with calf-thymus DNA: A FTIR spectroscopic approach

      Science.gov (United States)

      Jangir, Deepak K.; Tyagi, Gunjan; Mehrotra, Ranjana; Kundu, Suman

      2010-04-01

      Carboplatin is a chemotherapeutic drug, used for the treatment of different types of cancers, particularly solid tumors. Carboplatin, like other platinum containing drugs, exerts its cytotoxic effect through DNA binding via cross-linking. It forms interstrand and intrastrand cross-linking with DNA. Intrastrand cross-linking is dominant and believed to be conferring antitumoral efficacy of the drug. This cross-linking results in alteration of DNA winding and bending, which hampers DNA replication and transcription and finally leads to cell death. In the present work, we studied the interaction of carboplatin with calf-thymus DNA in buffer solution under physiological conditions. Different concentrations of carboplatin were incubated with a constant DNA concentration to form carboplatin-DNA complexes. These complexes were studied with Fourier Transform Infrared (FTIR) spectroscopy and circular dichroism (CD) spectroscopy to understand the binding modes of carboplatin with DNA and its effect on DNA conformation. The results showed that carboplatin binds to DNA through direct interaction of platin-DNA bases (guanine, thymine, adenine and cytosine), with a small perturbation of phosphate group of DNA backbone, while DNA remains in the B-conformation. DNA aggregation was also observed at higher drug concentrations.

    • Four-Week Consumption of Malaysian Honey Reduces Excess Weight Gain and Improves Obesity-Related Parameters in High Fat Diet Induced Obese Rats

      Science.gov (United States)

      Kanyan Enchang, Francis; Nor Hussein, Fuzina

      2017-01-01

      Many studies revealed the potential of honey consumption in controlling obesity. However, no study has been conducted using Malaysian honey. In this study, we investigated the efficacy of two local Malaysian honey types: Gelam and Acacia honey in reducing excess weight gain and other parameters related to obesity. The quality of both honey types was determined through physicochemical analysis and contents of phenolic and flavonoid. Male Sprague-Dawley rats were induced to become obese using high fat diet (HFD) prior to introduction with/without honey or orlistat for four weeks. Significant reductions in excess weight gain and adiposity index were observed in rats fed with Gelam honey compared to HFD rats. Moreover, levels of plasma glucose, triglycerides, and cholesterol, plasma leptin and resistin, liver enzymes, renal function test, and relative organ weight in Gelam and Acacia honey treated groups were reduced significantly when compared to rats fed with HFD only. Similar results were also displayed in rats treated with orlistat, but with hepatotoxicity effects. In conclusion, consumption of honey can be used to control obesity by regulating lipid metabolism and appears to be more effective than orlistat. PMID:28246535

    • Four-Week Consumption of Malaysian Honey Reduces Excess Weight Gain and Improves Obesity-Related Parameters in High Fat Diet Induced Obese Rats.

      Science.gov (United States)

      Samat, Suhana; Kanyan Enchang, Francis; Nor Hussein, Fuzina; Wan Ismail, Wan Iryani

      2017-01-01

      Many studies revealed the potential of honey consumption in controlling obesity. However, no study has been conducted using Malaysian honey. In this study, we investigated the efficacy of two local Malaysian honey types: Gelam and Acacia honey in reducing excess weight gain and other parameters related to obesity. The quality of both honey types was determined through physicochemical analysis and contents of phenolic and flavonoid. Male Sprague-Dawley rats were induced to become obese using high fat diet (HFD) prior to introduction with/without honey or orlistat for four weeks. Significant reductions in excess weight gain and adiposity index were observed in rats fed with Gelam honey compared to HFD rats. Moreover, levels of plasma glucose, triglycerides, and cholesterol, plasma leptin and resistin, liver enzymes, renal function test, and relative organ weight in Gelam and Acacia honey treated groups were reduced significantly when compared to rats fed with HFD only. Similar results were also displayed in rats treated with orlistat, but with hepatotoxicity effects. In conclusion, consumption of honey can be used to control obesity by regulating lipid metabolism and appears to be more effective than orlistat.

    • Four-Week Consumption of Malaysian Honey Reduces Excess Weight Gain and Improves Obesity-Related Parameters in High Fat Diet Induced Obese Rats

      Directory of Open Access Journals (Sweden)

      Suhana Samat

      2017-01-01

      Full Text Available Many studies revealed the potential of honey consumption in controlling obesity. However, no study has been conducted using Malaysian honey. In this study, we investigated the efficacy of two local Malaysian honey types: Gelam and Acacia honey in reducing excess weight gain and other parameters related to obesity. The quality of both honey types was determined through physicochemical analysis and contents of phenolic and flavonoid. Male Sprague-Dawley rats were induced to become obese using high fat diet (HFD prior to introduction with/without honey or orlistat for four weeks. Significant reductions in excess weight gain and adiposity index were observed in rats fed with Gelam honey compared to HFD rats. Moreover, levels of plasma glucose, triglycerides, and cholesterol, plasma leptin and resistin, liver enzymes, renal function test, and relative organ weight in Gelam and Acacia honey treated groups were reduced significantly when compared to rats fed with HFD only. Similar results were also displayed in rats treated with orlistat, but with hepatotoxicity effects. In conclusion, consumption of honey can be used to control obesity by regulating lipid metabolism and appears to be more effective than orlistat.

  1. Risk-stratification protocol for carboplatin and oxaliplatin hypersensitivity: repeat skin testing to identify drug allergy.

    Science.gov (United States)

    Wang, Alberta L; Patil, Sarita U; Long, Aidan A; Banerji, Aleena

    2015-11-01

    Hypersensitivity reactions (HSRs) to platinum-based chemotherapies are increasingly being recognized. The authors developed a novel risk-stratification protocol that was used successfully in a small number of patients with carboplatin-induced HSRs. To describe the utility of this protocol in a large number of patients with carboplatin- or oxaliplatin-induced HSRs. A 5-year retrospective review of patients referred to Massachusetts General Hospital with carboplatin- or oxaliplatin-induced HSR was performed. Patients were managed using a risk-stratification protocol using 3 repeat skin tests (STs) with intervening desensitizations. If the repeat ST result remained negative 3 times, patients received subsequent infusions without desensitization. From 2008 to 2012, 142 patients (92 treated with carboplatin, 50 treated with oxaliplatin) completed 574 desensitizations. Most patients were women (84.5%, mean ± SD 58.1 ± 9.3 years). Patients with carboplatin-induced HSRs were classified as having positive (n = 32, 34.8%), negative (n = 38, 41.3%), or converted (n = 22, 23.9%) ST reactions when the initial negative ST reaction converted to positive at repeat ST. Of those with oxaliplatin-induced HSRs, 22 (44%) had positive, 25 (50%) had negative, and 3 (6%) had converted ST reactions. Of the patients with negative ST reactions, 17 with carboplatin-induced HSRs and 16 with oxaliplatin-induced HSRs safely completed 59 and 95 outpatient infusions, respectively, without desensitizations. For carboplatin and oxaliplatin, ST conversion was associated with an interval of at least 6 months from the HSR to the initial ST (carboplatin, P = .002; oxaliplatin, P = .045). This risk-stratification protocol for presumed carboplatin- and oxaliplatin-induced HSRs safely identifies false-negative ST reactions and nonallergic patients who can receive infusions without desensitizations. This leads to fewer unnecessary desensitizations and improved patient care. Copyright © 2015 American

  2. Ectopic overexpression of haem oxygenase-1 protects kidneys from carboplatin-mediated apoptosis

    Science.gov (United States)

    Sue, Yuh-Mou; Cheng, Ching-Feng; Chou, Ying; Chang, Chih-Cheng; Lee, Pei-Shan; Juan, Shu-Hui

    2011-01-01

    BACKGROUND AND PURPOSE We previously reported that the activation of the nuclear factor of activated T-lymphocyte-3 (NFAT3) by carboplatin leads to renal apoptosis as a result of oxidative stress, which is reversed by N-acetylcysteine. Herein, we extend our previous work to provide evidence of the molecular mechanisms of haem oxygenase (HO)-1 in protecting against injury. EXPERIMENTAL APPROACH Protective mechanisms of HO-1 in carboplatin-mediated renal apoptosis were examined in C57BL/6 mice and rat renal tubular cells (RTC) with HO-1 induction or inactivation/knockdown. KEY RESULTS The HO-1, induced by cobalt protoporphyrin, protected against carboplatin-induced renal injury in vivo. This protection was decreased by an inhibitor of HO-1 action, tin protoporphyrin. In cultures of RTC, carboplatin-induced apoptosis was similarly affected by HO-1 overexpression or knockdown. Carboplatin-mediated NFAT3 activation and apoptosis involve activation of the signalling kinases, extracellular signal regulated kinase, Jun N-terminal kinase and protein kinase C, and such activation was reversed in cells overexpressing HO-1. Both products of the HO-1 reaction, CO and bilirubin, inhibited (by 30–40%) NFAT3 activation and production of the pro-apoptotic proteins Bcl-XS/Bax. Additionally, the activation of NFκB was markedly decreased by HO-1 induction. CONCLUSION AND IMPLICATIONS HO-1 and its reaction products show anti-apoptotic effects in carboplatin-mediated renal injury. A novel functional NFAT3 binding site identified in the rat HO-1 promoter region was involved in producing a 1.5-fold to 2.5-fold increase in HO-1 induction by carboplatin. Nevertheless, only HO-1 overexpression and activation prior to the carboplatin challenge provided protection against carboplatin-induced injury. PMID:21198546

  3. Performance of formulae based estimates of glomerular filtration rate for carboplatin dosing in stage 1 seminoma.

    Science.gov (United States)

    Shepherd, Scott T C; Gillen, Gerry; Morrison, Paula; Forte, Carla; Macpherson, Iain R; White, Jeff D; Mark, Patrick B

    2014-03-01

    Single cycle carboplatin, dosed by glomerular filtration rate (GFR), is standard adjuvant therapy for stage 1 seminoma. Accurate measurement of GFR is essential for correct dosing. Isotopic methods remain the gold standard for the determination of GFR. Formulae to estimate GFR have improved the assessment of renal function in non-oncological settings. We assessed the utility of these formulae for carboplatin dosing. We studied consecutive subjects receiving adjuvant carboplatin for stage 1 seminoma at our institution between 2007 and 2012. Subjects underwent 51Cr-ethylene diamine tetra-acetic acid (EDTA) measurement of GFR with carboplatin dose calculated using the Calvert formula. Theoretical carboplatin doses were calculated from estimated GFR using Chronic Kidney Disease-Epidemiology (CKD-EPI), Management of Diet in Renal Disease (MDRD) and Cockcroft-Gault (CG) formulae with additional correction for actual body surface area (BSA). Carboplatin doses calculated by formulae were compared with dose calculated by isotopic GFR; a difference formula had greatest accuracy. The CKD-EPI formula, corrected for actual BSA, performed best; 45.9% of patients received within 10% of correct carboplatin dose. Patients predicted as underdosed (13.5%) by CKD-EPI were more likely to be obese (p=0.013); there were no predictors of the 40.5% receiving an excess dose. Our data support further evaluation of the CKD-EPI formula in this patient population but clinically significant variances in carboplatin dosing occur using non-isotopic methods of GFR estimation. Isotopic determination of GFR should remain the recommended standard for carboplatin dosing when accuracy is essential. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Impact of a new assay for measuring serum creatinine levels on carboplatin dosing.

    Science.gov (United States)

    Murray, Brian; Bates, Jill; Buie, Larry

    2012-07-01

    The impact of converting to the isotope dilution mass spectrometry (IDMS)-traceable serum creatinine (SCr) assay for determining the calculated and delivered dose of carboplatin was studied. A single-center, retrospective, observational chart review of adult patients who received a dose of carboplatin within one month before and after implementation of the IDMS-traceable SCr assay was conducted using information available in medical records and chemotherapy orders. Patient-specific data were collected and used to calculate a carboplatin dose before and after the SCr assay change using the Cockcroft-Gault equation, with the Calvert et al. formula used to calculate the carboplatin dose based on the target area under the concentration-time curve in the chemotherapy order forms. The primary outcome was the difference in calculated carboplatin dose, assessed as the percent difference between the mean carboplatin dose before and after the assay change. Results Fifty-six patients were included in the data analysis. The mean calculated carboplatin dose was 9.6% greater when the IDMS-traceable assay was used compared with the previous institutional standard enzymatic assay. This difference was statistically significant (p 10% compared with the dose received before conversion to the IDMS-traceable assay for SCr measurement. After implementation of the IDMS-traceable assay, the mean calculated carboplatin dose was 9.6% larger than before implementation, and nearly 50% of patients received a dose of carboplatin that was increased by greater than 10% compared with the dose received before the assay change.

  5. Reduced muscular fatigue after a 12-week leucine-rich amino acid supplementation combined with moderate training in elderly: a randomised, placebo-controlled, double-blind trial.

    Science.gov (United States)

    Reule, Claudia A; Scholz, Claudia; Schoen, Christiane; Brown, Niklas; Siepelmeyer, Anne; Alt, Wilfried W

    2016-01-01

    Age-related muscle loss is characterised by a progressing decrease in muscle mass, strength and function. Besides resistance training and physical activity, appropriate nutrition that is rich in protein, especially branched-chain amino acids, is very important to support training effects and positively influence the protein synthesis to degradation ratio. The purpose of this study was to evaluate the effect of a 12-week leucine-rich amino acid supplementation in combination with moderate training. Forty-eight healthy subjects exercised for 30 min three times per week and received either a leucine-rich amino acid supplementation or a placebo. Before and after supplementation, volunteers performed an exhaustive eccentric exercise protocol. Maximal concentric strength, muscle soreness, creatine kinase (CK), type II collagen collagenase cleavage neoepitope (C2C), C propeptide of type II procollagen (CP2) and safety assessments were performed before exercise and after 3, 24, 48 and 72 hours. The supplementation with leucine resulted in reduced loss of strength at 0 and 3 hours after downhill walking compared with the placebo (p=0.0439). The reduction of C2C/CP2 ratio deflection was significantly increased (p=0.038) due to leucine compared with the placebo. The same tendency could be observed for the recovery phase. No significant supplement effects for muscle soreness and CK could be observed. The principle findings show that leucine-rich amino acid supplementation can counteract the negative effects of eccentric exercise. The treatment resulted in a reduction of exercise-induced strength loss.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    ), the primary endpoint of CALYPSO, overall survival (OS) and safety. RESULTS: A total of 259 very platinum-sensitive patients were included (n=131, CD; n=128, CP). Median PFS was 12.0 months for the CD arm and 12.3 months for CP [HR=1.05 (95% CI, 0.79-1.40); P=0.73 for superiority] and median OS was 40.2 months......AIM: To perform a subset analysis of patients with very platinum-sensitive recurrent ovarian cancer (ROC) enrolled in the phase III CALYPSO trial. PATIENTS AND METHODS: The international non-inferiority trial enrolled women with ROC that relapsed >6 months following first- or second-line platinum......- and paclitaxel-based therapies. Patients were randomised to CD [carboplatin-pegylated liposomal doxorubicin (PLD)] or CP (carboplatin-paclitaxel) and stratified by treatment-free interval (TFI). In this analysis, patients with a TFI>24 months were analysed separately for progression free survival (PFS...

  7. Randomized, Placebo-Controlled, Phase II Study of Veliparib in Combination with Carboplatin and Paclitaxel for Advanced/Metastatic Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Ramalingam, Suresh S; Blais, Normand; Mazieres, Julien; Reck, Martin; Jones, C Michael; Juhasz, Erzsebet; Urban, Laszlo; Orlov, Sergey; Barlesi, Fabrice; Kio, Ebenezer; Keiholz, Ulrich; Qin, Qin; Qian, Jiang; Nickner, Caroline; Dziubinski, Juliann; Xiong, Hao; Ansell, Peter; McKee, Mark; Giranda, Vincent; Gorbunova, Vera

    2017-04-15

    Purpose: PARP plays an important role in DNA repair. Veliparib, a PARP inhibitor, enhances the efficacy of platinum compounds and has been safely combined with carboplatin and paclitaxel. The primary endpoint of this phase II trial determined whether addition of veliparib to carboplatin and paclitaxel improved progression-free survival (PFS) in previously untreated patients with advanced/metastatic non-small cell lung cancer.Experimental Design: Patients were randomized 2:1 to carboplatin and paclitaxel with either veliparib or placebo. Veliparib (120 mg) or placebo was given on days 1 to 7 of each 3-week cycle, with carboplatin (AUC = 6 mg/mL/min) and paclitaxel (200 mg/m2) administered on day 3, for a maximum of 6 cycles.Results: Overall, 158 were included (median age, 63 years; male 68%, squamous histology 48%). Median PFS was 5.8 months in the veliparib group versus 4.2 months in the placebo group [HR, 0.72; 95% confidence interval (CI), 0.45-1.15; P = 0.17)]. Median overall survival (OS) was 11.7 and 9.1 months in the veliparib and placebo groups, respectively (HR, 0.80; 95% CI, 0.54-1.18; P = 0.27). In patients with squamous histology, median PFS (HR, 0.54; 95% CI, 0.26-1.12; P = 0.098) and OS (HR, 0.73; 95% CI, 0.43-1.24; P = 0.24) favored veliparib treatment. Objective response rate was similar between groups (veliparib: 32.4%; placebo: 32.1%), but duration of response favored veliparib treatment (HR, 0.47; 95% CI, 0.16-1.42; P = 0.18). Grade III/IV neutropenia, thrombocytopenia, and anemia were comparable between groups.Conclusions: Veliparib combination with carboplatin and paclitaxel was well-tolerated and demonstrated a favorable trend in PFS and OS versus chemotherapy alone. Patients with squamous histology had the best outcomes with veliparib combination. Clin Cancer Res; 23(8); 1937-44. ©2016 AACR. ©2016 American Association for Cancer Research.

  8. Salvage chemotherapy in recurrent platinum-resistant or refractory epithelial ovarian cancer with Carboplatin and distearoylphosphatidylcholine pegylated liposomal Doxorubicin (lipo-dox®).

    Science.gov (United States)

    Khemapech, Nipon; Oranratanaphan, S; Termrungruanglert, W; Lertkhachonsuk, R; Vasurattana, A

    2013-01-01

    To evaluate the efficacy and safety of distearoylphosphatidylcholine pegylated liposomal doxorubicin (DPLD) combined with carboplatin for the treatment of platinum resistant or refractory epithelial ovarian cancer (EOC) or fallopian tube cancer. A retrospective analysis of women who received DPLD with carboplatin for recurrent EOC or fallopian tube cancer in King Chulalongkorn Memorial Hospital Thailand from January 2006 to August 2011 was conducted. Patients were identified from the medical records and data on demographic factors, stage, histology, surgical findings, cytoreduction status, and prior chemotherapies were abstracted. The efficacy and toxicity of DPLD/carboplatin were evaluated. Progression-free (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. A total of 65 patients, 64 with platinum resistant or refractory epithelial ovarian cancer and 1 with fallopian tube cancer, were enrolled. DPLD and carboplatin were given for an average of 4.46 cycles per patient with a total of 273 cycles. Among the 65 evaluable patients, 0% achieved CR, 7.69% PR, 15.4% SD and 76.% PD. The overall response rate was 23.1%. With a median follow-up of 27.4 months, the median progression-free and median overall survival in the 36 patients was 4.46 months and 8.76 months respectively. In the aspect of side effects, palmar-plantar erythrodysesthesia (PPE) occurred in 33.3% (Grade I 22.2%, Grade II 11.1%) and mucositis in 41.7% (Grade I 27.8%, Grade II 13.9%) of all treatment cycles, all Grade 1 or 2. Anemia, leukopenia and thrombocytopenia occurred in 58.3% (Grade I 41.7%, Grade II 16.7%), 66.7% (Grade I 47.2%, Grade II 19.4%), and 22.2% (Grade I 16.6%, Grade II 5.56%) of cycle respectively, and were mostly Grade 1 or 2. DPLD, the second-generation PLD drug combined with carboplatin every 4 weeks, is effective and has low toxicity for treatment of patients with recurrent platinum-resistant or refractory epithelial ovarian cancer.

  9. RUNX3 contributes to carboplatin resistance in epithelial ovarian cancer cells.

    Science.gov (United States)

    Barghout, Samir H; Zepeda, Nubia; Vincent, Krista; Azad, Abul K; Xu, Zhihua; Yang, Christine; Steed, Helen; Postovit, Lynne-Marie; Fu, YangXin

    2015-09-01

    Resistance to platinum-based therapeutic agents represents a major hurdle in the treatment of epithelial ovarian cancer (EOC). There is an urgent need to better understand the underlying mechanisms. Here, we investigated the role of RUNX3 in carboplatin resistance in EOC cells. Expression of RUNX3 was determined in human EOC cell line A2780s (cisplatin-sensitive) and A2780cp (cisplatin-resistant), human ovarian surface epithelium (OSE) and primary EOC cells. The effects of RUNX3 expression on sensitivity to carboplatin were determined in A2780s and A2780cp cells using neutral red uptake and clonogenic assays. Carboplatin-induced apoptosis was determined by measuring cleaved PARP using Western blotting. The expression of cellular inhibitor of apoptosis protein-2 (cIAP2) and its regulation by RUNX3 were assessed by quantitative RT-PCR and Western blotting. The expression of RUNX3 was elevated in A2780cp cells compared to A2780s cells and in EOC tissues from chemoresistant patients compared to those from chemosensitive patients. Overexpression of RUNX3 rendered A2780s cells more resistant to carboplatin, whereas inhibition of RUNX3 increased sensitivity to carboplatin in A2780cp cells. Inhibition of RUNX3 potentiated carboplatin-induced apoptosis in A2780cp cells as demonstrated by more pronounced PARP cleavage. Interestingly, the expression of cIAP2 was elevated in A2780cp cells compared to A2780s cells. Overexpression of RUNX3 increased cIAP2 expression in A2780s cells, whereas inhibition of RUNX3 decreased cIAP2 expression and potentiated carboplatin-induced decrease of cIAP2 in A2780cp cells. RUNX3 contributes to carboplatin resistance in EOC cells and may hold promise as a therapeutic target to treat EOC and/or a biomarker to predict chemoresistance. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Stability study of carboplatin infusion solutions in 0.9% sodium chloride in polyvinyl chloride bags.

    Science.gov (United States)

    Myers, Alan L; Zhang, Yang-Ping; Kawedia, Jitesh D; Trinh, Van A; Tran, Huyentran; Smith, Judith A; Kramer, Mark A

    2016-02-01

    Carboplatin is a platinum-containing compound with efficacy against various malignancies. The physico-chemical stability of carboplatin in dextrose 5% water (D5W) has been thoroughly studied; however, there is a paucity of stability data in clinically relevant 0.9% sodium chloride infusion solutions. The manufacturer's limited stability data in sodium chloride solutions hampers the flexibility of carboplatin usage in oncology patients. Hence, the purpose of this study is to determine the physical and chemical stability of carboplatin-sodium chloride intravenous solutions under different storage conditions. The physico-chemical stability of 0.5 mg/mL, 2.0 mg/mL, and 4.0 mg/mL carboplatin-sodium chloride solutions prepared in polyvinyl chloride bags was determined following storage at room temperature under ambient fluorescent light and under refrigeration in the dark. Concentrations of carboplatin were measured at predetermined time points up to seven days using a stability-indicating high-performance liquid chromatography method. All tested solutions were found physically stable for at least seven days. The greatest chemical stability was observed under refrigerated storage conditions. At 4℃, all tested solutions were found chemically stable for at least seven days, with nominal losses of ≤6%. Following storage at room temperature exposed to normal fluorescent light, the chemical stability of 0.5 mg/mL, 2.0 mg/mL, and 4.0 mg/mL solutions was three days, five days, and seven days, respectively. The extended physico-chemical stability of carboplatin prepared in sodium chloride reported herein permits advance preparation of these admixtures, facilitating pharmacy utility and operations. Since no antibacterial preservative is contained within these carboplatin solutions, we recommend storage, when prepared under specified aseptic conditions, no greater than 24 h at room temperature or three days under refrigeration. © The Author(s) 2014.

  11. Elution of platinum from carboplatin-impregnated calcium sulfate hemihydrate beads in vitro.

    Science.gov (United States)

    Tulipan, Rachel J; Phillips, Heidi; Garrett, Laura D; Dirikolu, Levent; Mitchell, Mark A

    2016-11-01

    OBJECTIVE To characterize the elution of platinum from carboplatin-impregnated calcium sulfate hemihydrate (CSH) beads in vitro. SAMPLE 60 carboplatin-impregnated CSH beads and 9 CSH beads without added carboplatin (controls). PROCEDURES Carboplatin-impregnated CSH beads (each containing 4.6 mg of carboplatin [2.4 mg of platinum]) were placed into separate 10-mL plastic tubes containing 5 mL of PBSS in groups of 1, 3, 6, or 10; 3 control beads were placed into a single tube of PBSS at the same volume. Experiments were conducted in triplicate at 37°C and a pH of 7.4 with constant agitation. Eluent samples were collected at 1, 2, 3, 6, 12, 24, and 72 hours. Samples were analyzed for platinum content by inductively coupled plasma-mass spectrometry. RESULTS The mean concentration of platinum released per carboplatin-impregnated bead over 72 hours was 445.3 mg/L. Cumulative concentrations of platinum eluted increased as the number of beads per tube increased. There was a significant difference in platinum concentrations over time, with values increasing over the first 12 hours and then declining for all tubes. There was also a significant difference in percentage of total incorporated platinum released into tubes with different numbers of beads: the percentage of eluted platinum was higher in tubes containing 1 or 3 beads than in those containing 6 or 10 beads. CONCLUSIONS AND CLINICAL RELEVANCE Carboplatin-impregnated CSH beads eluted platinum over 72 hours. Further studies are needed to determine whether implantation of carboplatin-impregnated CSH beads results in detectable levels of platinum systemically and whether the platinum concentrations eluted locally are toxic to tumor cells.

  12. Knockdown of FUSE binding protein 1 enhances the sensitivity of epithelial ovarian cancer cells to carboplatin.

    Science.gov (United States)

    Zhang, Jinli; Xiong, Xifeng; Hua, Xing; Cao, Wenjuan; Qin, Shengnan; Dai, Libing; Liang, Peihong; Zhang, Huiling; Liu, Zhihe

    2017-11-01

    Epithelial ovarian cancer (EOC) affects almost 25,000 women annually and is the fifth most common malignancy in women in North America. A combination of surgery and cytotoxic chemotherapy may produce a favorable clinical response. The platinum-paclitaxel combination regimen is the chemotherapy gold-standard for advanced ovarian cancer, and carboplatin is one of the agents in this combination therapy. However, the majority of patients eventually experience a relapse due to the development of platinum resistance. FUSE binding protein 1 (FBP1) has been identified as an anti-apoptotic and pro-proliferative oncoprotein that is overexpressed in hepatocellular carcinoma. Its high expression is also associated with carboplatin resistance. In the present study, it was identified that the expression of FBP1 was significantly higher in EOC tissues than in normal epithelial ovarian or in epithelial ovarian adenoma tissue. FBP1 expression was significantly correlated with the grade of epithelial ovarian cancer. Carboplatin inhibited the expression of FBP1 in epithelial ovarian cancer cells and the knockdown of FBP1 enhanced the inhibition of cell viability and migration by carboplatin. In addition to FBP1, carboplatin also inhibited the expression of β-catenin and matrix metalloproteinase (MMP)-9. Furthermore, the expression of β-catenin and MMP-9 were lower in FBP1 knockdown cells compared with control EOC cells. FBP1 may thus serve a role in the regulation of the expression of β-catenin and MMP-9; the inhibition of β-catenin and MMP-9 by carboplatin may be mediated through the inhibition of FBP1. The inhibition of FBP1 expression by carboplatin may be a mechanism in the treatment of EOC by carboplatin.

  13. Shear induced carboplatin binding within the cavity of a phospholipid mimic for increased anticancer efficacy

    Science.gov (United States)

    Mo, Jingxin; Eggers, Paul K.; Chen, Xianjue; Ahamed, Muhammad Rizwan Hussain; Becker, Thomas; Yong Lim, Lee; Raston, Colin L.

    2015-01-01

    Vesicles 107 ± 19 nm in diameter, based on the self-assembly of tetra-para-phosphonomethyl calix[4]- arene bearing n-hexyl moieties attached to the phenolic oxygen centres, are effective in binding carboplatin within the cavity of the macrocycle under shear induced within a dynamic thin film in a continuous flow vortex fluidic device. Post shearing the vesicles maintain similar diameters and retain carboplatin within the cavity of the calixarene in a hierarchical structure, with their size and morphology investigated using DLS, TEM, SEM and AFM. Location of the carboplatin was confirmed using NMR, FTIR, ESI-MS and EFTEM, with molecular modelling favouring the polar groups of carboplatin hydrogen bonded to phosphonic acid moieties and the four member cyclobutane ring directed into the cavity of the calixarene. The loading efficiency and release profile of carboplatin was investigated using LC-TOF/MS, with the high loading of the drug achieved under shear and preferential released at pH 5.5, offering scope for anti-cancer drug delivery. The hierarchical structured vesicles increase the efficacy of carboplatin by 4.5 fold on ovarian cancer cells, lowered the IC50 concentration by 10 fold, and markedly increased the percent of cells in the S-phase (DNA replication) of the cell cycle. PMID:26000441

  14. Comparative study of hydrolytic and electron-driven processes in carboplatin biotransformation.

    Science.gov (United States)

    Kuduk-Jaworska, Janina; Jański, Jerzy J; Roszak, Szczepan

    2017-05-01

    The results of computational simulation of reaction courses mimicking the transformation of carboplatin from pro-drug into its active shape, responsible for cytotoxic effect, are reported. Implementing the density functional theory (DFT) calculations and the supermolecular approach, we explored the pathways representing two disparate models of carboplatin bioactivation: (1) based on paradigm of carboplatin aquation, and (2) based on new hypothesis that transformation is controlled by electron-transfer processes. The calculated geometrical and thermodynamic parameters were used for evaluation of pathways. In contrast to carboplatin hydrolysis, representing a typical two stage SN2 mechanism, the postulated electron-driven reactions proceed under the dissociative electron attachment (DEA) mechanism. The reaction profiles predict endothermic effect in both stages of hydrolytic course and final exothermic effects for electron-driven processes. The most effective are hybrid processes including two-stages: water and subsequent electron impact on transformed carboplatin. The aqua-products, manifesting strong electron-affinity, can be the active form of drug capable to cytotoxic interaction with DNA, not only as alkylating agent but also as electron-acceptor. Concluding, the hybrid transformation of carboplatin is more favourable than hydrolytic. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. An adapted, four-week mind-body skills group for medical students: reducing stress, increasing mindfulness, and enhancing self-care.

    Science.gov (United States)

    Greeson, Jeffrey M; Toohey, Michael J; Pearce, Michelle J

    2015-01-01

    Despite the well-known stress of medical school, including adverse consequences for mental and behavioral health, there is little consensus about how to best intervene in a way that accommodates students׳ intense training demands, interest in science, and desire to avoid being stigmatized. The objective of this study, therefore, was to evaluate the feasibility, acceptability, and initial effectiveness of an adapted, four-week stress management and self-care workshop for medical students, which was based on the science and practice of mind-body medicine. The current study used a prospective, observational, and mixed methods design, with pretest and posttest evaluations. Participants (n = 44) included medical and physician-scientist (MD/PhD) students from a large, southeastern medical school. Feasibility was assessed by rates of workshop enrollment and completion. Acceptability was assessed using qualitative ratings and open-ended responses that queried perceived value of the workshop. Quantitative outcomes included students׳ ratings of stress and mindfulness using validated self-report surveys. Enrollment progressively increased from 6 to 15 to 23 students per workshop in 2007, 2009, and 2011, respectively. Of the 44 enrolled students, 36 (82%) completed the workshop, indicating that the four-session extracurricular format was feasible for most students. Students reported that the workshop was acceptable, stating that it helped them cope more skillfully with the stress and emotional challenges of medical school, and helped increase self-care behaviors, such as exercise, sleep, and engaging in social support. Students also reported a 32% decrease in perceived stress (P stress and mindfulness were significantly correlated (r = -0.42; P = .01). Together, these findings suggest that a brief, voluntary mind-body skills workshop specifically adapted for medical students is feasible, acceptable, and effective for reducing stress, increasing mindfulness, and enhancing

  16. [A case of pseudomenbranous colitis after paclitaxel and carboplatin chemotherapy].

    Science.gov (United States)

    Yang, Sung Woo; Moon, Won

    2009-11-01

    Antibiotics-associated pseudomembranous colitis is well documented and caused by abnormal overgrowth of toxin producing Clostridium difficile colonizing the large bowel of patients undergoing antibiotic therapy. Administration of chemotherapeutic agents is frequently complicated by diarrhea and enterocolitis. However, pseudomembranous colitis related to chemotherapeutic agent usage is very rare. We experienced a 67 old-years male patient diagnosed of non-small cell lung carcinoma who complained of watery diarrhea and abdominal pain after treated with paclitaxel and carboplatin. Sigmoidoscopic examination revealed diffusely scattered, whitish to yellowish pseudomembrane with background edematous hyperemic mucosa from sigmoid colon to rectum. Histopathologic findings were consistent with pseudomembranous colitis as typical volcano-like exudate. The symptoms improved after stopping chemotherapy and treatment with metronidazole. In patients with persistent diarrhea and abdominal pain after receiving chemotherapy agents, although rare, pseudomembranous colitis should be considered as a differential diagnosis.

  17. Carboplatin-docetaxel-induced activity against ovarian cancer is dependent on up-regulated lncRNA PVT1.

    Science.gov (United States)

    Liu, Enling; Liu, Zheng; Zhou, Yuxiu

    2015-01-01

    Ovarian cancer is the fourth most ordinary cause of cancer-related deaths in women. In recent, combination chemotherapy with carboplatin and docetaxel was developed as first-line drug to treat ovarian carcinoma. However, the detailed molecular mechanism, which accounts for the cells to apoptosis induced by administration of carboplatin and docetaxel, was unrecognized. In present study, we provide the mechanistic link between mixture of carboplatin plus docetaxel and its anticancer activity. Primarily, a majority of 30 cancer-related long non-coding RNA (lncRNA) showed differential alteration in carboplatin-docetaxel-treated 3AO cells. Among six up-regulating lncRNAs, we screened out carboplatin-docetaxel-induced lncRNA PVT1 which may be a central downstream target of carboplatin plus docetaxel because expression of PVT1 positively correlates with anticancer action of carboplatin plus docetaxel. Besides, p53 and tissue inhibitor of matrix metalloproteinases-1 (TIMP1) were mediated by lncRNA PVT1, which may explain partially the anticancer activity of lncRNA PVT1. Collectively, we have identified a potential mechanism by which PVT1 regulated by carboplatin plus docetaxel contributes to the carboplatin-docetaxel-induced anticancer action in ovarian cancer. These discoveries also give proof of the potential of PVT1 as significant downstream targets for therapeutic intervention in ovarian cancer.

  18. Cost–utility analysis for platinum-sensitive recurrent ovarian cancer therapy in South Korea: results of the polyethylene glycolated liposomal doxorubicin/carboplatin sequencing model

    Directory of Open Access Journals (Sweden)

    Lee HY

    2013-07-01

    Full Text Available Hwa-young Lee,1 Bong-Min Yang,1 Ji-min Hong,1 Tae-Jin Lee,1 Byoung-Gie Kim,2 Jae-Weon Kim,3 Young-Tae Kim,4 Yong-Man Kim,5 Sokbom Kang61Graduate School of Public Health, Seoul National University, Seoul, South Korea; 2Department of Obstetrics and Gynecology, Samsung Medical Center, Seoul, South Korea; 3Department of Obstetrics and Gynecology, Seoul National University, Seoul, South Korea; 4Department of Obstetrics and Gynecology, Yonsei University, Seoul, South Korea; 5Department of Obstetrics and Gynecology, University of Ulsan, Ulsan, South Korea; 6Department of Obstetrics and Gynecology, National Cancer Center, Kyeonggi-do, South KoreaObjective: We performed a cost–utility analysis to assess the cost-effectiveness of a chemotherapy sequence including a combination of polyethylene glycolated liposomal doxorubicin (PLD/carboplatin versus paclitaxel/carboplatin as a second-line treatment in women with platinum-sensitive ovarian cancer.Methods: A Markov model was constructed with a 10-year time horizon. The treatment sequence consisted of first- to sixth-line chemotherapies and best supportive care (BSC before death. Cycle length, a time interval for efficacy evaluation of chemotherapy, was 9 weeks. The model consisted of four health states: responsive, progressive, clinical remission, and death. At any given time, a patient may have remained on a current therapy or made a transition to the next therapy or death. Median time to progressions and overall survivals data were obtained through a systematic literature review and were pooled using a meta-analytical approach. If unavailable, this was elicited from an expert panel (eg, BSC. These outcomes were converted to transition probabilities using an appropriate formula. Direct costs included drug-acquisition costs for chemotherapies, premedication, adverse-event treatment and monitoring, efficacy evaluation, BSC, drug administration, and follow-up tests during remission. Indirect costs were

  19. Continuous-Course Reirradiation With Concurrent Carboplatin and Paclitaxel for Locally Recurrent, Nonmetastatic Squamous Cell Carcinoma of the Head-and-Neck

    Energy Technology Data Exchange (ETDEWEB)

    Kharofa, Jordan [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Choong, Nicholas [Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Wang, Dian; Firat, Selim; Schultz, Christopher [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Sadasiwan, Chitra [Medical College of Wisconsin, Milwaukee, WI (United States); Wong, Stuart, E-mail: Swong@mcw.edu [Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI (United States)

    2012-06-01

    Purpose: To examine the efficacy and toxicity of continuous-course, conformal reirradiation with weekly paclitaxel and carboplatin for the treatment of locally recurrent, nonmetastatic squamous cell carcinoma of the head and neck (SCCHN) in a previously irradiated field. Methods and Materials: Patients treated with continuous course-reirradiation with concurrent carboplatin and paclitaxel at the Medical College of Wisconsin and the Clement J. Zablocki VA from 2001 through 2009 were retrospectively reviewed. Patients included in the analysis had prior radiation at the site of recurrence of at least 45 Gy. The analysis included patients who received either intensity-modulated radiotherapy (RT) or three-dimensional conformal RT techniques. All patients received weekly concurrent carboplatin (AUC2) and paclitaxel (30-50 mg/m{sup 2}). Results: Thirty-eight patients with nonmetastatic SCCHN met the entry criteria for analysis. The primary sites at initial diagnosis were oropharyngeal or laryngeal in most patients (66%). Median reirradiation dose was 60 Gy (range, 54-70 Gy). Acute toxicity included Grade 2 neutropenia (5%), Grade 3 neutropenia (15%), and Grade 1/2 thrombocytopenia (8%). No deaths occurred from hematologic toxicity. Chemotherapy doses held (50%) was more prevalent than radiation treatment break (8%). Sixty-eight percent of patients required a gastrostomy tube in follow-up. Significant late toxicity was experienced in 6 patients (16%): 1 tracheoesophageal fistula, 1 pharyngocutaneous fistula, 3 with osteoradionecrosis, and 1 patient with a lingual artery bleed. Patients treated with three-dimensional conformal RT had more frequent significant late toxicites than patients treated with intensity-modulated RT (44% and 7% respectively, p < 0.05). The median time to progression was 7 months and progression-free rates at 1, 2, and 5 years was 44%, 34%, and 29% respectively. The median overall survival was 16 months. Overall survival at 1, 3, and 5 years was 54

  20. A 12-week clinical comparison of an oscillating-rotating power brush versus a marketed sonic brush with self-adjusting technology in reducing plaque and gingivitis.

    Science.gov (United States)

    Klukowska, Malgorzata; Grender, Julie M; Conde, Erinn; Goyal, C Ram

    2013-01-01

    The aim of this investigation was to assess the comparative gingivitis and plaque reduction efficacy of a leading oscillating-rotating power toothbrush and a recently introduced sonic toothbrush in adults with gingivitis. This was a 12-week, randomized and controlled, parallel group, examiner-blind, single-center clinical study of 130 adults with pre-existing gingivitis and plaque. At baseline, the Modified Gingival Index (MGI), Gingival Bleeding Index (GBI), and total number of bleeding sites were assessed, along with plaque levels (whole mouth, gingival margin, and interproximal) via the Rustogi Modified Navy Plaque Index (RMNPI). Qualified subjects were randomly assigned to one of two power toothbrush test groups: the Oral-B Triumph with SmartGuide (marketed in the United States as the Oral-B Professional Care SmartSeries 5000 [D34]) oscillating-rotating brush, or the Colgate ProClinical A1500 (also marketed as elmex ProClinical) sonic brush. Subjects brushed at home for two minutes twice daily with their assigned power toothbrush and a marketed sodium fluoride dentifrice, and were reevaluated for gingivitis at Week 4 and Week 12 via the MGI, GBI, and total number of bleeding sites, and for plaque reduction via the RMNPI. Ninety-seven percent (97%) of the 130 enrolled subjects completed the trial and 62 and 65 subjects in the oscillating-rotating and sonic brush groups, respectively, had evaluable data for analysis. Statistically significant mean reductions in all three gingivitis parameters and plaque relative to baseline were seen at both Weeks 4 and 12 with unsupervised use of both test toothbrushes (p gingival margin plaque (36% at Week 4; p = 0.004), and interproximal plaque (39% and 26% at Weeks 4 and 12, respectively; p gingivitis via multiple outcome measures compared to a new sonic toothbrush after both four weeks and 12 weeks of tooth brushing.

  1. Increasing weaning age of piglets from 4 to 7 weeks reduces stress, increases post-weaning feed intake but does not improve intestinal functionality

    OpenAIRE

    Meulen, van der, J.; Koopmans, S.J.; Dekker, R. A.; Hoogendoorn, A.

    2010-01-01

    This study tested the hypothesis that late weaning and the availability of creep feed during the suckling period compared with early weaning, improves feed intake, decreases stress and improves the integrity of the intestinal tract. In this study with 160 piglets of 16 litters, late weaning at 7 weeks of age was compared with early weaning at 4 weeks, with or without creep feeding during the suckling period, on post-weaning feed intake, plasma cortisol (as an indicator of stress) and plasma i...

  2. Final overall survival results of phase III GCIG CALYPSO trial of pegylated liposomal doxorubicin and carboplatin vs paclitaxel and carboplatin in platinum-sensitive ovarian cancer patients

    Science.gov (United States)

    Wagner, U; Marth, C; Largillier, R; Kaern, J; Brown, C; Heywood, M; Bonaventura, T; Vergote, I; Piccirillo, M C; Fossati, R; Gebski, V; Lauraine, E P

    2012-01-01

    Background: The CALYPSO phase III trial compared CD (carboplatin-pegylated liposomal doxorubicin (PLD)) with CP (carboplatin-paclitaxel) in patients with platinum-sensitive recurrent ovarian cancer (ROC). Overall survival (OS) data are now mature. Methods: Women with ROC relapsing >6 months after first- or second-line therapy were randomised to CD or CP for six cycles in this international, open-label, non-inferiority trial. The primary endpoint was progression-free survival. The OS analysis is presented here. Results: A total of 976 patients were randomised (467 to CD and 509 to CP). With a median follow-up of 49 months, no statistically significant difference was observed between arms in OS (hazard ratio=0.99 (95% confidence interval 0.85, 1.16); log-rank P=0.94). Median survival times were 30.7 months (CD) and 33.0 months (CP). No statistically significant difference in OS was observed between arms in predetermined subgroups according to age, body mass index, treatment-free interval, measurable disease, number of lines of prior chemotherapy, or performance status. Post-study cross-over was imbalanced between arms, with a greater proportion of patients randomised to CP receiving post-study PLD (68%) than patients randomised to CD receiving post-study paclitaxel (43% P<0.001). Conclusion: Carboplatin-PLD led to delayed progression and similar OS compared with carboplatin-paclitaxel in platinum-sensitive ROC. PMID:22836511

  3. The cytotoxic activity of cisplatin, carboplatin and teniposide alone and combined determined on four human small cell lung cancer cell lines by the clonogenic assay

    DEFF Research Database (Denmark)

    Roed, H; Vindeløv, L L; Christensen, I J

    1988-01-01

    Using the clonogenic assay to compare the cytotoxic activity of cisplatin and carboplatin on four human small cell lung cancer cell lines, cisplatin was shown to be equally or more potent than carboplatin at equitoxic doses with 1 h incubation. Increased potency of carboplatin was revealed when...

  4. Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy

    DEFF Research Database (Denmark)

    De Santis, Maria; Bellmunt, Joaquim; Mead, Graham

    2012-01-01

    This is the first randomized phase II/III trial comparing two carboplatin-based chemotherapy regimens in patients with urothelial cancer who are ineligible ("unfit") for cisplatin chemotherapy.......This is the first randomized phase II/III trial comparing two carboplatin-based chemotherapy regimens in patients with urothelial cancer who are ineligible ("unfit") for cisplatin chemotherapy....

  5. A phase I study afatinib/carboplatin/paclitaxel induction chemotherapy followed by standard chemoradiation in HPV-negative or high-risk HPV-positive locally advanced stage III/IVa/IVb head and neck squamous cell carcinoma.

    Science.gov (United States)

    Chung, Christine H; Rudek, Michelle A; Kang, Hyunseok; Marur, Shanthi; John, Pritish; Tsottles, Nancy; Bonerigo, Sarah; Veasey, Andy; Kiess, Ana; Quon, Harry; Cmelak, Anthony; Murphy, Barbara A; Gilbert, Jill

    2016-02-01

    Afatinib is an ErbB family receptor inhibitor with efficacy in head and neck squamous cell carcinoma (HNSCC). A phase I trial was conducted to determine the maximally tolerated dose (MTD) of afatinib in combination with carboplatin and paclitaxel as induction chemotherapy (IC). Patients with newly diagnosed, locally advanced HPV-negative or HPV-positive HNSCC with a significant smoking history were enrolled. Afatinib alone was given daily for two weeks as lead-in and subsequently given with carboplatin AUC 6mg/mlmin and paclitaxel 175mg/m(2) every 21days as IC. Afatinib was started at a dose of 20mg daily and dose escalated using a modified Fibonacci design. After completion of IC, afatinib was discontinued and patients received concurrent cisplatin 40mg/m(2) weekly and standard radiation. Toxicity was assessed using CTCAE version 4.0. Seven of nine patients completed afatinib lead-in and IC. Five patients had partial response and two patients had stable disease after IC. Dose level 1 (afatinib 20mg) was well tolerated with one grade 3 (ALT elevation) and one grade 4 (neutropenia) toxicities. However, dose level 2 (afatinib 30mg) was not well tolerated with nine grade 3 (pneumonia, abdominal pain, diarrhea, pancytopenia, and UTI), two grade 4 (sepsis) and one grade 5 (death) toxicities. The MTD of afatinib given with carboplatin AUC 6mg/mlmin and paclitaxel 175mg/m(2) is 20mg daily. Combination of afatinib at doses higher than 20mg with carboplatin and paclitaxel should be administered with caution due to the toxicities. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Reduced plasma glucose and leptin after 12 weeks of functional electrical stimulation-rowing exercise training in spinal cord injury patients.

    Science.gov (United States)

    Jeon, Justin Y; Hettinga, Dries; Steadward, Robert D; Wheeler, Garry D; Bell, Gordon; Harber, Vicki

    2010-12-01

    To investigate the effects of exercise training with a functional electrical stimulation (FES) rowing machine on insulin resistance, plasma leptin levels, and body composition in people with spinal cord injury (SCI). Experimental study. A fitness and research center for people with disabilities. Healthy male participants with paraplegia (N=6) participated in the study (mean age, 48.6±6y; mean weight, 70.06±3.28kg; injury levels between T4-5 and T10). Twelve weeks of FES-rowing exercise training 3 to 4 times a week (600-800kcal). Peak oxygen consumption, plasma leptin, insulin, and glucose levels, insulin sensitivity, body composition. Twelve weeks of FES-rowing training improved aerobic fitness significantly (P=.048). In addition, plasma glucose and leptin levels were significantly decreased after exercise training by 10% and 28% (P<.028), respectively. A trend toward fat mass reduction was seen in 4 of the 6 subjects; this change did not reach statistical significance (P=.08). A 12-week training program that included FES rowing improved aerobic fitness and fasting glucose and leptin levels in the absence of significant change to body composition, fasting insulin levels, or calculated insulin sensitivity in people with SCI. Copyright © 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  7. Chemoradiation With Paclitaxel and Carboplatin in High-Risk Cervical Cancer Patients After Radical Hysterectomy: A Korean Gynecologic Oncology Group Study

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Taek Sang [Department of Obstetrics and Gynecology, SMG-SNU Boramae Medical Center, Seoul (Korea, Republic of); Kang, Soon Beom, E-mail: tslee70@gmail.com [Department of Obstetrics and Gynecology, Konkuk University Medical Center, Seoul (Korea, Republic of); Kim, Young Tak [Department of Obstetrics and Gynecology, Asan Medical Center, Seoul (Korea, Republic of); Park, Byung Joo [Department of Preventive Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Yong Man [Department of Obstetrics and Gynecology, Asan Medical Center, Seoul (Korea, Republic of); Lee, Jong Min [Department of Obstetrics and Gynecology, Kyung Hee University Hospital at Gangdong, Seoul (Korea, Republic of); Kim, Seok Mo [Department of Obstetrics and Gynecology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Kim, Young Tae [Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Jae Hoon [Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Seoul (Korea, Republic of); Kim, Kyung Tai [Department of Obstetrics and Gynecology, Hanyang University Medical Center, Seoul (Korea, Republic of)

    2013-06-01

    Purpose: To evaluate the efficacy and toxicity of concurrent chemoradiation with paclitaxel and carboplatin in patients with high-risk cervical cancer. Methods and Materials: Patients after radical hysterectomy for cervical cancer, with at least 1 high-risk characteristic, were administered paclitaxel 135 mg/m{sup 2}, carboplatin area under the curve = 5 every 3 weeks for 3 cycles concomitant with radiation therapy as adjuvant treatment. Results: This prospective study enrolled 71 consecutive patients. Sixty-six patients (93%) completed the planned treatment. The majority of grade 3/4 neutropenia or nonhematologic toxicities were usually self-limited. Diarrhea grades 3/4 were observed in 4 patients (5.6%). One patient developed anaphylactic shock after infusion of paclitaxel. With a median follow-up of 57 months, recurrences occurred in 16 patients. Multivariable analysis indicated that common iliac lymph node involvement is an independent risk factor for disease recurrence (odds ratio 13.48; 95% confidence interval 2.93-62.03). In the intent-to-treat population (n=71), the estimated 5-year disease-free survival and overall survival rates were 77.3% and 80.3% respectively. In the per-protocol population (n=62), disease-free survival was 78.9% and overall survival was 83.9%. Conclusions: Concurrent chemoradiation with paclitaxel/carboplatin is well tolerated and seems to be effective for patients who undergo radical hysterectomy. Therefore, a prospective, randomized controlled study should be designed to evaluate efficacy of this approach for patients with high-risk cervical cancer.

  8. Time-Frequency Analysis of Transient-Evoked Otoacoustic Emissions in Children exposed to Carboplatin Chemotherapy

    Science.gov (United States)

    Bhagat, Shaum; Bass, Johnnie; Qaddoumi, Ibrahim; Brennan, Rachel; Wilson, Matthew; Wu, Jianrong; Galindo, Carlos-Rodriguez; Paglialonga, Alessia; Tognola, Gabriella

    2013-01-01

    The aims of this study were to characterize and quantify time-frequency changes in transient-evoked otoacoustic emissions (TEOAEs) recorded in children diagnosed with retinoblastoma who were receiving carboplatin chemotherapy. A signal processing technique, the wavelet transform (WT), was used to analyze TEOAE waveforms in narrow-band frequency components. Ten children (aged 3–72 months) diagnosed with unilateral or bilateral retinoblastoma were enrolled in the study. TEOAEs were acquired from the children with linear sequences of 70 dB peSPL clicks. After WT analysis, TEOAE energy, latency, and normalized energy in the narrow-band frequency components were compared before and during carboplatin (average dose 1693 mg/m2) chemotherapy treatment. On a group basis, no significant differences (p>0.05) in pre- and post-carboplatin TEOAE energy, latency, or normalized energy were observed. There were decreases in normalized energy on an individual basis in 10/18 ears in the sample. Exposure to carboplatin chemotherapy did not cause significant changes in TEOAE energy, latency, and normalized energy during treatment. However, long-term monitoring of hearing with measurements of TEOAEs is warranted given the risks of delayed hearing loss in some children receiving carboplatin chemotherapy. PMID:23147804

  9. Ischemic necrosis and atrophy of the optic nerve after periocular carboplatin injection for intraocular retinoblastoma.

    Science.gov (United States)

    Schmack, Ingo; Hubbard, G Baker; Kang, Shin J; Aaberg, Thomas M; Grossniklaus, Hans E

    2006-08-01

    To report four cases of optic nerve neuropathy in three children treated with periocular carboplatin injections for unilateral or bilateral intraocular retinoblastoma. Retrospective, observational case series. University-based Ophthalmology Practice. Four eyes of three children with retinoblastoma enucleated after nonsuccessful multimodality treatment including periocular carboplatin injections. The enucleated eyes were routinely processed and evaluated by light microscopy. A retrospective chart review of all four cases was performed. Three enucleated eyes (Reese-Ellsworth groups III and VB) were obtained from two children with bilateral multifocal retinoblastoma, and one eye (Reese-Ellsworth group IIB) was harvested from a child with unilateral retinoblastoma. All affected eyes underwent three to seven periocular carboplatin injections before enucleation. Additional treatment modalities included systemic chemotherapy, transpupillary thermotherapy, transscleral cryotherapy, and external beam radiotherapy. Histopathologic evaluation of the enucleated eyes revealed focal areas of ischemic necrosis or atrophy of the optic nerve along with dystrophic calcification and mild inflammation in the surrounding fibrovascular adipose tissue. Periocular injections of carboplatin may be a useful treatment approach in the management of patients with advanced intraocular retinoblastoma and may minimize systemic side-effects. However, ophthalmologists and pediatric oncologists should be aware of potential marked local complications with periocular carboplatin delivery, including ischemic optic neuropathy. Modifying the injection site/location (for example, subtenon space) or adding other delivery routes adjuncts (for example, fibrin sealant) deserves further study.

  10. Impact of Isotope Dilution Mass Spectrometry (IDMS) Standardization on Carboplatin Dose and Adverse Events.

    Science.gov (United States)

    Lawson, Justin; Switchenko, Jeffrey M; McKibbin, Trevor; Donald Harvey, R

    2016-06-01

    When using area under the concentration-time curve-based strategies for dosing carboplatin, accurate estimation of glomerular filtration rate is required for determining dose. Commonly, the Cockcroft-Gault equation is used, which is dependent on measurement of serum creatinine (SCr). Because analysis of SCr changed to an isotope dilution mass spectrometry (IDMS) standard, we sought to determine the impact of this assay change on carboplatin dosing and related toxicity. This was a single-center, retrospective chart review of adults treated with carboplatin between April 2008 and April 2010 divided into cohorts that initiated carboplatin before or after IDMS standardization. End points included grade 3 thrombocytopenia, decrease in platelet count, and hospitalization and were evaluated in cohorts based on concomitant chemotherapy. The chart review identified 158 patients, with 63 patients in the pre-IDMS group and 95 patients in the post-IDMS group. Average SCr (pre 1.01 mg/dl vs post 0.86 mg/dl, pIDMS implementation. IDMS standardization led to an overall decrease in SCr with subsequent increase in carboplatin doses. However, no increase in recorded adverse events was observed, suggesting that the clinical relevance in toxicity from higher doses was minimal. © 2016 Pharmacotherapy Publications, Inc.

  11. Cocoa extract intake for 4 weeks reduces postprandial systolic blood pressure response of obese subjects, even after following an energy-restricted diet

    Directory of Open Access Journals (Sweden)

    Idoia Ibero-Baraibar

    2016-03-01

    Full Text Available Background: Cardiometabolic profile is usually altered in obesity. Interestingly, the consumption of flavanol-rich foods might be protective against those metabolic alterations. Objective: To evaluate the postprandial cardiometabolic effects after the acute consumption of cocoa extract before and after 4 weeks of its daily intake. Furthermore, the bioavailability of cocoa extract was investigated. Design: Twenty-four overweight/obese middle-aged subjects participated in a 4-week intervention study. Half of the volunteers consumed a test meal enriched with 1.4 g of cocoa extract (415 mg flavanols, while the rest of the volunteers consumed the same meal without the cocoa extract (control group. Glucose and lipid profile, as well as blood pressure and cocoa metabolites in plasma, were assessed before and at 60, 120, and 180 min post-consumption, at the beginning of the study (Postprandial 1 and after following a 4-week 15% energy-restricted diet including meals containing or not containing the cocoa extract (Postprandial 2. Results: In the Postprandial 1 test, the area under the curve (AUC of systolic blood pressure (SBP was significantly higher in the cocoa group compared with the control group (p=0.007, showing significant differences after 120 min of intake. However, no differences between groups were observed at Postprandial 2. Interestingly, the reduction of postprandial AUC of SBP (AUC_Postprandial 2-AUC_Postprandial 1 was higher in the cocoa group (p=0.016. Furthermore, cocoa-derived metabolites were detected in plasma of the cocoa group, while the absence or significantly lower amounts of metabolites were found in the control group. Conclusions: The daily consumption of cocoa extract within an energy-restricted diet for 4 weeks resulted in a greater reduction of postprandial AUC of SBP compared with the effect of energy-restricted diet alone and independently of body weight loss. These results suggest the role of cocoa flavanols on

  12. Cocoa extract intake for 4 weeks reduces postprandial systolic blood pressure response of obese subjects, even after following an energy-restricted diet

    Science.gov (United States)

    Ibero-Baraibar, Idoia; Suárez, Manuel; Arola-Arnal, Anna; Zulet, M. Angeles; Martinez, J. Alfredo

    2016-01-01

    Background Cardiometabolic profile is usually altered in obesity. Interestingly, the consumption of flavanol-rich foods might be protective against those metabolic alterations. Objective To evaluate the postprandial cardiometabolic effects after the acute consumption of cocoa extract before and after 4 weeks of its daily intake. Furthermore, the bioavailability of cocoa extract was investigated. Design Twenty-four overweight/obese middle-aged subjects participated in a 4-week intervention study. Half of the volunteers consumed a test meal enriched with 1.4 g of cocoa extract (415 mg flavanols), while the rest of the volunteers consumed the same meal without the cocoa extract (control group). Glucose and lipid profile, as well as blood pressure and cocoa metabolites in plasma, were assessed before and at 60, 120, and 180 min post-consumption, at the beginning of the study (Postprandial 1) and after following a 4-week 15% energy-restricted diet including meals containing or not containing the cocoa extract (Postprandial 2). Results In the Postprandial 1 test, the area under the curve (AUC) of systolic blood pressure (SBP) was significantly higher in the cocoa group compared with the control group (p=0.007), showing significant differences after 120 min of intake. However, no differences between groups were observed at Postprandial 2. Interestingly, the reduction of postprandial AUC of SBP (AUC_Postprandial 2-AUC_Postprandial 1) was higher in the cocoa group (p=0.016). Furthermore, cocoa-derived metabolites were detected in plasma of the cocoa group, while the absence or significantly lower amounts of metabolites were found in the control group. Conclusions The daily consumption of cocoa extract within an energy-restricted diet for 4 weeks resulted in a greater reduction of postprandial AUC of SBP compared with the effect of energy-restricted diet alone and independently of body weight loss. These results suggest the role of cocoa flavanols on postprandial blood

  13. Reduced muscular fatigue after a 12-week leucine-rich amino acid supplementation combined with moderate training in elderly: a randomised, placebo-controlled, double-blind trial

    OpenAIRE

    Reule, Claudia A; Scholz, Claudia; Schoen, Christiane; Brown, Niklas; Siepelmeyer, Anne; Alt, Wilfried W

    2017-01-01

    Background Age-related muscle loss is characterised by a progressing decrease in muscle mass, strength and function. Besides resistance training and physical activity, appropriate nutrition that is rich in protein, especially branched-chain amino acids, is very important to support training effects and positively influence the protein synthesis to degradation ratio. Aim The purpose of this study was to evaluate the effect of a 12-week leucine-rich amino acid supplementation in combination wit...

  14. Does antenatal steroids treatment prior to elective cesarean section at 34-37 weeks of gestation reduce neonatal morbidity? Evidence from a case control study.

    Science.gov (United States)

    Kirshenbaum, Michal; Mazaki-Tovi, Shali; Amikam, Uri; Mazkereth, Ram; Sivan, Eyal; Schiff, Eyal; Yinon, Yoav

    2017-10-24

    To determine whether antenatal corticosteroids administration prior to an elective cesarean section (ECS) at 34-37 weeks gestation is associated with improved neonatal outcome. A case control study of women with singleton pregnancies who underwent ECS between 34 and 37 weeks of gestation including two groups: (1) study group in which patients were treated with betamethasone prior to ECS (n = 58) and (2) control group matched for gestational age at delivery in which patients did not receive betamethasone (n = 107). Neonatal measures including respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTN), oxygen requirement, admission to the special care unit, hypoglycemia, hyperbilirubinemia and length of hospitalization were determined in both groups. Composite respiratory morbidity was defined as the presence of either RDS, TTN, mechanical ventilation or oxygen requirement. There was no significant difference in the rate of composite respiratory morbidity nor its components between patients with and without betamethasone treatment (25.9 vs. 25.2%, respectively, p = 0.9). Antenatal treatment with corticosteroids prior to ECS at 34-37 weeks of gestation did not result in significant reduction in neonatal respiratory morbidity in our cohort of patients.

  15. Drug-induced immune hemolytic anemia associated with anti-carboplatin and the first example of anti-paclitaxel.

    Science.gov (United States)

    Leger, Regina M; Jain, Shweta; Nester, Theresa A; Kaplan, Henry

    2015-12-01

    Combined chemotherapy with carboplatin and paclitaxel is first-line treatment for lung and ovarian cancer. Drug-induced antibodies to carboplatin are rare but can cause severe, even fatal, hemolysis. Paclitaxel-induced immune hemolysis has not been reported. We describe a case of immune-mediated hemolysis associated with antibodies to carboplatin and paclitaxel in a woman with ovarian cancer who had received multiple chemotherapeutic agents over 7 years, including several courses of these two drugs. She required many transfusions. During a chemotherapy infusion the patient became hypotensive, was pale, and had rigors and red urine. The nadir hematocrit was 12.4%; peak bilirubin and lactate dehydrogenase were 16.3 mg/dL and 1188 units/L, respectively. Blood samples collected within hours after chemotherapy and 2 days later were tested for antibodies to carboplatin and paclitaxel. The direct antiglobulin test was positive with anti-IgG (3+) and anti-C3 (2+). The plasma collected shortly after chemotherapy agglutinated carboplatin-treated red blood cells (RBCs); untreated and paclitaxel-treated RBCs both reacted at the antiglobulin test most likely due to circulating carboplatin, paclitaxel, or both drugs. Serum collected 2 days later agglutinated (titer 2) and sensitized (titer 128) carboplatin-treated RBCs; untreated and paclitaxel-treated RBCs were nonreactive. An acid eluate reacted weakly in the presence of polyethylene glycol with carboplatin-treated RBCs. The serum reacted with untreated and enzyme-treated RBCs in the presence of soluble carboplatin and paclitaxel. Anti-carboplatin and the first example of anti-paclitaxel were detected in this patient's sample. © 2015 AABB.

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

    Science.gov (United States)

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

    2016-09-01

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

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

    Science.gov (United States)

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

    2018-01-01

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

  18. Curative and organ-preserving treatment with intra-arterial carboplatin induction followed by surgery and/or radiotherapy for advanced head and neck cancer: single-center five-year results

    Directory of Open Access Journals (Sweden)

    Tinelli Carmine

    2007-04-01

    Full Text Available Abstract Background This study evaluated the feasibility, toxicity, response rate and survival of neoadjuvant superselective intra-arterial infusion of high dose carboplatin in advanced head and neck cancer. Methods Forty-six patients with primary head and neck squamous cell carcinoma received 3 cycles of intra-arterial carboplatin (300 to 350 mg/m2 per cycle every 2 weeks, followed by radiotherapy or surgery plus radiotherapy. Results No complications or severe toxicity occurred. Sixteen patients (35% were complete responders, 20 (43% partial responders while 10 (22% did not respond to treatment. After completion of the multimodality treatment, 38/46 patients (83% were complete responders. After a 5-year follow-up period, 18/46 patients (39% are alive and disease-free, 3 (6,5% have died of a second primary tumor and 25 (54,5% have died of the disease. Conclusion Intra-arterial carboplatin induction chemotherapy is a safe, well-tolerated technique that discriminates between responders and non-responders and so may have prognostic significance in planning further integrated treatments aimed to organ preservation for advanced head and neck carcinomas.

  19. TNF-alpha inhibition could reduce biomarkers of endothelial dysfunction in patients with moderate to severe psoriasis: A 52-week echo-Doppler based quasi-experimental study.

    Science.gov (United States)

    Molina-Leyva, Alejandro; Garrido-Pareja, Fermín; Ruiz-Carrascosa, José Carlos; Ruiz-Villaverde, Ricardo

    2017-10-28

    Psoriasis is associated to endothelial dysfunction, which causes impaired vascular functioning. TNF-α blockers have shown the ability to improve vascular functioning in psoriasis. The nailfold vessel resistance index (NVRI) assesses microvascular functioning at nailfold. The objectives of the study is to assess the effect of the TNF-α inhibition with adalimumab on NVRI. Quasi-experimental study. Fifteen patients with moderate-severe psoriasis received adalimumab 40mg sc according to label information. Participants were assessed at baseline and at 12, 24 and 52 weeks after study intervention. A reduction of -0.09±0.02 (P<.01) in NVRI and a -11.2±2,41ng/ml (P<.001) in E-selectin was observed at week 52. Adalimumab could produce a progressive and sustained reduction of vessel resistance at nailfold and E-selectin in patients with psoriasis. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  20. Ten weeks of physical-cognitive-mindfulness training reduces fear-avoidance beliefs about work-related activity: Randomized controlled trial.

    Science.gov (United States)

    Jay, Kenneth; Brandt, Mikkel; Jakobsen, Markus Due; Sundstrup, Emil; Berthelsen, Kasper Gymoese; Schraefel, Mc; Sjøgaard, Gisela; Andersen, Lars L

    2016-08-01

    People with chronic musculoskeletal pain often experience pain-related fear of movement and avoidance behavior. The Fear-Avoidance model proposes a possible mechanism at least partly explaining the development and maintenance of chronic pain. People who interpret pain during movement as being potentially harmful to the organism may initiate a vicious behavioral cycle by generating pain-related fear of movement accompanied by avoidance behavior and hyper-vigilance.This study investigates whether an individually adapted multifactorial approach comprised of biopsychosocial elements, with a focus on physical exercise, mindfulness, and education on pain and behavior, can decrease work-related fear-avoidance beliefs.As part of a large scale 10-week worksite randomized controlled intervention trial focusing on company initiatives to combat work-related musculoskeletal pain and stress, we evaluated fear-avoidance behavior in 112 female laboratory technicians with chronic neck, shoulder, upper back, lower back, elbow, and hand/wrist pain using the Fear-Avoidance Beliefs Questionnaire at baseline, before group allocation, and again at the post intervention follow-up 10 weeks later.A significant group by time interaction was observed (P cognitive-mindfulness training in female laboratory technicians with chronic pain.

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

    Directory of Open Access Journals (Sweden)

    Briasoulis Evangelos

    2010-01-01

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

  2. Cross section calculations for electron scattering from platinum chemotherapeutic compounds. Electron scattering from carboplatin and oxaliplatin

    Science.gov (United States)

    Żywicka, B.; Możejko, P.

    2013-10-01

    Cross section for electron impact ionization of carboplatin, C6H12N2O4Pt, and oxaliplatin, C8H14N2O4Pt, have been calculated within binary-encounter-Bethe model for energies from the ionization threshold up to 5000 eV. Cross section for elastic electron scattering from carboplatin and oxaliplatin molecules have also been derived using independent atom method (IAM) and additivity rule for collision energies ranging from 50 eV to 3000 eV. Obtained cross sections have been compared with relevant cross sections for cisplatin molecules.

  3. Reduced-Sodium Lunches Are Well-Accepted by Uninformed Consumers Over a 3-Week Period and Result in Decreased Daily Dietary Sodium Intakes: A Randomized Controlled Trial

    NARCIS (Netherlands)

    Janssen, A.M.; Kremer, S.; Stipriaan, W.L. van; Noort, M.W.J.; Vries, J.H.M. de; Temme, E.H.M.

    2015-01-01

    Background: Processed foods are major contributors to excessive sodium intake in Western populations. We investigated the effect of food reformulation on daily dietary sodium intake. Objective: To determine whether uninformed consumers accept reduced-sodium lunches and to determine the effect of

  4. Caprylic acid reduces Salmonella Enteritidis populations in various segments of digestive tract and internal organs of 3- and 6-week-old broiler chickens, therapeutically

    NARCIS (Netherlands)

    Kollanoor-Johny, A.; Mattson, T.; Baskaran, S.A.; Amalaradjou, M.A.; Hoagland, T.A.; Darre, M.J.; Khan, M.I.; Schreiber, D.T.; Donoghue, A.M.; Donoghue, D.J.; Venkitanarayanan, K.

    2012-01-01

    We investigated the efficacy of feed supplemented with caprylic acid (CA), a natural, 8-carbon fatty acid for reducing Salmonella enterica serovar Enteritidis colonization in commercial broiler chickens. In separate 3- and 6-wk trials, 1-d-old straight-run broiler chicks (n = 70 birds/trial) were

  5. Comparative study analyzing survival and safety of bevacizumab/carboplatin/paclitaxel and cisplatin/pemetrexed in chemotherapy-naïve patients with advanced non-squamous bronchogenic carcinoma not harboring EGFR mutation

    Directory of Open Access Journals (Sweden)

    Abdel Kader Y

    2013-07-01

    Full Text Available Yasser Abdel Kader,1 Thierry Le Chevalier,2 Tamer El-Nahas,1 Amr Sakr11Department of Clinical Oncology, Cairo University, Cairo, Egypt; 2Department of Medical Oncology, Institut Gustave Roussy, Villejuif, Paris, FrancePurpose: The majority of Egyptian patients with lung cancer present at a late stage of the disease. Bevacizumab/carboplatin/paclitaxel, as well as cisplatin plus pemetrexed, are both standard regimens for advanced non-squamous bronchogenic cancer. This study compares both regimens, in terms of efficacy and toxicity profile, in Egyptian patients.Patients and methods: This is a randomized Phase II study comparing toxicity profile and survival in 41 chemotherapy-naïve patients with stage IIIB or IV non-squamous NSCLC, with an ECOG performance status of 0 to 2. The epidermal growth factor receptor (EGFR mutation detection was performed prior to treatment of all patients. Patients in the first group received: bevacizumab 7.5 mg/m2 on Day 1 and Day 15; carboplatin area under the curve-5 on Day 1; and paclitaxel 60 mg/m2 on Day 1, Day 8, and Day 15 every 4 weeks. In the second group, patients received cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 every 3 weeks.Results: The combination of bevacizumab/carboplatin/paclitaxel demonstrated higher Grade III–IV toxicity than cisplatin/pemetrexed regarding sensory/motor neuropathy (P = 0.06, DVT (P = 0.23, proteinuria (P = 0.23, and hypertension (P = 0.11, as well as Grade II alopecia (P = 0.001; however, no significant difference in toxicities between both arms was recorded regarding nausea and vomiting (P = 0.66, hematological toxicity, febrile neutropenia (P = 1 and fatigue (P = 0.66. Progression-free survival was similar for both treatment arms with a median of 6 months (P = 0.978. Overall median survival was comparable in both arms, 16.07 months versus 16.01 months (P = 0.89.Conclusion: Bevacizumab/carboplatin/paclitaxel and cisplatin/pemetrexed provided meaningful and comparable efficacy

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-08-29

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

  7. Dacarbazine DTIC and carboplatin as an outpatient treatment for disseminated malignant melanoma

    NARCIS (Netherlands)

    Nieboer, P; Mulder, NH; Van Der Graaf, WTA; Willemse, PHB; Hospers, GAP

    2001-01-01

    Occasionally long-term survival in disseminated melanoma can be obtained through chemotherapy, We treated 22 patients with disseminated melanoma with an outpatient regimen consisting of dacarbazine (DTIC) and carboplatin. Three patients had a complete response lasting 4+, 9 and 9 months (survival

  8. Phase II study of docetaxel and carboplatin as second-line treatment in NSCLC

    NARCIS (Netherlands)

    Wachters, FM; van Putten, JWG; Boezen, HM; Groen, HJM

    Aim of this study was to evaluate activity and toxicity of docetaxel and carboplatin as second-tine treatment in advanced non-small-cell lung cancer (NSCLC) patients who failed or relapsed after previous chemotherapy. Patients had to have unresectable stage IIIb or IV NSCLC, previous chemotherapy, a

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

    Science.gov (United States)

    Arlt, M.; Haase, D.; Hampel, S.; Oswald, S.; Bachmatiuk, A.; Klingeler, R.; Schulze, R.; Ritschel, M.; Leonhardt, A.; Fuessel, S.; Büchner, B.; Kraemer, K.; Wirth, M. P.

    2010-08-01

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

  10. Flat dosing of carboplatin is justified in adult patients with normal renal function

    NARCIS (Netherlands)

    Ekhart, Corine; de Jonge, Milly E.; Huitema, Alwin D. R.; Schellens, Jan H. M.; Rodenhuis, Sjoerd; Beijnen, Jos H.

    2006-01-01

    PURPOSE: The Calvert formula is a widely applied algorithm for the a priori dosing of carboplatin based on patients glomerular filtration rate (GFR) as accurately measured using the 51Cr-EDTA clearance. Substitution of the GFR in this formula by an estimate of creatinine clearance or GFR as

  11. Extremely high exposures in an obese patient receiving high-dose cyclophosphamide, thiotepa and carboplatin

    NARCIS (Netherlands)

    de Jonge, Milly E.; Mathôt, Ron A. A.; van Dam, Selma M.; Beijnen, Jos H.; Rodenhuis, Sjoerd

    2002-01-01

    An obese 53-year-old woman (height 167 cm, weight 130 kg) with metastatic breast cancer received high-dose chemotherapy comprising cyclophosphamide, thiotepa and carboplatin (CTC). The cyclophosphamide (1 g/m(2) per day) and thiotepa (80 mg/m(2) per day) doses were based on body surface area (BSA)

  12. Carboplatin dosing in overweight and obese patients with normal renal function, does weight matter?

    NARCIS (Netherlands)

    Ekhart, Corine; Rodenhuis, Sjoerd; Schellens, Jan H. M.; Beijnen, Jos H.; Huitema, Alwin D. R.

    2009-01-01

    PURPOSE: The purpose of this study was to determine the potential utility of alternative weight descriptors in the Cockcroft-Gault equation to more accurately predict carboplatin clearance in underweight, normal weight, overweight and obese patients. METHODS: Clearance values obtained from

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-08-20

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

  14. Insensitivity of the Audiogram to Carboplatin Induced Inner hair cell loss in Chinchillas

    Science.gov (United States)

    Lobarinas, Edward; Salvi, Richard; Ding, Dalian

    2013-01-01

    Noise trauma, aging, and ototoxicity preferentially damage the outer hair cells of the inner ear, leading to increased hearing thresholds and poorer frequency resolution. Whereas outer hair cells make synaptic connections with less than 10% of afferent auditory nerve fibers (type-II), inner hair cells make connections with over 90% of afferents (type-I). Despite these extensive connections, little is known about how selective inner hair cell loss impacts hearing. In chinchillas, moderate to high doses of the anticancer compound carboplatin produce selective inner hair cell and type-I afferent loss with little to no effect on outer hair cells. To determine the effects of carboplatin-induced inner hair cell loss on the most widely used clinical measure of hearing, the audiogram, pure-tone thresholds were determined behaviorally before and after 75 mg/kg carboplatin. Following carboplatin treatment, small effects on audiometric thresholds were observed even with extensive inner hair cell losses that exceed 80%. These results suggest that conventional audiometry is insensitive to inner hair cell loss and that only small populations of inner hair cells appear to be necessary for detecting tonal stimuli in a quiet background. PMID:23566980

  15. Methylseleninic acid sensitizes Notch3-activated OVCA429 ovarian cancer cells to carboplatin

    Science.gov (United States)

    Ovarian cancer, the deadliest of gynecologic cancers, is usually diagnosed at advanced stage due to invalidated screening test and non-specific symptoms presented. Although carboplatin has been popular for treating ovarian cancer for decades, patients eventually develop resistance to this platinum-c...

  16. Characterization and carboplatin loaded chitosan nanoparticles for the chemotherapy against breast cancer in vitro studies.

    Science.gov (United States)

    Khan, Md Asad; Zafaryab, Md; Mehdi, Syed Hassan; Quadri, Javed; Rizvi, M Moshahid A

    2017-04-01

    Aim of the studies to synthesized chitosan nanoparticles by an ionic interaction procedure. The nanoparticles were characterized by physicochemical methods like, DLS, TEM, Surface potential measurements, FT-IR and DSC. The average particle size of chitosan and carboplatin nanoparticles was found to be 277.25±11.37nm and 289.30±8.15nm and zeta potential was found to be 31±3.14mV and 33±2.15mV respectively with low polydispersity index. The maximum entrapment of carboplatin in nanoparticles was a spherical shape with a positive charge. The maximum encapsulation and loading efficiencies of carboplatin (5mg/ml) were obtained to be 58.43% and 13.27% respectively. The nanocarboplatin was better blood compatibility as compared to chitosan nanoparticles. Finally, the cytotoxic effects of the carboplatin loaded chitosan nanoparticles were tested in-vitro against breast cancer (MCF-7) cell lines. Our studies showed that the chitosan nanoparticles could be used as a promising candidate for drug delivery for the therapeutic treatment of breast cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Insensitivity of the audiogram to carboplatin induced inner hair cell loss in chinchillas.

    Science.gov (United States)

    Lobarinas, Edward; Salvi, Richard; Ding, Dalian

    2013-08-01

    Noise trauma, aging, and ototoxicity preferentially damage the outer hair cells of the inner ear, leading to increased hearing thresholds and poorer frequency resolution. Whereas outer hair cells make synaptic connections with less than 10% of afferent auditory nerve fibers (type-II), inner hair cells make connections with over 90% of afferents (type-I). Despite these extensive connections, little is known about how selective inner hair cell loss impacts hearing. In chinchillas, moderate to high doses of the anticancer compound carboplatin produce selective inner hair cell and type-I afferent loss with little to no effect on outer hair cells. To determine the effects of carboplatin-induced inner hair cell loss on the most widely used clinical measure of hearing, the audiogram, pure-tone thresholds were determined behaviorally before and after 75 mg/kg carboplatin. Following carboplatin treatment, small effects on audiometric thresholds were observed even with extensive inner hair cell losses that exceed 80%. These results suggest that conventional audiometry is insensitive to inner hair cell loss and that only small populations of inner hair cells appear to be necessary for detecting tonal stimuli in a quiet background. Published by Elsevier B.V.

  18. Paclitaxel-carboplatin chemotherapy induced hematologic toxicities among epithelial ovarian cancer patients

    Directory of Open Access Journals (Sweden)

    Afandi Charles

    2016-11-01

    This study confirmed the hematologic toxicities after paclitaxel-carboplatin chemotherapy in EOC patients treated in Hasan Sadikin General Hospital, West Java. The hemoglobin concentration may serve as prognostic factor. Further studies directed to other factors such as genetic factor for polymorphisms may be encouraged to explore the decrease of the hematologic indices.

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

    Directory of Open Access Journals (Sweden)

    Gunther Antonissen

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

  20. Detection of adducts formed upon treatment of DNA with cisplatin and carboplatin

    NARCIS (Netherlands)

    Fichtinger-Schepman, A.M.J.; Welters, M.J.P.; Dijk-Knijnenburg, H.C.M. van; Sterre, M.L.T. van der; Tilby, M.J.; Berends, F.; Baan, R.A.

    1996-01-01

    In order to determine the nature of the cytotoxic lesion(s) formed by the antitumour drugs cisplatin and carboplatin, a comparative study was made of bifunctional DNA-adduct formation by these drugs. The kinetics of bifunctional cisplatin adduct formation were studied with DNA in vitro and in

  1. Phase II study of adjuvant docetaxel and carboplatin with/without doxorubicin and cyclophosphamide in triple negative breast cancer: a randomised controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Safa Najafi

    2017-03-01

    Full Text Available Aim of the study: The aim of this trial was to compare overall survival (OS, disease-free survival (DFS, and toxicity of two adjuvant regimens in triple negative patients with Iranian ethnicity. Material and methods: In a phase II trial, patients with previously untreated triple negative breaststroke cancer were randomly assigned by using docetaxel 70 mg/m 2 and carboplatin AUC = 7 every three weeks with granulocyte colony-stimulating factor for sin courses (arm A or doxorubicin hydrochloride 60 mg/m 2 and cyclophosphamide 600 mg/m 2 every three weeks with G-CSF for four courses followed by docetaxel 70 mg/m 2 and carboplatin AUC = 7 every three weeks with G-CSF for four courses (arm B. Results : A total of 119 patients were randomly enrolled in our study (60 patients in Arm A and 59 patients in Arm B between 2011 and 2016. The mean follow-up was 40 months at the time of treatment analysis. The 2-year and 5-year DFS rates for Arm A were 92.7% vs. 85% and for Arm B were 82.6% vs. 64.4%. The 2-year and 5-year OS rates for Arm A were 96.5% vs. 91.7% and for Arm B were 90.5% vs. 81.3%. There was a significant correlation for DFS and OS in the two arms. There was no significant difference between adverse events with the two regimens. Conclusions : In our research, less progression was found with Arm A as compared to Arm B. Adding of anthracyclines such as doxorubicin hydrochloride did not increase OS and DFS in triple negative breast cancer (TNBC patients.

  2. Comparative study analyzing survival and safety of bevacizumab/carboplatin/paclitaxel versus carboplatin/docetaxel in initial treatment of metastatic Her-2-negative breast cancer

    Directory of Open Access Journals (Sweden)

    Abdel Kader Y

    2013-06-01

    Full Text Available Yasser Abdel Kader,1 Marc Spielmann,2 Tamer El-Nahas,1 Amr Sakr,1 Hassan Metwally31Department of Clinical Oncology, Cairo University, Cairo, Egypt; 2Department of Medical Oncology, Institute Gustave Rousssy, VuilleJuif, Paris, France; 3Department of Clinical Oncology, Monufia University, Monufia, EgyptPurpose: In view of the previous reports demonstrating the positive outcome of bevacizumab in metastatic breast cancer, we aimed at comparing the role of bevacizumab-based metronomic combination with taxane (paclitaxel versus a different taxane (docetaxel-based regimen in addition to carboplatin as initial treatment for metastatic Her-2-negative breast cancer.Patients and methods: This is a randomized Phase III study comparing the progression-free survival (PFS and safety in Her-2-negative female patients with initial diagnosis of metastatic breast cancer with World Health Organization performance status of 0–II. Forty-one patients were randomized from September 2008 to July 2009 to receive either; (1 bevacizumab 5 mg/kg day 1 and day 15, carboplatin area under the curve (AUC-2 day 1, day 8, and day 15, and paclitaxel 60 mg/m2 day 1, day 8, and day 15 (arm-I; or (2 carboplatin AUC-5 day 1, docetaxel 75 mg/m2 day 1 (arm-II. The Kaplan–Meier method was used for estimating survival; log-rank test for comparing survival curves. The primary end point was PFS, and secondary end points were overall survival (OS and safety.Results: PFS was 10 months in arm I versus 10.2 months in arm II (P = 0.9. The OS rate was similar in both arms: 37.6 months for arm I versus 37.4 months for arm II (P = 0.92. The toxicity revealed higher incidence of hypertension and proteinuria in arm I; however, with higher incidence of grade III–IV neutropenia and neutropenic fever in arm II. No treatment-related mortality was recorded.Conclusion: Bevacizumab/carboplatin/paclitaxel and carboplatin/docetaxel show comparable PFS and OS with different toxicity profiles

  3. Responses and adverse effects of carboplatin-based chemotherapy for pediatric intracranial germ cell tumors

    Directory of Open Access Journals (Sweden)

    Suntae Ji

    2011-03-01

    Full Text Available Purpose : Cisplatin-based chemotherapy has been commonly used for the treatment of intracranial germ cell tumors (IC-GCTs. However, this treatment exhibits some adverse effects such as renal problems and hearing difficulty. Carboplatin-based chemotherapy was administered to pediatric patients with IC-GCTs from August 2004 at the Samsung Medical Center. In this study, we assessed the responses and adverse effects of carboplatin-based chemotherapy in pediatric IC-GCTs patients according to the risk group, and compared the results with those of the previous cisplatin-based chemotherapy. Methods : We examined 35 patients (27 men and 8 women diagnosed with IC-GCTs between August 2004 and April 2008 and received riskadapted carboplatin-based chemotherapy at the Samsung Medical Center. Patients were divided into either low-risk (LR or high-risk (HR groups and a retrospective analysis was performed using information from the medical records. Results : Although hematological complications were common, hearing difficulties or grade 3 or 4 creatinine level elevation were not observed in patients who underwent carboplatin-based chemotherapy. The frequency of febrile neutropenia did not differ between the risk groups. The overall survival was 100% and event-free survival (EFS was 95.7 %. The EFS rate was 100% in the LR group and 90% in the HR group, respectively. Conclusion : Despite their common occurrence in high-risk patients, no lethal hematological complications were associated with carboplatinbased treatment. The current carboplatin-based chemotherapy protocol is safe and effective for the treatment of pediatric patients with IC-GCTs.

  4. Pegylated liposomal doxorubicin/carboplatin combination in ovarian cancer, progressing on single-agent pegylated liposomal doxorubicin

    OpenAIRE

    Grenader, Tal; Rosengarten, Ora; Isacson, Rut; Plotkin, Yevgeni; Gabizon, Alberto

    2012-01-01

    AIM: To assess the efficacy and safety of the combination of pegylated liposomal doxorubicin (PLD) and carboplatin in patients with recurrent epithelial ovarian carcinoma (ROC), following disease progression on single agent PLD.

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

    NARCIS (Netherlands)

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

    2002-01-01

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

  6. Paclitaxel, Carboplatin and 1,25-D3 Inhibit Proliferation of Endometrial Cancer CellsIn Vitro.

    Science.gov (United States)

    Kuittinen, Tea; Rovio, Päivi; Staff, Synnöve; Luukkaala, Tiina; Kallioniemi, Anne; Grénman, Seija; Laurila, Marita; Mäenpää, Johanna

    2017-12-01

    Endometrial cancer cells are known to be sensitive to carboplatin and paclitaxel. Furthermore, vitamin D (1,25-D3) has been reported to inhibit endometrial cancer cell growth both as a single agent and combined with carboplatin. However, there are no studies comparing the effect of paclitaxel and carboplatin as single agents vs. in combination in endometrial cancer cell lines. Neither has the effect of 1,25-D3 been studied with paclitaxel. The present study investigated the effect of paclitaxel, carboplatin and 1,25-D3 on the growth of endometrial cancer cells in vitro. Two endometrial adenocarcinoma cell lines (UT-EC-1 and UT-EC-3) were cultured with different doses of paclitaxel, carboplatin and 1,25-D3. The cellular VDR (vitamin D receptor) mRNA levels were measured and the expression of estrogen (ER) and progesterone (PR) receptors by the cells was determined. In the UT-EC-1 cell line the growth inhibition was 72% with paclitaxel, 54% with carboplatin and 73% with the combination of these compounds. The corresponding numbers in UT-EC-3 were 70%, 33% and 65%, respectively. 1,25-D3 suppressed cell growth 88% with paclitaxel, 63% with carboplatin and 87% with their combination in the UT-EC-1 cell line. In both cell lines, single-agent paclitaxel was as effective as the combination of the compounds and more effective than single carboplatin. 1,25-D3 may further contribute to the cytotoxic effect of these agents. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  7. Enhanced brain distribution of carboplatin in a primate model after blood-brain barrier disruption using an implantable ultrasound device.

    Science.gov (United States)

    Goldwirt, Lauriane; Canney, Michael; Horodyckid, Catherine; Poupon, Joel; Mourah, Samia; Vignot, Alexandre; Chapelon, Jean-Yves; Carpentier, Alexandre

    2016-01-01

    Glioblastoma is both the most common and aggressive primary brain tumor in adults. Carboplatin chemotherapy has shown only modest efficacy in progressive high-grade gliomas. The limited clinical efficacy of carboplatin may be due to its low concentration in tissue when the drug is delivered intravenously. The aim of this study was to assess whether the tissue concentration of intravenously administered carboplatin could be enhanced by ultrasound-induced blood-brain disruption in a primate model. Carboplatin was administered intravenously for 60 min to a single primate following blood-brain barrier opening induced by an implantable ultrasound device. Blood and brain samples were collected after animal killing, which occurred 60 min after the end of carboplatin administration. Platinum quantification in ultrafiltrate plasma and brain samples was performed using inductively coupled plasma mass spectrometry. The brain concentration of platinum was highly enhanced (5.2×) in the 3.9 cm(3) region sonicated by the US beam, with a higher concentration in more vascularized anatomical structures. At 5 and 10 mm from the US beam axis, platinum concentrations were slightly enhanced (2.2× and 1.3× respectively). This study demonstrates that BBB opening using an implantable ultrasound transducer enhances the brain distribution of carboplatin in a loco-regional manner. Such a treatment approach is of significant interest for the treatment of primary brain tumors and is under current evaluation in a phase 1 clinical trial (NCT02253212).

  8. A two-site, two-arm, 34-week, double-blind, parallel-group, randomized controlled trial of reduced nicotine cigarettes in smokers with mood and/or anxiety disorders: trial design and protocol

    Directory of Open Access Journals (Sweden)

    Sophia I. Allen

    2017-01-01

    Full Text Available Abstract Background The U.S. Food and Drug Administration can set standards for cigarettes that could include reducing their nicotine content. Such a standard should improve public health without causing unintended serious consequences for sub-populations. This study evaluates the effect of progressive nicotine reduction in cigarettes on smoking behavior, toxicant exposure, and psychiatric symptoms in smokers with comorbid mood and/or anxiety disorders using a two-site, two-arm, double-blind, parallel group, randomized controlled trial (RCT in four phases over 34 weeks. Methods Adult smokers (N = 200 of 5 or more cigarettes per day will be randomized across two sites (Penn State and Massachusetts General. Participants must have not had a quit attempt in the prior month, nor be planning to quit in the next 6 months, meet criteria for a current or lifetime unipolar mood and/or anxiety disorder based on the structured Mini-International Neuropsychiatric Interview, and must not have an unstable medical or psychiatric condition. After a week of smoking their own cigarettes, participants receive two weeks of Spectrum research cigarettes with usual nicotine content (11.6 mg. After this baseline period, participants will be randomly assigned to continue smoking Spectrum research cigarettes that contain either (a Usual Nicotine Content (11.6 mg; or (b Reduced Nicotine Content: the nicotine content per cigarette is progressively reduced from approximately 11.6 mg to 0.2 mg in five steps over 18 weeks. At the end of the randomization phase, participants will be offered the choice to either (a quit smoking with assistance, (b continue smoking free research cigarettes, or (c return to purchasing their own cigarettes, for the final 12 weeks of the study. The primary outcome measure is blood cotinine; key secondary outcomes are: exhaled carbon monoxide, urinary total NNAL- 4-(methylnitrosamino-1-(3-pyridyl-1-butanol and 1-hydroxypyrene, oxidative

  9. [Safety and efficacy of pegylated liposomal Doxorubicin and Carboplatin on platinum-sensitive recurrent epithelial ovarian cancer].

    Science.gov (United States)

    Nishio, Shin; Ushijima, Kimio; Shimizu, Takahiro; Tachibana, Takashi; Nasu, Hiroki; Aiko, Kei; Kawano, Ryosuke; Kurokawa, Yusuke; Sumino, Yuka; Yokomine, Masato; Takemoto, Shuji; Kamura, Toshiharu

    2013-12-01

    We evaluated the safety and efficacy of pegylated liposomal doxorubicin(PLD)and carboplatin(CBDCA)(CD) for platinum-sensitive recurrent epithelial ovarian cancer. From December 2010 to June 2011, 9 eligible patients with histologically confirmed, recurrent epithelial ovarian cancer, which was deemed platinum-sensitive, were enrolled onto the study. PLD(30mg/m2)and CBDCA(area under the curve[AUC]5)were administered intravenously on day 1 of the cycle. The chemotherapy regimen was repeated every 4 weeks, until disease progression or completion of 6 cycles. A total of 49 treatment cycles of CD were administered to 9 patients. The median platinum-free interval was 18.3 months. Patients with Grade 3/4 hematological toxicities were observed to have leucopenia(11.1%), neutropenia(44.4%), anemia (22.2%), and thrombocytopenia (22.2%). No Grade 3/4 non-hematological toxicities were observed, and no treatment related death occurred. Seven patients(77.7%)responded to CD(4 complete responses and 3 partial responses). The median progression-free survival and overall survival times were 15.1 and 23.7 months. CD treatment seems to be a safe and effective chemotherapy regimen for platinum-sensitive recurrent epithelial ovarian cancer.

  10. Monitoring carboplatin ototoxicity with distortion-product otoacoustic emissions in children with retinoblastoma

    Science.gov (United States)

    Bhagat, Shaum P.; Bass, Johnnie K.; White, Stephanie T.; Qaddoumi, Ibrahim; Wilson, Matthew W.; Wu, Jianrong; Rodriguez-Galindo, Carlos

    2016-01-01

    Objective Carboplatin is a common chemotherapy agent with potential ototoxic side effects that is used to treat a variety of pediatric cancers, including retinoblastoma. Retinoblastoma is a malignant tumor of the retina that is usually diagnosed in young children. Distortion-product otoacoustic emission tests offer an effective method of monitoring for ototoxicity in young children. This study was designed to compare measurements of distortion-product otoacoustic emissions obtained before and after several courses of carboplatin chemotherapy in order to examine if (a) mean distortion-product otoacoustic emission levels were significantly different; and (b) if criterion reductions in distortion-product otoacoustic emission levels were observed in individual children. Methods A prospective repeated measures study. Ten children with a median age of 7.6 months (range, 3–72 months) diagnosed with unilateral or bilateral retinoblastoma were examined. Distortion-product otoacoustic emissions were acquired from both ears of the children with 65/55 dB SPL primary tones (f2= 793–7996 Hz) and a frequency resolution of 3 points/octave. Distortion-product otoacoustic emission levels in dB SPL were measured before chemotherapy treatment (baseline measurement) and after 3–4 courses of chemotherapy (interim measurement). Comparisons were made between baseline and interim distortion-product otoacoustic emission levels (collapsed across ears). Evidence of ototoxicity was based on criterion reductions (≥ 6 dB) in distortion-product otoacoustic emission levels. Results Significant differences between baseline and interim mean distortion-product otoacoustic emission levels were only observed at f2=7996 Hz. Four children exhibited criterion reductions in distortion-product otoacoustic emission levels. Conclusions Mean distortion-product otoacoustic emission levels at most frequencies were not changed following 3–4 courses of carboplatin chemotherapy in children with

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

    Directory of Open Access Journals (Sweden)

    Lv X

    2016-08-01

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

  12. A comparison of carboplatin and paclitaxel with cisplatinum and 5-fluorouracil in definitive chemoradiation in esophageal cancer patients

    Science.gov (United States)

    Honing, J.; Smit, J. K.; Muijs, C. T.; Burgerhof, J. G. M.; de Groot, J. W.; Paardekooper, G.; Muller, K.; Woutersen, D.; Legdeur, M. J. C.; Fiets, W. E.; Slot, A.; Beukema, J. C.; Plukker, J. Th. M.; Hospers, G. A. P.

    2014-01-01

    Background In esophageal cancer (EC) patients who are not eligible for surgery, definitive chemoradiation (dCRT) with curative intent using cisplatinum with 5-fluorouracil (5-FU) is the standard chemotherapy regimen. Nowadays carboplatin/paclitaxel is also often used. In this study, we compared survival and toxicity rates between both regimens. Patients and methods This multicenter study included 102 patients treated in five centers in the Northeast Netherlands from 1996 till 2008. Forty-seven patients received cisplatinum/5-FU (75 mg/m2 and 1 g/m2) and 55 patients carboplatin/paclitaxel (AUC2 and 50 mg/m2). Results Overall survival (OS) was not different between the cisplatinum/5-FU and carboplatin/paclitaxel group {[P = 0.879, hazard ratio (HR) 0.97 [confidence interval (CI) 0.62–1.51]}, with a median survival of 16.1 (CI 11.8–20.5) and 13.8 months (CI 10.8–16.9). Median disease-free survival (DFS) was comparable [P = 0.760, HR 0.93 (CI 0.60–1.45)] between the cisplatinum/5-FU group [11.1 months (CI 6.9–15.3)] and the carboplatin/paclitaxel group [9.7 months (CI 5.1–14.4)]. Groups were comparable except clinical T stage was higher in the carboplatin/paclitaxel group (P = 0.008). High clinical T stage (cT4) was not related to OS and DFS in a univariate analysis (P = 0.250 and P = 0.201). A higher percentage of patients completed the carboplatin/paclitaxel regimen (82% versus 57%, P = 0.010). Hematological and nonhematological toxicity (≥grade 3) in the carboplatin/paclitaxel group (4% and 18%) was significantly lower than in the cisplatinum/5-FU (19% and 38%, P = 0.001). Conclusions In this study, we showed comparable outcome, in terms of DFS and OS for carboplatin/paclitaxel compared with cisplatinum/5-FU as dCRT treatment in EC patients. Toxicity rates were lower in the carboplatin/paclitaxel group together with higher treatment compliance. Carboplatin/paclitaxel as an alternative treatment of cisplatinum/5-FU is a good candidate regimen for

  13. A review of 18 cases of feline colonic adenocarcinoma treated with subtotal colectomies and adjuvant carboplatin.

    Science.gov (United States)

    Arteaga, Theresa A; McKnight, JoAnne; Bergman, Philip J

    2012-01-01

    Feline colonic adenocarcinoma is a locally invasive, highly metastatic tumor that is most often treated with wide surgical excision (subtotal colectomy) and systemic chemotherapy either with or without nonsteroidal anti-inflammatory medications. In this retrospective study, the outcome of subtotal colectomy and adjuvant carboplatin in 18 client-owned cats is described. The median carboplatin dose was 200 mg/m(2) (range, 200-254 mg/m(2)) q 4 wk with a median of five doses/cat (range was two to seven doses/cat). Limited toxicities were noted. Positive prognostic factors for the disease-free interval included cats that had weight loss as a presenting sign (P adenocarcinoma.

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

    Science.gov (United States)

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

    2017-10-01

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

  15. Expression of drug targets in patients treated with sorafenib, carboplatin and paclitaxel.

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    Lucia B Jilaveanu

    Full Text Available Sorafenib, a multitarget kinase inhibitor, targets members of the mitogen-activated protein kinase (MAPK pathway and VEGFR kinases. Here we assessed the association between expression of sorafenib targets and biomarkers of taxane sensitivity and response to therapy in pre-treatment tumors from patients enrolled in ECOG 2603, a phase III comparing sorafenib, carboplatin and paclitaxel (SCP to carboplatin, paclitaxel and placebo (CP.Using a method of automated quantitative analysis (AQUA of in situ protein expression, we quantified expression of VEGF-R2, VEGF-R1, VEGF-R3, FGF-R1, PDGF-Rβ, c-Kit, B-Raf, C-Raf, MEK1, ERK1/2, STMN1, MAP2, EB1 and Bcl-2 in pretreatment specimens from 263 patients.An association was found between high FGF-R1 and VEGF-R1 and increased progression-free survival (PFS and overall survival (OS in our combined cohort (SCP and CP arms. Expression of FGF-R1 and VEGF-R1 was higher in patients who responded to therapy ((CR+PR vs. (SD+PD+ un-evaluable.In light of the absence of treatment effect associated with sorafenib, the association found between FGF-R1 and VEGF-R1 expression and OS, PFS and response might reflect a predictive biomarker signature for carboplatin/paclitaxel-based therapy. Seeing that carboplatin and pacitaxel are now widely used for this disease, corroboration in another cohort might enable us to improve the therapeutic ratio of this regimen.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-12-04

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

  17. Novel antitumor effect of carboplatin delivered by intracerebral microinfusion in a rat malignant glioma model.

    Science.gov (United States)

    Tange, Yuichi; Miyazaki, Masahiro; Iwata, Junko; Aiko, Yasuhisa; Sakamoto, Shinichi; Mori, Kentaro

    2009-12-01

    Carboplatin loaded osmotic mini-pumps were implanted in 24 9L malignant glioma-bearing rats to investigate the implications of direct intracerebral microinfusion. Carboplatin using 0.1 mg/ml (low dose group) or 1.0 mg/ml (high dose group) with eight rats in each group, or 5% D-glucose (control group) in eight rats were infused at 1 microl/hr for 7 days. The tumor volume was serially measured by magnetic resonance (MR) imaging with gadolinium as the enhanced area, and the survival periods and histological findings were also examined. Separately, to examine the effects of intracerebral carboplatin infusion on vascular permeability, tumor-bearing rats received intravenous administration of 2% Evans blue at 21 days after infusion. The high dose group showed transient increase of enhanced volume at 21 days associated with mass effect, and significantly decreased tumor volume at 28 and 35 days compared with the control and low dose groups. The high dose group showed significant longer survival time than the control and low dose groups. Histological examination of the high dose group at 21 days showed the central tumor necrotic area around the infusion site and Evans blue leakage into the surrounding enhanced rim and the necrotic core. Therefore, leakage of plasma fluid into the necrotic area was considered to be the cause of apparent transient swelling. The present study demonstrated quantitatively using MR imaging that intracerebral carboplatin microinfusion significantly inhibited the rapid growth of experimental rat glioma but that the high dose required carries the risk of transient swelling of the target tumor.

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

    OpenAIRE

    Allen, Valerie A.; Manahan, Kelly J; Geisler, John P.

    2016-01-01

    Background. Diarrhea is a common problem in ovarian cancer patients undergoing chemotherapy and Clostridium difficile infection has been identified as a cause. The proper diagnosis and treatment of diarrhea are critical to patient care, especially to prevent the serious complications from a severe Clostridium difficile infection (CDI). Case. We present a heavily pretreated ovarian cancer patient who developed recurrent pseudomembranous colitis while receiving carboplatin chemotherapy. Despite...

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

    Science.gov (United States)

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

    2017-07-01

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

  20. Doxorubicin and carboplatin trials in Tasmanian devils (Sarcophilus harrisii) with Tasmanian devil facial tumor disease.

    Science.gov (United States)

    Phalen, David N; Frimberger, Angela E; Peck, Sarah; Pyecroft, Stephen; Harmsen, Colette; Lola, Suzanneth; Moore, Antony S

    2015-12-01

    The devil facial tumor disease (DFTD) is having a devastating impact on Tasmanian devils (Sarcophilus harrisii) (devils) in the wild. Only a single study has been published regarding treatment of DFTD, where vincristine was not found to be an effective chemotherapeutic agent. In the current study, devils were treated with escalating dosages of carboplatin (8-26 mg/kg) (n = 13) and doxorubicin (0.75-1.0 mg/kg) (n = 5). Dosages for carboplatin (20 mg/kg) and doxorubicin (1.0 mg/kg) were identified as maximally tolerated dosages. Limiting toxicities for carboplatin were anorexia and weight loss (gastrointestinal signs) and azotemia. Limiting toxicities for doxorubicin were neutropenia, anorexia and weight loss. None of the treated devils responded to either drug, suggesting that, based on the clonality of this tumour, it is unlikely that either drug individually or in combination would be effective treatments for DFTD. These results, however, provide valuable information for practitioners who may choose to treat other neoplastic diseases in the devil or other marsupials. In addition, these results show that even drugs that are metabolized and excreted in the same manner can be tolerated to different degrees by the same species. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Maurie Markman

    2009-02-01

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

  2. Efficacy of carboplatin-based preoperative chemotherapy for triple-negative breast cancer. A meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Wang, Li-Yang; Xie, Hua; Zhou, Hang; Yao, Wen-Xiu; Zhao, Xin; Wang, Yi

    2017-01-01

    To evaluate the efficacy and safety of carboplatin-based preoperative chemotherapy in triple-negative breast cancer patients (TNBC). PubMed, EMBASE, the Web of Science, the Cochrane Library, major clinical trial registries, and abstract collections from major international meetings were systematically searched for relevant randomized controlled trials. Endpoints included rates of pathologic complete response (pCR), overall response (ORR), breast-conserving surgery (BCS) and toxicity. Pooled relative risk (RR) was calculated for each endpoint using a fixed- or random-effect model depending on the heterogeneity among included studies. A total of 5 randomized controlled trials involving 1007 patients were included in the meta-analysis. Carboplatin-based chemotherapy was associated with a pooled pCR rate of 53.3%, which was significantly higher than the rate associated with non-carboplatin therapy (37.8%, RR: 1.41, 95% confidence interval [CI]: 1.23 to 1.62, p less than 0.00001). Compared with non-carboplatin therapy (48.1%), carboplatin-based chemotherapy increased BCS rate (59.7%, RR: 1.24, 95%CI: 1.06 to 1.46, p=0.007). Carboplatin-based chemotherapy was associated with similar ORR as non-carboplatin therapy. Carboplatin-based chemotherapy was associated with higher incidence of grade 3 or 4 anemia, neutropenia, febrile neutropenia, and thrombocytopenia than non-carboplatin therapy, while the 2 regimens were associated with similar incidence of fatigue, leucopenia, and nausea/vomiting. The available evidence suggests that carboplatin-based preoperative chemotherapy is associated with significantly better pCR and BCS rates than non-carboplatin-based therapy in TNBC patients.

  3. Low energy intake during the first week in an emergency intensive care unit is associated with reduced duration of mechanical ventilation in critically ill, underweight patients: a single-center retrospective chart review.

    Science.gov (United States)

    Ichimaru, Satomi; Fujiwara, Hidetoshi; Amagai, Teruyoshi; Atsumi, Takahiro

    2014-06-01

    Although nutrition support is essential in intensive care units, optimal energy intake remains unclear. Here, we assessed the influence of energy intake on outcomes of critically ill, underweight patients. A retrospective chart review was conducted in patients with body mass index (BMI) of intensive care unit (EICU). Patients were categorized into 4 groups by initial Sequential Organ Failure Assessment score (I-SOFA) and average daily energy intake during the first week: group M-1, I-SOFA ≤8 and 8 and 8 and ≥16 kcal/kg/d. The study included 51 patients with a median age of 69 years. No significant differences were noted in all-cause mortality and length of stay in the EICU and hospital between groups M-1 and M-2 or groups S-1 and S-2. The mechanical ventilation duration (MVD) was significantly shorter in group M-1 than M-2 (2.7 [1.0-5.7] vs 9.2 [4.2-17.4] days; P = .040) and in group S-1 than S-2 (3.1 [0.7-6.0] vs 8.8 [6.1-23.1] days; P = .006). The number of patients who underwent tracheostomy in hospital was significantly lower in group S-1 than in S-2 (20% vs 32%; P = .002). Multivariable analyses to adjust for confounders revealed that average energy intake during the first week in EICU was a significant factor independently associated with MVD but not with the requirement of tracheostomy. Reduced energy intake during the first week in EICU was associated with a reduced MVD in clinically ill patients with BMI <20.0 kg/m(2).

  4. Dose-dense paclitaxel plus carboplatin as neoadjuvant chemotherapy for advanced ovarian, fallopian tube, or primary peritoneal carcinomas.

    Science.gov (United States)

    Ebata, T; Yunokawa, M; Bun, S; Shimomura, A; Shimoi, T; Kodaira, M; Yonemori, K; Shimizu, C; Fujiwara, Y; Kato, T; Tamura, K

    2016-12-01

    Weekly dose-dense paclitaxel with carboplatin every 3 weeks (dose-dense TC) provides good efficacy, and neoadjuvant chemotherapy is common for advanced-stage disease. However, it is unclear the efficacy and safety of dose-dense TC as neoadjuvant chemotherapy. Therefore, we evaluated neoadjuvant dose-dense TC chemotherapy for advanced-stage ovarian carcinoma. We retrospectively reviewed cases of ovarian carcinoma that were not suited for primary debulking surgery (2003-2014). The patients received neoadjuvant dose-dense TC chemotherapy, followed by interval debulking surgery and adjuvant chemotherapy. We identified 74 patients (mean age 60 years, range 39-85 years). The FIGO stages were IIIC (39/74, 52.7%) and IV (34/74, 45.9%). Fifty-six patients (75.6%) had a performance status of 0-1. The adverse events were grade 3/4 neutropenia (55.4%), anemia (44.6%), thrombocytopenia (21.6%), and peripheral neuropathy (8.1%); no treatment-related deaths were observed. Among the 66 patients who underwent debulking (89.2%), 55 patients (74.3%) achieved optimal debulking and 47 patients (63.5%) achieved complete resection. The median progression-free and overall survivals were 19.0 months (95% CI 16.2-23.7 months) and 55.1 months (95% CI 44.6 months to not estimable), respectively. A performance status of 2-3 was independently associated with poor prognosis (hazard ratio 3.84; p = 0.001). Neoadjuvant dose-dense TC chemotherapy was effective (complete resection in >60% of cases) and tolerable for advanced-stage ovarian carcinoma.

  5. An open-label, multicenter, phase I trial of a cremophor-free, polymeric micelle formulation of paclitaxel combined with carboplatin as a first-line treatment for advanced ovarian cancer: a Korean Gynecologic Oncology Group study (KGOG-3016).

    Science.gov (United States)

    Lee, Shin Wha; Kim, Yong Man; Kim, Young Tae; Kang, Soon Beom

    2017-05-01

    This phase I study aimed to determine the maximum tolerated dose (MTD) of Genexol-PM, when combined with carboplatin, as a first-line treatment in patients with advanced ovarian cancer. This open-label, multicenter, phase I, dose-escalation study included 18 patients (median age: 59.0 years, range: 40-75 years) diagnosed with advanced epithelial ovarian cancer. All patients had measurable residual disease after debulking surgery. Patients were assigned to groups (n=6 each group) that received different doses of Genexol-PM (220, 260, and 300 mg/m², once every 3 weeks) and 5 area under the curve (AUC) carboplatin. Safety and efficacy were analyzed for each dose group. In this intention-to-treat population, 3 out of 18 patients dropped out of the study: 1 due to dose-limiting toxicity (DLT), 1 due to hypersensitivity, and 1 was lost during follow-up. DLTs were not reported at 220 mg/m² or 260 mg/m², but at 300 mg/m², 1 patient experienced DLT (grade 3 general pain). The MTD of Genexol-PM was not determined, but a dose of 300 mg/m² or less could be recommended for the phase II study. Most patients (73.9%) with adverse events recovered without sequelae, and no death occurred that was related to the disease or treatment. The best overall response rate was 94.1%. Genexol-PM combined with carboplatin was well tolerated as a first-line treatment, and good responses were observed in patients with advanced ovarian cancer. Based on these results, we recommended a dose of 300 mg/m² or less for a phase II study.

  6. DNA damage induced by cis- and carboplatin as indicator for in vitro sensitivity of ovarian carcinoma cells

    Directory of Open Access Journals (Sweden)

    de Wilde Rudy L

    2009-10-01

    Full Text Available Abstract Background The DNA damage by platinum cytostatics is thought to be the main cause of their cytotoxicity. Therefore the measurement of the DNA damage induced by cis- and carboplatin should reflect the sensitivity of cancer cells toward the platinum chemotherapeutics. Methods DNA damage induced by cis- and carboplatin in primary cells of ovarian carcinomas was determined by the alkaline comet assay. In parallel, the reduction of cell viability was measured by the fluorescein diacetate (FDA hydrolysis assay. Results While in the comet assay the isolated cells showed a high degree of DNA damage after a 24 h treatment, cell viability revealed no cytotoxicity after that incubation time. The individual sensitivities to DNA damage of 12 tumour biopsies differed up to a factor of about 3. DNA damage after a one day treatment with cis- or carboplatin correlated well with the cytotoxic effects after a 7 day treatment (r = 0,942 for cisplatin r = 0.971 for carboplatin. In contrast to the platinum compounds the correlation of DNA damage and cytotoxicity induced by adriamycin was low (r = 0,692, or did not exist for gemcitabine. Conclusion The measurement of DNA damage induced by cis- and carboplatin is an accurate method to determine the in vitro chemosensitivity of ovarian cancer cells towards these cytostatics, because of its quickness, sensitivity, and low cell number needed.

  7. Population pharmacokinetic analyses of the effect of carboplatin pretreatment on olaparib in recurrent or refractory women's cancers.

    Science.gov (United States)

    Peer, Cody J; Lee, Jung-Min; Roth, Jeffrey; Rodgers, Louis; Nguyen, Jeffers; Annunziata, Christina M; Minasian, Lori; Kohn, Elise C; Figg, William D

    2017-07-01

    Combining olaparib with carboplatin was recently shown to be active in both BRCA and non-BRCA mutant cancers in a recent phase I/Ib combination trial. The optimal drug sequence recommended was carboplatin 1-day before olaparib. However, carboplatin pre-treatment induced a ~50% faster olaparib clearance. To further explore this drug interaction, a population pharmacokinetic (PK) model was designed that included a lag time parameter, a second absorption compartment from tablet formulation, a single distribution/elimination compartment, and covariance among the clearance and volume parameters. Clearance (6.8 L/h) and volume (33 L) estimates were comparable with literature. The only significant covariate was the presence of carboplatin on olaparib clearance, consistent with published noncompartmental PK and in vitro data. Simulations predicted lower steady-state peak/trough olaparib exposure through 24-36 h post carboplatin pre-treatment, but this effect was lost by day 2 and thus no dose adjustment is recommended.

  8. Retrospective analysis of chronomodulated chemotherapy versus conventional chemotherapy with paclitaxel, carboplatin, and 5-fluorouracil in patients with recurrent and/or metastatic head and neck squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Chen D

    2013-10-01

    Full Text Available Dan Chen, Jue Cheng, Kai Yang, Yue Ma, Fang Yang Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China Background: Chronomodulated chemotherapy has emerged as a new therapy as a result of recent studies focusing on the biological clock. It has been demonstrated that combination chronomodulated chemotherapy of platinum-based drugs and 5-fluorouracil (5-Fu can significantly improve efficacy and reduce the incidence of adverse events in patients with metastatic colorectal cancer, as compared with conventional chemotherapy. However, the results may be different in different tumors. Recurrent and metastatic head and neck squamous cell carcinoma (HNSCC is very difficult to treat, with an extremely unfavorable prognosis. So far, no report is available on chronomodulated chemotherapy for HNSCC. Methods: Retrospective analyses were made on 49 patients with local recurrent and/or metastatic HNSCC who underwent palliative treatments with paclitaxel, carboplatin, and 5-Fu. The patients were divided into a chronomodulated chemotherapy group (28 patients and a conventional chemotherapy group (21 patients according to their administration times. The two groups were compared for tumor objective response rate, overall survival (OS, progression-free survival (PFS, and the incidence of adverse events. Results: The tumor objective response rate and patients' OS were significantly higher and longer in the chronomodulated chemotherapy group than in the conventional chemotherapy group (71.43% versus 42.86%, respectively, P0.05. The global incidence of adverse events in the chronomodulated chemotherapy group was significantly lower than that in the conventional chemotherapy group (46.43% versus 76.19%, P<0.05, with significantly lower incidence of grade 3–4 adverse events (7.14% versus 33.33%, P<0.05. Conclusion: Chronomodulated chemotherapy with paclitaxel, carboplatin, and

  9. Combination of gemcitabine and carboplatin in urothelial cancer patients unfit for cisplatin due to impaired renal or cardiac function

    Directory of Open Access Journals (Sweden)

    Avishay Sella

    2012-02-01

    Full Text Available PURPOSE: Combination of gemcitabine and carboplatin is the accepted treatment for metastatic urothelial cancer patients unfit for cisplatin-based chemotherapy. MATERIALS AND METHODS: Gemcitabine 1000 mg/m² (days 1, 8 and carboplatin AUC-4.5 (day 1 were given every 21 days to 23 patients with creatinine clearance grade 2 in 3 (13% patients and fatigue grade 3 in 2 (9% patients. Hematologic toxicity included grade 4 thrombocytopenia in 2 (9% patients and grade 4 neutropenia in 3 (13% patients. Five (22% patients discontinued therapy due to toxicity. CONCLUSIONS: Combination of gemcitabine and carboplatin demonstrated clinical activity in patients with advanced urothelial cancer unfit for cisplatin. It was associated with considerable toxicity. Resection of residual disease is feasible in this population.

  10. Pharmacokinetics of Carboplatin in a One-Year-Old Anuric Boy Undergoing Hemodialysis and a Review of the Literature.

    Science.gov (United States)

    Kamei, Koichi; Sako, Mayumi; Ishikawa, Tomoaki; Sato, Mai; Ogura, Masao; Uno, Teruaki; Kiyotani, Chikako; Mori, Tetsuya; Tanaka, Hideaki; Ito, Shuichi; Nakamura, Hidefumi

    2015-10-01

    There have been few reports of carboplatin-based chemotherapy for anuric infants. As we had a chance to treat a one-year-old anuric hepatoblastoma patient with carboplatin, we performed a pharmacokinetic analysis and examined the optimal treatment strategy. A one-year-old anuric boy under peritoneal dialysis was diagnosed with hepatoblastoma. Surgical resection was performed, and administration of carboplatin was scheduled postoperatively aiming at 5 mg·min/mL of the area under the curve from the time of dosing to the time of the last observation (AUC(0-t)). We set the initial dose at 50 mg, higher than that calculated by the Calvert formula (34 mg); the time from the end of carboplatin infusion to the initiation of hemodialysis at 2 h; and the hemodialysis duration at 24 h. The actual AUC0-t was 3.05 mg·min/mL because the elimination half-lives before and during hemodialysis were shorter than expected. The AUC(0-t) after the second dose (100 mg) and the third dose (80 mg) were 7.00 and 4.68 mg·min/mL, respectively. The Calvert formula is not suitable for hemodialysis patients because removal of platinum by hemodialysis is not taken into account. It appears that extrarenal clearance in anuric infants is different from that in adults. We obtained an optimal AUC(0-t) using a dose of 80 mg (200 mg/m(2)), setting the time from the end of carboplatin infusion to the initiation of hemodialysis at 2 h, and performing 8-h hemodialysis. Further accumulation of the pharmacokinetic data of carboplatin is necessary for anuric children. ©2015 The Authors. Therapeutic Apheresis and Dialysis © 2015 International Society for Apheresis.

  11. Paclitaxel, carboplatin followed by a concomitant chemoradiotherapy in the undifferentiated cavum cancers; Paclitaxel, carboplatine suivi d'une chimioradiotherapie concomitante dans les carcinomes indifferencies du cavum

    Energy Technology Data Exchange (ETDEWEB)

    Djekkoun, R.; Ferdi, N.; Boudaoud, K. [CAC CHU, Constantine (Algeria); Bouzid, K. [CPMC, Alger (Algeria)

    2009-10-15

    Purpose: for more than two decades, the association of cisplatin and 5-fluoro-uracil stayed the standard treatment for epidermoid carcinomas of aero digestive system. Recently, the taxanes showed their efficiency in this pathology during studies of phase 2 and it is expected from the paclitaxel and carboplatin association followed by a concomitant radio chemotherapy a better rate of local control of the metastatic disease and complete remission for a long time. Conclusion: the use of the protocol of chemotherapy followed by a concomitant chemoradiotherapy can be a standard of therapy for the locally evolved injuries. It gives a high objective response rate and local control and a global survival rate at five years at 58%. (N.C.)

  12. Inclusion complexes of α-cyclodextrin and the cisplatin analogues oxaliplatin, carboplatin and nedaplatin: A theoretical approach

    Science.gov (United States)

    Anconi, Cleber P. A.; da Silva Delgado, Luciano; Alves dos Reis, João B.; De Almeida, Wagner B.; Costa, Luiz Antônio S.; Dos Santos, Hélio F.

    2011-10-01

    Quantum mechanics theoretical methodology has been applied in order to access and compare the relative stability of inclusion compounds formed by α-CD and the platinum (II) based drugs carboplatin, oxaliplatin and nedaplatin. The relative stability of the studied inclusion compounds has been discussed based on the number and type of hydrogen bonds identified between host and guest molecules. The evaluated energies at B3LYP/6-31G ∗ level of theory strongly indicates that α-CD forms stable supramolecular systems with all studied cisplatin analogues, being the carboplatin@α-CD found as the most favorable inclusion complex among the platinum (II) derivatives studied in the present paper.

  13. Carboplatin and pegylated liposomal doxorubicin versus carboplatin and paclitaxel in very platinum-sensitive ovarian cancer patients: results from a subset analysis of the CALYPSO phase III trial.

    Science.gov (United States)

    Mahner, Sven; Meier, Werner; du Bois, Andreas; Brown, Chris; Lorusso, Domenica; Dell'Anna, Tiziana; Cretin, Jacques; Havsteen, Hanne; Bessette, Paul; Zeimet, Alain G; Vergote, Ignace; Vasey, Paul; Pujade-Lauraine, Eric; Gladieff, Laurence; Ferrero, Annamaria

    2015-02-01

    To perform a subset analysis of patients with very platinum-sensitive recurrent ovarian cancer (ROC) enrolled in the phase III CALYPSO trial. The international non-inferiority trial enrolled women with ROC that relapsed >6 months following first- or second-line platinum- and paclitaxel-based therapies. Patients were randomised to CD [carboplatin-pegylated liposomal doxorubicin (PLD)] or CP (carboplatin-paclitaxel) and stratified by treatment-free interval (TFI). In this analysis, patients with a TFI>24 months were analysed separately for progression free survival (PFS), the primary endpoint of CALYPSO, overall survival (OS) and safety. A total of 259 very platinum-sensitive patients were included (n=131, CD; n=128, CP). Median PFS was 12.0 months for the CD arm and 12.3 months for CP [HR=1.05 (95% CI, 0.79-1.40); P=0.73 for superiority] and median OS was 40.2 months for CD and 43.9 for CP [HR=1.18 (95% CI 0.85-1.63); P=0.33 for superiority]. Overall response rates were 42% and 38%, respectively (P=0.46). Toxicities were more common with CP versus CD, including grade 3/4 neutropenia (40.8% versus 27.5%; P=0.025), nausea (4.8% versus 3.1%; P=0.47), allergic reaction (8% versus 3.1%; P=0.082) sensory neuropathy (4.8% versus 2.3%; P=0.27) and grade 2 alopecia (88% versus 9.2%; Pcarboplatin-PLD as treatment of choice for these patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Health-related quality of life outcomes from CABARET: a randomized phase 2 trial of carboplatin and bevacizumab in recurrent glioblastoma.

    Science.gov (United States)

    Field, Kathryn M; King, Madeleine T; Simes, John; Espinoza, David; Barnes, Elizabeth H; Sawkins, Kate; Rosenthal, Mark A; Cher, Lawrence; Hovey, Elizabeth; Wheeler, Helen; Nowak, Anna K

    2017-07-01

    In recurrent glioblastoma, health-related quality of life (HRQL) is a crucial trial endpoint. We examined HRQL outcomes as a secondary endpoint for patients in the CABARET randomized phase 2 trial. 122 patients were randomly allocated to bevacizumab monotherapy or bevacizumab plus carboplatin. We calculated change scores from baseline for each HRQL measure on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the Brain Cancer Module (QLQ-BN20), together with time to deterioration in HRQL, and the proportion of participants with clinically meaningful improvements in specific disease-related symptoms. At baseline, 117 of 122 randomized patients (96%) attempted questionnaires. Questionnaire participation rates were >90% for patients continuing on treatment, however at the end-of-treatment visit only 72 (64% of eligible participants) returned a form. There were no differences between arms in change scores over the treatment period. Time to ≥10 point deterioration in scores from baseline was also similar between arms. HRQL deterioration occurred largely before progression for the domains tested, but scores in HRQL domains specifically relevant to symptoms of recurrent glioblastoma also improved for about 50% of patients with symptoms at baseline. Neither detrimental nor beneficial effects on HRQL were seen with carboplatin added to bevacizumab, with a proportion of patients on both arms experiencing symptomatic benefit. Given the reduced questionnaire completion at end of treatment, time to HRQL deterioration is a feasible and robust clinical trial endpoint in this patient population. Clinical trials registration number: ACTRN12610000915055.

  15. Sorafenib in combination with carboplatin and paclitaxel as neoadjuvant chemotherapy in patients with advanced ovarian cancer.

    Science.gov (United States)

    Pölcher, Martin; Eckhardt, Meike; Coch, Christoph; Wolfgarten, Matthias; Kübler, Kirsten; Hartmann, Gunther; Kuhn, Walther; Rudlowski, Christian

    2010-05-01

    Sorafenib is a novel oral anticancer agent targeting signal transduction and angiogenic pathways through inhibitory effects against MAP kinases and vascular endothelial growth factor receptor-2. The objectives of this neoadjuvant phase II-trial in patients with advanced epithelial ovarian cancer were to assess the activity and tolerability of the combination therapy of carboplatin/paclitaxel with multi-target tyrosine kinase inhibitor sorafenib. Patients with histologically proven stage IIIC or IV disease and large volume ascites were eligible. Enrolled patients received 2 of 6 cycles carboplatin (area under the curve 5) and paclitaxel (175 mg/m(2)) preoperatively and concomitant sorafenib 400 mg twice daily. After four cycles of postoperative chemotherapy, a maintenance phase of single agent oral sorafenib through 1 year was planned. This phase II-study was planned with a sample size of 102 patients and progression-free survival as primary study endpoint. Four patients were enrolled. After preoperative treatment and cytoreductive surgery, all patients were excluded from protocol due to severe toxicities. Three patients had life threatening events (cardiac output failure, myocardial infarction, anastomotic leak); two patients had primary progressive disease. The study was terminated on the basis of the recommendation of an independent data safety monitoring board. The addition of sorafenib to carboplatin/paclitaxel chemotherapy was not feasible within this neoadjuvant regimen in primary advanced ovarian cancer. Although the occurrence of serious adverse events might have emerged at random, a detrimental effect of preoperative study medication could not be denied. Further evaluations of sorafenib in ovarian cancer are warranted.

  16. Aprepitant in patients with advanced non-small-cell lung cancer receiving carboplatin-based chemotherapy.

    Science.gov (United States)

    Ito, Yasuhiro; Karayama, Masato; Inui, Naoki; Kuroishi, Shigeki; Nakano, Hideki; Nakamura, Yutaro; Yokomura, Koshi; Toyoshima, Mikio; Shirai, Toshihiro; Masuda, Masafumi; Yamada, Takashi; Yasuda, Kazumasa; Hayakawa, Hiroshi; Suda, Takafumi; Chida, Kingo

    2014-06-01

    Chemotherapy-induced nausea and vomiting (CINV) is an unanswered problem in cancer therapy. We evaluated the efficacy and safety of triple antiemetic therapy with aprepitant, a 5-hydroxytryptamine-3 (5-HT(3)) receptor antagonist, and dexamethasone in patients with advanced non-small-cell lung cancer (NSCLC) who received carboplatin-based first-line chemotherapy. Chemotherapy-naïve patients with NSCLC were enrolled in this randomized phase-II study. Patients were randomized to standard antiemetic therapy with a 5-HT(3) receptor antagonist and dexamethasone, and aprepitant add-on triple antiemetic therapy. The primary endpoint was the complete response rate (no vomiting and no rescue therapy) during the 120 h post-chemotherapy. A total of 134 patients were assigned randomly to the aprepitant group or the control group. The aprepitant group and the control group showed an overall complete response rate of 80.3% (95% confidence interval (CI), 69.2-88.1%) and 67.2% (95% CI, 55.3-77.2%; odds ratio (OR), 0.50; 95% CI, 0.22-1.10; p = 0.085), respectively. Among patients taking carboplatin and pemetrexed, adding aprepitant significantly improved the complete response rate in the overall phase (83.8% in the aprepitant group and 56.8% in the control group; OR, 0.26; 95% CI, 0.08-0.70; p chemotherapy has considerable emetic potential. Triple antiemetic therapy with aprepitant, a 5-HT(3) receptor antagonist, and dexamethasone improved the control of CINV prevention in patients receiving carboplatin and pemetrexed chemotherapy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Evaluation of a Seven-Week Web-Based Happiness Training to Improve Psychological Well-Being, Reduce Stress, and Enhance Mindfulness and Flourishing: A Randomized Controlled Occupational Health Study

    Directory of Open Access Journals (Sweden)

    T. Feicht

    2013-01-01

    Full Text Available Background. As distress in society increases, including work environments, individual capacities to compete with stress have to be strengthened. Objective. We examined the impact of a web-based happiness training on psychological and physiological parameters, by self-report and objective means, in an occupational health setting. Methods. Randomized controlled trial with 147 employees. Participants were divided into intervention (happiness training and control groups (waiting list. The intervention consisted of a seven-week online training. Questionnaires were administered before, after, and four weeks after training. The following scales were included: VAS (happiness and satisfaction, WHO-5 Well-being Index, Stress Warning Signals, Freiburg Mindfulness Inventory, Recovery Experience Questionnaire, and Flourishing Scale. Subgroup samples for saliva cortisol and alpha-amylase determinations were taken, indicating stress, and Attention Network Testing for effects on attention regulation. Results. Happiness (P=0.000; d=0.93, satisfaction (P=0.000; d=1.17, and quality of life (P=0.000; d=1.06 improved; perceived stress was reduced (P=0.003; d=0.64; mindfulness (P=0.006; d=0.62, flourishing (P=0.002; d=0.63, and recovery experience (P=0.030; d=0.42 also increased significantly. No significant differences in the Attention Network Tests and saliva results occurred (intergroup, except for one saliva value. Conclusions. The web-based training can be a useful tool for stabilizing health/psychological well-being and work/life balance.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  19. Effects of sequential paclitaxel-carboplatin followed by gemcitabine-based chemotherapy compared with paclitaxel-carboplatin therapy administered to patients with advanced epithelial ovarian cancer: A retrospective, STROBE-compliant study.

    Science.gov (United States)

    Wang, Fei; Du, Xuelian; Li, Xiaoxia; Liu, Naifu; Yu, Hao; Sheng, Xiugui

    2016-12-01

    We aimed to compare the efficacy of paclitaxel and carboplatin followed by gemcitabine-based combination chemotherapy with paclitaxel-carboplatin for treating advanced epithelial ovarian cancer in this retrospective, STROBE-compliant study. Patients' tolerance to treatment was also assessed.We retrospectively analyzed the records of 178 women who underwent initial optimal debulking surgery between January 2003 and December 2011 to treat FIGO stage IIIc epithelial ovarian cancer. Patients in arm 1 (n = 88) received 4 cycles of paclitaxel and carboplatin followed by 2 to 4 cycles of gemcitabine-based combination chemotherapy. Patients in arm 2 (n = 90) received 6 to 8 cycles of paclitaxel and carboplatin. The granulocyte-colony stimulating factor was administered prophylactically to all patients.The median follow-up for both arms was 62 months. Medianprogression-free survival (PFS) between arms 1 and 2 (28 and 19 months [P = 0.003]) as well as 5-year OS (34.1% and 18.9% [P = 0.021]) differed significantly. The neurotoxicity rate was significantly higher in arm 2 than in arm 1 (45.2% vs 27.1%, P = 0.026). There was no significant difference between study arms in hematological toxicity.The sequential regimen significantly improved PFS and 5-year OS with tolerable toxicity compared with the single regimen, and offers an alternative for treating patients with advanced epithelial ovarian cancer.

  20. Activation of a nuclear factor of activated T-lymphocyte-3 (NFAT3) by oxidative stress in carboplatin-mediated renal apoptosis

    Science.gov (United States)

    Lin, Heng; Sue, Yuh-Mou; Chou, Ying; Cheng, Ching-Feng; Chang, Chih-Cheng; Li, Hsiao-Fen; Chen, Chien-Chang; Juan, Shu-Hui

    2010-01-01

    BACKGROUND AND PURPOSE Although carboplatin is currently used as a therapeutic drug for ovarian, breast, and non-small cell lung cancers, it has serious side effects including renal and cardiac toxicity. Herein, we examined the effect of carboplatin on murine renal tubular cell (RTC) apoptosis both in vivo and in vitro and the underlying molecular mechanisms associated with its activation of the nuclear factor of activated T-lymphocytes-3 (NFAT3). EXPERIMENTAL APPROACH Mechanisms of carboplatin-mediated renal apoptosis were examined using NFAT-reporter transgenic mice and RTCs with NFAT3 overexpression or knockdown. KEY RESULTS We demonstrated that carboplatin initiated an intrinsic apoptotic pathway of activating caspase-3 and -9, accompanied by a decrease in the ratio of Bcl-XL/Bax and a significant increase in Bcl-XS. Carboplatin increased NFAT activation in NFAT-luciferase reporter transgenic mice, RTCs and cells exogenously overexpressing NFAT3 that exacerbated cell death. Furthermore, the addition of either N-acetylcysteine (NAC, an antioxidant) or NFAT inhibitors, including FK-506 (tacrolimus), cyclosporin A (CsA, a calcineurin inhibitor), and BAPTA-AM (a calcium chelator) successfully reversed carboplatin-mediated cell apoptosis, which was further confirmed using siNFAT3. Additionally, NAC blocked NFAT3 activation by inhibition of NADPH oxidase activation, and ERK/JNK and PKC pathways, resulting in a decrease in cell apoptosis; the therapeutic effect of NAC was verified in vivo. CONCLUSION AND IMPLICATIONS The results presented herein show that carboplatin-mediated reactive oxygen species might signal calcineurin and NFAT3 activation in RTCs, whereas NAC and NFAT inhibitors reversed carboplatin-mediated RTC apoptosis, suggesting that oxidative stress-mediated NFAT3 activation is essential for carboplatin-mediated RTC apoptosis. PMID:20718735

  1. Graphene oxide - gelatin nanohybrids as functional tools for enhanced Carboplatin activity in neuroblastoma cells.

    Science.gov (United States)

    Makharza, Sami; Vittorio, Orazio; Cirillo, Giuseppe; Oswald, Steffen; Hinde, Elizabeth; Kavallaris, Maria; Büchner, Bernd; Mertig, Michael; Hampel, Silke

    2015-06-01

    Preparation of Nanographene oxide (NGO) - Gelatin hybrids for efficient treatment of Neuroblastoma. Nanohybrids were prepared via non-covalent interactions. Spectroscopic tools have been used to discriminate the chemical states of NGO prior and after gelatin coating, with UV visible spectroscopy revealing the maximum binding capacity of gelatin to NGO. Raman and X-ray photoelectron spectroscopy (XPS) demonstrated NGO and Gelatin_NGO nanohybrids through a new chemical environments produced after noncovalent interaction. Microscopic analyses, atomic force microscopy (AFM) and scanning electron microscopy (SEM) are used to estimate the thickness of samples and the lateral width in the nanoscale, respectively. The cell viability assay validated Gelatin_NGO nanohybrids as a useful nanocarrier for Carboplatin (CP) release and delivery, without obvious signs of toxicity. The nano-sized NGO (200 nm and 300 nm) did not enable CP to kill the cancer cells efficiently, whilst the CP loaded Gel_NGO 100 nm resulted in a synergistic activity through increasing the local concentration of CP inside the cancer cells. The nanohybrids provoked high stability and dispersibility in physiological media, as well as enhanced the anticancer activity of the chemotherapy agent Carboplatin (CP) in human neuroblastoma cells.

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

    Directory of Open Access Journals (Sweden)

    Songliang ZHANG

    2015-06-01

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

  3. Incidence and physiological mechanism of carboplatin-induced electrolyte abnormality among patients with non-small cell lung cancer.

    Science.gov (United States)

    Ma, Yushui; Hou, Likun; Yu, Fei; Lu, Gaixia; Qin, Shanshan; Xie, Ruting; Yang, Huiqiong; Wu, Tingmiao; Luo, Pei; Chai, Li; Lv, Zhongwei; Peng, Xiaodong; Wu, Chunyan; Fu, Da

    2017-03-14

    To clarify the association between carboplatin and electrolyte abnormality, a pooled-analysis was performed with the adverse event reports of non-small cell lung cancer patients. A total of 19901 adverse events were retrieved from the FDA Adverse Event Reporting System (FAERS). Pooled reporting odds ratios (RORs) and 95% CIs suggested that carboplatin was significantly associated with hyponatremia (pooled ROR = 1.57, 95% CI 1.18-2.09, P = 1.99×10-3) and hypokalemia (pooled ROR = 2.37, 95% CI 1.80-3.10, P = 5.24×10-10) as compared to other therapies. In addition, we found that dehydration was frequently concurrent with carboplatin therapy (pooled ROR = 2.01, 95% CI 1.52-2.66, P = 8.37×10-7), which may prompt excessive water ingestion and decrease serum electrolyte concentrations. This information has not been mentioned in the FDA-approved drug label and could help explain the physiological mechanism of carboplatin-induced electrolyte abnormality. In conclusion, the above results will facilitate clinical management and prompt intervention of life-threatening electrolyte imbalance in the course of cancer treatment.

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

    Science.gov (United States)

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

    2017-08-01

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

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  6. Effects of ambroxol hydrochloride on concentrations of paclitaxel and carboplatin in lung cancer patients at different administration times.

    Science.gov (United States)

    Li, J; Yi, W; Jiang, P; Sun, R; Li, T

    2016-11-30

    Our previous preliminary study revealed a synergistic effect of ambroxol hydrochloride with chemotherapeutic agents such as paclitaxel and carboplatin in lung cancer. However, the optimal conditions such as administration time and drug concentration of ambroxol hydrochloride to achieve the maximum synergistic effect remained unclear. Therefore, concentration changes of the chemotherapy drugs paclitaxel and carboplatin in the sputum were observed after ambroxol hydrochloride administration at different times in order to determine the most effective time frame of ambroxol hydrochloride administration. In this study, 470 cases of non-small cell lung cancer (NSCLC) were divided into different groups with ambroxol hydrochloride administered at different time points prior to chemotherapy, while another 171 cases received no ambroxol hydrochloride prior to chemotherapy. The results showed the concentrations of paclitaxel and carboplatin in sputum of patients treated with ambroxol hydrochloride were significantly higher than those of the control group, suggesting that ambroxol hydrochloride significantly increased the local concentrations of chemotherapeutic agents in lung tissues of NSCLC. Furthermore, the intravenous administration of ambroxol hydrochloride more than 48 hours before chemotherapy showed an optimized schedule and much greater efficacy in increasing drug concentrations than that of the control group. No statistical differences were found in the rates of grade 2 or above myelosuppression between the ambroxol intervention and control groups. Taken together, these results demonstrate that ambroxol hydrochloride administered intravenously more than 48 hours prior to chemotherapy optimally increased the concentrations of paclitaxel and carboplatin in lung tissue without significantly increasing hematologic toxicity.

  7. Weekly iron supplementation reduces anemia prevalence by 1/3 in preschool children Suplementação semanal com sulfato ferroso reduz em 1/3 a prevalência de anemia em pré-escolares

    Directory of Open Access Journals (Sweden)

    Gisela Soares Brunken

    2004-06-01

    Full Text Available A weekly medication scheme, followed by nutritional guidance on diets in child-care centers, was evaluated in order to make it feasible for routine use. The study was conducted in six child-care centers in the town of Cuiabá - Brazil. The supplement (6 mg/kg was provided on a weekly basis to all children (n=178 less than three years old during four months at the institution by the classroom staff. After this initial phase, nutritional guidance was provided regarding the child-care center's normal diet as a way to control hemoglobin levels. This is an intervention study whose individuals were examined at three different periods: at the beginning of treatment (T0; after four months of iron supplementation (T1 and after five months of nutritional guidance (T2. Hemoglobin measurements were obtained using a portable hemoglobinometer - HemoCue. A significant improvement was observed in the hemoglobin levels of anemic children after controlling for age and initial hemoglobin. The hemoglobin concentration of these children improved an average of 0.1 g/l after each dose of iron sulfate. At the end of four months there was an average gain of 1.6 g/l, and prevalence of anemia reduced by 1/3, sufficient to meet the United Nations target adopted by Brazil. At the end of nine months (four months of weekly drug intervention followed by 5 months of nutritional guidance the prevalence of anemia dropped by 1/4 in the child-care centers. The intervention proved to be feasible for child-care centers and pre-school population.Um esquema terapêutico semanal, seguido de orientação alimentar aos cardápios, foi avaliado com o intuito de verificar viabilidade como rotina em creches. O estudo foi realizado em seis creches no município de Cuiabá. O suplemento (6 mg/kg foi oferecido semanalmente a todas as crianças (n=178 menores de 3 anos durante 4 meses, na própria Instituição, pelas funcionárias. Após essa primeira etapa seguiram-se orientações alimentares

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

    Science.gov (United States)

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

    2017-07-01

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

  9. Efficacy of the neurokinin-1 receptor antagonist rolapitant in preventing nausea and vomiting in patients receiving carboplatin-based chemotherapy.

    Science.gov (United States)

    Hesketh, Paul J; Schnadig, Ian D; Schwartzberg, Lee S; Modiano, Manuel R; Jordan, Karin; Arora, Sujata; Powers, Dan; Aapro, Matti

    2016-08-01

    Rolapitant, a novel neurokinin-1 receptor antagonist, provided effective protection against chemotherapy-induced nausea and vomiting (CINV) in a randomized, double-blind phase 3 trial of patients receiving moderately emetogenic chemotherapy or an anthracycline and cyclophosphamide regimen. The current analysis explored the efficacy and safety of rolapitant in preventing CINV in a subgroup of patients receiving carboplatin. Patients were randomized 1:1 to receive oral rolapitant (180 mg) or a placebo 1 to 2 hours before chemotherapy administration; all patients received oral granisetron (2 mg) on days 1 to 3 and oral dexamethasone (20 mg) on day 1. A post hoc analysis examined the subgroup of patients receiving carboplatin in cycle 1. The efficacy endpoints were as follows: complete response (CR), no emesis, no nausea, no significant nausea, complete protection, time to first emesis or use of rescue medication, and no impact on daily life. In the subgroup administered carboplatin-based chemotherapy (n = 401), a significantly higher proportion of patients in the rolapitant group versus the control group achieved a CR in the overall phase (0-120 hours; 80.2% vs 64.6%; P 24-120 hours; 82.3% vs 65.6%; P < .001) after chemotherapy administration. Superior responses were also observed by the measures of no emesis, no nausea, and complete protection in the overall and delayed phases and by the time to first emesis or use of rescue medication. The incidence of treatment-emergent adverse events was similar for the rolapitant and control groups. Rolapitant provided superior CINV protection to patients receiving carboplatin-based chemotherapy in comparison with the control. These results support rolapitant use as part of the antiemetic regimen in carboplatin-treated patients. Cancer 2016;122:2418-2425. © 2016 American Cancer Society. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

  10. Docetaxel-carboplatin in combination with erlotinib and/or bevacizumab in patients with non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Boutsikou E

    2013-03-01

    Full Text Available Eftimia Boutsikou,1 Theodoros Kontakiotis,1 Paul Zarogoulidis,1 Kaid Darwiche,2 Ellada Eleptheriadou,1 Konstantinos Porpodis,1 Grammati Galaktidou,3 Leonidas Sakkas,4 Wolfgang Hohenforst-Schmidt,5 Kosmas Tsakiridis,6 Theodoros Karaiskos,7 Konstantinos Zarogoulidis11Pulmonary Department-Oncology Unit, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Greece; 2University Pulmonary Department-Interventional Unit, Ruhrland Klinic, University of Duisburg-Essen, Essen, Germany; 3Theagenio Anticancer Institute Research Laboratory, 4Department of Pathology, G Papanikolaou Hospital, Thessaloniki, Greece; 5II Medical Clinic, Hospital Coburg, University of Wuerzburg, Coburg, Germany; 6Cardiothoracic Surgery Department, Saint Luke Private Hospital, Panorama, 7Cardiothoracic Surgery Department, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, GreeceBackground: Bevacizumab and erlotinib have been demonstrated to prolong overall survival in patients with non-squamous non-small cell lung cancer (NSCLC. We designed a four-arm Phase III trial to evaluate the efficacy and toxicity of the combination of docetaxel, carboplatin, bevacizumab, and erlotinib in the first-line treatment of patients with NSCLC.Methods: A total of 229 patients with stage IIIb/IV non-squamous NSCLC were treated with two cycles of carboplatin (area under the concentration-time curve 5.5 and docetaxel 100 mg/m2 as chemotherapy. After completion of two treatment cycles, patients were evaluated for response and divided into four groups: 61/229 continued with four more cycles of chemotherapy (control group, 52/229 received chemotherapy plus erlotinib 150 mg daily, 56/229 received chemotherapy plus bevacizumab 7.5 mg/kg, and 60/229 were treated with the combination of chemotherapy, erlotinib, and bevacizumab until disease progression. The primary endpoint was overall survival.Results: Over 4 years of follow-up, there was no statistically

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: The objective of this study was to evaluate the efficacy of belinostat, a histone deacetylase inhibitor, when added to paclitaxel/carboplatin in the empiric first-line treatment of patients with carcinoma of unknown primary site (CUP). METHODS: In this randomized phase 2 trial......, previously untreated patients with CUP were randomized to receive belinostat plus paclitaxel/carboplatin (group A) or paclitaxel/carboplatin alone (group B) repeated every 21 days. Patients were re-evaluated every 2 cycles, and those without disease progression continued treatment for 6 cycles. Patients...... in group A then continued receiving single-agent belinostat, whereas patients in group B stopped treatment. The primary endpoint was progression-free survival (PFS): The authors postulated that the addition of belinostat would improve PFS from 5 months (expected with paclitaxel/carboplatin) to 8 months...

  12. Isorhamnetin flavonoid synergistically enhances the anticancer activity and apoptosis induction by cis-platin and carboplatin in non-small cell lung carcinoma (NSCLC)

    Science.gov (United States)

    Zhang, Bao-Yi; Wang, Yan-Ming; Gong, Hai; Zhao, Hui; Lv, Xiao-Yan; Yuan, Guang-Hui; Han, Shao-Rong

    2015-01-01

    The development of novel antitumor drugs for the treatment of non-small cell lung carcinoma NSCLC is imperative in order to improve the efficacy of lung cancer therapy and prognosis. In the current study, we demonstrated the antitumor activity of isorhamnetin and its combinations with cisplatin and carboplatin against A-549 lung cancer cells. In order to assess the anticancer enhancing effect of isorhamnetin on cisplatin and carboplatin, A-549 cells were treated with isorhamnetin, cisplatin, carboplatin and their combinations and cell viability, cell apoptosis, cell cycle arrest as well as loss of mitochondrial membrane potential were evaluated by MTT assay, flow cytometry, confocal microscopy and fluorescence microscopy. The effect of the drugs on cancer cell migration, microtubule depolymerization as well activation of caspases was also studied. The results revealed that, as compared to single drug treatment, the combination of isorhamnetin with cisplatin and carboplatin resulted in greater effect in inhibiting cancer cell growth and inducing apoptosis. Combination of isorhamnetin with cisplatin and carboplatin resulted in more potent apoptosis induction as revealed by fluorescence microscopy using AO/PI double staining. Isorhamnetin and its combinations also triggered microtubule distortion and depolymerization. The combination of isorhamnetin with cisplatin and carboplatin increased the number of cells in G2/M phase dramatically as compared to single drug treatment. Moreover, isorhamnetin and its combinations with known anticancer drugs induced disruption of the mitochondrial membrane potential as well as activation of caspases 3, 9 and poly-(ADP-ribose) polymerase in A-549 cells. Isorhamnetin as well as its combinations with cisplatin and carboplatin resulted in inhibition of cancer cell migration significantly. Results of the current study suggest that isorhamnetin combinations with cisplatin and carboplatin might be a potential clinical chemotherapeutic

  13. Evaluation of carboplatin dosing in non-small cell lung carcinoma patients using Calvert formula and Cockroft and Gault equation for glomerular filtration rate estimation.

    Science.gov (United States)

    Bar-Sela, Gil; Kaidar-Person, Orit; Mari, Fadi; Assady, Suheir; Haim, Nissim

    2012-11-01

    The aim of this study was to evaluate the reliability of the Cockroft and Gault (CG) equation for glomerular filtration rate (GFR) estimation in carboplatin dosing based on the Calvert formula. The records of 117 patients with advanced non-small cell lung carcinoma treated with carboplatin were retrospectively analyzed. Theoretical carboplatin doses derived from the Calvert formula using the CG equation were calculated for each chemotherapy cycle. Fluctuations in the theoretical carboplatin doses were analyzed, and discrepancies between actual carboplatin doses prescribed by the physician and theoretical doses were assessed. It was found that, compared with the first-cycle dose, subsequent theoretical doses were more than 10% higher in 79/320 cycles (24.7%) and more than 10% lower in 53/320 cycles (16.6%; P=0.015). A body mass index greater than or equal to 30 was associated with a tendency for increased CG-estimated GFR during subsequent chemotherapy cycles (P=0.009). Physicians tended to lower the prescribed dose (32.2% of the cycles) by using a higher serum creatinine (Scr) level for dose calculation than was actually measured. We concluded that Calvert formula-derived carboplatin doses fluctuate widely during repeated cycles when actual Scr is used for CG-estimated GFR. The measurement of 24-h creatinine clearance is advised as an alternative in selected patients with reduction in serum creatinine observed during treatments.

  14. Induction concurrent chemoradiotherapy using Paclitaxel and Carboplatin combination followed by surgery in locoregionally advanced non-small cell lung cancer--Asian experience.

    Science.gov (United States)

    Yap, Swee-Peng; Lim, Wan-Teck; Foo, Kian-Fong; Hee, Siew-Wan; Leong, Swan-Swan; Fong, Kam-Weng; Eng, Philip; Hsu, Anne Al; Wee, Joseph Ts; Agasthian, Thirugnanam; Koong, Heng-Nung; Tan, Eng-Huat

    2008-05-01

    It has been established that combined chemoradiotherapy treatment benefits selected patients with stage III Non Small Cell Lung Cancer (NSCLC). However, locoregional recurrence still poses a problem. The addition of surgery as the third modality may provide a possible solution. We report our experience of using the triple-modality approach in this group of patients. This is a retrospective review of 33 patients with stage III NSCLC treated between 1997 and 2005. Patients have good performance status and no significant weight loss. There were 26 males (79 %) with median age of 63 years (range, 43 to 74) and median follow-up of 49 months. Seventy-six percent had Stage IIIA disease. Chemotherapy consisted of paclitaxel at 175 mg/m2 over 3 hours followed by carboplatin at AUC of 5 over 1 hour. Thoracic radiotherapy was given concurrently with the second and third cycles of chemotherapy. All patients received 50 Gray in 25 fractions over 5 weeks. The main toxicities were grade 3/4 neutropenia (30%), grade 3 infection (15 %) and grade 3 oesophagitis (9%). Twenty-five patients (76%) underwent surgery. Of the 8 who did not undergo surgery, 1 was deemed medically unfit after induction chemoradiotherapy and 4 had progressive disease; 3 declined surgery. Nineteen patients (58 %) had lobectomy and 6 had pneumonectomy. The median overall survival was 29.9 months and 12 patients are still in remission. The use of the triplemodality approach is feasible, with an acceptable tolerability and resectability rate in this group of patients.

  15. [A Case of Undifferentiated Carcinoma of the Sigmoid Colon That Responded to Paclitaxel and Carboplatin Chemotherapy].

    Science.gov (United States)

    Toyama, Shingo; Kudoh, Katsuyoshi; Ohnuma, Shinobu; Sato, Satoko; Tanaka, Naoki; Aoki, Takeshi; Imoto, Hirofumi; Karasawa, Hideaki; Watanabe, Kazuhiro; Nagao, Munenori; Abe, Tomoya; Musha, Hiroaki; Motoi, Fuyuhiko; Naitoh, Takeshi; Unno, Michiaki

    2016-11-01

    We report a case of a 72-year-old woman who was initially diagnosed with ovarian cancer with peritoneal carcinomatosis. Systemic chemotherapy consisting of paclitaxel and carboplatin(TC)was administered. Although a partial response(PR)was achieved after the 4 courses of TC, this regimen was discontinued due to severe adverse events. Ten months after discontinuation of TC, because abdominal CT and colonoscopy showed an intra-tumoral abscess caused by invasion of the tumor to the sigmoid colon, abdominal total hysterectomy, bilateral salpingo-oophorectomy, and a Hartmann's operation were performed to control the disease symptoms. Pathological examination revealed that the tumor was an undifferentiated carcinoma of the sigmoid colon. This case report suggests that the TC regimen may be effective for treating undifferentiated carcinoma of the colon.

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

    Directory of Open Access Journals (Sweden)

    Valerie A. Allen

    2016-01-01

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

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

    Science.gov (United States)

    Allen, Valerie A; Manahan, Kelly J; Geisler, John P

    2016-01-01

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

  18. Carboplatin and taxol resistance develops more rapidly in functional BRCA1 compared to dysfunctional BRCA1 ovarian cancer cells.

    Science.gov (United States)

    Busschots, Steven; O'Toole, Sharon; O'Leary, John J; Stordal, Britta

    2015-08-01

    A major risk factor for ovarian cancer is germline mutations of BRCA1/2. It has been found that (80%) of cellular models with acquired platinum or taxane resistance display an inverse resistance relationship, that is collateral sensitivity to the other agent. We used a clinically relevant comparative selection strategy to develop novel chemoresistant cell lines which aim to investigate the mechanisms of resistance that arise from different exposures of carboplatin and taxol on cells having BRCA1 function (UPN251) or dysfunction (OVCAR8). Resistance to carboplatin and taxol developed quicker and more stably in UPN251 (BRCA1-wildtype) compared to OVCAR8 (BRCA1-methylated). Alternating carboplatin and taxol treatment delayed but did not prevent resistance development when compared to single-agent administration. Interestingly, the sequence of drug exposure influenced the resistance mechanism produced. UPN251-6CALT (carboplatin first) and UPN251-6TALT (taxol first) have different profiles of cross resistance. UPN251-6CALT displays significant resistance to CuSO4 (2.3-fold, p=0.004) while UPN251-6TALT shows significant sensitivity to oxaliplatin (0.6-fold, p=0.01). P-glycoprotein is the main mechanism of taxol resistance found in the UPN251 taxane-resistant sublines. UPN251 cells increase cellular glutathione levels (3.0-fold, p=0.02) in response to carboplatin treatment. However, increased glutathione is not maintained in the carboplatin-resistant sublines. UPN251-7C and UPN251-6CALT are low-level resistant to CuSO4 suggesting alterations in copper metabolism. However, none of the UPN251 sublines have alterations in the protein expression of ATP7A or CTR1. The protein expression of BRCA1 and MRP2 is unchanged in the UPN251 sublines. The UPN251 sublines remain sensitive to parp inhibitors veliparib and CEP8983 suggesting that these agents are candidates for the treatment of platinum/taxane resistant ovarian cancer patients. Copyright © 2014 Elsevier Inc. All rights

  19. Enhanced Antiproliferative Effect of Carboplatin in Cervical Cancer Cells Utilizing Folate-Grafted Polymeric Nanoparticles

    Science.gov (United States)

    Ji, Jing; Zuo, Ping; Wang, Yue-Ling

    2015-11-01

    Carboplatin (CRB) possesses superior anticancer effect in cervical cancer cells with lower incidence of side effects compared to that of cisplatin. However, CRB suffers from severe side effects due to undesirable tissue distributions which contribute to the low therapeutic efficacy. Here, we report a unique folic acid-conjugated chitosan-coated poly( d- l-lactideco-glycolide) (PLGA) nanoparticles (FPCC) prepared for the selective delivery of carboplatin to the cervical cancer cells. The particles were nanosized and spherical shaped with size less than <200 nm. The presence of protective chitosan layer controlled the overall release rate of CRB from chitosan-coated PLGA nanoparticles (PCC) and FPCC. FPCC displayed a higher cellular uptake capacity in HeLa cells than compared to non-targeted nanoparticles. Selective uptake of FPCC was due to an interaction of folic acid (FA) with the folate receptors alpha (FRs-α) which is overexpressed on the HeLa and promoted active targeting. These results indicated that FPCC had a specific affinity for the cancerous, HeLa cells owing to ligand-receptor (FA-FR-α) recognition. Consistently, FPCC showed superior cytotoxic effect than any other formulations. The IC50 (concentration of the drug required to kill 50 % of the cells) value of FPCC was 0.65 μg/ml while it was 1.08, 1.56, and 2.35 μg/ml for PCC, PLGA NP, and free CRB, respectively. Consistent with the cytotoxicity assay, FPCC induced higher fraction of early as well as late apoptosis cells. Especially, FPCC induced nearly 45 % of early apoptosis cells and more than 35 % in late apoptosis. Therefore, we propose that folate-conjugated nanoparticles might have potential applications in cervical cancer therapy.

  20. Carboplatin loaded Surface modified PLGA nanoparticles: Optimization, characterization, and in vivo brain targeting studies.

    Science.gov (United States)

    Jose, S; Juna, B C; Cinu, T A; Jyoti, H; Aleykutty, N A

    2016-06-01

    The carboplatin (CP) loaded poly-lactide-co-glycolide (PLGA) nanoparticles (NPs) were formulated by modified solvent evaporation method. Its surface modification is done by 1% polysorbate80 (P80) to improve their entry into the brain after intraperitoneal administration (i.p) via receptor-mediated pathways. A formulation with maximum entrapment efficiency and minimal particle size was optimized by central composite design (CCD) based on mean particle size, and entrapment efficiencies as responses. The optimized formulation was characterized by mean particle size, entrapment efficiency, zeta potential, Fourier transform infrared (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) analysis. The surface modified NPs were analysed for mean particle, zeta potential, FTIR, and in vitro release studies. The spherical particles with mean particle size 161.9nm, 162.4nm and zeta potential value of -26.5, -23.9 were obtained for unmodified and surface modified NPs respectively. The in vitro release experiments of the surface modified PLGA NPs exhibited sustained release for more than 48h, which was in accordance with Higuchi's equation with Fickian diffusion-based release mechanism. The in vivo bio distribution of P80 coated CP loaded PLGA NPs was compared with CP solution, and CP loaded NPs, in adult wistar rats. In the brain, compared with CP solution, both types of NPs especially NPs coated with P80 increased the concentration of carboplatin by 3.27 fold. All these results suggest that the developed formulation may improve the targeted therapy for malignant brain tumors in future. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. FDA Drug Approval Summary: Bevacizumab (Avastin®) Plus Carboplatin and Paclitaxel as First‐Line Treatment of Advanced/Metastatic Recurrent Nonsquamous Non‐Small Cell Lung Cancer

    National Research Council Canada - National Science Library

    Cohen, Martin H; Gootenberg, Joe; Keegan, Patricia; Pazdur, Richard

    2007-01-01

    ...., South San Francisco, CA), administered in combination with carboplatin and paclitaxel, for the initial treatment of patients with unresectable, locally advanced, recurrent, or metastatic, nonsquamous...

  2. Phun Week: Understanding Physiology

    Science.gov (United States)

    Limson, Mel; Matyas, Marsha Lakes

    2009-01-01

    Topics such as sports, exercise, health, and nutrition can make the science of physiology relevant and engaging for students. In addition, many lessons on these topics, such as those on the cardiovascular, respiratory, and digestive systems, align with national and state life science education standards. Physiology Understanding Week (PhUn…

  3. Efficacy and toxicity of carboplatin and cytarabine chemotherapy for dogs with relapsed or refractory lymphoma (2000-2013).

    Science.gov (United States)

    Gillem, J; Giuffrida, M; Krick, E

    2017-06-01

    Medical records of 22 dogs treated with carboplatin (n = 8) or carboplatin and cytarabine (n = 14) chemotherapy for relapsed or refractory lymphoma between 2000 and 2013 were retrospectively reviewed. The clinical response rate was 18.2% (4/22). Median time to progression was 18 days (56 for responders; 12 for non-responders, P = 0.0006). Median overall survival time was 28 days (109 for responders; 21 for non-responders, P = 0.0007). Thrombocytopenia and neutropenia occurred in 84.2% (16/19) and 52.6% (10/19), respectively. Grade IV thrombocytopenia and neutropenia occurred in 56.3% (9/16) and 60.0% (6/10), respectively. Dogs that received both drugs were more likely to become neutropenic (P = 0.022) or thrombocytopenic (P = 0.001) than dogs receiving carboplatin alone. All responders received both drugs giving a 28.6% (4/14) response rate for the combination. Although some dogs responded to the combination, toxicity was high and the responses were not durable. With adequate supportive care, this protocol may be an acceptable rescue option for some dogs. © 2015 John Wiley & Sons Ltd.

  4. Radiosensitizing effect of carboplatin and paclitaxel to carbon-ion beam irradiation in the non-small-cell lung cancer cell line H460.

    Science.gov (United States)

    Kubo, Nobuteru; Noda, Shin-ei; Takahashi, Akihisa; Yoshida, Yukari; Oike, Takahiro; Murata, Kazutoshi; Musha, Atsushi; Suzuki, Yoshiyuki; Ohno, Tatsuya; Takahashi, Takeo; Nakano, Takashi

    2015-03-01

    The present study investigated the ability of carboplatin and paclitaxel to sensitize human non-small-cell lung cancer (NSCLC) cells to carbon-ion beam irradiation. NSCLC H460 cells treated with carboplatin or paclitaxel were irradiated with X-rays or carbon-ion beams, and radiosensitivity was evaluated by clonogenic survival assay. Cell proliferation was determined by counting the number of viable cells using Trypan blue. Apoptosis and senescence were evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and senescence-associated β-galactosidase (SA-β-gal) staining, respectively. The expression of cleaved caspase-3, Bax, p53 and p21 was analyzed by western blotting. Clonogenic survival assays demonstrated a synergistic radiosensitizing effect of carboplatin and paclitaxel with carbon-ion beams; the sensitizer enhancement ratios (SERs) at the dose giving a 10% survival fraction (D10) were 1.21 and 1.22, respectively. Similarly, carboplatin and paclitaxel showed a radiosensitizing effect with X-rays; the SERs were 1.41 and 1.29, respectively. Cell proliferation assays validated the radiosensitizing effect of carboplatin and paclitaxel with both carbon-ion beam and X-ray irradiation. Carboplatin and paclitaxel treatment combined with carbon-ion beams increased TUNEL-positive cells and the expression of cleaved caspase-3 and Bax, indicating the enhancement of apoptosis. The combined treatment also increased SA-β-gal-positive cells and the expression of p53 and p21, indicating the enhancement of senescence. In summary, carboplatin and paclitaxel radiosensitized H460 cells to carbon-ion beam irradiation by enhancing irradiation-induced apoptosis and senescence. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  5. Blood fatty acid changes in healthy young Americans in response to a 10-week diet that increased n-3 and reduced n-6 fatty acid consumption: a randomised controlled trial.

    Science.gov (United States)

    Young, Andrew J; Marriott, Bernadette P; Champagne, Catherine M; Hawes, Michael R; Montain, Scott J; Johannsen, Neil M; Berry, Kevin; Hibbeln, Joseph R

    2017-05-01

    Military personnel generally under-consume n-3 fatty acids and overconsume n-6 fatty acids. In a placebo-controlled, double-blinded study, we investigated whether a diet suitable for implementation in military dining facilities and civilian cafeterias could benefit n-3/n-6 fatty acid status of consumers. Three volunteer groups were provided different diets for 10 weeks. Control (CON) participants consumed meals from the US Military's Standard Garrison Dining Facility Menu. Experimental, moderate (EXP-Mod) and experimental-high (EXP-High) participants consumed the same meals, but high n-6 fatty acid and low n-3 fatty acid containing chicken, egg, oils and food ingredients were replaced with products having less n-6 fatty acids and more n-3 fatty acids. The EXP-High participants also consumed smoothies containing 1000 mg n-3 fatty acids per serving, whereas other participants received placebo smoothies. Plasma and erythrocyte EPA and DHA in CON group remained unchanged throughout, whereas EPA, DHA and Omega-3 Index increased in EXP-Mod and EXP-High groups, and were higher than in CON group after 5 weeks. After 10 weeks, Omega-3 Index in EXP-High group had increased further. No participants exhibited changes in fasting plasma TAG, total cholesterol, LDL, HDL, mood or emotional reactivity. Replacing high linoleic acid (LA) containing foods in dining facility menus with similar high oleic acid/low LA and high n-3 fatty acid foods can improve n-6/n-3 blood fatty acid status after 5 weeks. The diets were well accepted and suitable for implementation in group feeding settings like military dining facilities and civilian cafeterias.

  6. Eight weeks of supplementation with a multi-ingredient weight loss product enhances body composition, reduces hip and waist girth, and increases energy levels in overweight men and women.

    Science.gov (United States)

    Lopez, Hector L; Ziegenfuss, Tim N; Hofheins, Jennifer E; Habowski, Scott M; Arent, Shawn M; Weir, Joseph P; Ferrando, Arny A

    2013-04-19

    Numerous natural products are marketed and sold claiming to decrease body weight and fat, but few undergo finished product-specific research demonstrating their safety and efficacy. To determine the safety and efficacy of a multi-ingredient supplement containing primarily raspberry ketone, caffeine, capsaicin, garlic, ginger and Citrus aurantium (Prograde Metabolism™ [METABO]) as an adjunct to an eight-week weight loss program. Using a randomized, placebo-controlled, double-blind design, 70 obese but otherwise healthy subjects were randomly assigned to METABO or a placebo and underwent 8 weeks of daily supplementation, a calorie restricted diet, and exercise training. Subjects were tested for changes in body composition, serum adipocytokines (adiponectin, resistin, leptin, TNF-α, IL-6) and markers of health including heart rate and blood pressure. Of the 45 subjects who completed the study, significant differences were observed in: body weight (METABO -2.0% vs. placebo -0.5%, P weight loss program by augmenting improvements in body composition, waist and hip girth. Adherence to the eight-week weight loss program also led to beneficial changes in body fat in placebo. Ongoing studies to confirm these results and clarify the mechanisms (i.e., biochemical and neuroendocrine mediators) by which METABO exerts the observed salutary effects are being conducted.

  7. Eight weeks of supplementation with a multi-ingredient weight loss product enhances body composition, reduces hip and waist girth, and increases energy levels in overweight men and women

    Science.gov (United States)

    2013-01-01

    Background Numerous natural products are marketed and sold claiming to decrease body weight and fat, but few undergo finished product-specific research demonstrating their safety and efficacy. Objective To determine the safety and efficacy of a multi-ingredient supplement containing primarily raspberry ketone, caffeine, capsaicin, garlic, ginger and Citrus aurantium (Prograde Metabolism™ [METABO]) as an adjunct to an eight-week weight loss program. Methods Using a randomized, placebo-controlled, double-blind design, 70 obese but otherwise healthy subjects were randomly assigned to METABO or a placebo and underwent 8 weeks of daily supplementation, a calorie restricted diet, and exercise training. Subjects were tested for changes in body composition, serum adipocytokines (adiponectin, resistin, leptin, TNF-α, IL-6) and markers of health including heart rate and blood pressure. Results Of the 45 subjects who completed the study, significant differences were observed in: body weight (METABO -2.0% vs. placebo -0.5%, P < 0.01), fat mass (METABO -7.8 vs. placebo -2.8%, P < 0.001), lean mass (METABO +3.4% vs. placebo +0.8%, P < 0.03), waist girth (METABO -2.0% vs. placebo -0.2%, P < 0.0007), hip girth (METABO -1.7% vs. placebo -0.4%, P < 0.003), and energy levels per anchored visual analogue scale (VAS) (METABO +29.3% vs. placebo +5.1%, P < 0.04). During the first 4 weeks, effects/trends for maintaining elevated serum leptin (P < 0.03) and decreased serum resistin (P < 0.08) in the METABO group vs. placebo were also observed. No changes in systemic hemodynamics, clinical blood chemistries, adverse events, or dietary intake were noted between groups. Conclusions METABO administration is a safe and effective adjunct to an eight-week diet and exercise weight loss program by augmenting improvements in body composition, waist and hip girth. Adherence to the eight-week weight loss program also led to beneficial changes in body fat in

  8. CERN safety week

    CERN Multimedia

    DG Unit

    2009-01-01

    Following an increase in the number of accidents in 2008, the Safety Commission is organising a CERN safety week from 8 to 12 June for riders of bicycles, scooters and motorbikes. We invite you to take part in the programme, which will be held in the Main Building (Bldg. 500) and will consist of an exhibition, organised events and hands-on activities, including demonstrations of emergency braking, a driving simulator, simulation of what it feels like to drive under the influence of alcohol, demonstrations by the Fire Brigade, video projections, etc. There will also be a number of prizes to be won. Please sign up via your DSO.

  9. Soft Robotics Week

    CERN Document Server

    Rossiter, Jonathan; Iida, Fumiya; Cianchetti, Matteo; Margheri, Laura

    2017-01-01

    This book offers a comprehensive, timely snapshot of current research, technologies and applications of soft robotics. The different chapters, written by international experts across multiple fields of soft robotics, cover innovative systems and technologies for soft robot legged locomotion, soft robot manipulation, underwater soft robotics, biomimetic soft robotic platforms, plant-inspired soft robots, flying soft robots, soft robotics in surgery, as well as methods for their modeling and control. Based on the results of the second edition of the Soft Robotics Week, held on April 25 – 30, 2016, in Livorno, Italy, the book reports on the major research lines and novel technologies presented and discussed during the event.

  10. Preoperative combined modality therapy with paclitaxel, carboplatin, prolonged infusion 5-fluorouracil, and radiation therapy in localized esophageal cancer: preliminary results of a Minnie Pearl Cancer Research Network phase II trial.

    Science.gov (United States)

    Meluch, A A; Hainsworth, J D; Gray, J R; Thomas, M; Whitworth, P L; Davis, J L; Greco, F A

    1999-01-01

    To evaluate the feasibility, toxicity, and therapeutic efficacy of 1-hour paclitaxel, carboplatin, continuous low-dose infusional 5-fluorouracil, and concurrent radiation therapy administered preoperatively in patients with localized esophageal cancer. Forty-nine patients with localized esophageal cancer, of either squamous cell carcinoma or adenocarcinoma histology, were enrolled into this phase II trial. All patients were candidates for surgical resection and received the following neoadjuvant therapy: paclitaxel, 200 mg/m2, 1 hour IV on days 1 and 22; carboplatin, AUC 6.0, IV on days 1 and 22; 5-fluorouracil, 225 mg/m2/day, continuous IV infusion on days 1 to 42; and radiation therapy, 45 Gy, administered by 1.8-Gy daily fractions beginning on day 1 of chemotherapy. Upon completion of this neoadjuvant regimen, patients were reevaluated, and all responding patients were resected within 6 weeks of completing neoadjuvant treatment. Administration of this combined modality regimen was associated with moderate toxicity and was tolerated by most patients. Leukopenia (65%) and esophagitis (31%) were the most common toxicities. Most patients did not require nutritional support. There were no treatment-related deaths during neoadjuvant therapy; however, three patients (9%) experienced postoperative death. Preliminary assessment of treatment efficacy is encouraging, with 17 of 37 evaluable patients (46%) achieving pathologic complete remission and an additional 11 patients (30%) having only microscopic residual disease. This novel, combined-modality neoadjuvant approach for the treatment of localized esophageal carcinoma is feasible and can be administered with toxicity that compares favorably to previously reported neoadjuvant regimens containing high-dose cisplatin. Preliminary assessment of efficacy is also encouraging, with 46% of patients having pathologic complete response. Further follow-up and larger numbers of patients are required to assess efficacy more

  11. At Least 39 Weeks

    Medline Plus

    Full Text Available ... Folic acid Medicine safety and pregnancy Birth defects prevention Learn how to help reduce your risk of ... Make United States a Leader in Preterm Birth Prevention March of Dimes Names 13-Year Old Boy ...

  12. At Least 39 Weeks

    Medline Plus

    Full Text Available ... impact of premature birth on society Featured articles How long should you wait before getting pregnant again? ... Medicine safety and pregnancy Birth defects prevention Learn how to help reduce your risk of some birth ...

  13. At Least 39 Weeks

    Medline Plus

    Full Text Available ... Global Map Premature birth report card Careers Archives Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal ... virus and pregnancy Folic acid Medicine safety and pregnancy Birth defects prevention Learn how to help reduce ...

  14. At Least 39 Weeks

    Medline Plus

    Full Text Available ... Preterm labor and premature birth: Are you at risk? Zika virus and pregnancy Folic acid Medicine safety ... defects prevention Learn how to help reduce your risk of some birth defects by getting a preconception ...

  15. ATLAS overview week highlights

    CERN Document Server

    D. Froidevaux

    2005-01-01

    A warm and early October afternoon saw the beginning of the 2005 ATLAS overview week, which took place Rue de La Montagne Sainte-Geneviève in the heart of the Quartier Latin in Paris. All visitors had been warned many times by the ATLAS management and the organisers that the premises would be the subject of strict security clearance because of the "plan Vigipirate", which remains at some level of alert in all public buildings across France. The public building in question is now part of the Ministère de La Recherche, but used to host one of the so-called French "Grandes Ecoles", called l'Ecole Polytechnique (in France there is only one Ecole Polytechnique, whereas there are two in Switzerland) until the end of the seventies, a little while after it opened its doors also to women. In fact, the setting chosen for this ATLAS overview week by our hosts from LPNHE Paris has turned out to be ideal and the security was never an ordeal. For those seeing Paris for the first time, there we...

  16. Quantification of intact carboplatin in human plasma ultrafitrates using hydrophilic interaction liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study.

    Science.gov (United States)

    Ito, Hajime; Yamaguchi, Hiroaki; Fujikawa, Asuka; Shiida, Narumi; Tanaka, Nobuaki; Ogura, Jiro; Kobayashi, Masaki; Yamada, Takehiro; Mano, Nariyasu; Iseki, Ken

    2013-02-15

    Carboplatin is a platinum agent that is used for treatment of non-small-cell lung cancer and ovarian cancer. A sensitive and selective analytical method for the quantification of carboplatin in human plasma ultrafiltrates using liquid chromatography-tandem mass spectrometry was developed. Human plasma ultrafiltrates were precipitated by acetonitrile containing carboplatin-d4 as an internal standard and were further diluted with acetonitrile. Chromatographic separation was performed on a Accucore HILIC (50mm×2.1mm i.d., 2.6μm) column using mobile phase (acetonitrile-water-acetic acid=90:10:0.1, v/v/v) at the flow rate of 0.2mL/min. Detection was performed on electrospray ionization triple quadrupole tandem mass spectrometer using low-energy collision induced dissociation (CID-MS/MS) analysis operating in the selected reaction monitoring (SRM) scan mode. The lower limit of quantification for carboplatin was 0.025μg/mL. This method covered a linearity range of 0.025-50μg/mL. The intra-day precision and inter-day precision (R.S.D.) ranged from 1.5 to 4.3%, and the accuracy (R.E.) was within ±2.9%. The present method was applied to a clinical pharmacokinetic study of carboplatin in a cancer patient. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Chemogenomic Study of Carboplatin in Saccharomyces cerevisiae: Inhibition of the NEDDylation Process Overcomes Cellular Resistance Mediated by HuR and Cullin Proteins

    Science.gov (United States)

    Custodio, Débora Fernandes; Freitas, Vanessa Morais; Monteiro, Gisele

    2015-01-01

    The use of carboplatin in cancer chemotherapy is limited by the emergence of drug resistance. To understand the molecular basis for this resistance, a chemogenomic screen was performed in 53 yeast mutants that had previously presented strong sensitivity to this widely used anticancer agent. Thirty-four mutants were responsive to carboplatin, and from these, 21 genes were selected for further studies because they have human homologues. Sixty percent of these yeast genes possessed human homologues which encoded proteins that interact with cullin scaffolds of ubiquitin ligases, or whose mRNA are under the regulation of Human antigen R (HuR) protein. Both HuR and cullin proteins are regulated through NEDDylation post-translational modification, and so our results indicate that inhibition of this process should sensitise resistant tumour cells to carboplatin. We showed that treatment of a tumour cell line with MLN4924, a NEDDylation inhibitor, overcame the resistance to carboplatin. Our data suggest that inhibition of NEDDylation may be a useful strategy to resensitise tumour cells in patients that have acquired carboplatin resistance. PMID:26692264

  18. Synchronous lung and gastric cancers successfully treated with carboplatin and pemetrexed: a case report

    Directory of Open Access Journals (Sweden)

    Sato Takashi

    2012-08-01

    Full Text Available Abstract Introduction Lung and gastric cancers are the first and second leading causes of death from cancer worldwide, and are especially prevalent in Eastern Asia. Relatively few reports are available in relation to the treatment and outcome of synchronous lung and gastric cancers, although there are increasing numbers of patients with these cancers. Efforts to develop more effective drugs for the treatment of synchronous cancers, without serious adverse effects, have been intensifying. Pemetrexed, a multi-targeted antifolate enzyme inhibitor, was approved by the United States Food and Drug Administration as a first-line chemotherapy for advanced non-squamous non-small cell lung cancer in 2007. Although clinical activity against several tumor types of adenocarcinoma, including gastric cancer, has been demonstrated, the efficacy of pemetrexed for gastric cancer remains to be fully evaluated. Case presentation We report a case involving a 62-year-old Japanese woman with synchronous locally-advanced poorly-differentiated lung adenocarcinoma and poorly-differentiated gastric adenocarcinoma, containing signet-ring cells distinguished by immunohistochemical profiles. She had been treated with carboplatin and pemetrexed as a first-line chemotherapy for lung cancer, and had achieved partial responses for both lung and gastric cancers. These responses led to a favorable 12-month progression-free survival after the initiation of chemotherapy, and the patient is still alive more than 33 months after diagnosis. Conclusions This case suggests a new chemotherapeutic regimen for patients with synchronous multiple primary cancers that have an adenocarcinoma background.

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

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Fonseca-Alves

    2014-01-01

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

  20. Synchronous lung and gastric cancers successfully treated with carboplatin and pemetrexed: a case report.

    Science.gov (United States)

    Sato, Takashi; Tomaru, Koji; Koide, Tomoko; Masuda, Makoto; Yamamoto, Masaki; Miyazawa, Naoki; Inayama, Yoshiaki; Kaneko, Takeshi; Ishigatsubo, Yoshiaki

    2012-08-31

    Lung and gastric cancers are the first and second leading causes of death from cancer worldwide, and are especially prevalent in Eastern Asia. Relatively few reports are available in relation to the treatment and outcome of synchronous lung and gastric cancers, although there are increasing numbers of patients with these cancers. Efforts to develop more effective drugs for the treatment of synchronous cancers, without serious adverse effects, have been intensifying. Pemetrexed, a multi-targeted antifolate enzyme inhibitor, was approved by the United States Food and Drug Administration as a first-line chemotherapy for advanced non-squamous non-small cell lung cancer in 2007. Although clinical activity against several tumor types of adenocarcinoma, including gastric cancer, has been demonstrated, the efficacy of pemetrexed for gastric cancer remains to be fully evaluated. We report a case involving a 62-year-old Japanese woman with synchronous locally-advanced poorly-differentiated lung adenocarcinoma and poorly-differentiated gastric adenocarcinoma, containing signet-ring cells distinguished by immunohistochemical profiles. She had been treated with carboplatin and pemetrexed as a first-line chemotherapy for lung cancer, and had achieved partial responses for both lung and gastric cancers. These responses led to a favorable 12-month progression-free survival after the initiation of chemotherapy, and the patient is still alive more than 33 months after diagnosis. This case suggests a new chemotherapeutic regimen for patients with synchronous multiple primary cancers that have an adenocarcinoma background.

  1. A memorable week

    CERN Multimedia

    2012-01-01

    This has been a memorable week for CERN, starting with the award of a Special Fundamental Physics Prize and ending with the handover of the CERN Council Presidency from Michel Spiro to Agnieszka Zalewska. In between, the LHC team demonstrated its expertise with a successful pilot run with 25 nanosecond bunch spacing, a new application for Associate Membership was received, and we had good news on the budget.   The award of the Fundamental Physics Prize, and the manner in which it was divided between ATLAS, CMS and the LHC, is fitting recognition of the efforts of the thousands of people who have contributed over many years to the success of our flagship scientific endeavour. In making the award, the Milner Foundation aims to raise the profile of fundamental physics and its value to society. The Fundamental Physics Prize comes hot on the heels of the European Physical Society’s first Edison Volta Prize, which Sergio Bertolucci, Steve Myers and I were honoured to accept on behalf of t...

  2. Reduced-Sodium Lunches Are Well-Accepted by Uninformed Consumers Over a 3-Week Period and Result in Decreased Daily Dietary Sodium Sodium Intakes: A Randomized Controlled Trial

    NARCIS (Netherlands)

    Janssen, A.M.; Kremer, S.; Stipriaan, van W.L.; Noort, M.W.J.; Vries, de J.H.M.; Temme, E.H.M.

    2015-01-01

    Background Processed foods are major contributors to excessive sodium intake in Western populations. We investigated the effect of food reformulation on daily dietary sodium intake. Objective To determine whether uninformed consumers accept reduced-sodium lunches and to determine the effect of

  3. Imaging of treatment response to the combination of carboplatin and paclitaxel in human ovarian cancer xenograft tumors in mice using FDG and FLT PET

    DEFF Research Database (Denmark)

    Munk Jensen, Mette; Erichsen, Kamille Dumong; Björkling, Fredrik

    2013-01-01

    A combination of carboplatin and paclitaxel is often used as first line chemotherapy for treatment of ovarian cancer. Therefore the use of imaging biomarkers early after initiation of treatment to determine treatment sensitivity would be valuable in order to identify responders from non-responder......A combination of carboplatin and paclitaxel is often used as first line chemotherapy for treatment of ovarian cancer. Therefore the use of imaging biomarkers early after initiation of treatment to determine treatment sensitivity would be valuable in order to identify responders from non......-responders. In this study we describe the non-invasive PET imaging of glucose uptake and cell proliferation using 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) and 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) for early assessment of treatment response in a pre-clinical mouse model of human ovarian cancer treated with carboplatin...

  4. Randomized cross-over study of patient preference for oral or intravenous vinorelbine in combination with carboplatin in the treatment of advanced NSCLC

    DEFF Research Database (Denmark)

    Jensen, Lars Henrik; Osterlind, Kell; Rytter, Carsten

    2008-01-01

    BACKGROUND: Most chemotherapeutics are administrated intravenously (iv), but some are also available in an oral (po) formulation. This study was designed with the primary objective to estimate the patients' preference for po or iv vinorelbine in combination with carboplatin for the palliative...... treatment of non-small cell lung cancer (NSCLC). Secondary aims were to evaluate toxicity, efficacy, and subjective reasons the preference. PATIENTS AND METHODS: Sixty-one patients were randomized in a cross-over trial to two cycles of carboplatin day 1 and vinorelbine day 1 and day 8 iv followed by two...... cycles of carboplatin and vinorelbine po, or the opposite. Patients, who did not show progressive disease after four cycles, had a free choice of iv or po vinorelbine for the next two cycles. RESULTS: Forty-three patients were evaluable for preference and 32 (74%, 95% CI 61-88%) chose po (p

  5. The suppression of immune activation during enfuvirtide-based salvage therapy is associated with reduced CCR5 expression and decreased concentrations of circulating interleukin-12 and IP-10 during 48 weeks of longitudinal follow-up.

    Science.gov (United States)

    Carsenti-Dellamonica, H; Saïdi, H; Ticchioni, M; Guillouet de Salvador, F; Dufayard Cottalorda, J; Garraffo, R; Dellamonica, P; Durant, J; Gougeon, M-L

    2011-02-01

    It has been suggested that patients who initiate highly active antiretroviral therapy (HAART) late in their course of infection may have suboptimal CD4 T-cell gains, persistent alterations in T-cell subsets and residual inflammation. To address this issue, we carried out a comprehensive 48-week immunological study in HIV-infected patients who had experienced failures of prior therapies, had low CD4 cell counts, and were receiving enfuvirtide-based salvage therapy. Immunological monitoring of peripheral lymphocytes from enfuvirtide-responder patients was performed over a 48-week period. A detailed assessment of immune cell subsets, their activation state [CD38 and human leucocyte antigen (HLA)-DR expression] and homeostasis [activation-induced cell death (AICD) and Ki67 expression], and the expression of co-receptors was performed by flow cytometry. Cytokine and chemokine signatures were assessed using multianalyte profiling technology. Enfuvirtide-based salvage therapy induced a progressive restoration of naïve and central memory CD4 T cells, associated with a decrease in their activation state, suppression of premature priming for AICD and increased expression of Ki67. In addition, a significant decrease in C-C chemokine receptor 5 (CCR5) expression was detected on CD4 T cells, which was strongly correlated with the suppression of immune activation. Changes in circulating proinflammatory molecules occurred; i.e. there were decreases in the concentrations of interleukin (IL)-12, macrophage inflammatory protein MIP-1α, MIP-1β, monokine induced by IFNγ (MIG) and interferon-γ-inducible protein-10 (IP-10). The decline in circulating IL-12 and IP-10 was correlated with both the reduction in the viral load and CD4 T-cell restoration. This study shows that suppression of HIV-1 replication with enfuvirtide-based salvage therapy in patients with low CD4 cell counts may result in an immunological benefit, characterized by the restoration of CD4 T-cell subsets associated

  6. A phase I pharmacokinetic study of intraperitoneal bortezomib and carboplatin in patients with persistent or recurrent ovarian cancer: An NRG Oncology/Gynecologic Oncology Group study.

    Science.gov (United States)

    Jandial, Danielle A; Brady, William E; Howell, Stephen B; Lankes, Heather A; Schilder, Russell J; Beumer, Jan H; Christner, Susan M; Strychor, Sandra; Powell, Matthew A; Hagemann, Andrea R; Moore, Kathleen N; Walker, Joan L; DiSilvestro, Paul A; Duska, Linda R; Fracasso, Paula M; Dizon, Don S

    2017-05-01

    Intraperitoneal (IP) therapy improves survival compared to intravenous (IV) treatment for women with newly diagnosed, optimally cytoreduced, ovarian cancer. However, the role of IP therapy in recurrent disease is unknown. Preclinical data demonstrated IP administration of the proteasome inhibitor, bortezomib prior to IP carboplatin increased tumor platinum accumulation resulting in synergistic cytotoxicity. We conducted this phase I trial of IP bortezomib and carboplatin in women with recurrent disease. Women with recurrent ovarian cancer were treated with escalating doses of IP bortezomib - in combination with IP carboplatin (AUC 4 or 5) every 21days for 6cycles. Pharmacokinetics of both agents were evaluated in cycle 1. Thirty-three women participated; 32 were evaluable for safety. Two patients experienced dose-limiting toxicity (DLT) at the first dose level (carboplatin AUC 5, bortezomib 0.5mg/m2), prompting carboplatin reduction to AUC 4 for subsequent dose levels. With carboplatin dose fixed at AUC 4, bortezomib was escalated from 0.5 to 2.5mg/m2 without DLT. Grade 3/4 related toxicities included abdominal pain, nausea, vomiting, and diarrhea which were infrequent. The overall response rate in patients with measurable disease (n=21) was 19% (1 complete, 3 partial). Cmax and AUC in peritoneal fluid and plasma increased linearly with dose, with a favorable exposure ratio of the peritoneal cavity relative to peripheral blood plasma. IP administration of this novel combination was feasible and showed promising activity in this phase I trial of heavily pre-treated women with ovarian cancer. Further evaluation of this IP combination should be conducted. Copyright © 2017. Published by Elsevier Inc.

  7. A Phase I Study of Topotecan, Carboplatin and the PARP Inhibitor Veliparib in Acute Leukemias, Aggressive Myeloproliferative Neoplasms, and Chronic Myelomonocytic Leukemia.

    Science.gov (United States)

    Pratz, Keith W; Rudek, Michelle A; Gojo, Ivana; Litzow, Mark R; McDevitt, Michael A; Ji, Jiuping; Karnitz, Larry M; Herman, James G; Kinders, Robert J; Smith, B Douglas; Gore, Steven D; Carraway, Hetty E; Showel, Margaret M; Gladstone, Douglas E; Levis, Mark J; Tsai, Hua-Ling; Rosner, Gary; Chen, Alice; Kaufmann, Scott H; Karp, Judith E

    2017-02-15

    Purpose: The PARP inhibitor veliparib delays DNA repair and potentiates cytotoxicity of multiple classes of chemotherapy drugs, including topoisomerase I inhibitors and platinating agents. This study evaluated veliparib incorporation into leukemia induction therapy using a previously described topotecan/carboplatin backbone.Experimental Design: Employing a 3+3 trial design, we administered escalating doses of veliparib combined with topotecan + carboplatin in relapsed or refractory acute leukemias, aggressive myeloproliferative neoplasms (MPN), and chronic myelomonocytic leukemia (CMML).Results: A total of 99 patients received veliparib 10-100 mg orally twice daily on days 1-8, 1-14, or 1-21 along with continuous infusion topotecan 1.0-1.2 mg/m2/d + carboplatin 120-150 mg/m2/d on days 3-7. The MTD was veliparib 80 mg twice daily for up to 21 days with topotecan 1.2 mg/m2/d + carboplatin 150 mg/m2/d. Mucositis was dose limiting and correlated with high veliparib concentrations. The response rate was 33% overall (33/99: 14 CR, 11 CRi, 8 PR) but was 64% (14/22) for patients with antecedent or associated aggressive MPNs or CMML. Leukemias with baseline DNA repair defects, as evidenced by impaired DNA damage-induced FANCD2 monoubiquitination, had improved survival [HR = 0.56 (95% confidence interval, 0.27-0.92)]. A single 80-mg dose of veliparib, as well as veliparib in combination with topotecan + carboplatin, induced DNA damage as manifested by histone H2AX phosphorylation in CD34+ leukemia cells, with greater phosphorylation in cells from responders.Conclusions: The veliparib/topotecan/carboplatin combination warrants further investigation, particularly in patients with aggressive MPNs, CMML, and MPN- or CMML-related acute leukemias. Clin Cancer Res; 23(4); 899-907. ©2016 AACR. ©2016 American Association for Cancer Research.

  8. Concurrent Chemo-Radiation With or Without Induction Gemcitabine, Carboplatin, and Paclitaxel: A Randomized, Phase 2/3 Trial in Locally Advanced Nasopharyngeal Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Terence, E-mail: trdtwk@nccs.com.sg [Division of Radiation Oncology, National Cancer Centre Singapore (Singapore); Lim, Wan-Teck [Division of Medical Oncology, National Cancer Centre Singapore (Singapore); Fong, Kam-Weng; Cheah, Shie-Lee; Soong, Yoke-Lim [Division of Radiation Oncology, National Cancer Centre Singapore (Singapore); Ang, Mei-Kim; Ng, Quan-Sing; Tan, Daniel [Division of Medical Oncology, National Cancer Centre Singapore (Singapore); Ong, Whee-Sze; Tan, Sze-Huey [Division of Clinical Trial and Epidemiological Sciences, National Cancer Centre Singapore (Singapore); Yip, Connie; Quah, Daniel [Division of Radiation Oncology, National Cancer Centre Singapore (Singapore); Soo, Khee-Chee [Division of Surgical Oncology, National Cancer Centre Singapore (Singapore); Wee, Joseph [Division of Radiation Oncology, National Cancer Centre Singapore (Singapore)

    2015-04-01

    Purpose: To compare survival, tumor control, toxicities, and quality of life of patients with locally advanced nasopharyngeal carcinoma (NPC) treated with induction chemotherapy and concurrent chemo-radiation (CCRT), against CCRT alone. Patients and Methods: Patients were stratified by N stage and randomized to induction GCP (3 cycles of gemcitabine 1000 mg/m{sup 2}, carboplatin area under the concentration-time-curve 2.5, and paclitaxel 70 mg/m{sup 2} given days 1 and 8 every 21 days) followed by CCRT (radiation therapy 69.96 Gy with weekly cisplatin 40 mg/m{sup 2}), or CCRT alone. The accrual of 172 was planned to detect a 15% difference in 5-year overall survival (OS) with a 5% significance level and 80% power. Results: Between September 2004 and August 2012, 180 patients were accrued, and 172 (GCP 86, control 86) were analyzed by intention to treat. There was no significant difference in OS (3-year OS 94.3% [GCP] vs 92.3% [control]; hazard ratio 1.05; 1-sided P=.494]), disease-free survival (hazard ratio 0.77, 95% confidence interval 0.44-1.35, P=.362), and distant metastases–free survival (hazard ratio 0.80, 95% confidence interval 0.38-1.67, P=.547) between the 2 arms. Treatment compliance in the induction phase was good, but the relative dose intensity for concurrent cisplatin was significantly lower in the GCP arm. Overall, the GCP arm had higher rates of grades 3 and 4 leukopenia (52% vs 37%) and neutropenia (24% vs 12%), but grade 3 and 4 acute radiation toxicities were not statistically different between the 2 arms. The global quality of life scores were comparable in both arms. Conclusion: Induction chemotherapy with GCP before concurrent chemo-irradiation did not improve survival in locally advanced NPC.

  9. Paclitaxel and carboplatin in early phase studies: Roswell Park Cancer Institute experience in the subset of patients with lung cancer.

    Science.gov (United States)

    Creaven, P J; Raghavan, D; Pendyala, L; Loewen, G; Kindler, H L; Berghorn, E J

    1997-08-01

    The combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given by 3-hour infusion followed by carboplatin infused over 30 minutes has been evaluated in a series of phase I studies and is currently being explored in a phase II study in patients with limited- and extensive-stage small cell lung cancer. Pharmacokinetic measurements were performed at all dose levels in the phase I studies, in which the use of granulocyte colony-stimulating factor in previously treated patients enabled more than twice the dose of paclitaxel to be given with low to moderate doses of carboplatin (dosed to a target area under the concentration-time curve of 4.0 mg x min x mL[-1]). Treatment-naive patients tolerated high paclitaxel doses (270 mg/m2) with carboplatin (dosed to a target area under the curve of 4.5 mg x min x mL[-1]) without granulocyte colony-stimulating factor support. Twenty-three patients (including previously treated and untreated) with non-small cell lung cancer were entered at a variety of paclitaxel doses in the phase I studies. At 100 to 205 mg/m2 paclitaxel, none of nine treated patients responded; at 230 to 290 mg/m2, four (29%) of 14 responded. In the phase II study of paclitaxel 250 mg/m2 in previously untreated patients with small cell lung cancer, two of five evaluable patients with extensive-stage disease have shown a partial response. In a preliminary analysis of the pharmacodynamics of paclitaxel in relation to neurotoxicity (dose limiting in two of three phase I studies), neurotoxicity correlated with the total dose of paclitaxel, the area under the curve, and the peak paclitaxel concentration, but not with the length of time plasma paclitaxel levels remained above 0.05 micromol/L. These correlations were not strong, however, and analysis of these data is ongoing.

  10. Carboplatin plus pemetrexed for the elderly incurable chemo-naive nonsquamous non-small cell lung cancer: Meta-analysis.

    Science.gov (United States)

    Ito, Masaru; Horita, Nobuyuki; Nagashima, Akimichi; Kaneko, Takeshi

    2018-01-08

    In some developed countries, a proportion of nonsquamous non-small cell lung cancer (NSq NSCLC) patients are aged over 70 years when they are diagnosed. However, evidence of lung cancer chemotherapy usually comes from randomized controlled trials that only recruit younger patients with good performance status. In daily practice, less-toxic carboplatin + pemetrexed regimen is often used for elderly patients, although this regimen is not sufficiently supported by rigid evidence for elderly cases. The protocol was registered on PROSPERO website (42017058508). Any phase trial that evaluated the efficacy and safety of carboplatin + pemetrexed in the elderly (aged 70 or higher) was included. Binary data were meta-analyzed with the random-model generic inverse variance method. Median survival duration was pooled after logarithmic transformation. Eight studies consisting of 285 patients were included among 882 articles that met the preliminary criteria. The pooled median overall survival and progression-free survivals were 14.9 months (95% confidence interval [95% CI], 12.0-18.4) and 5.4 months (95% CI, 4.5-6.4), respectively. The pooled response rate was 34.0% (95% CI, 27.5-40.5). Hematological adverse events such as neutropenia (≥grade 3; 48.3%; 95% CI, 40.1-56.6), thrombocytopenia (≥grade 3; 27.9%; 95% CI, 15.8-39.9), and anemia (≥grade 3; 17.1%; 95% CI, 8.3-25.8) were frequently observed. However, febrile neutropenia (6.8%; 95% CI, 0.2-13.3), nausea (≥grade 3; 0%; 95% CI, 0.0-4.4%) and treatment-related death (0.6%; 95% CI, 0-5.4%) were rare. Carboplatin + pemetrexed can be a good option for the treatment of the elderly with NSq NSCLC. © 2018 John Wiley & Sons Australia, Ltd.

  11. Cost-effectiveness analysis of paclitaxel + carboplatin vs. alternative combinations in the treatment of non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Mario Eandi

    2006-06-01

    Full Text Available Non-small cell lung cancer (NSCLC is the most common type of lung cancer and its medical and economical burden represents a serious matter in Europe and Usa, due to its high mortality rates and drug costs. Lung cancer is responsible for about 30% of cancer death in men and women; in Europe only about 8 per cent of people with lung cancer survive for 5 years. At present combination chemotherapy based on cisplatin or carboplatin associated with paclitaxel, vinorelbine or gemcitabine is the state of the art for the treatment in patients with stage IIIb or IV NSCLC. Aim of this study was to compare the cost-effectiveness of paclitaxel/carboplatin (PCb, gemcitabine/cisplatin (GC and vinorelbine/cisplatin (VC in the perspective of the Italian National Health Service. Therefore we perfomed a semi-Markov decision model mainly based on clinical results from the Italian Lung Cancer Project. The model included differential direct medical costs registered for two years from starting chemotherapy, using tariffs valid for 2005. Benefits was measured by years of life saved (YOLs. The model also allowed to estimate only costs accrued over the period of time, performing a cost-minimisation analysis. According to cost-effectiveness analysis, VC is dominated because it’s more costly and less effective than GC. On the contrary, combination chemotherapy with GC is more inexpensive but less effective than paclitaxel/carboplatin (PCb: in this case we compared the incremental cost-effectiveness ratio (ICER with a maximum acceptable willingness-to-pay (WTP value. In the base scenario the ICER of PCb over GC treatment is 52,326 euro/ YOLs, which is definitely lower than the maximum acceptable WTP value. Sensitivity analyses confirmed the robustness of the results from cost-effectiveness analysis in the base scenario.

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

    Science.gov (United States)

    Dizon, Don S; Damstrup, Lars; Finkler, Neil J; Lassen, Ulrik; Celano, Paul; Glasspool, Ros; Crowley, Elizabeth; Lichenstein, Henri S; Knoblach, Poul; Penson, Richard T

    2012-07-01

    Preclinical data show that belinostat (Bel) is synergistic with carboplatin and paclitaxel in ovarian cancer. To further evaluate the clinical activity of belinostat, carboplatin, and paclitaxel (BelCaP), a phase 1b/2 study was performed, with an exploratory phase 2 expansion planned specifically for women with recurrent epithelial ovarian cancer (EOC). Thirty-five women were treated on the phase 2 expansion cohort. BelCap was given as follows: belinostat, 1000 mg/m² daily for 5 days with carboplatin, AUC 5; and paclitaxel, 175 mg/m² given on day 3 of a 21-day cycle. The primary end point was overall response rate (ORR), using a Simon 2 stage design. The median age was 60 years (range, 39-80 years), and patients had received a median of 3 prior regimens (range, 1-4). Fifty-four percent had received more than two prior platinum-based combinations, sixteen patients (46%) had primary platinum-resistant disease, whereas 19 patients (54%) recurred within 6 months of their most recent platinum treatment. The median number of cycles of BelCaP administered was 6 (range, 1-23). Three patients had a complete response, and 12 had a partial response, for an ORR of 43% (95% confidence interval, 26%-61%). When stratified by primary platinum status, the ORR was 44% among resistant patients and 63% among sensitive patients. The most common drug-related adverse events related to BelCaP were nausea (83%), fatigue (74%), vomiting (63%), alopecia (57%), and diarrhea (37%). With a median follow-up of 4 months (range, 0-23.3 months), 6-month progression-free survival is 48% (95% confidence interval, 31%-66%). Median overall survival was not reached during study follow-up. Belinostat, carboplatin, and paclitaxel combined was reasonably well tolerated and demonstrated clinical benefit in heavily-pretreated patients with EOC. The addition of belinostat to this platinum-based regimen represents a novel approach to EOC therapy and warrants further exploration.

  13. Three weeks of murine hindlimb unloading induces shifts from B to T and from th to tc splenic lymphocytes in absence of stress and differentially reduces cell-specific mitogenic responses.

    Directory of Open Access Journals (Sweden)

    Fanny Gaignier

    Full Text Available Extended space missions are known to induce stress and immune dysregulation. Hindlimb unloading is a ground-based model used to reproduce most spaceflight conditions. The aim of this study was to better characterize the consequences of prolonged exposure to hindlimb unloading on murine splenic lymphocyte sub-populations. To ensure that the observed changes were not due to tail restraint but to the antiorthostatic position, three groups of mice were used: control (C, orthostatic restrained (R and hindlimb unloaded (HU. After 21 days of exposure, no difference in serum corticosterone levels nor in thymus and spleen weights were observed between HU mice and their counterparts, revealing a low state of stress. Interestingly, flow cytometric analyses showed that B cells were drastically reduced in HU mouse spleens by 59% and, while the T cells number did not change, the Th/Tc ratio was decreased. Finally, the use of a fluorescent dye monitoring lymphoproliferation demonstrated that lymphocyte response to mitogen was reduced in Th and Tc populations and to a greater extent in B cells. Thus, we showed for the first time that, even if restraint has its own effects on the animals and their splenic lymphocytes, the prolonged antiorthostatic position leads, despite the absence of stress, to an inversion of the B/T ratio in the spleen. Furthermore, the lymphoproliferative response was impaired with a strong impact on B cells. Altogether, these results suggest that B cells are more affected by hindlimb unloading than T cells which may explain the high susceptibility to pathogens, such as gram-negative bacteria, described in animal models and astronauts.

  14. Carboplatin and oxaliplatin in sequenced combination with bortezomib in ovarian tumour models

    Science.gov (United States)

    2013-01-01

    Background Ovarian cancer remains an on-going challenge mainly due to the development of drug resistance and also because the cancer is likely to have metastasized at the time of diagnosis. Currently, chemotherapy based on platinum drugs such as cisplatin is the primary treatment for the disease. Copper transporter 1 is involved in the transport of cisplatin into the cell, but is also down-regulated by the drug. Bortezomib, a proteasome inhibitor, has been reported to block this platinum-induced down-regulation of CTR1, so that in the presence of bortezomib, the cellular uptake of platinum drugs may be increased. Increased platinum accumulation may result in increased platinum − DNA binding so that the platinum drug in combination with bortezomib may produce enhanced cell kill. Methods In this study the efficacy of the sequential combinations of carboplatin, oxaliplatin and a trans-platinum compound coded as CH1 with BORT on the human ovarian A2780, A2780cisR, A2780ZD0473R and SKOV-3 cancer cell lines was evaluated. The levels of cellular platinum accumulation and platinum-DNA binding were determined following the treatment with these combinations. In order to investigate the effect of the combinations of the formation of ROS, the total and oxidized glutathione levels were also determined. Results Prevention of copper transporter 1 degradation by bortezomib is found to enhance the cellular accumulation of platinum, the level of Platinum − DNA binding and increases oxidative stress especially in the resistant cell lines. Conclusions The results suggest that the prevention of CTR1 degradation by bortezomib may be playing a major role in increasing the cellular uptake of platinum drugs and platinum-DNA binding level. Furthermore, the generation of oxidative stress appears to be a major contributor to the enhanced cell kill. PMID:24209693

  15. Ameliorative Effect of Coenzyme Q10 and/or Candesartan on Carboplatin-Induced Nephrotoxicity: Roles of Apoptosis, Transforming Growth Factor-Β1, Nuclear Factor Kappa-B And The Nrf2/HO-1 Pathway

    Science.gov (United States)

    Kabel, Ahmed M; Elkhoely, Abeer A

    2017-06-25

    Background: Carboplatin is a drug that is used for treatment of many types of cancer. However, it may produce serious nephrotoxicity. Candesartan is angiotensin II receptor antagonist employed mainly for control of hypertension. Coenzyme Q10 (CoQ10) is a fat-soluble substance which was proven to have potent antioxidant and anti-inflammatory properties. Aim: Our aim was to study the effects of candesartan and/or CoQ10 on carboplatin-induced nephrotoxicity in mice. Methods: Sixty mice were divided into 6 equal groups: Control untreated; carboplatin; carboplatin + candesartan; carboplatin + CoQ10; carboplatin + carboxymethyl cellulose; and carboplatin + candesartan + CoQ10 group. Kidney weight/body weight ratio, blood urea, serum creatinine, creatinine clearance, urinary N-acetyl beta-D-glucosaminidase (NAG), gamma glutamyl transpeptidase (GGT) and the urinary albumin excretion rate (UAER) were determined. Renal tissue catalase (CAT), glutathione reductase (GR), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase-1 (HO-1), transforming growth factor beta-1 (TGF-β1), tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were also determined, along with mitochondrial complex I activity. In addition, portions of the kidney were subjected to histopathological and immunohistochemical examination. Results: Candesartan and/or CoQ10 induced significant improvement of renal and mitochondrial functions with significant increase in tissue CAT, GR, Nrf2 and HO-1 content associated with significant decrease in the kidney weight/body weight ratio, tissue TGF-β1, TNF-α and IL-6 and alleviation of the histopathological and immunohistochemical changes as compared to carboplatin alone group. These effects were more significant in candesartan/CoQ10 combination group compared to either candesartan or CoQ10 alone. Conclusion: Candesartan/CoQ10 combination might represent a beneficial therapeutic modality for amelioration of carboplatin-induced nephrotoxicity

  16. Surgical excision of a feline orbital lacrimal gland adenocarcinoma with adjunctive cryotherapy and carboplatin-impregnated bead implantation.

    Science.gov (United States)

    Dorbandt, Daniel M; Lundberg, Alycen P; Roady, Patrick J; Huey, Jane A; Phillips, Heidi; Hamor, Ralph E

    2017-08-10

    The purpose of this report was to discuss the diagnosis, treatment, and outcome of a cat with an orbital lacrimal gland adenocarcinoma. A 14.5-year-old spayed female domestic shorthair cat was evaluated for a firm swelling at the left dorsotemporal orbital rim. The orbital mass was excised with preservation of the globe, and adjunctive cryotherapy was performed. A definitive diagnosis of lacrimal gland adenocarcinoma was obtained after histopathologic evaluation and histochemical staining with periodic acid-Schiff and mucicarmine. Thirteen months postoperatively, tumor regrowth occurred with a much larger osteolytic lesion, and a second surgery was performed consisting of tumor excision with implantation of carboplatin-impregnated calcium sulfate hemihydrate beads. The cat has remained free of recurrence 11 months after the second surgery (26 months after initial diagnosis and surgery). A feline orbital lacrimal gland adenocarcinoma was successfully managed utilizing globe-preserving surgical excision with adjunctive cryotherapy and subsequent carboplatin-impregnated bead implantation. Orbital lacrimal gland adenocarcinoma in cats may not be as aggressive as other forms of periocular, head, and neck adenocarcinomas. © 2017 American College of Veterinary Ophthalmologists.

  17. Differences in RRM1 protein expression between diagnostic biopsies and resection specimens, and changes during carboplatin and paclitaxel treatment, in non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Jakobsen, Jan N; Santoni-Rugiu, Eric; Sørensen, Jens B

    2014-01-01

    was performed on tumour samples from a total of 118 NSCLC patients with stage T1-4N0-2M0 disease. Samples were included from 65 patients treated with paclitaxel and carboplatin before surgery [neoadjuvant chemotherapy (NAC) group], and 53 patients who had undergone surgery but not chemotherapy [operation (OP...

  18. Dose-finding and pharmacological study of ifosfamide in combination with paclitaxel and carboplatin in resistant small-cell lung cancer

    NARCIS (Netherlands)

    van Putten, JWG; Kerbush, T; Smit, EF; van Rijswijk, R; Beijnen, JH; Sleijfer, DT; Groen, HJM

    Background: To find the maximum tolerated dose for ifosfamide in combination with paclitaxel and carboplatin in small-cell lung cancer patients (SCLC), who are resistant to cyclophosphamide, doxorubicin and etoposide (CDE). Patients and methods: Different dose schedules of ifosfamide were combined

  19. Randomized cross-over study of patient preference for oral or intravenous vinorelbine in combination with carboplatin in the treatment of advanced NSCLC

    DEFF Research Database (Denmark)

    Jensen, Lisa Helene Toft; Østerlind, Kell Erik; Rytter, C.

    2008-01-01

    treatment of non-small cell lung cancer (NSCLC). Secondary aims were to evaluate toxicity, efficacy, and subjective reasons the preference. PATIENTS AND METHODS: Sixty-one patients were randomized in a cross-over trial to two cycles of carboplatin day 1 and vinorelbine day 1 and day 8 iv followed by two...

  20. WBDOC Weekly Workload Status Report

    Data.gov (United States)

    Social Security Administration — Weekly reports of workloads processed in the Wilkes Barre Data Operation Center. Reports on quantities of work received, processed, pending and average processing...

  1. Artemisia Annua L. Infusion Consumed Once a Week Reduces Risk ...

    African Journals Online (AJOL)

    Methods: 132 flower farm workers who met the study inclusion criteria and were not yet using A. annua infusion were randomized either to A. annua or placebo ... However, its bitter taste and the risk of development of malaria parasite resistance to the artemisinin contained in it remain major challenges for its use in the mass ...

  2. A phase I study of the safety and pharmacokinetics of the histone deacetylase inhibitor belinostat administered in combination with carboplatin and/or paclitaxel in patients with solid tumours

    DEFF Research Database (Denmark)

    Lassen, U; Molife, L R; Sorensen, Janice Marie

    2010-01-01

    This phase I study assessed the maximum tolerated dose, dose-limiting toxicity (DLT) and pharmacokinetics of belinostat with carboplatin and paclitaxel and the anti-tumour activity of the combination in solid tumours....

  3. A phase II trial of dose-dense (biweekly) paclitaxel plus carboplatin as neoadjuvant chemotherapy for operable breast cancer.

    Science.gov (United States)

    Zhu, T; Liu, C L; Zhang, Y F; Liu, Y H; Xu, F P; Zu, J; Zhang, G C; Li, X R; Liao, N; Wang, K

    2016-02-01

    The aim of the present study is to investigate the efficacy and safety of dose-dense (biweekly) carboplatin and paclitaxel as a neoadjuvant treatment for operable breast cancer. Patients with previously untreated breast cancer (stages Ic-III) were treated with four cycles of paclitaxel (175 mg/m(2), intravenous drip, D1) and carboplatin (area under the curve of 5, D1). Patients with HER2+ disease simultaneously received trastuzumab (6 mg/kg initial dose with subsequent doses of 4 mg/kg biweekly). The primary endpoint was a pathologically complete response (pCR). Between January 2012 and February 2014, 110 patients were enrolled. The overall pCR rate was 35.45 % (39 of 110). The pCR rates for the different cancer subtypes were as follows: 10.53 % (2 of 19) among the patients with the luminal A subtype, 12.50 % (5 of 40) among the patients with the luminal B (HER2-) subtype, 58.33 % (14 of 24) among the patients with the luminal B (HER2+) subtype, 57.14 % (8 of 14) among the patients with the triple-negative subtype, and 76.92 % (10 of 13) among the patients with the HER2+ subtype. The patients experienced the following toxicity side effects: grade 3/4 neutropenia (N = 27, 24.55 %), grade 3/4 anemia (N = 6, 5.45 %), grade 3/4 thrombocytopenia (N = 2, 1.82 %), grade 3 alanine aminotransferase (ALT) elevation (N = 1, 0.91 %), grade 3 neuropathy (N = 3, 2.73 %), grade 3 pain (N = 2, 1.82 %), and grade 3 fatigue (N = 1, 0.91 %). In total, 19.09 % of the patients experienced treatment delay or discontinuation due to hematological toxicity, and one patient discontinued treatment due to non-hematological toxicity. Neoadjuvant biweekly paclitaxel plus carboplatin is a feasible therapy that achieved high pCR rates in patients with the HER2+, triple-negative, and luminal B (HER2+) cancer subtypes (NCT0205986).

  4. A phase I study of the safety and pharmacokinetics of the histone deacetylase inhibitor belinostat administered in combination with carboplatin and/or paclitaxel in patients with solid tumours

    DEFF Research Database (Denmark)

    Lassen, U; Molife, L R; Sorensen, Janice Marie

    2010-01-01

    This phase I study assessed the maximum tolerated dose, dose-limiting toxicity (DLT) and pharmacokinetics of belinostat with carboplatin and paclitaxel and the anti-tumour activity of the combination in solid tumours.......This phase I study assessed the maximum tolerated dose, dose-limiting toxicity (DLT) and pharmacokinetics of belinostat with carboplatin and paclitaxel and the anti-tumour activity of the combination in solid tumours....

  5. Pemetrexed/Carboplatin/Bevacizumab followed by Maintenance Pemetrexed/Bevacizumab in Hispanic Patients with Non-Squamous Non-Small Cell Lung Cancer: Outcomes according to Thymidylate Synthase Expression.

    Directory of Open Access Journals (Sweden)

    Andrés Felipe Cardona

    Full Text Available To evaluate the efficacy and safety of pemetrexed, carboplatin and bevacizumab (PCB followed by maintenance therapy with pemetrexed and bevacizumab (PB in chemotherapy-naïve patients with stage IV non-squamous non-small cell lung cancer (NSCLC through the influence of thymidylate synthase (TS protein and mRNA expression on several outcomes. The primary endpoints were the overall response rate (ORR, progression-free survival (PFS and overall survival (OS.A cohort of 144 patients were administered pemetrexed (500 mg/m2, carboplatin (AUC, 5.0 mg/ml/min and bevacizumab (7.5 mg/kg intravenously every three weeks for up to four cycles. Maintenance PB was administered until disease progression or unacceptable toxicity.One hundred forty-four Colombian patients with a median follow-up of 13.8 months and a median number of 6 maintenance cycles (range, 1-32 were assessed. The ORR among the patients was 66% (95% CI, 47% to 79%. The median PFS and (OS rates were 7.9 months (95% CI, 5.9-10.0 months and 21.4 months (95% CI, 18.3 to 24.4 months, respectively. We documented grade 3/4 hematologic toxicities, including anemia (14%, neutropenia (8%, and thrombocytopenia (16%. The identified grade 3/4 non-hematologic toxicities were proteinuria (2%, venous thrombosis (4%, fatigue (11%, infection (6%, nephrotoxicity (2%, and sensory neuropathy (4%. No grade >3 hemorrhagic events or hypertension cases were reported. OS was significantly higher in patients with the lowest TS mRNA levels [median, 29.6 months (95% CI, 26.2-32.9] compared with those in patients with higher levels [median, 9.3 months (95% CI, 6.6-12.0; p = 0.0001]. TS expression (mRNA levels or protein expression did not influence the treatment response.Overall, PCB followed by maintenance pemetrexed and bevacizumab was effective and tolerable in Hispanic patients with non-squamous NSCLC. This regimen was associated with acceptable toxicity and prolonged OS, particularly in patients with low TS expression

  6. BEYOND: A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase III Study of First-Line Carboplatin/Paclitaxel Plus Bevacizumab or Placebo in Chinese Patients With Advanced or Recurrent Nonsquamous Non-Small-Cell Lung Cancer.

    Science.gov (United States)

    Zhou, Caicun; Wu, Yi-Long; Chen, Gongyan; Liu, Xiaoqing; Zhu, Yunzhong; Lu, Shun; Feng, Jifeng; He, Jianxing; Han, Baohui; Wang, Jie; Jiang, Guoliang; Hu, Chunhong; Zhang, Hao; Cheng, Gang; Song, Xiangqun; Lu, You; Pan, Hongming; Zheng, Wenjuan; Yin, Anny-Yue

    2015-07-01

    The phase III BEYOND trial was undertaken to confirm in a Chinese patient population the efficacy seen with first-line bevacizumab plus platinum doublet chemotherapy in globally conducted studies. Patients age ≥ 18 years with locally advanced, metastatic, or recurrent advanced nonsquamous non-small-cell lung cancer (NSCLC) were randomly assigned to receive carboplatin (area under the curve, 6) intravenously and paclitaxel (175 mg/m(2)) intravenously (CP) on day 1 of each 3-week cycle, for ≤ six cycles, plus placebo (Pl+CP) or bevacizumab (B+CP) 15 mg/kg intravenously, on day 1 of each cycle, until progression, unacceptable toxicity, or death. The primary end point was progression-free survival (PFS); secondary end points were objective response rate, overall survival, exploratory biomarkers, safety. A total of 276 patients were randomly assigned, 138 to each arm. PFS was prolonged with B+CP versus Pl+CP (median, 9.2 v 6.5 months, respectively; hazard ratio [HR], 0.40; 95% CI, 0.29 to 0.54; P CP compared with Pl+CP (54% v 26%, respectively). Overall survival was also prolonged with B+CP compared with Pl+CP (median, 24.3 v 17.7 months, respectively; HR, 0.68; 95% CI, 0.50 to 0.93; P = .0154). Median PFS was 12.4 months with B+CP and 7.9 months with Pl+CP (HR, 0.27; 95% CI, 0.12 to 0.63) in EGFR mutation-positive tumors and 8.3 and 5.6 months, respectively (HR, 0.33; 95% CI, 0.21 to 0.53), in wild-type tumors. Safety was similar to previous studies of B+CP in NSCLC; no new safety signals were observed. The addition to bevacizumab to carboplatin/paclitaxel was well tolerated and resulted in a clinically meaningful treatment benefit in Chinese patients with advanced nonsquamous NSCLC. © 2015 by American Society of Clinical Oncology.

  7. Pemetrexed/Carboplatin/Bevacizumab followed by Maintenance Pemetrexed/Bevacizumab in Hispanic Patients with Non-Squamous Non-Small Cell Lung Cancer: Outcomes according to Thymidylate Synthase Expression

    Science.gov (United States)

    Carranza, Hernán; Vargas, Carlos; Otero, Jorge; Cuello, Mauricio; Corrales, Luis; Martín, Claudio; Ortiz, Carlos; Franco, Sandra; Rosell, Rafael

    2016-01-01

    Objective To evaluate the efficacy and safety of pemetrexed, carboplatin and bevacizumab (PCB) followed by maintenance therapy with pemetrexed and bevacizumab (PB) in chemotherapy-naïve patients with stage IV non-squamous non-small cell lung cancer (NSCLC) through the influence of thymidylate synthase (TS) protein and mRNA expression on several outcomes. The primary endpoints were the overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Methods A cohort of 144 patients were administered pemetrexed (500 mg/m2), carboplatin (AUC, 5.0 mg/ml/min) and bevacizumab (7.5 mg/kg) intravenously every three weeks for up to four cycles. Maintenance PB was administered until disease progression or unacceptable toxicity. Results One hundred forty-four Colombian patients with a median follow-up of 13.8 months and a median number of 6 maintenance cycles (range, 1–32) were assessed. The ORR among the patients was 66% (95% CI, 47% to 79%). The median PFS and (OS) rates were 7.9 months (95% CI, 5.9–10.0 months) and 21.4 months (95% CI, 18.3 to 24.4 months), respectively. We documented grade 3/4 hematologic toxicities, including anemia (14%), neutropenia (8%), and thrombocytopenia (16%). The identified grade 3/4 non-hematologic toxicities were proteinuria (2%), venous thrombosis (4%), fatigue (11%), infection (6%), nephrotoxicity (2%), and sensory neuropathy (4%). No grade >3 hemorrhagic events or hypertension cases were reported. OS was significantly higher in patients with the lowest TS mRNA levels [median, 29.6 months (95% CI, 26.2–32.9)] compared with those in patients with higher levels [median, 9.3 months (95% CI, 6.6–12.0); p = 0.0001]. TS expression (mRNA levels or protein expression) did not influence the treatment response. Conclusion Overall, PCB followed by maintenance pemetrexed and bevacizumab was effective and tolerable in Hispanic patients with non-squamous NSCLC. This regimen was associated with acceptable toxicity and

  8. Phase II trial of sorafenib in combination with carboplatin and paclitaxel in patients with metastatic uveal melanoma: SWOG S0512.

    Directory of Open Access Journals (Sweden)

    Shailender Bhatia

    Full Text Available Sorafenib, a multikinase inhibitor of cell proliferation and angiogenesis, inhibits the mitogen-activated protein kinase pathway that is activated in most uveal melanoma tumors. This phase II study was conducted by the SWOG cooperative group to evaluate the efficacy of sorafenib in combination with carboplatin and paclitaxel (CP in metastatic uveal melanoma.Twenty-five patients with stage IV uveal melanoma who had received 0-1 prior systemic therapy were enrolled. Treatment included up to 6 cycles of carboplatin (AUC = 6 and paclitaxel (225 mg/m(2 administered IV on day 1 plus sorafenib (400 mg PO twice daily, followed by sorafenib monotherapy until disease progression. The primary endpoint was objective response rate (ORR; a two-stage design was used with the study to be terminated if no confirmed responses were observed in the first 20 evaluable patients. Secondary efficacy endpoints included progression-free survival (PFS and overall survival (OS.No confirmed objective responses occurred among the 24 evaluable patients (ORR = 0% [95% CI: 0-14%] and the study was terminated at the first stage. Minor responses (tumor regression less than 30% were seen in eleven of 24 (45% patients. The median PFS was 4 months [95% CI: 1-6 months] and the 6-month PFS was 29% [95% CI: 13%-48%]. The median OS was 11 months [95% CI: 7-14 months].In this study, the overall efficacy of CP plus sorafenib in metastatic uveal melanoma did not warrant further clinical testing when assessed by ORR, although minor tumor responses and stable disease were observed in some patients.ClinicalTrials.govNCT00329641.

  9. The effects of taurolidine alone and in combination with doxorubicin or carboplatin in canine osteosarcoma in vitro

    Directory of Open Access Journals (Sweden)

    Marley Kevin

    2013-01-01

    Full Text Available Abstract Background Osteosarcoma (OS affects over 8000 dogs/year in the United States. The disease usually arises in the appendicular skeleton and metastasizes to the lung. Dogs with localized appendicular disease benefit from limb amputation and chemotherapy but most die within 6–12 months despite these treatments. Taurolidine, a derivative of taurine, has anti-tumor and anti-angiogenic effects against a variety of cancers. The following in vitro studies tested taurolidine as a candidate for adjuvant therapy for canine OS. Tests for p53 protein status and caspase activity were used to elucidate mechanisms of taurolidine-induced cell death. Results Taurolidine was cytotoxic to osteosarcoma cells and increased the toxicity of doxorubicin and carboplatin in vitro. Apoptosis was greatly induced in cells exposed to 125 μM taurolidine and less so in cells exposed to 250 μM taurolidine. Taurolidine cytotoxicity appeared caspase-dependent in one cell line; with apparent mutant p53 protein. This cell line was the most sensitive to single agent taurolidine treatment and had a taurolidine-dependent reduction in accumulated p53 protein suggesting taurolidine’s effects may depend on the functional status of p53 in canine OS. Conclusion Taurolidine’s cytotoxic effect appears dependent on cell specific factors which may be explained, in part, by the functional status of p53. Taurolidine initiates apoptosis in canine OS cells and this occurs to a greater extent at lower concentrations. Mechanisms of cell death induced by higher concentrations were not elucidated here. Taurolidine combined with doxorubicin or carboplatin can increase the toxicity of these chemotherapy drugs and warrants further investigation in dogs with osteosarcoma.

  10. Multimodality Molecular Imaging of [18F]-Fluorinated Carboplatin Derivative Encapsulated in [111In]-Labeled Liposomes

    Science.gov (United States)

    Lamichhane, Narottam

    Platinum based chemotherapy is amongst the mainstream DNA-damaging agents used in clinical cancer therapy today. Agents such as cisplatin, carboplatin are clinically prescribed for the treatment of solid tumors either as single agents, in combination, or as part of multi-modality treatment strategy. Despite the potent anti-tumor activity of these drugs, overall effectiveness is still hampered by inadequate delivery and retention of drug in tumor and unwanted normal tissue toxicity, induced by non-selective accumulation of drug in normal cells and tissues. Utilizing molecular imaging and nanoparticle technologies, this thesis aims to contribute to better understanding of how to improve the profile of platinum based therapy. By developing a novel fluorinated derivative of carboplatin, incorporating a Flourine-18 (18F) moiety as an inherent part of the molecule, quantitative measures of drug concentration in tumors and normal tissues can be directly determined in vivo and within the intact individual environment. A potential impact of this knowledge will be helpful in predicting the overall response of individual patients to the treatment. Specifically, the aim of this project, therefore, is the development of a fluorinated carboplatin drug derivative with an inherent positron emission tomography (PET) imaging capability, so that the accumulation of the drug in the tumor and normal organs can be studied during the course of therapy . A secondary objective of this research is to develop a proof of concept for simultaneous imaging of a PET radiolabeled drug with a SPECT radiolabeled liposomal formulation, enabling thereby bi-modal imaging of drug and delivery vehicle in vivo. The approach is challenging because it involves development in PET radiochemistry, PET and SPECT imaging, drug liposomal encapsulation, and a dual-modal imaging of radiolabeled drug and radiolabeled vehicle. The principal development is the synthesis of fluorinated carboplatin 19F-FCP using 2

  11. Survival over ten years after chemotherapy by paclitaxel and carboplatin, followed by a concomitant chemo-radiotherapy in nasopharyngeal undifferentiated carcinomas; Survie a dix ans apres chimiotherapie par paclitaxel et carboplatine, suivie d'une chimioradiotherapie concomitante dans les carcinomes indifferencies du nasopharynx

    Energy Technology Data Exchange (ETDEWEB)

    Djekkoun, R.; Ferdi, N.; Bouzid, K. [CHU de Constantine, Constantine (Algeria)

    2011-10-15

    Based on 28 patients suffering from a cavum carcinoma and having been treated by neo-adjuvant chemotherapy (with paclitaxel and carboplatin) followed by a concomitant chemo-radiotherapy and an adjuvant chemotherapy, the authors analyse the response over time and identify the main causes of death. They also conclude that randomized studies are necessary to better asses the treatment efficiency. Short communication

  12. High-dose thiotepa, etoposide and carboplatin as conditioning regimen for autologous stem cell transplantation in patients with high-risk Hodgkin's lymphoma.

    Science.gov (United States)

    Di Ianni, Mauro; Ballanti, Stelvio; Iodice, Giuseppe; Reale, Antonia; Falzetti, Franca; Minelli, Olivia; Serio, Gabriella; Martelli, Massimo F; Dammacco, Franco; Vacca, Angelo; Ria, Roberto

    2012-01-01

    Autologous stem cell transplantation (ASCT) generally provides good results in Hodgkin's lymphoma (HL). We studied a high-dose chemotherapy regimen based on thiotepa, etoposide and carboplatin (TECA). Fifty-eight patients with advanced HL were treated with thiotepa, etoposide and carboplatin for transplant induction. The overall response rate was 79·3% (39 CR: 67·2%; and 7 PR: 12·1%); 12 patients (20·1%) were non-responders. The 5-year overall survival rate was 77·6%; five initially responder patients relapsed within the first 5 years of follow-up and underwent salvage therapy. The TECA conditioning regimen for ASCT in HL results in a good anti-HL effect, positive response to treatment and high 5-year overall survival rate. It was also well tolerated and did not induce excessive toxicity, suggesting that TECA may be a very useful conditioning regimen for HL.

  13. Potentiation of carboplatin-mediated DNA damage by the Mdm2 modulator Nutlin-3a in a humanized orthotopic breast-to-lung metastatic model

    Science.gov (United States)

    Tonsing-Carter, Eva; Bailey, Barbara J.; Saadatzadeh, M. Reza; Ding, Jixin; Wang, Haiyan; Sinn, Anthony L.; Peterman, Kacie M.; Spragins, Tiaishia K.; Silver, Jayne M.; Sprouse, Alyssa A.; Georgiadis, Taxiarchis M.; Gunter, T. Zachary; Long, Eric C.; Minto, Robert E.; Marchal, Christophe C.; Batuello, Christopher N.; Safa, Ahmad R.; Hanenberg, Helmut; Territo, Paul R.; Sandusky, George E.; Mayo, Lindsey D.; Eischen, Christine M.; Shannon, Harlan E.; Pollok, Karen E.

    2015-01-01

    Triple-negative breast cancers (TNBCs) are typically resistant to treatment, and strategies that build upon frontline therapy are needed. Targeting the murine double minute 2 (Mdm2) protein is an attractive approach as Mdm2 levels are elevated in many therapy-refractive breast cancers. The Mdm2 protein-protein interaction inhibitor Nutlin-3a blocks the binding of Mdm2 to key signaling molecules such as p53 and p73α, and can result in activation of cell-death signaling pathways. In the present study, the therapeutic potential of carboplatin and Nutlin-3a to treat TNBC was investigated, as carboplatin is under evaluation in clinical trials for TNBC. In mutant p53 TMD231 TNBC cells, carboplatin and Nutlin-3a led to increased Mdm2 and was strongly synergistic in promoting cell death in vitro. Furthermore, sensitivity of TNBC cells to combination treatment was dependent on p73α. Following combination treatment, γH2AX increased and Mdm2 localized to a larger degree to chromatin compared to single-agent treatment, consistent with previous observations that Mdm2 binds to the Mre11/Rad50/Nbs1 complex associated with DNA and inhibits the DNA-damage response. In vivo efficacy studies were conducted in the TMD231 orthotopic mammary fat pad model in NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice. Using an intermittent dosing schedule of combined carboplatin and Nutlin-3a, there was a significant reduction in primary tumor growth and lung metastases compared to vehicle and single-agent treatments. Additionally, there was minimal toxicity to the bone marrow and normal tissues. These studies demonstrate that Mdm2 holds promise as a therapeutic target in combination with conventional therapy and may lead to new clinical therapies for TNBC. PMID:26494859

  14. Phase 1 and 2 study of carboplatin and pralatrexate in patients with recurrent, platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer.

    Science.gov (United States)

    Del Carmen, Marcela G; Supko, Jeff G; Horick, Nora K; Rauh-Hain, J Alejandro; Clark, Rachel M; Campos, Susana M; Krasner, Carolyn N; Atkinson, Tina; Birrer, Michael J

    2016-11-15

    The objective of this phase 1 and 2 trial was to identify the appropriate dose of combined carboplatin and pralatrexate for patients with recurrent, platinum-sensitive ovarian, fallopian tube, and primary peritoneal cancer. In phase 1, patients received carboplatin (at an area under the curve of 5) and increasing doses of pralatrexate until the maximum-tolerated dose (MTD) of pralatrexate was achieved. The primary endpoint was the response rate. Additional endpoints were safety, response duration, progression-free survival, overall survival, and pharmacokinetics. Thirty patients were enrolled in phase 1, and 20 were enrolled in phase 2. Of all 50 patients, 49 completed the study. The mean patient age was 59 years, and patients completed a median of 6 cycles. The MTD for pralatrexate was 105 mg/m(2) . The clinical benefit rate (complete responses plus partial responses plus stable disease) was 86%. Of 26 patients who received the MTD, 12 had a partial response, 11 had stable disease, and 2 had disease progression. The progression-free survival rate at 3 and 6 months was 87% and 79%, respectively; and the overall survival rate was 98% at 6 and 12 months and 66% at 24 months. Of 30 patients, 18 (60%) in phase 1 experienced an adverse event of any grade; and, of those, 4 patients (13%) had a grade 3 or greater adverse event. In phase 2, 12 patients (60%) had an adverse event of any grade, and 4 (20%) had grade 3 or greater toxicity. There was a significant reduction in the total body clearance of pralatrexate when it was received concurrently with carboplatin. Most patients responded to carboplatin-pralatrexate combination. This regimen is well tolerated and effective in this patient population. Cancer 2016;122:3297-3306. © 2016 American Cancer Society. © 2016 American Cancer Society.

  15. Usefulness of antiemetic therapy with aprepitant, palonosetron, and dexamethasone for lung cancer patients on cisplatin-based or carboplatin-based chemotherapy.

    Science.gov (United States)

    Kitazaki, Takeshi; Fukuda, Yuichi; Fukahori, Susumu; Oyanagi, Kazuhiko; Soda, Hiroshi; Nakamura, Yoichi; Kohno, Shigeru

    2015-01-01

    The purpose of the study is to investigate the usefulness of the triplet regimen comprising aprepitant, palonosetron, and dexamethasone in patients treated with highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC). Patients with lung cancer (aged 65.8 ± 8.4 years) who received carboplatin-based MEC and those treated with cisplatin-based HEC were enrolled. The antiemetic regimen for both types of chemotherapy consisted of aprepitant, palonosetron, and dexamethasone based on the May 2010 guidelines prepared by the Japan Society of Clinical Oncology. The incidence of chemotherapy-induced nausea and vomiting (CINV) and the use of salvage treatment were assessed. The primary endpoints were the percentage of patients with a complete response (CR: no nausea and no salvage treatment) during the entire study period (5 days) after chemotherapy, during the acute phase (day 1), and during the delayed phase (days 2-5). CR rates for the entire period were 86 and 71% in patients receiving carboplatin-based and cisplatin-based chemotherapy, respectively. CR rates were respectively 98 and 100% in the acute phase versus 87 and 71% in the delayed phase. Most of the patients could ingest food throughout the entire period after chemotherapy. Assessment of various risk factors for acute and delayed CINV (gender, age, prior vomiting due to antineoplastic therapy, prior experience of motion sickness, and history of drinking) revealed no significant influence of these factors on the CR rate for the entire period in patients receiving either carboplatin-based or cisplatin-based chemotherapy. The present triple therapy can be recommended for supporting both carboplatin-based and cisplatin-based chemotherapy regimens.

  16. The ATLAS Glasgow Overview Week

    CERN Multimedia

    Richard Hawkings

    2007-01-01

    The ATLAS Overview Weeks always provide a good opportunity to see the status and progress throughout the experiment, and the July week at Glasgow University was no exception. The setting, amidst the traditional buildings of one of the UK's oldest universities, provided a nice counterpoint to all the cutting-edge research and technology being discussed. And despite predictions to the contrary, the weather at these northern latitudes was actually a great improvement on the previous few weeks in Geneva. The meeting sessions comprehensively covered the whole ATLAS project, from the subdetector and TDAQ systems and their commissioning, through to offline computing, analysis and physics. As a long-time ATLAS member who remembers plenary meetings in 1991 with 30 people drawing detector layouts on a whiteboard, the hardware and installation sessions were particularly impressive - to see how these dreams have been translated into 7000 tons of reality (and with attendant cabling, supports and services, which certainly...

  17. Results of a Phase II Study to Evaluate the Efficacy of Docetaxel and Carboplatin in Metastatic Malignant Melanoma Patients Who Failed First-Line Therapy Containing Dacarbazine.

    Science.gov (United States)

    Lee, Choong-kun; Jung, Minkyu; Choi, Hye Jin; Kim, Hye Ryun; Kim, Hyo Song; Roh, Mi Ryung; Ahn, Joong Bae; Chung, Hyun Cheol; Heo, Su Jin; Rha, Sun Young; Shin, Sang Joon

    2015-10-01

    There is no standard second-line regimen for malignant melanoma patients with disease progression after first-line chemotherapy, and platinum-alkylating agents combined with paclitaxel have shown modest efficacy. We conducted a phase II, open-label, single-arm study to test the efficacy of docetaxel combined with carboplatin for malignant melanoma patients who failed previous treatment with dacarbazine. Intravenous docetaxel (35 mg/m(2) on days 1 and 8 of each cycle) and carboplatin (area under the curve 3 on days 1 and 8 of each cycle) was administered every 21 days. Primary end point was objective response rate (ORR). Thirty patients were enrolled in the study, and the median follow-up duration was 19.8 months. Among 25 per-protocol patients, there were three responders (1 with complete response and 2 with partial response) and 17 stable disease patients (ORR, 12.0%). Among the per-protocol population, the median progression-free survival (PFS) was 4.3 months and the median overall survival (OS) was 9.6 months. Uveal melanoma patients (n=9) showed the best prognosis compared to other subtypes (median PFS, 7.6 months; OS, 9.9 months). The most common grade 3 or 4 adverse event was neutropenia (n=15, 50.0%). Docetaxel combined with carboplatin showed association with an acceptable safety profile and overall efficacy for patients with malignant melanoma who had progressed on chemotherapy containing dacarbazine.

  18. Non-specificity and synergy at the binding site of the carboplatin-induced DNA adduct via molecular dynamics simulations of the MutSα-DNA recognition complex

    Science.gov (United States)

    Negureanu, Lacramioara; Salsbury, Freddie R

    2013-01-01

    MutSα is the most abundant mismatch binding factor of human DNA mismatch repair (MMR) proteins. MMR maintain genetic stability by recognizing and repairing DNA defects. Failure to accomplish their function may lead to cancer. In addition, MutSα recognizes at least some types of DNA damage making it a target for anticancer agents. Here, complementing scarce experimental data, we report unique hydrogen bonding motifs associated with the recognition of the carboplatin induced DNA damage by MutSα. These data predict that carboplatin and cisplatin induced damaging DNA adducts are recognized by MutSα in a similar manner. Our simulations also indicate that loss of base pairing at the damage site results in (1) non-specific binding and (2) changes in the atomic flexibility at the lesion site and beyond. To further quantify alterations at MutSα-DNA interface in response to damage recognition non-bonding interactions and salt bridges were investigated. These data indicate (1) possible different packing and (2) disruption of the salt bridges at the MutSα-DNA interface in the damaged complex. These findings (1) underscore the general observation of disruptions at the MutSα-DNA interface and (2) highlight the nature of the anticancer effect of the carboplatin agent. The analysis was carried out from atomistic simulations. PMID:23799640

  19. Experiences with archived raw diffraction images data: capturing cisplatin after chemical conversion of carboplatin in high salt conditions for a protein crystal

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-10-01

    Archiving of raw diffraction images data has led to new structural chemistry information being obtained for previously published results, which leads to the conclusion that carboplatin has partially converted to cisplatin in the high NaCl concentration conditions used in the crystallization procedure. The archiving of raw diffraction images data is the focus of an IUCr Diffraction Data Deposition Working Group. Experience in archiving and sharing of raw diffraction images data in collaboration between Manchester and Utrecht Universities, studying the binding of the important anti-cancer agents, cisplatin and carboplatin to histidine in a protein, has recently been published. Subsequently, these studies have been expanded due to further analyses of each data set of raw diffraction images using the diffraction data processing program XDS. The raw diffraction images, measured at Manchester University, are available for download at Utrecht University and now also mirrored at the Tardis Raw Diffraction Data Archive in Australia. Thus a direct comparison of processed diffraction and derived protein model data from XDS with the published results has been made. The issue of conversion of carboplatin to cisplatin under a high chloride salt concentration has been taken up and a detailed crystallographic assessment is provided. Overall, these new structural chemistry research results are presented followed by a short summary of developing raw data archiving policy and practicalities as well as documenting the challenge of making appropriate and detailed recording of the metadata for crystallography.

  20. Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage      I seminoma: a randomised trial

    DEFF Research Database (Denmark)

    Oliver, R. T. D.; Mason, M. D.; Mead, G. M.

    2005-01-01

    BACKGROUND: Adjuvant radiotherapy is effective treatment for stage I       seminoma, but is associated with a risk of late non-germ-cell cancer and       cardiovascular events. After good results in initial studies with one       injection of carboplatin, we undertook a large randomised trial...... to compare       the approaches of radiotherapy with chemotherapy in seminoma treatment.       METHODS: Between 1996 and 2001, 1477 patients from 70 hospitals in 14       countries were randomly assigned to receive radiotherapy (para-aortic       strip or dog-leg field; n=904) or one injection of carboplatin...... was by intention to treat and       per protocol. This trial has been assigned the International Standard       Randomised Controlled Trial Number ISRCTN27163214. FINDINGS: 885 and 560       patients received radiotherapy and carboplatin, respectively. With a       median follow-up of 4 years (IQR 3...

  1. Safety of Same-day Pegfilgrastim Administration in Metastatic Castration-resistant Prostate Cancer Treated With Cabazitaxel With or Without Carboplatin.

    Science.gov (United States)

    Bilen, Mehmet Asim; Cauley, Diana H; Atkinson, Bradley J; Chen, Hsiang-Chun; Kaya, Diana H; Wang, Xuemei; Vikram, Raghu; Tu, Shi-Ming; Corn, Paul G; Kim, Jeri

    2017-06-01

    Although myeloid growth factors are commonly used to treat metastatic castration-resistant prostate cancer (mCRPC), the optimal timing of administration has not been well studied. We assessed the effects of same-day pegfilgrastim, a neutrophil stimulator, after cabazitaxel treatment with or without carboplatin in patients with mCRPC. We also evaluated the frequency of urinary tract inflammation during treatment. Between September 2010 and September 2014, 151 consecutive patients with mCRPC underwent cabazitaxel treatment with or without the addition of carboplatin at a single institution. We assessed absolute neutrophil count recovery, incidence of neutropenia, neutropenic fever, antibiotic usage, treatment delays or discontinuation, dose reduction, and hospitalization with pegfilgrastim administration. Radiologists blinded to therapy reviewed computed tomography scans to detect urinary tract inflammation. The median patient age was 69 years (range, 41-88 years); 78% of patients were white, and 54% had a Gleason score ≥ 9. Median overall survival was 9 months (95% confidence interval, 8-11 months). One patient (cabazitaxel treatment with or without carboplatin in patients with mCRPC is feasible. The urinary tract inflammation rate (21%) was higher than that reported anecdotally. Results need to be prospectively validated. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Efficacy benefit of an NK1 receptor antagonist (NK1RA) in patients receiving carboplatin: supportive evidence with NEPA (a fixed combination of the NK1 RA, netupitant, and palonosetron) and aprepitant regimens.

    Science.gov (United States)

    Jordan, Karin; Gralla, Richard; Rizzi, Giada; Kashef, Kimia

    2016-11-01

    Antiemetic guideline recommendations are inconsistent as to whether a neurokinin-1 receptor antagonist (NK1 RA) should be administered with a 5-hydroxytryptamine-3 (5HT3) RA + dexamethasone (DEX) in patients receiving carboplatin. Patients receiving cisplatin routinely receive an NK1 RA-containing regimen with a resulting 14-22 % benefit in no emesis rates over a 5-HT3 RA/DEX control. Recent studies suggest a similar benefit in patients receiving carboplatin. NEPA is the first fixed antiemetic combination agent and comprises the highly selective NK1 RA, netupitant, and pharmacologically distinct 5-HT3 RA, palonosetron (PALO). This paper presents the efficacy of NEPA in the subset of patients receiving carboplatin in a phase 3 trial (NCT01376297), in the context of aprepitant (APR) data in the carboplatin setting. One hundred ninety-six patients (47 % of all study patients: n = 145 NEPA + DEX; n = 51 APR + PALO + DEX) received carboplatin in a multinational, double-blind, randomized phase 3 study. Complete response (CR: no emesis/rescue) and no significant nausea (NSN: score ≤25 on 100 mm visual analog scale) rates were calculated. Cycle 1-4 overall (0-120 h) CR rates were similar for NEPA (80, 91, 92, and 93 %) and APR (82, 88, 88, and 90 %). Overall NSN rates were also similar (NEPA 84-96 %; APR 82-90 %). Response rates for NEPA and APR regimens were similar and consistent with prior studies evaluating the contribution of adding NK1 RAs in patients receiving carboplatin. Considering such evidence, guideline groups/practitioners should consider giving a NK1 RA antiemetic triplet in patients receiving carboplatin.

  3. A week of Israeli restraint

    NARCIS (Netherlands)

    Reinhart, T.

    2006-01-01

    In Israeli discourse, Israel is always the side exercising restraint in its conflict with the Palestinians. This was true again for the events of the past week: As the Qassam rockets were falling on the Southern Israeli town of Sderot, it was “leaked” that the Israeli Minister of Defense had

  4. Randomized trial comparing weekly versus 3-week chemotherapy in small-cell lung cancer: a Cancer Research Campaign trial.

    Science.gov (United States)

    Souhami, R L; Rudd, R; Ruiz de Elvira, M C; James, L; Gower, N; Harper, P G; Tobias, J S; Partridge, M R; Davison, A G; Trask, C

    1994-09-01

    A randomized trial of chemotherapy, given on either a 1-week or a 3-week schedule, was performed in small-cell lung cancer (SCLC) patients. The aim was to determine if weekly scheduling produced survival superior to conventional treatment. Four hundred thirty-eight patients with SCLC with either limited disease (LD; 276 patients) or good-prognosis extensive disease (ED; 162 patients) were randomized. Weekly chemotherapy was 12 alternating cycles of ifosfamide/doxorubicin and cis-platin/etoposide (PE), while 3-week treatment was six alternating cycles of cyclophosphamide/doxorubicin/vincristine (CAV) and PE. Thoracic irradiation was administered 3 weeks after completion of chemotherapy to LD patients who attained a complete response (CR) or partial response (PR). Patients were well matched for clinical characteristics and prognostic factors. Overall response was the same in both arms: 82.3% (39.4% CR) with weekly and 81.1% (36.9% CR) with 3-week treatment. The median survival (MS) durations were 10.8 and 10.6 months for weekly and 3-week chemotherapy, respectively. The 2-year survival rates were 11.8% and 11.7% in the weekly and 3-week arms, respectively. Received dose-intensity (DI) was 73.9% of projected for weekly treatment and 92.7% for 3-week treatment. Hematologic toxicity was the major dose-limiting toxicity for the weekly treatment. This trial excludes at 90% power a benefit of greater than 10% for 2-year survival for weekly treatment. The received DI was reduced to a greater extent with weekly treatment, mainly due to hematologic toxicity.

  5. Comparison of Concurrent Use of Thoracic Radiation With Either Carboplatin-Paclitaxel or Cisplatin-Etoposide for Patients With Stage III Non-Small-Cell Lung Cancer: A Systematic Review.

    Science.gov (United States)

    Steuer, Conor E; Behera, Madhusmita; Ernani, Vinicius; Higgins, Kristin A; Saba, Nabil F; Shin, Dong M; Pakkala, Suchita; Pillai, Rathi N; Owonikoko, Taofeek K; Curran, Walter J; Belani, Chandra P; Khuri, Fadlo R; Ramalingam, Suresh S

    2017-08-01

    The 2 most common chemotherapy regimens used concurrently with thoracic radiation for patients with unresectable IIIA and IIIB non-small-cell lung cancer (NSCLC) are carboplatin-paclitaxel and cisplatin-etoposide. There are no prospective comparisons of these 2 regimens in this setting. To conduct a systematic review of published trials to compare outcomes and toxic effects between cisplatin-etoposide and carboplatin-paclitaxel in patients with non-small-cell lung cancer receiving thoracic radiation. Studies that enrolled patients with stage III disease receiving radiotherapy (RT) with carboplatin-paclitaxel or cisplatin-etoposide were identified using electronic databases (MEDLINE, EMBASE, and Cochrane library) and meeting abstracts. Trials were excluded if they were phase 1, enrolled less than 10 patients, or included surgical resection. A systematic analysis of extracted data was performed with software using random and fixed effect models. Clinical outcomes were compared using point estimates for weighted values of median overall survival, progression-free survival, response rate, and toxic effects. A 2-tailed t test with a significance level of .05 was used for all comparisons. Overall, 3090 patients were included from 31 studies in the cisplatin-etoposide groups (median age, 61 years; 65% male; 40% squamous histology; median radiation dose, 63.0 Gy), and 3728 patients from 48 studies in carboplatin-paclitaxel groups (median age, 63 years; 65% male; 40% squamous histology; median radiation dose, 64.6 Gy). There was no significant difference in response rates between cisplatin-etoposide and carboplatin-paclitaxel (58% vs 56%; P = .26), respectively. For cisplatin-etoposide vs carboplatin-paclitaxel, there was no significant difference in median progression free survival (12 months vs 9.3 months; P = .20), overall survival (19.6 months vs 18.4 months; P = .40), or 3-year survival rate (31% vs 25%; P = .50). Cisplatin-etoposide was associated with

  6. ATLAS Overview Week at Brookhaven

    CERN Multimedia

    Pilcher, J

    Over 200 ATLAS participants gathered at Brookhaven National Laboratory during the first week of June for our annual overview week. Some system communities arrived early and held meetings on Saturday and Sunday, and the detector interface group (DIG) and Technical Coordination also took advantage of the time to discuss issues of interest for all detector systems. Sunday was also marked by a workshop on the possibilities for heavy ion physics with ATLAS. Beginning on Monday, and for the rest of the week, sessions were held in common in the well equipped Berkner Hall auditorium complex. Laptop computers became the norm for presentations and a wireless network kept laptop owners well connected. Most lunches and dinners were held on the lawn outside Berkner Hall. The weather was very cooperative and it was an extremely pleasant setting. This picture shows most of the participants from a view on the roof of Berkner Hall. Technical Coordination and Integration issues started the reports on Monday and became a...

  7. Continuous ambulatory peritoneal dialysis: Pharmacokinetics and clinical outcome of paclitaxel and carboplatin treatment

    NARCIS (Netherlands)

    J.B. Heijns (Joan); M.E.L. van der Burg (Maria); T. van Gelder (Teun); M.W.J.A. Fieren (Marien); P. de Bruijn (Peter); A. van der Gaast (Ate); W.J. Loos (Walter)

    2008-01-01

    textabstractPurpose: Administration of chemotherapy in patients with renal failure, treated with hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) is still a challenge and literature data is scarce. Here we present a case study of a patient on CAPD, treated with weekly and

  8. Advanced papillary serous carcinoma of the uterine cervix: a case with a remarkable response to paclitaxel and carboplatin combination chemotherapy

    Directory of Open Access Journals (Sweden)

    Tomoyuki Shirase

    2012-01-01

    Full Text Available Papillary serous carcinoma of the uterine cervix (PSCC is a very rare tumor, and is a recently described variant of cervical adenocarcinoma. We experienced a case of stage IV PSCC. The main tumor existed in the uterine cervix and invaded one third of the inferior part of the anterior and posterior vaginal walls. Furthermore, it had metastasized from the para-aortic lymph nodes to bilateral neck lymph nodes. Immnoreactivity for CA125 was positive, whereas the staining for p53 and WT-1 were negative in both the original tumor and the metastatic lymph nodes. We administered six courses of paclitaxel and carboplatin combination chemotherapy against this advanced PSCC. The PSCC therefore dramatically decreased in size. The main tumor of the uterine cervix showed a complete response by magnetic resonance imaging (MRI, and more than 95% of the tumor cells in the cervix had microscopically disapperared. This is the first report of PSCC in which combination chemotherapy was used and showed a remarkable response.

  9. Lethal Clostridium difficile Colitis Associated with Paclitaxel and Carboplatin Chemotherapy in Ovarian Carcinoma: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    V. Masciullo

    2010-01-01

    Full Text Available Clostridium difficile colitis, although rare, could represent a serious complication following chemotherapy. Prior antibiotic use has been considered the single most important risk factor in the development of C. difficile infection. Recently, the association between antineoplastic therapy and C. difficile-associated diarrhea in the absence of a prior antibiotic therapy has become more apparent. A 75-year-old woman with serous adenocarcinoma of the ovary developed lethal pancolitis caused by C. difficile after five cycles of paclitaxel- and carboplatin-based chemotherapy. She presented with diarrhea, coffee-ground emesis, and oliguria and was hospitalized immediately for aggressive treatment. Despite all the medical efforts, her condition worsened and she died after twenty days. We describe the second case reported of a patient developing a severe C. difficile colitis following chemotherapy without any recent antibiotic use and review the data of the literature, emphasizing the need to a prompt diagnosis and management that can significantly decrease the morbidity and life-threatening complications associated with this infection.

  10. Different impact of excision repair cross-complementation group 1 on survival in male and female patients with inoperable non-small-cell lung cancer treated with carboplatin and gemcitabine

    DEFF Research Database (Denmark)

    Holm, Bente; Mellemgaard, Anders; Skov, Torsten

    2009-01-01

    PURPOSE: The excision repair cross-complementation group 1 (ERCC1) status was assessed in patients receiving carboplatin and gemcitabine for inoperable non-small-cell lung cancer (NSCLC). We analyzed the association between the ERCC1 status and the overall survival after the chemotherapy. PATIENTS...... AND METHODS: We retrospectively identified 163 patients with inoperable NSCLC and sufficient tumor tissue for ERCC1 analysis, who had received carboplatin and gemcitabine as first-line treatment. Immunohistochemistry was used to assess the expression of ERCC1. RESULTS: One hundred sixty-three patients were...... included. Seventy (42%) were ERCC1 positive. Patients treated with carboplatin and gemcitabine and having ERCC1-negative tumors had a significantly increased survival when compared to patients with ERCC1-positive tumors (median survival, 12.0 months v 8.2 months; P = .02). This difference was mainly seen...

  11. Superiority of cisplatin or carboplatin in combination with teniposide and vincristine in the induction chemotherapy of small-cell lung cancer. A randomized trial with 5 years follow up

    DEFF Research Database (Denmark)

    Lassen, U; Kristjansen, P E; Osterlind, K

    1996-01-01

    . PATIENTS AND METHODS: From November 1985 to September 1991, 484 consecutive, previously untreated patients with SCLC, performance status 0-4, entered a three armed randomized trial with three cycles of cisplatin (arm I) or carboplatin (arm II) in combination with teniposide and vincristine alternating...... with three treatment blocks of cyclophosphamide, etoposide, lomustine and vincristine (block A), doxorubicin and vincristine (block B) and cisplatin, hexamethylmelamine and vindesine (block C) versus alternating treatment with block A, B and C (arm III). RESULTS: No difference in efficacy or toxicity...... was found between cisplatin and carboplatin at the present dosages. Induction chemotherapy with teniposide plus cisplatin or carboplatin did not result in higher complete response rates (objective response rates 63%, 72% and 65%, respectively) or in significantly greater toxicity, but overall survival...

  12. Weekly Cycle of Lightning: Evidence of Storm Invigoration by Pollution

    Science.gov (United States)

    Bell, Thomas L.; Rosenfeld, Daniel; Kim, Kyu-Myong

    2009-01-01

    We have examined summertime 1998 2009 U.S. lightning data from the National Lightning Detection Network (NLDN) to look for weekly cycles in lightning activity. As was found by Bell et al. (2008) for rain over the southeast U.S., there is a significant weekly cycle in afternoon lightning activity that peaks in the middle of the week there. The weekly cycle appears to be reduced over population centers. Lightning activity peaks on weekends over waters near the SE U.S. The statistical significance of weekly cycles over the western half of the country is generally small. We found no evidence of a weekly cycle of synoptic-scale forcing that might explain these patterns. The lightning behavior is entirely consistent with the explanation suggested by Bell et al. (2008) for the cycles in rainfall and other atmospheric data from the SE U.S., that aerosols can cause storms to intensify in humid, convectively unstable environments.

  13. Phase I study of the CD40 agonist antibody CP-870,893 combined with carboplatin and paclitaxel in patients with advanced solid tumors.

    Science.gov (United States)

    Vonderheide, Robert H; Burg, Jennifer M; Mick, Rosemarie; Trosko, Jennifer A; Li, Dongguang; Shaik, M Naveed; Tolcher, Anthony W; Hamid, Omid

    2013-01-01

    CD40 is a cell-surface molecule that critically regulates immune responses. CP-870,893 is a fully human, CD40-specific agonist monoclonal antibody (mAb) exerting clinical antineoplastic activity. Here, the safety of CP-870,893 combined with carboplatin and paclitaxel was assessed in a Phase I study. Patients with advanced solid tumors received standard doses of paclitaxel and carboplatin on day 1 followed by either 0.1 mg/Kg or 0.2 mg/Kg CP-870,893 on day 3 (Schedule A) or day 8 (Schedule B), repeated every 21 d. The primary objective was to determine safety and maximum-tolerated dose (MTD) of CP-870,893. Secondary objectives included the evaluation of antitumor responses, pharmacokinetics and immune modulation. Thirty-two patients were treated with CP-870,893, 16 patients on each schedule. Two dose-limiting toxicities were observed (grade 3 cytokine release and transient ischemic attack), each at the 0.2 mg/Kg dose level, which was estimated to be the MTD. The most common treatment-related adverse event was fatigue (81%). Of 30 evaluable patients, 6 (20%) exhibited partial responses constituting best responses as defined by RECIST. Following CP-870,893 infusion, the peripheral blood manifested an acute depletion of B cells associated with upregulation of immune co-stimulatory molecules. T-cell numbers did not change significantly from baseline, but transient tumor-specific T-cell responses were observed in a small number of evaluable patients. The CD40 agonist mAb CP-870,893, given on either of two schedules in combination with paclitaxel and carboplatin, was safe for patients affected with advanced solid tumors. Biological and clinical responses were observed, providing a rationale for Phase II studies.

  14. A Phase II clinical trial of pegylated liposomal doxorubicin and carboplatin in Japanese patients with platinum-sensitive recurrent ovarian, fallopian tube or primary peritoneal cancer.

    Science.gov (United States)

    Nakanishi, Toru; Aoki, Daisuke; Watanabe, Yoh; Ando, Yuichi; Tomotsugu, Naoki; Sato, Yuji; Saito, Toshiaki

    2015-05-01

    This single-arm Phase II trial was designed to assess the safety and efficacy of pegylated liposomal doxorubicin and carboplatin combination chemotherapy in patients with platinum-sensitive recurrent ovarian cancer. Patients with a histological diagnosis of epithelial ovarian, fallopian tube or primary peritoneal carcinoma, who were relapse-free at least 6 months after completion of first-line platinum-based chemotherapy, and who had measurable disease and gave consent to participate in this study received infusions of pegylated liposomal doxorubicin (30 mg/m(2)) at 1 mg/min, followed by carboplatin (AUC 5 mg min/ml) over 30 min every 28 days. Thirty-three of 35 enrolled patients were eligible for efficacy analysis. One patient (3.0%) achieved a complete response, while 16 (48.5%) achieved a partial response, with an overall objective response rate of 51.5% (95% confidence interval, 34.5-68.6%). Among the 22 patients who had evaluable CA125 levels at entry, responses were observed in 18 patients, with a response rate of 81.8% (95% confidence interval, 65.3-98.3%). The median progression-free survival and overall survival rates for all 35 patients were 10.7 months (95% confidence interval, 8.1-13.2 months) and 38.8 months (95% confidence interval, 31.0-46.7 months), respectively. The most frequent Grade 3-4 toxicities, regardless of cause, were neutropenia (82.9%), thrombocytopenia (51.4%), leukopenia (45.7%) and anemia (17.1%). The safety and efficacy of pegylated liposomal doxorubicin and carboplatin combination chemotherapy in patients with platinum-sensitive recurrent ovarian cancer were confirmed. Although there were concerns of severe hematological toxicity with this therapy, this potential complication was safely managed through adequate monitoring of bone marrow function. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Carboplatin with intravenous and subsequent oral administration of vinorelbine in resected non-small-cell-lung cancer in real-world set-up.

    Science.gov (United States)

    Kolek, Vítězslav; Grygárková, Ivona; Koubková, Leona; Skřičková, Jana; Švecová, Jiřina; Sixtová, Dimka; Bartoš, Jiří; Tichopád, Aleš

    2017-01-01

    Adjuvant cisplatin-based chemotherapy is recommended for routine use in patients with Stage IIA, IIB or IIIA non-small cell lung cancer (NSCLC) after complete resection. Results obtained for Stage IB were not conclusive. While vinorelbine plus cisplatin is the preferred choice after resection, combining vinorelbine with carboplatin promises improved compliance and delivery of drugs due to lower toxicity. We evaluated the impact of this option on treatment compliance and survival under real-world conditions. A prospective, single-arm, multicenter, non-interventional study evaluated the tolerability, dose intensity and survival resulting from adjuvant use of intravenous carboplatin (AUC 5 on day 1) with vinorelbine administered both intravenously (25 mg/m2 on day 1) and orally (60 mg/m2 on day 8) within four cycles of 21 days each. A total of 74 patients with a median age of 64 years were observed. The mean number of accomplished cycles was 3.78, and 62 patients (83.7%) completed all four planned cycles. Relative dose intensity for carboplatin was 88.9%, for intravenous vinorelbine 93.1%, and for oral vinorelbine 83.2%. Median follow-up was 4.73 years. Median disease-specific survival (DSS) was 7.63 years, median overall survival (OS) was 5.90 years, median disease-free survival (DFS0) was 4.43 years, and five-year survival was 56.2%. TNM stage of disease significantly affected DSS and OS. Favorable survival was observed in females, nonsmokers, patients aged over 65 years, patient with prior lobectomy, patients with tumor of squamous histology, and those who finished the planned therapy, but the differences were non-significant. Adjuvant carboplatin with vinorelbine switched from intravenous to oral administration was shown to be a favorable regimen with regard to tolerability and safety. Compliance to therapy was high, and survival parameters were promising, showing that applied regimen can be another potential option for adjuvant chemotherapy in patients with NSCLC.

  16. Influence of gemcitabine thermal-chemotherapy infusion combined with carboplatin chemotherapy embolization on liver function, renal function and immune function in patients with primary carcinoma of liver

    Directory of Open Access Journals (Sweden)

    Bo Du

    2017-04-01

    Full Text Available Objective: To observe the influence of Gemcitabine Thermal-chemotherapy infusion combined with Carboplatin Chemotherapy embolization on liver function, renal function and immune function in patients with primary carcinoma of liver. Method: A total of 90 paitents with primary carcinoma of liver in our hospital were selected and randomly divided into 2 groups: the control group (45 cases and the observation group (45 cases. The patients in the observation group were treated by Gemcitabine Thermal-chemotherapy infusion combined with Carboplatin Chemotherapy embolization. And the patients in the control group were treated by Gemcitabine normal temperature chemotherapy infusion combined with Carboplatin Chemotherapy embolization. The changes of liver function, renal function and immune function were compared in 2 groups before and after treatment. Result: The comparison of ALT and AST in the two groups before treatment was not statistically significant. 3 d after treatment, the ALT and AST in both groups increased compared with that before treatment. And the ALT (175.35±10.06 U/L , AST (173.54±13.47 U/L, in control group were increased more significantly compared with ALT (84.21±12.07 U/L and AST (94.20±11.31 U/L in observation group. The difference was statistically significant. 30 d after treatment, The ALT and AST in both groups came back to the former level. The difference was not statistically significant. The comparison of BUN, Crea in the two groups before treatment, 3 d after treatment and 30 d after treatment were not statistically significant. The comparison of CD3+, CD4+, CD8+, CD4+/CD8+ and NK cells in the two groups before treatment were not statistically significant. 7 d after treatment, CD3+ (72.34±6.95, NK cells (23.56±6.62 increased compared with that before treatment. And they increased more significantly compared with CD3+ (64.78±5.46 and NK cells (18.32±5.72 in the control group. CD8+, (22.01±2.77 in observation group

  17. Weekly Multi-agent Chemotherapy (CMF-b) for Advanced Non-melanoma Skin Cancer.

    Science.gov (United States)

    Espeli, Vittoria; Ruegg, Eva; Hottinger, Andreas F; Modarressi, Ali; Dietrich, Pierre-Yves

    2016-05-01

    Advanced unresectable and metastatic non-melanoma skin cancers (NMSC) are rare, but often arise in elderly patients. When surgery or irradiation are no longer feasible, chemotherapy is often precluded by the patient's age and comorbidities. Whether low-dose multi-agent chemotherapy could be an alternative for this vulnerable population in an outpatient setting was the issue examined in this retrospective analysis. Twenty-six patients with advanced unresectable or metastatic NMSC received weekly multi-agent chemotherapy with carboplatin at an area under the curve of 2 or 40 mg total dose of cisplatin, with 15 IU total dose of bleomycin, 40 mg total dose of methotrexate, and 500 mg total dose of 5-fluorouracil (CMF-b) until best response, toxicity, or progression of their disease. Twenty-four patients were treated as outpatients; two were hospitalized. Twenty-three patients were previously treated with surgery or radiotherapy. The median age was 68 years (range=44-100 years). The median number of cycles was 6 (range=1 to 17). The overall response rate was 61.5% (seven complete remissions, nine partial remissions) for the entire cohort and 63.6% (two complete remissions and five partial remissions) for patients >80 years. The median duration of response was 6.1 months (range=1.6-63 months). Responses longer than 6 months were obtained in 11/26 (42.3%) of the entire cohort and in 4/11 (36.3%) patients >80 years. Symptom improvement was observed in 17 patients (65.3%). Toxicity was acceptable, with grade 3 renal failure (n=1) and grade 3 or 4 myelotoxicity (n=2). CMF-b is a safe, weekly low-dose multi-agent regimen that offers palliation for vulnerable patients with NMSC. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  18. Web Lectures - ATLAS Overview Week

    CERN Multimedia

    Tushar Bhatnagar; Jeremy Herr; Mitch McLachlan; Homer A. Neal

    2007-01-01

    ATLAS Web Archives Web Archives of the ATLAS Overview Week in Glasgow are now available from the University of Michigan portal here. Archives of ATLAS Plenary Sessions, Workshops, Meetings, and Tutorials recorded over the past two years are available via the University of Michigan Lecture Portal. Other recent additions include the ROOT Workshop held at CERN on March 26-27, the Physics Analysis Tools Workshop held in Bergen, Norway on April 23-27, and the CTEQ Workshop: "Physics at the LHC: Early Challenges" held at Michigan State University on May 14-15. Viewing requires a standard Web browser with RealPlayer plug-in (included in most browsers automatically) and works on any major platform. Lectures can be viewed directly over the Web or downloaded locally. In addition, you will find access to a variety of general tutorials and events via the portal. Feedback & Suggestions Welcome Suggestions for events or tutorials to record in 2007, as well as feedback on existing archives, is always welcome...

  19. A busy week for Council

    CERN Multimedia

    2009-01-01

    This has been a busy week for the CERN Council, and there is much to report. Firstly, I’m pleased to say that Council approved the Organization’s Medium Term Plan, and with it the budget for financial year 2010. In a time of global recession, this is a strong vote of confidence from the Member States. This meeting of Council provided an opportunity for the working group on the scientific and geographical enlargement of CERN to set out a roadmap towards its final report, which is to be made at Council’s December session this year. One part of the process over the coming months is to bring the major players in particle physics from beyond the European region into the discussion, ensuring that the working group’s recommendations lead to an optimum position for CERN and European particle physics in the global context. An indicator of the continuing attractiveness of CERN is the fact that Council has received four new applications...

  20. Phase I trial of carboplatin and gemcitabine chemotherapy and stereotactic ablative radiosurgery for the palliative treatment of persistent or recurrent gynecologic cancer

    Directory of Open Access Journals (Sweden)

    Charles A Kunos

    2015-06-01

    Full Text Available Background: We conducted a phase I trial to determine the safety of systemic chemotherapy prior to abdominopelvic robotic stereotactic ablative radiotherapy (SABR in women with persistent or recurrent gynecologic cancers. Methods: Patients were assigned to dose-finding cohorts of day-1 carboplatin (AUC 2 or 4 and gemcitabine (600 or 800 mg/m2 followed by day-2 to day-4 Cyberknife SABR (8Gy X 3 consecutive daily doses. Toxicities were graded prospectively by common terminology criteria for adverse events, version 4.0. SABR target and best overall treatment responses were recorded according to response evaluation criteria in solid tumors, version 1.1. Findings: The maximum tolerated dose of chemotherapy preceding SABR was carboplatin AUC 4 and gemcitabine 600 mg/m2. One patient experienced manageable, dose-limiting grade 4 neutropenia, grade 4 hypokalemia, and grade 3 nausea attributed to study treatment. One patient had a late grade 3 rectovaginal fistula 16 months after trial therapy. Among 28 SABR targets, 22 (79% showed a partial response and six (21% remained stable. Interpretation: Systemic chemotherapy may be given safely prior to abdominopelvic robotic SABR with further investigation warranted.Funding: National Institutes of Health grant P30 CA43703

  1. The translational blocking of α5 and α6 integrin subunits affects migration and invasion, and increases sensitivity to carboplatin of SKOV-3 ovarian cancer cell line.

    Science.gov (United States)

    Villegas-Pineda, Julio César; Toledo-Leyva, Alfredo; Osorio-Trujillo, Juan Carlos; Hernández-Ramírez, Verónica Ivonne; Talamás-Rohana, Patricia

    2017-02-15

    Epithelial ovarian cancer is the most lethal gynecologic malignancy. Integrins, overexpressed in cancer, are involved in various processes that favor the development of the disease. This study focused on determining the degree of involvement of α5, α6 and β3 integrin subunits in the establishment/development of epithelial ovarian cancer (EOC), such as proliferation, migration, invasion, and response to carboplatin. The translation of the α5, α6 and β3 integrins was blocked using morpholines, generating morphant cells for these proteins, which were corroborated by immunofluorescence assays. WST-1 proliferation assay showed that silencing of α5, α6, and β3 integrins does not affect the survival of morphants. Wound healing and transwell chamber assays showed that blocking α5 and α6 integrins decrease, in lesser and greater level respectively, the migratory and the invasive capacity of SKOV-3 cells. Finally, blocking α5 and α6 integrins partially sensitized the cells response to carboplatin, while blocking integrin β3 generated resistance to this drug. Statistical analyses were performed with the GraphPad Prism 5.0 software employing one way and two-way ANOVA tests; data are shown as average±SD. Results suggest that α5 and α6 integrins could become good candidates for chemotherapy targets in EOC. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Biweekly carboplatin/gemcitabine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: report of efficacy, quality of life and geriatric assessment.

    Science.gov (United States)

    Bamias, Aristotle; Lainakis, George; Kastritis, Efstathios; Antoniou, Nikos; Alivizatos, Gerassimos; Koureas, Andreas; Chrisofos, Michael; Skolarikos, Andreas; Karayiotis, Evangelos; Dimopoulos, Meletios A

    2007-01-01

    We evaluated safety and efficacy of first-line gemcitabine/carboplatin in unfit-for-cisplatin patients with advanced urothelial carcinoma and the effect on the quality of life and functional status of elderly patients (aged >70). Unfit patients had ECOG performance status (PS) > or =2, creatinine clearance patients were stratified into group 1 (no activities of daily living (ADL) or instrumental ADL dependency and no comorbidities), group 2 (instrumental ADL dependency or 1-2 comorbidities) and group 3 (ADL dependency or > or =2 comorbidities). Thirty-four patients were enrolled: 68% had PS 2-3, 69% a creatinine clearance Patients in geriatric assessment groups 1 and 2 had a significantly longer median progression-free survival compared to group 3 [6.9 months (95% CI 1.3-12.4) vs. 1.9 months (95% CI 0.5-3.2); p = 0.005]. First-line gemcitabine/carboplatin combination is active in unfit-for-cisplatin patients with advanced urothelial carcinoma. Pretreatment quality of life and geriatric assessment may be useful in selecting patients likely to benefit from this treatment. 2008 S. Karger AG, Basel.

  3. The translational blocking of α5 and α6 integrin subunits affects migration and invasion, and increases sensitivity to carboplatin of SKOV-3 ovarian cancer cell line

    Energy Technology Data Exchange (ETDEWEB)

    Villegas-Pineda, Julio César, E-mail: jcvillegas@cinvestav.mx; Toledo-Leyva, Alfredo, E-mail: toledo_leyva@hotmail.com; Osorio-Trujillo, Juan Carlos, E-mail: clostrujillo2@yahoo.com.mx; Hernández-Ramírez, Verónica Ivonne, E-mail: arturomvi@hotmail.com; Talamás-Rohana, Patricia, E-mail: ptr@cinvestav.mx

    2017-02-15

    Epithelial ovarian cancer is the most lethal gynecologic malignancy. Integrins, overexpressed in cancer, are involved in various processes that favor the development of the disease. This study focused on determining the degree of involvement of α5, α6 and β3 integrin subunits in the establishment/development of epithelial ovarian cancer (EOC), such as proliferation, migration, invasion, and response to carboplatin. The translation of the α5, α6 and β3 integrins was blocked using morpholines, generating morphant cells for these proteins, which were corroborated by immunofluorescence assays. WST-1 proliferation assay showed that silencing of α5, α6, and β3 integrins does not affect the survival of morphants. Wound healing and transwell chamber assays showed that blocking α5 and α6 integrins decrease, in lesser and greater level respectively, the migratory and the invasive capacity of SKOV-3 cells. Finally, blocking α5 and α6 integrins partially sensitized the cells response to carboplatin, while blocking integrin β3 generated resistance to this drug. Statistical analyses were performed with the GraphPad Prism 5.0 software employing one way and two-way ANOVA tests; data are shown as average±SD. Results suggest that α5 and α6 integrins could become good candidates for chemotherapy targets in EOC.

  4. Pemetrexed plus carboplatin versus pemetrexed in pretreated patients with advanced non-squamous non-small-cell lung cancer : treating the right patients based on individualized treatment effect prediction

    NARCIS (Netherlands)

    van Kruijsdijk, R. C. M.; Visseren, F. L. J.; Boni, L.; Groen, H. J. M.; Dingemans, A. M. C.; Aerts, J. G. J. V.; van der Graaf, Y.; Ardizzoni, A.; Smit, E. F.

    In this study, it is shown that there is important heterogeneity in the effects of pemetrexed-carboplatin versus pemetrexed on progression-free survival in pretreated patients with advanced non-squamous non-small-cell lung cancer. Treatment effect can be predicted for individual patients using a

  5. Population pharmacokinetics and pharmacodynamics of paclitaxel and carboplatin in ovarian cancer patients : A study by the European Organization for Research and Treatment of Cancer-Pharmacology and Molecular Mechanisms Group and New Drug Development Group

    NARCIS (Netherlands)

    Joerger, Markus; Huitema, Alwin D. R.; Richel, Dick J.; Dittrich, Christian; Pavlidis, Nikolas; Briasoulis, Evangelos; Vermorken, Jan B.; Strocchi, Elena; Martoni, Andrea; Sorio, Roberto; Sleeboom, Henk P.; Izquierdo, Miguel A.; Jodrell, Duncan I.; Calvert, Hilary; Boddy, Alan V.; Hollema, Harry; Fety, Regine; Van der Vijgh, Wjf J. F.; Hempel, Georg; Chatelut, Etienne; Karlsson, Mats; Wilkins, Justin; Tranchand, Brigitte; Schrijvers, Ad H. G. J.; Twelves, Christian; Beijnen, Jos H.; Schellens, Jan H. M.

    2007-01-01

    Purpose: Paclitaxel and carboplatin are frequently used in advanced ovarian cancer following cytoreductive surgery. Threshold models have been used to predict paclitaxel pharmacokinetic-pharmacodynamics, whereas the time above paclitaxel plasma concentration of 0.05 to 0.2 mu mol/L (t(c > 0.05-0.2))

  6. Population pharmacokinetics and pharmacodynamics of paclitaxel and carboplatin in ovarian cancer patients: a study by the European organization for research and treatment of cancer-pharmacology and molecular mechanisms group and new drug development group

    NARCIS (Netherlands)

    Joerger, Markus; Huitema, Alwin D. R.; Richel, Dick J.; Dittrich, Christian; Pavlidis, Nikolas; Briasoulis, Evangelos; Vermorken, Jan B.; Strocchi, Elena; Martoni, Andrea; Sorio, Roberto; Sleeboom, Henk P.; Izquierdo, Miguel A.; Jodrell, Duncan I.; Calvert, Hilary; Boddy, Alan V.; Hollema, Harry; Féty, Regine; van der Vijgh, Wjf J. F.; Hempel, Georg; Chatelut, Etienne; Karlsson, Mats; Wilkins, Justin; Tranchand, Brigitte; Schrijvers, Ad H. G. J.; Twelves, Christian; Beijnen, Jos H.; Schellens, Jan H. M.

    2007-01-01

    PURPOSE: Paclitaxel and carboplatin are frequently used in advanced ovarian cancer following cytoreductive surgery. Threshold models have been used to predict paclitaxel pharmacokinetic-pharmacodynamics, whereas the time above paclitaxel plasma concentration of 0.05 to 0.2 micromol/L (t(C >

  7. Superiority of cisplatin or carboplatin in combination with teniposide and vincristine in the induction chemotherapy of small-cell lung cancer. A randomized trial with 5 years follow up

    DEFF Research Database (Denmark)

    Lassen, U; Kristjansen, P E; Osterlind, K

    1996-01-01

    PURPOSE: The introduction of platinum compounds and epipodophyllotoxins in combination with vincristine as induction chemotherapy in small-cell lung cancer (SCLC) was investigated in order to: (1) compare the efficacy of cisplatin with that of carboplatin in combination with teniposide and vincri......PURPOSE: The introduction of platinum compounds and epipodophyllotoxins in combination with vincristine as induction chemotherapy in small-cell lung cancer (SCLC) was investigated in order to: (1) compare the efficacy of cisplatin with that of carboplatin in combination with teniposide...... and vincristine as inducers of remission over three cycles; (2) compare the toxicity pattern of carboplatin and of cisplatin when given in combination regimens; and (3) compare a chemotherapeutic regimen consisting of three alternating combinations with that of regimens consisting of four alternating combinations....... PATIENTS AND METHODS: From November 1985 to September 1991, 484 consecutive, previously untreated patients with SCLC, performance status 0-4, entered a three armed randomized trial with three cycles of cisplatin (arm I) or carboplatin (arm II) in combination with teniposide and vincristine alternating...

  8. A prescrição semanal de sulfato ferroso pode ser altamente efetiva para reduzir níveis endêmicos de anemia na infância Long-term preventive mass prescription of weekly doses of iron sulfate may be highly effective to reduce endemic child anemia

    Directory of Open Access Journals (Sweden)

    Carlos Augusto Monteiro

    2002-04-01

    important nutritional problems faced by developing countries. Well-controlled efficacy studies show that intermittent iron supplementation can improve children's iron status as well as the traditional daily schedule. This gives new impetus to controlling child anemia by weekly preventive iron supplementation. The objective of this study is to evaluate the effectiveness of long-term preventive provision of weekly doses of iron sulfate to all children from 6 to 59 months of age, in a child population in which anemia is highly prevalent. Children from both the intervention and control groups were selected from a random cross-sectional sample of the child population of the city of São Paulo, Brazil. Parents in the intervention group were visited in their homes and received nutrition education plus a solution of iron sulfate with the request to give it to their children once a week until a follow-up visit occurred in approximately six months. Parents in the control group received only nutrition education. The effect of the intervention was assessed by changes in hemoglobin concentration and the prevalence of anemia. Comparisons between the two groups were made based on an intention-to-treat approach, and all estimates were adjusted for initial hemoglobin concentration, initial age, total duration of follow-up and family income. The average hemoglobin gain due to the intervention was 4.0 g/l, with a fall of more than 50% in the prevalence of anemia among the children. The intervention was particularly effective in preventing declines in hemoglobin concentration during the first two years of life. This study demonstrates that long-term preventive weekly iron supplementation for preschool children significantly reduces the risk of anemia under conditions similar to those possible in routine public health programs.

  9. 75 FR 70999 - National Entrepreneurship Week, 2010

    Science.gov (United States)

    2010-11-19

    ... Proclamation 8600--National Entrepreneurship Week, 2010 Proclamation 8601--America Recycles Day, 2010 #0; #0... 15, 2010 National Entrepreneurship Week, 2010 By the President of the United States of America A... and work hard enough, the American dream is within your reach. During National Entrepreneurship Week...

  10. Understanding Infidelity: An Interview with Gerald Weeks

    Science.gov (United States)

    Smith, Travis

    2011-01-01

    In this interview, Gerald Weeks shares his expertise on the topic of infidelity and couples counseling. Dr. Weeks defines infidelity, presents assessment strategies for treating the issue of infidelity, and discusses an intersystemic model for infidelity treatment when counseling couples. Dr. Weeks also provides insight into common mistakes made…

  11. Carboplatin-pemetrexed in treatment of patients with recurrent/metastatic cancers of the head and neck; superior outcomes in oropharyngeal primaries.

    Directory of Open Access Journals (Sweden)

    Binu eMalhotra

    2015-01-01

    Full Text Available Background – Platinum based therapy in combination with 5-fluorouracil with cetuximab has shown the best survival in pts with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN. The purpose of this study is to evaluate the efficacy and tolerability of carboplatin, pemetrexed and to assess differential outcomes in patients with oropharyngeal primary and HPV related disease.Patients and Methods –The charts of consecutive patients with R/M SCCHN were reviewed. All patients receiving at least 1 cycle of the 2-drug regimen (pemetrexed 500 mg/m2, carboplatin area under the curve of 5 intravenously, were included for assessment of response, safety, toxicity and survival.Results - A total of 86 patients received this regimen between January 2008 and December 2012, of which, 63 were included in this analysis. Forty one percent (26 of the patients had cancers of the oropharynx, and of those, 50% had HPV positive disease, 32% (20 had cancers of the larynx and 24% (15 of the oral cavity. Median number of cycles administered was 4 (range 1-14 cycles with 50% of the patients receiving 4 or more cycles. Half the patients achieved stable disease as their best response, 8% (5 attained a partial response, 24% progressed on therapy and the remaining patients (12 could not have their response assessed.On the basis of Kaplan Meier analysis, median progression free survival (PFS was 5.1 months (95% CI 3.2, 6.2 and median overall survival (OS was 9.4 months (95% CI 4.3, 13.1. Among pts with oropharyngeal primary (n=26, median PFS was 6.4 months (95% CI 2.8, 7.9 and median OS was 16.6 months (95% CI 9.6, 19.5. Among HPV+ pts (n=13, median PFS was 7.0 months (95% CI 4.8, ne and median OS was 17.1 months (95% CI 11.2, 21.7. Conclusion: Combination carboplatin-pemetrexed is an effective and well tolerated treatment, associated with a median PFS of 5.1 months and a clinical benefit in at least 57% of the patients treated.

  12. Circumcision weeks: making circumcision part of routine training ...

    African Journals Online (AJOL)

    Circumcision weeks: making circumcision part of routine training and service delivery at district-level hospitals in South Africa. ... It also helps reduce herpes simplex virus type 2, a key biological co-factor thought to account for some human susceptibility to HIV infection and human papillomavirus. To address these needs ...

  13. 78 FR 24319 - National Crime Victims' Rights Week, 2013

    Science.gov (United States)

    2013-04-24

    ... that give law enforcement, schools, mental health professionals, and public health officials better tools to reduce violent crime. But we cannot solve this problem alone. That is why I will continue to... fellow citizens and the basic values that unite us. Let us renew that common cause this week, and let us...

  14. [18F]FDG PET/CT-based response assessment of stage IV non-small cell lung cancer treated with paclitaxel-carboplatin-bevacizumab with or without nitroglycerin patches

    Energy Technology Data Exchange (ETDEWEB)

    Jong, Evelyn E.C. de; Elmpt, Wouter van; Leijenaar, Ralph T.H.; Lambin, Philippe [Maastricht University Medical Centre, Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht (Netherlands); Hoekstra, Otto S. [VU University Medical Center, Department of Nuclear Medicine and PET Research, Amsterdam (Netherlands); Groen, Harry J.M. [University of Groningen and University Medical Center Groningen, Department of Pulmonary Diseases, Groningen (Netherlands); Smit, Egbert F. [VU University Medical Center, Department of Pulmonary Diseases, Amsterdam (Netherlands); The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Thoracic Oncology, Amsterdam (Netherlands); Boellaard, Ronald [University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); Noort, Vincent van der [The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Biometrics, Amsterdam (Netherlands); Troost, Esther G.C. [Maastricht University Medical Centre, Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht (Netherlands); Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology, Dresden (Germany); Medical Faculty and University Hospital Carl Gustav Carus of Technische Universitaet Dresden, Department of Radiotherapy and Radiation Oncology, Dresden (Germany); Dingemans, Anne-Marie C. [Maastricht University Medical Centre, Department of Pulmonology, GROW-School for Oncology and Developmental Biology, Maastricht (Netherlands)

    2017-01-15

    Nitroglycerin (NTG) is a vasodilating drug, which increases tumor blood flow and consequently decreases hypoxia. Therefore, changes in [18F] fluorodeoxyglucose positron emission tomography ([18F]FDG PET) uptake pattern may occur. In this analysis, we investigated the feasibility of [18F]FDG PET for response assessment to paclitaxel-carboplatin-bevacizumab (PCB) treatment with and without NTG patches. And we compared the [18F]FDG PET response assessment to RECIST response assessment and survival. A total of 223 stage IV non-small cell lung cancer (NSCLC) patients were included in a phase II study (NCT01171170) randomizing between PCB treatment with or without NTG patches. For 60 participating patients, a baseline and a second [18F]FDG PET/computed tomography (CT) scan, performed between day 22 and 24 after the start of treatment, were available. Tumor response was defined as a 30 % decrease in CT and PET parameters, and was compared to RECIST response at week 6. The predictive value of these assessments for progression free survival (PFS) and overall survival (OS) was assessed with and without NTG. A 30 % decrease in SUVpeak assessment identified more patients as responders compared to a 30 % decrease in CT diameter assessment (73 % vs. 18 %), however, this was not correlated to OS (SUVpeak30 p = 0.833; CTdiameter30 p = 0.557). Changes in PET parameters between the baseline and the second scan were not significantly different for the NTG group compared to the control group (p value range 0.159-0.634). The CT-based (part of the [18F]FDG PET/CT) parameters showed a significant difference between the baseline and the second scan for the NTG group compared to the control group (CT diameter decrease of 7 ± 23 % vs. 19 ± 14 %, p = 0.016, respectively). The decrease in tumoral FDG uptake in advanced NSCLC patients treated with chemotherapy with and without NTG did not differ between both treatment arms. Early PET-based response assessment showed more tumor responders

  15. [18F]FDG PET/CT-based response assessment of stage IV non-small cell lung cancer treated with paclitaxel-carboplatin-bevacizumab with or without nitroglycerin patches.

    Science.gov (United States)

    de Jong, Evelyn E C; van Elmpt, Wouter; Leijenaar, Ralph T H; Hoekstra, Otto S; Groen, Harry J M; Smit, Egbert F; Boellaard, Ronald; van der Noort, Vincent; Troost, Esther G C; Lambin, Philippe; Dingemans, Anne-Marie C

    2017-01-01

    Nitroglycerin (NTG) is a vasodilating drug, which increases tumor blood flow and consequently decreases hypoxia. Therefore, changes in [18F] fluorodeoxyglucose positron emission tomography ([18F]FDG PET) uptake pattern may occur. In this analysis, we investigated the feasibility of [18F]FDG PET for response assessment to paclitaxel-carboplatin-bevacizumab (PCB) treatment with and without NTG patches. And we compared the [18F]FDG PET response assessment to RECIST response assessment and survival. A total of 223 stage IV non-small cell lung cancer (NSCLC) patients were included in a phase II study (NCT01171170) randomizing between PCB treatment with or without NTG patches. For 60 participating patients, a baseline and a second [18F]FDG PET/computed tomography (CT) scan, performed between day 22 and 24 after the start of treatment, were available. Tumor response was defined as a 30 % decrease in CT and PET parameters, and was compared to RECIST response at week 6. The predictive value of these assessments for progression free survival (PFS) and overall survival (OS) was assessed with and without NTG. A 30 % decrease in SUVpeak assessment identified more patients as responders compared to a 30 % decrease in CT diameter assessment (73 % vs. 18 %), however, this was not correlated to OS (SUVpeak30 p = 0.833; CTdiameter30 p = 0.557). Changes in PET parameters between the baseline and the second scan were not significantly different for the NTG group compared to the control group (p value range 0.159-0.634). The CT-based (part of the [18F]FDG PET/CT) parameters showed a significant difference between the baseline and the second scan for the NTG group compared to the control group (CT diameter decrease of 7 ± 23 % vs. 19 ± 14 %, p = 0.016, respectively). The decrease in tumoral FDG uptake in advanced NSCLC patients treated with chemotherapy with and without NTG did not differ between both treatment arms. Early PET-based response assessment

  16. OEO SRB Weekly Workload Status Report

    Data.gov (United States)

    Social Security Administration — Weekly reports of workloads processed in the Security Records Branch in Boyers, PA. Reports on quantities of work received, processed, pending and average processing...

  17. ET-37EFFICACY OF INTRACRANIAL DELIVERY OF DICHLOROACETATE AND CARBOPLATIN VIA AN LCP POLYMER MICROCAPSULE DEVICE IN AN EXPERIMENTAL GLIOMA MODEL

    Science.gov (United States)

    Mangraviti, Antonella; Jin, Yike; Sy, Jay; Wang, Yuan; Raghavan, Tula; Hastings-Spaine, Lindsey; Olivi, Alessandro; Tyler, Betty; Brem, Henry

    2014-01-01

    BACKGROUND: Multi-targeted therapy is a promising strategy for patients with glioblastoma and controlled delivery of these chemotherapeutics is crucial for effective intracranial chemotherapy. Studies combining platinum pharmacophores with apoptosis inducers, such as Dichloroacetae (DCA), suggest that DCA enhances the sensitivity of cancer cells to platinum compounds. We assessed the efficacy of DCA in combination with Carboplatin (CB) delivered from a biocompatible liquid crystal polymer (LCP) microcapsule in an experimental glioma model in rats. METHODS: In vitro studies were performed to assess the cytotoxicity of DCA and CB on F98 rodent glioma cells. Efficacy was assessed in vivo in rats with intracranially implanted F98 with intracranial implantation of 50% DCA and 5% CB wafers, in monotherapy and in combination. A second study assessed the efficacy of DCA and CB released from an LCP microcapsule as a multi-drug delivery device. RESULTS: The IC50 values for DCA and CB at 24 hours were 70mM and 39mM(R2 =0.989 and 0.948, respectively). The initial efficacy study showed no difference in median survival between the control group and either DCA or CB monotherapy treatments. However, the animals that received CB wafer in combination with DCA wafer had significantly increased survival as compared to the control group (p = 0.016). The microcapsule efficacy study showed that animals given intracranial LCP microcapsule loaded with 5% CB/pCPP:SA and 50% DCA/pCPP:SA had significant improvement in survival (p= 0.0042 vs. control). CONCLUSION: We show that the intracranial delivery of Dichloroacetate and Carboplatin significantly increases survival in an experimental glioma model, when delivered via polymeric wafer as well as when delivered from LCP microcapsule. The LCP microcapsule is a safe and effective method for intracranial dual-drug delivery and may be a novel strategy for obtaining controlled release of multiple drugs with drug-specific kinetics and independent

  18. Metformin, at Concentrations Corresponding to the Treatment of Diabetes, Potentiates the Cytotoxic Effects of Carboplatin in Cultures of Ovarian Cancer Cells

    Science.gov (United States)

    Erices, Rafaela; Bravo, Maria Loreto; Gonzalez, Pamela; Oliva, Bárbara; Racordon, Dusan; Garrido, Marcelo; Ibañez, Carolina; Kato, Sumie; Brañes, Jorge; Pizarro, Javier; Barriga, Maria Isabel; Barra, Alejandro; Bravo, Erasmo; Alonso, Catalina; Bustamente, Eva; Cuello, Mauricio A.

    2013-01-01

    The use of the type 2 diabetics drug metformin has been correlated with enhanced progression-free survival in ovarian cancer. The literature has speculated that this enhancement is due to the high concentration of metformin directly causing cancer cell death. However, this explanation does not fit with clinical data reporting that the women exposed to constant micromolar concentrations of metformin, as present in the treatment of diabetes, respond better to chemotherapy. Herein, our aim was to examine whether micromolar concentrations of metformin alone could bring about cancer cell death and whether micromolar metformin could increase the cytotoxic effect of commonly used chemotherapies in A2780 and SKOV3 cell lines and primary cultured cancer cells isolated from the peritoneal fluid of patients with advanced ovarian cancer. Our results in cell lines demonstrate that no significant loss of viability or change in cell cycle was observed with micromolar metformin alone; however, we observed cytotoxicity with micromolar metformin in combination with chemotherapy at concentrations where the chemotherapy alone produced no loss in viability. We demonstrate that previous exposure and maintenance of metformin in conjunction with carboplatin produces a synergistic enhancement in cytotoxicity of A2780 and SKOV3 cells (55% and 43%, respectively). Furthermore, in 5 (44%) of the 11 ovarian cancer primary cultures, micromolar metformin improved the cytotoxic response to carboplatin but not paclitaxel or doxorubicin. In conclusion, we present data that support the need for a clinical study to evaluate the adjuvant maintenance or prescription of currently approved doses of metformin during the chemotherapeutic treatment of ovarian cancer. PMID:23653391

  19. Characterization of long-term elution of platinum from carboplatin-impregnated calcium sulfate hemihydrate beads in vitro by two distinct sample collection methods.

    Science.gov (United States)

    Tulipan, Rachel J; Phillips, Heidi; Garrett, Laura D; Dirikolu, Levent; Mitchell, Mark A

    2017-05-01

    OBJECTIVE To characterize long-term elution of platinum from carboplatin-impregnated calcium sulfate hemihydrate (CI-CSH) beads in vitro by comparing 2 distinct sample collection methods designed to mimic 2 in vivo environments. SAMPLES 162 CI-CSH beads containing 4.6 mg of carboplatin (2.4 mg of platinum/bead). PROCEDURES For method 1, which mimicked an in vivo environment with rapid and complete fluid exchange, each of 3 plastic 10-mL conical tubes contained 3 CI-CSH beads and 5 mL of PBS solution. Eluent samples were obtained by evacuation of all fluid at 1, 2, 3, 6, 9, and 12 hours and 1, 2, 3, 6, 9, 12, 15, 18, 22, 26, and 30 days. Five milliliters of fresh PBS solution was then added to each tube. For method 2, which mimicked an in vivo environment with no fluid exchange, each of 51 tubes (ie, 3 tubes/17 sample collection times) contained 3 CI-CSH beads and 5 mL of PBS solution. Eluent samples were obtained from the assigned tubes for each time point. All samples were analyzed for platinum content by inductively coupled plasma-mass spectrometry. RESULTS Platinum was released from CI-CSH beads for 22 to 30 days. Significant differences were found in platinum concentration and percentage of platinum eluted from CI-CSH beads over time for each method. Platinum concentrations and elution percentages in method 2 samples were significantly higher than those of method 1 samples, except for the first hour measurements. CONCLUSIONS AND CLINICAL RELEVANCE Sample collection methods 1 and 2 may provide estimates of the minimum and maximum platinum release, respectively, from CI-CSH beads in vivo.

  20. Cytokine-induced killer cells co-cultured with complete tumor antigen-loaded dendritic cells, have enhanced selective cytotoxicity on carboplatin-resistant retinoblastoma cells.

    Science.gov (United States)

    Wang, Ya-Feng; Kunda, Patricia E; Lin, Jian-Wei; Wang, Han; Chen, Xue-Mei; Liu, Qiu-Ling; Liu, Tao

    2013-05-01

    Retinoblastoma (RB) is a challenging disease that affects mostly young children. Chemical therapy has been shown to have limitations during clinical practice, principally because of the ability of RB to become resistant to the treatment. Nevertheless, chemotherapy is still the main treatment for RB, and immunotherapy has become a promising treatment for most solid tumors with fewer side effects than traditional therapies. In this study, we explored the antitumor effects of cytokine-induced killer (CIK) cells co-cultured with dendritic cells (DCs) pulsed with complete tumor antigens (DC-Ag). Cytotoxicity and specificity were evaluated on an RB cell line (RB-Y79), on a human normal retina cell line (hTERT-RPE1) and a carboplatin-resistant RB cell line. Our results showed that CIK differentiation and cytotoxicity were enhanced by co-culturing CIKs with DC-Ag. Moreover, the co-culture improved the CIK proliferation rate by increasing IL-6 and decreasing IL-10 levels in the culture medium. Furthermore, the use of DC-Ag-CIK cells had little effect on normal retinal cells but high cytotoxicity on RB cells even on carboplatin-resistant retinoblastoma cells. This is the first study showing that DC cells pulsed with the complete tumor antigen improve proliferation, differentiation and cytotoxic activity of CIKs specific not only for RB but also for the chemotherapy-resistant form of the malady. Thus highly efficient immunotherapy based on DC-Ag-CIK cells may be a potential effective and safe mean of treating RB especially to patients where traditional chemical therapy has failed.

  1. An optimal decision making model for supporting week hospital management.

    Science.gov (United States)

    Conforti, Domenico; Guerriero, Francesca; Guido, Rosita; Cerinic, Marco Matucci; Conforti, Maria Letizia

    2011-03-01

    Week Hospital is an innovative inpatient health care organization and management, by which hospital stay services are planned in advance and delivered on week-time basis to elective patients. In this context, a strategic decision is the optimal clinical management of patients, and, in particular, devising efficient and effective admission and scheduling procedures, by tackling different requirements such as beds' availability, diagnostic resources, and treatment capabilities. The main aim is to maximize the patient flow, by ensuring the delivery of all clinical services during the week. In this paper, the optimal management of Week Hospital patients is considered. We have developed and validated an innovative integer programming model, based on clinical resources allocation and beds utilization. In particular, the model aims at scheduling Week Hospital patients' admission/discharge, possibly reducing the length of stay on the basis of an available timetable of clinical services. The performance of the model has been evaluated, in terms of efficiency and robustness, by considering real data coming from a Week Hospital Rheumatology Division. The experimental results have been satisfactory and demonstrate the effectiveness of the proposed approach.

  2. 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/m2 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/m2) 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/m2 per day for 4 days, and melphalan 70 mg/m2 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

  3. 77 FR 22177 - National Volunteer Week, 2012

    Science.gov (United States)

    2012-04-12

    ... April 12, 2012 Part III The President Proclamation 8797--National Volunteer Week, 2012 Proclamation 8798--Pan American Day and Pan American Week, 2012 Proclamation 8799--National Former Prisoner of War... achieving our highest ambitions--from a world-class education for every child to an economy built to last...

  4. IRVINGIA GABONENSIS FOR TWENTY-FOUR WEEKS

    African Journals Online (AJOL)

    Bark Extracts oflrvingia Gubonensis For Twenty-four eeIWeek 2 recorded an increase while week 12 neutrophil count significantly decreased. (Figure 9). The other values ...

  5. 78 FR 71431 - National Family Week, 2013

    Science.gov (United States)

    2013-11-27

    ... sharing a family meal, reading a bedtime story, or creating a holiday tradition, let us carve out a place... November 27, 2013 Part V The President Proclamation 9061--National Family Week, 2013 #0; #0; #0... National Family Week, 2013 By the President of the United States of America A Proclamation Whether united...

  6. Student Time Usage during Fall Reading Week

    Science.gov (United States)

    Cramer, Ken; Pschibul, Rebecca

    2017-01-01

    The present study investigated the time usage and levels of perceived stress, academic workload, and recreation time for 177 students at the University of Windsor before, during, and after Fall Reading Week (FRW). Over a three-week span (at various times of the day), students received a message to their smartphone to complete a 20-second survey…

  7. Vehicle Technologies Fact of the Week 2015

    Energy Technology Data Exchange (ETDEWEB)

    Davis, Stacy C. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Diegel, Susan W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Moore, Sheila A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Boundy, Robert G. [Roltek, Inc., Clinton, TN (United States)

    2016-05-01

    Each week the U.S. Department of Energy s Vehicle Technology Office (VTO) posts a Fact of the Week on their website: http://www1.eere.energy.gov/vehiclesandfuels/ . These Facts provide statistical information, usually in the form of charts and tables, on vehicle sales, fuel economy, gasoline prices, and other transportation-related trends. Each Fact is a stand-alone page that includes a graph, text explaining the significance of the data, the supporting information on which the graph was based, and the source of the data. A link to the current week s Fact is available on the VTO homepage, but older Facts (back to 2009) are archived and still available at: http://energy.gov/eere/vehicles/current-and-past-years-facts-week. Each Fact of the Week website page includes a link to an Excel file. That file contains the data from the Supporting Information section of the page so that researchers can easily use data from the Fact of the Week in their work. Beginning in August of 2015, a subscription list is available on the DOE website so that those interested can sign up for an email to be sent each Monday which includes the text and graphic from the current week s Fact. This report is a compilation of the Facts that were posted during calendar year 2015. The Facts were created, written and prepared by staff in Oak Ridge National Laboratory's Center for Transportation Analysis.

  8. Determination of mRNA, and protein levels of p53, MDM2 and protein kinase CK2 subunits in F9 cells after treatment with the apoptosis-inducing drugs cisplatin and carboplatin

    DEFF Research Database (Denmark)

    Siemer, S; Ornskov, D; Guerra, B

    1999-01-01

    cisplatin and carboplatin on the mRNA and protein levels of p53, MDM2 and CK2 in a murine teratocarcinoma cell line F9. Northern and Western blot analyses were performed and the CK2 activity was determined. The degree of apoptosis after drug treatment was assessed using the TUNEL test. Six hours after...... cisplatin and carboplatin treatment, the RNA level of p53 dropped by 59% +/- 9% and 86% +/- 8% respectively, whereas the observed level of p53 protein rose to 7 and 10 times over the untreated control, respectively. Treatment with 33 microM cisplatin prompted apoptosis as early as 4 h after drug treatment....... More than 50% apoptotic cells were seen after 6 h. We conclude that cisplatin and its second generation drug carboplatin act similarly i.e. both drugs cause a concomitant decrease in p53 mRNA and an increase in p53 protein level. After 4 h treatment with either of the two drugs, p53 levels reach...

  9. Safety and Efficacy of Once-Weekly Exenatide Compared With Insulin Glargine Titrated to Target in Patients With Type 2 Diabetes Over 84 Weeks

    NARCIS (Netherlands)

    Diamant, M.; Van Gaal, L.; Stranks, S.; Guerci, B.; MacConell, L.; Haber, H.; Scism-Bacon, J.; Trautmann, M.

    2012-01-01

    OBJECTIVE - We recently reported that after 26 weeks, exenatide once weekly (EQW) resulted in superior A1C reduction, reduced hypoglycemia, and progressive weight loss compared with daily insulin glargine (IG) in patients with type 2 diabetes who were taking metformin alone or with sulfonylurea.

  10. 75 FR 71005 - American Education Week, 2010

    Science.gov (United States)

    2010-11-22

    ... world's engine of discovery and innovation, my Administration is committed to ensuring that America has..., career, and life. This week, let us reaffirm the importance of education and recognize that we all share...

  11. Graduate Education Week celebrates successes, possibilities

    OpenAIRE

    Harris, Sally L.

    2005-01-01

    During this year's Graduate Education Week at Virginia Tech March 21-25, participants will celebrate graduate-student successes, such as student research, and explore future possibilities for graduate education, including a new Graduate Life Center.

  12. 4-Week Gluten-Free Meal Plan

    Science.gov (United States)

    ... beans, buttermilk drop biscuits, and coleslaw Weekly Dessert: Frozen yogurt with hot fudge or caramel 7 www.gluten. ... potatoes (Su, Th) Sliced cheese (T, Sa) Vanilla frozen yogurt (dessert) Bacon (Sa) Chicken breast, boneless & skinless (M) ...

  13. 75 FR 71519 - National Family Week, 2010

    Science.gov (United States)

    2010-11-24

    ... Middle Class, chaired by Vice President Joe Biden, which aims to protect working families' economic... loved ones safe here at home and abroad. This National Family Week, we recognize the importance of the...

  14. Bi-weekly waterfowl survey data entry

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Data sheet for the entry of bi-weekly waterfowl survey data from the state of Kansas. This Excel file contains the data entry sheet and a chart displaying waterfowl...

  15. A multicenter, non-randomized, phase II study of docetaxel and carboplatin administered every 3 weeks as second line chemotherapy in patients with first relapse of platinum sensitive epithelial ovarian, peritoneal or fallopian tube cancer

    DEFF Research Database (Denmark)

    Wang, Yun; Herrstedt, Jørn; Havsteen, Hanne

    2014-01-01

    of 398 cycles were given. Grade 3/4 neutropenia was seen in 80% (59 of 74) patients with an incidence of febrile neutropenia of 16%. Grade 2/3 sensory peripheral neuropathy occurred in 7% of patients, but no grade 4 sensory peripheral neuropathy was observed. Sixty patients were evaluable for response...... of platinum-sensitive ovarian, peritoneal and Fallopian tube cancer. The major toxicity was neutropenia, while the frequency of peripheral neuropathy was low....

  16. Lycopene reduces ovarian tumor growth and intraperitoneal metastatic load.

    Science.gov (United States)

    Holzapfel, Nina Pauline; Shokoohmand, Ali; Wagner, Ferdinand; Landgraf, Marietta; Champ, Simon; Holzapfel, Boris Michael; Clements, Judith Ann; Hutmacher, Dietmar Werner; Loessner, Daniela

    2017-01-01

    Mutagens like oxidants cause lesions in the DNA of ovarian and fallopian tube epithelial cells, resulting in neoplastic transformation. Reduced exposure of surface epithelia to oxidative stress may prevent the onset or reduce the growth of ovarian cancer. Lycopene is well-known for its excellent antioxidant properties. In this study, the potential of lycopene in the prevention and treatment of ovarian cancer was investigated using an intraperitoneal animal model. Lycopene prevention significantly reduced the metastatic load of ovarian cancer-bearing mice, whereas treatment of already established ovarian tumors with lycopene significantly diminished the tumor burden. Lycopene treatment synergistically enhanced anti-tumorigenic effects of paclitaxel and carboplatin. Immunostaining of tumor and metastatic tissues for Ki67 revealed that lycopene reduced the number of proliferating cancer cells. Lycopene decreased the expression of the ovarian cancer biomarker, CA125. The anti-metastatic and anti-proliferative effects were accompanied by down-regulated expression of ITGA5, ITGB1, MMP9, FAK, ILK and EMT markers, decreased protein expression of integrin α5 and reduced activation of MAPK. These findings indicate that lycopene interferes with mechanisms involved in the development and progression of ovarian cancer and that its preventive and therapeutic use, combined with chemotherapeutics, reduces the tumor and metastatic burden of ovarian cancer in vivo.

  17. Ethylbenzene: 4- and 13-week rat oral toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Mellert, Werner; Deckardt, Klaus; Kaufmann, Wolfgang; Ravenzwaay, Bennard van [BASF Aktiengesellschaft, Department of Product Safety, Ludwigshafen (Germany)

    2007-05-15

    Ethylbenzene was administered to groups of male and female Wistar rats by gavage for 4 (n = 5/dose/sex) and 13 weeks (n = 10/dose/sex) (OECD 408) at doses of 0 (vehicle control), 75, 250, and 750 mg/kg bodyweight/day (mg/kg bw/day), administered am/pm as half doses. In the 4-week study, {>=}250 mg/kg increased serum alanine aminotransferase, total bilirubin and cholesterol, liver weights and centrilobular hepatocyte hypertrophy, and kidney weights; males also had post-dose salivation, increased urinary epithelial cell casts and cells, and hyaline droplet nephropathy. In the 13-week study, {>=}250 mg/kg increased water consumption and produced post-dose salivation. Liver-related effects: increased serum alanine aminotransferase, gamma-glutamyltransferase, bilirubin, total protein, albumin and globulins, cholesterol, liver weights and centrilobular hepatocyte hypertrophy, and reduced prothrombin times. Kidney-related effects: increased serum potassium, calcium, magnesium, kidney weights, and (males only) urea and hyaline droplets in renal tubular epithelium, and reduced sodium (females only); creatinine was reduced in 750 mg/kg males. The NOAEL of ethylbenzene in these studies, based on hepatocyte hypertrophy and liver- and kidney-related clinical chemistry changes, was 75 mg/kg bw/day. (orig.)

  18. Functional and Histopathological Changes in Muscle after 6-weeks Repetitive Strain Injury: A 10-week Follow Up of Aged Rats

    Directory of Open Access Journals (Sweden)

    Taher Afshar Nezhad

    2016-12-01

    Full Text Available ABSTRACT: Repetitive eccentric contractions are associated with repetitive strain injury (RSI of muscle and tendon and were accompanied by an increase in extracellular matrix (ECM, atrophy, and reduce force. However, a research gap exists regarding the effect of aging on injury susceptibility and recovery to repetitive strain exposures. In this paper, we examined the response of gastrocnemius of aged rats to 6weeks chronic strain injury followed 10 weeks without specific rehabilitation. 16 elderly male rats divided to two groups: control (n=8 and RSI (n=8. RSI group underwent 6weeks (5 days/week of fast velocity submaximal eccentric contractions. After 4 and 10 weeks' post-injury non-active rest, isometric force, muscle wet mass, and histopathological changes of gastrocnemius muscle in RSI-model and control groups were measured. After 4 weeks' post-injury raw and relative (percent to body weight measures of isometric force and wet muscle mass of gastrocnemius in control group are significantly greater than RSI group. force deficit was reduction Masson Trichrome and Hematoxylin & eosin stains also showed histopathologic changes were present only in RSI group that included increase in fibrosis and non-contractile area, and decrease of myofiber area. After 10 weeks of injury protocol, decrease in IF of gastrocnemius (8% and 6% for raw and relative measures respectively were remained in RSI-Re group, but muscle wet mass was recovered. Also, myofiber area and non-contractile area were not fully recovered after 10-week rest in RSI-Re group (+2.77% and -3.6% respectively.  Six weeks repeated bouts of moderate eccentric contractions caused in the rat gastrocnemius muscle decreases in muscular size and strength and myofiber area, whereas the non-contractile area and fibrosis was markedly increased. These results suggest that in aged rat force deficit and histopathological changes of gastrocnemius muscle after chronic strain injury were reminded after

  19. Phase I/II study of induction chemotherapy using carboplatin plus irinotecan and sequential thoracic radiotherapy (TRT) for elderly patients with limited-disease small-cell lung cancer (LD-SCLC): TORG 0604.

    Science.gov (United States)

    Misumi, Yuki; Okamoto, Hiroaki; Sasaki, Jiichiro; Masuda, Noriyuki; Ishii, Mari; Shimokawa, Tsuneo; Hosomi, Yukio; Okuma, Yusuke; Nagamata, Makoto; Ogura, Takashi; Kato, Terufumi; Sata, Masafumi; Otani, Sakiko; Takakura, Akira; Minato, Koichi; Miura, Yosuke; Yokoyama, Takuma; Takata, Saori; Naoki, Katsuhiko; Watanabe, Koshiro

    2017-05-26

    The role of irinotecan for elderly patients with LD-SCLC has been unclear, and the timing of TRT combined with chemotherapy has not been fully evaluated. Patients aged > 70 years with untreated, measurable, LD-SCLC, performance status (PS) 0-2, and adequate organ function were eligible. Treatment consisted of induction with carboplatin on day 1 and irinotecan on days 1 and 8, every 21 days for 4 cycles, and sequential TRT (54Gy in 27 fractions). Carboplatin doses were based on AUC of 4 and 5 (levels 1 and 2, respectively), with a fixed irinotecan dose (50 mg/m2). Primary objective of the phase II study was overall responce rate. Forty-three patients were enrolled and forty-one were finally analyzed (median age: 75 years [range 70-86 years); males 31; PS 0/1/2, n = 22/18/1]. Two patients were excluded because of protocol violation (ascertained to be extensive disease). Twelve patients were accrued at phase I and the number of patients with carboplatin dose-limiting toxicities at levels-1 (n = 6) and -2 (n = 6) were 1(grade 3 hypertension) and 2 (grade 4 thrombocytopenia), respectively. The phase II trial was expanded to 29 additional patients receiving the level 1 carboplatin dose, total of 35 patients. The median number of chemotherapy cycles was 4 (range 1-4), and the median radiation dose was 54Gy (range 36-60). Toxicities were generally mild. There were 4 complete and 27 partial responses (response rate 88.6%). With a median follow-up of 52 months, the median progression-free and overall survival times of phase II were 11.2 and 27.1 months, respectively. Induction chemotherapy of carboplatin plus irinotecan and sequential TRT was well tolerated and effective for elderly patients with LD-SCLC. Additional confirmatory studies are warranted. Trial registration number: UMIN000007352 Name of registry: UMIN. Date of registration: 1/Dec/2006. Date of enrolment of the first participant to the trial: 6/Feb/2007. Clinical trial registration date: 1/Feb/2006

  20. Intensity-modulated whole abdomen irradiation following adjuvant carboplatin/taxane chemotherapy for FIGO stage III ovarian cancer. Four-year outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Rochet, Nathalie; Lindel, Katja; Katayama, Sonja; Schubert, Kai; Herfarth, Klaus; Harms, Wolfgang; Debus, Juergen [Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); University of Heidelberg, Department of Radiation Oncology, Heidelberg (Germany); Schneeweiss, Andreas [University of Heidelberg, Nationales Centrum fuer Tumorerkrankungen (NCT), Heidelberg (Germany); Sohn, Christoph [University of Heidelberg, Department of Gynecology, Heidelberg (Germany)

    2015-07-15

    A prospective study to assess toxicity and survival outcomes after intensity-modulated whole-abdominal irradiation (IM-WAI) following surgery and adjuvant intravenous carboplatin/taxane chemotherapy in advanced FIGO stage III ovarian cancer. Between 2006 and 2009, 16 patients with optimally resected FIGO stage III ovarian cancer, who had received six cycles of adjuvant carboplatin/taxane chemotherapy were treated with consolidation IM-WAI. Radiotherapy was delivered to a total dose of 30 Gy in 1.5-Gy fractions, using step-and-shoot (n = 3) or helical tomotherapy (n = 13). The first 10 patients were treated within a phase I trial; the following patients received the same treatment modality. The target volume included the entire peritoneal cavity, the diaphragm, the liver capsule, and the pelvic and para-aortic node regions. Organs at risk were kidneys, liver, heart, and bone marrow. Median follow-up was 44 months (range 19.2-67.2 months). No grade 4 toxicities occurred during IM-WAI. Common Toxicity Criteria for Adverse Events (CTCAE) grade 3 toxicities were: diarrhea (25 %), leucopenia (19 %), nausea/vomiting (6 %), and thrombocytopenia (6 %). No toxicity-related treatment break was necessary. Small bowel obstruction occurred in a total of 6 patients: in 3 cases (19 %) due to postsurgical adhesions and in 3 cases due to local tumor recurrence (19 %). Median recurrence-free survival (RFS) was 27.6 months (95 % confidence interval, CI = 24-44 months) and median overall survival (OS) was 42.1 months (95 %CI = 17-68 months). The peritoneal cavity was the most frequent site of initial failure. Consolidation IM-WAI following surgery and adjuvant chemotherapy is feasible and can be performed with manageable acute and late toxicity. The favorable RFS outcome is promising and justifies further clinical trials. (orig.) [German] Es wurden Akut- und Langzeittoxizitaet sowie Ueberlebensdaten der konsolidierenden intensitaetsmodulierten Ganzabdomenbestrahlung (&apos

  1. Drug Dose Per Kilogram Lean Body Mass Predicts Hematologic Toxicity From Carboplatin-Doublet Chemotherapy in Advanced Non-Small-Cell Lung Cancer.

    Science.gov (United States)

    Sjøblom, Bjørg; Benth, Jūratė Šaltytė; Grønberg, Bjørn H; Baracos, Vickie E; Sawyer, Michael B; Fløtten, Øystein; Hjermstad, Marianne J; Aass, Nina; Jordhøy, Marit

    2017-03-01

    Variations in lean body mass (LBM) have been suggested to explain variations in toxicity from systemic cancer treatment. We investigated if drug doses per kilogram of LBM were associated with severe hematologic toxicity (HT) in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) enrolled onto randomized trials comparing first-line carboplatin-doublets. Patients received carboplatin (AUC [area under the plasma concentration vs. time curve] = 5) plus either pemetrexed 500 mg/m2, gemcitabine 1000 mg/m2, or vinorelbine 60 mg/m2. LBM was estimated from the cross-sectional muscle area at the third lumbar vertebra on computed tomographic scans. Administered doses on day 1, first cycle, were recalculated as milligram of drug per kilogram of LBM. Primary outcome was Common Terminology Criteria for Adverse Events version 3.0 grade 3/4 HT after cycle 1. Data from 424 patients were analyzed. Mean age was 65 years, 57% were men, and 78% had stage IV disease. Despite dose individualization by body surface area for the nonplatinum drugs, mean (range) doses expressed as mg/kg LBM showed ∼3-fold range: gemcitabine 38.0 (22.5-61.7) mg/kg LBM, pemetrexed 19.1 (8.1-27.9) mg/kg LBM, and vinorelbine 2.4 (1.4-3.6) mg/kg LBM. For these drugs, dose per kilogram of LBM was associated with HT in adjusted multivariate models (P = .004). Taking mean dose per kilogram LBM for each drug as reference, a 1% increase (odds ratio [OR] = 1.03; 95% confidence interval [CI], 1.01-1.06) or 1% decrease (OR = 0.97; 95% CI, 0.95-0.99) was associated with altered risk of grade 3/4 HT. For doses > 20% above and below mean (14% and 15% of patients, respectively) the risk of grade 3/4 HT was almost doubled (OR = 1.93, 95% CI, 1.21-3.10) and halved (OR = 0.52; 95% CI, 0.32-0.83), respectively. Dose per kilogram of LBM varied considerably and was an independent predictor of HT. Computed tomography-defined LBM may provide a future basis for better dose individualization. Copyright © 2016

  2. Vehicle Technologies Fact of the Week 2013

    Energy Technology Data Exchange (ETDEWEB)

    Davis, Stacy Cagle [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Williams, Susan E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Moore, Sheila A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Boundy, Robert Gary [Roltek, Inc., Clinton, TN (United States)

    2014-03-01

    Each week the U.S. Department of Energy s Vehicle Technology Office (VTO) posts a Fact of the Week on their website: http://www1.eere.energy.gov/vehiclesandfuels/ . These Facts provide statistical information, usually in the form of charts and tables, on vehicle sales, fuel economy, gasoline prices, and other transportation-related trends. Each Fact is a stand-alone page that includes a graph, text explaining the significance of the data, the supporting information on which the graph was based, and the source of the data. A link to the current week s Fact is available on the VTO homepage, but older Facts are archived and still available at: http://www1.eere.energy.gov/vehiclesandfuels/facts/. This report is a compilation of the Facts that were posted during calendar year 2013. The Facts were written and prepared by staff in Oak Ridge National Laboratory's Center for Transportation Analysis.

  3. Planet Earth week featured at Fall Meeting

    Science.gov (United States)

    The Fall Meeting has been dubbed “Planet Earth Week,” in part to salute the upcoming 7-week PBS television series and university course that will be previewed at the meeting. At least four of the seven 1-hour segments of “Planet Earth” will be shown daily at the the Fall Meeting. AGU provided some of the seed money for the new series, which will have its television premiere on Wednesday, January 22, 1986, on PBS at 9 P.M. EST.

  4. The risk of perinatal mortality with each week of expectant management in obese pregnancies.

    Science.gov (United States)

    Yao, Ruofan; Schuh, Brittany L; Caughey, Aaron B

    2017-09-27

    The risk of stillbirth associated with maternal obesity increases with gestational age; however, it is unclear if earlier delivery reduces the overall perinatal mortality rate. Our objective was to compare the risk of perinatal mortality associated with each additional week of expectant management to that of immediate delivery. This was a retrospective cohort study of singleton non-anomalous births in Texas between 2006 and 2011. Analyses were stratified based on maternal pre-pregnancy BMI class. For each BMI class, we calculated the rate of neonatal death and stillbirth at each week of gestation from 34 to 41 weeks. A composite risk of perinatal mortality associated with 1 week of expectant management was estimated combining the stillbirth rate of the current week and the neonatal death rate of the following week. This was compared with the rate of neonatal death of the current week. After all exclusions, 2,149,771 births remained for analysis. In the normal weight group, stillbirth risk increased from 0.8 per 10,000 births at 34 weeks to 5.7 per 10,000 births at 42 weeks, whereas the neonatal death risk decreased from 76.5 per 10,000 births at 34 weeks to 30.4 per 10,000 births at 42 weeks, there were no differences between expectant management and delivery for any gestational week. In the obese group, stillbirth risk increased from 1.8 per 10,000 births at 34 weeks to 10.5 per 10,000 births at 42 weeks, whereas the neonatal death risk decreased from 67.7 per 10,000 births at 34 weeks to 26.2 per 10,000 births at 42 weeks, the perinatal mortality risk favored delivery at 39 weeks (RR: 1.17; 99% CI: 1.01-1.36) and not thereafter. In contrast, in the morbidly obese group, stillbirth risk increased from 8.8 per 10,000 births at 34 weeks to 83.7 per 10,000 births at 42 weeks, whereas the neonatal death risk decreased from 63.6 per 10,000 births at 34 weeks to 15.5 per 10,000 births at 42 weeks, the perinatal mortality risk favored delivery from 38 weeks (RR: 1.53; 99

  5. First week nutrition for broiler chickens

    NARCIS (Netherlands)

    Lamot, David

    2017-01-01

    During the first week of life, broiler chickens undergo various developmental changes that are already initiated during incubation. Ongoing development of organs such as the gastro- intestinal tract and the immune system may affect the nutritional requirements during this age period. Despite the

  6. IDRC celebrates Global Entrepreneurship Week | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2016-11-10

    Nov 10, 2016 ... Thousands of events and competitions in 160 countries mark Global Entrepreneurship Week every November. ... The study is the first in a series to examine the root causes of youth unemployment, gender bias, and enterprise fragility in Ethiopia and it will contribute to the design of lasting and efficient ...

  7. 77 FR 31151 - World Trade Week, 2012

    Science.gov (United States)

    2012-05-24

    ... universities, pioneering entrepreneurs, and productive workers, we have met a global demand for goods and services designed and produced by Americans. During World Trade Week, we reaffirm the essential role exports play in creating jobs and growing our economy. Two years ago, my Administration launched the...

  8. Persian: 12 Week Course. Volume 6: Dictionary.

    Science.gov (United States)

    Defense Language Inst., Monterey, CA.

    This two-way dictionary is a supplement to the Persian 12-Week Course. It consists of a Persian-English and an English-Persian section. Phonetic symbols are used for indicating Persian pronunciations. In addition to vocabulary, the Persian-English section contains idioms and expressions. With the infinitives, the present and past simple roots of…

  9. 78 FR 44867 - Captive Nations Week, 2013

    Science.gov (United States)

    2013-07-24

    ... worldwide have pledged themselves to a Universal Declaration of Human Rights. Corrupt dictatorships have... freedom's march and widening the circle of opportunity for all. Our commitment to universal rights is also... privileged few. Captive Nations Week is an opportunity to reaffirm America's role in advancing human rights...

  10. Rituximab plus Ifosfamide, Carboplatin and Etoposide for T-Cell/Histiocyte-Rich B-Cell Lymphoma Arising in Nodular Lymphocyte-Predominant Hodgkin’s Lymphoma

    Directory of Open Access Journals (Sweden)

    Hyung-Chul Park

    2012-08-01

    Full Text Available A small subset of patients with nodular lymphocyte-predominant Hodgkin’s lymphoma (NLPHLs develop a non-Hodgkin lymphoma either concurrently or subsequently, usuallyT-cell/histiocyte-rich B-cell lymphomas (T/HRBCL, which are subtypes of diffuse large B-cell lymphomas (DLBCL. The standard treatment of DLBCL patients is rituximab-based chemotherapy with cyclophosphamide, adriamycin, vincristine and prednisolone. However, the administration of this chemotherapy regimen to patients with DLBCL arising in NLPHL brings concern about the cardiac toxicity of anthracycline because the majority of these patients had already received anthracycline-based chemotherapy with doxorubicin, bleomycin, vinblastine and dacarbazine at the time of NLPHL. Herein, we report 2 patients with sequential transformation of NLPHL to T/HRBCL. They initially presented with limited-stage NLPHL and subsequently developed T/HRBCL after 16 and 8 months, respectively. At the time of T/HRBCL, they were treated with rituximab, ifosfamide, carboplatin and etoposide, and complete responses were obtained.

  11. Comparison of intracerebral delivery of carboplatin and photon irradiation with an optimized regimen for boron neutron capture therapy of the F98 rat glioma

    Energy Technology Data Exchange (ETDEWEB)

    Barth, Rolf F., E-mail: rolf.barth@osumc.edu [Department of Pathology, Ohio State University, 165 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210 (United States); Yang Weilian; Huo Tianyao [Department of Pathology, Ohio State University, 165 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210 (United States); Riley, Kent J.; Binns, Peter J. [Nuclear Reactor Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Grecula, John C., E-mail: john.grecula@osumc.edu [James Cancer Hospital and Solove Research Institute, Department of Radiation Oncology, Ohio State University, Columbus, OH, 43210 (United States); Gupta, Nilendu, E-mail: nilendu.gupta@osumc.edu [James Cancer Hospital and Solove Research Institute, Department of Radiation Oncology, Ohio State University, Columbus, OH, 43210 (United States); Rousseau, Julia, E-mail: julia.rousseau@yahoo.fr [INSERM, U836, Institute of Neurosciences, Grenoble (France); Elleaume, Helene, E-mail: h.elleaume@esrf.fr [INSERM, U836, Institute of Neurosciences, Grenoble (France)

    2011-12-15

    In this report we have summarized our studies to optimize the delivery of boronophenylalanine (BPA) and sodium borocaptate (BSH) for boron neutron capture therapy (BNCT) of F98 glioma bearing rats. These results have been compared to a chemoradiotherapeutic approach using the same tumor model. The best survival data from our BNCT studies were obtained using a combination of BPA and sodium borocaptate BSH administered via the internal carotid artery, in combination with blood-brain barrier disruption (BBB-D). This treatment resulted in a mean survival time (MST) of 140 d with a 25% cure rate. The other approach combined intracerebral administration of carboplatin by either convection enhanced delivery (CED) or Alzet pump infusion, followed by external beam photon irradiation. This resulted in MSTs of 83 d and 112 d, respectively, with a cure rate of 40% for the latter. However, a significant problem that must be solved for both BNCT and this new chemoradiotherapeutic approach is how to improve drug uptake and microdistribution within the tumor.

  12. Efficacy of doxorubicin after progression on carboplatin and paclitaxel in advanced or recurrent endometrial cancer: a retrospective analysis of patients treated at the Brazilian National Cancer Institute (INCA).

    Science.gov (United States)

    Moreira, Emeline; Paulino, Eduardo; Ingles Garces, Álvaro Henrique; Fontes Dias, Mariane S; Saramago, Marcos; de Moraes Lino da Silva, Flora; Thuler, Luiz Claudio Santos; de Melo, Andréia Cristina

    2018-01-31

    The treatment of endometrial cancer (EC) is challenging. There is no standard of care for patients who progressed after carboplatin and paclitaxel (CT) and all available drugs show a small response and poor long-term survival in this scenario. The objective of this study was to evaluate the efficacy and toxicity profile of palliative doxorubicin after progression to CT therapy in advanced or recurrent EC. A retrospective review of the Brazilian National Cancer Institute database between 2009 and 2013 was performed, and all patients with recurrent and advanced EC treated with palliative doxorubicin after progression on CT were included. Progression-free survival (PFS), overall survival (OS), objective response rates as well as toxicity were evaluated. A total of 33 patients were enrolled, with a median age of 65.7 years. Objective responses were documented in 12.1% (3.0% of complete responses and 9.1% of partial responses). The median PFS was 4.4 months, and the median OS was 8.1 months for patients exposed to doxorubicin. The most common adverse event was anemia observed in 60.6% of patients. This retrospective study suggests that doxorubicin has a modest activity in patients with advanced or recurrent EC after treatment with CT.

  13. Assessment of quality of life in patients with advanced non-small cell lung carcinoma treated with a combination of carboplatin and paclitaxel

    Directory of Open Access Journals (Sweden)

    Camila Uanne Resende Avelino

    2015-04-01

    Full Text Available OBJECTIVE: Non-small cell lung carcinoma (NSCLC is the most common type of lung cancer. Most patients are diagnosed at an advanced stage, palliative chemotherapy therefore being the only treatment option. This study was aimed at evaluating the health-related quality of life (HRQoL of advanced-stage NSCLC patients receiving palliative chemotherapy with carboplatin and paclitaxel. METHODS: This was a multiple case study of advanced-stage NSCLC outpatients receiving chemotherapy at a public hospital in Rio de Janeiro, Brazil. The European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire was used in conjunction with its supplemental lung cancer-specific module in order to assess HRQoL. RESULTS: Physical and cognitive functioning scale scores differed significantly among chemotherapy cycles, indicating improved and worsened HRQoL, respectively. The differences regarding the scores for pain, loss of appetite, chest pain, and arm/shoulder pain indicated improved HRQoL. CONCLUSIONS: Chemotherapy was found to improve certain aspects of HRQoL in patients with advanced-stage NSCLC.

  14. Simultaneous Integrated Boost Using Intensity-Modulated Radiotherapy Compared With Conventional Radiotherapy in Patients Treated With Concurrent Carboplatin and 5-Fluorouracil for Locally Advanced Oropharyngeal Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Clavel, Sebastien, E-mail: sebastien.clavel@umontreal.ca [Department of Radiation Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Nguyen, David H.A.; Fortin, Bernard [Department of Radiation Oncology, Hopital Maisonneuve-Rosemont, Montreal, QC (Canada); Despres, Philippe [Department of Radiation Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Khaouam, Nader [Department of Radiation Oncology, Hopital Maisonneuve-Rosemont, Montreal, QC (Canada); Donath, David [Department of Radiation Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Soulieres, Denis [Department of Medical Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Guertin, Louis [Department of Head and Neck Surgery, Centre Hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Nguyen-Tan, Phuc Felix [Department of Radiation Oncology, Hopital Maisonneuve-Rosemont, Montreal, QC (Canada)

    2012-02-01

    Purpose: To compare, in a retrospective study, the toxicity and efficacy of simultaneous integrated boost using intensity-modulated radiotherapy (IMRT) vs. conventional radiotherapy (CRT) in patients treated with concomitant carboplatin and 5-fluorouracil for locally advanced oropharyngeal cancer. Methods and Materials: Between January 2000 and December 2007, 249 patients were treated with definitive chemoradiation. One hundred patients had 70 Gy in 33 fractions using IMRT, and 149 received CRT at 70 Gy in 35 fractions. Overall survival, disease-free survival, and locoregional control were estimated using the Kaplan-Meier method. Results: Median follow-up was 42 months. Three-year actuarial rates for locoregional control, disease-free survival, and overall survival were 95.1% vs. 84.4% (p = 0.005), 85.3% vs. 69.3% (p = 0.001), and 92.1% vs. 75.2% (p < 0.001) for IMRT and CRT, respectively. The benefit of the radiotherapy regimen on outcomes was also observed with a Cox multivariate analysis. Intensity-modulated radiotherapy was associated with less acute dermatitis and less xerostomia at 6, 12, 24, and 36 months. Conclusions: This study suggests that simultaneous integrated boost using IMRT is associated with favorable locoregional control and survival rates with less xerostomia and acute dermatitis than CRT when both are given concurrently with chemotherapy.

  15. Citizen weeks or the psychologizing of citizenship.

    Science.gov (United States)

    Loredo-Narciandi, José Carlos; Castro-Tejerina, Jorge

    2013-02-01

    Arland Deyett Weeks (1871-1936) was an American educator and social reformer who published The Psychology of Citizenship in 1917 with the intention of compiling the psychological, psychobiological, and psychosocial knowledge needed for governing modern democratic Western industrialized societies, as well as offering suggestions for intervention and social reform in the educational, legal, and occupational domains. His point of view can be placed within the progressive social and intellectual movement that characterized the policies of the United States in the first decade of the 20th century. His sociopolitical ideas were fed by transcendental and pragmatic sources, especially with respect to the way of dealing with tension between the individual and the collective. Modern psychological techniques (occupational, educational, legal psychology, etc.) nourished his reform program. In this article, we contextualize Weeks's book within these ideas and show its historical significance in the sociocultural and intellectual context that gave it meaning.

  16. Intracorneal blood removal six weeks after canaloplasty

    Directory of Open Access Journals (Sweden)

    Alberto Rossetti

    2013-01-01

    Full Text Available In a 71-year-old patient with bilateral open-angle glaucoma, intracorneal blood was found after a canaloplasty procedure in the right eye. Six weeks after surgery on ultrasound biomicroscopy examination, liquified blood and blood clots could be observed nasally in the deep corneal stroma close to the Descemet′s membrane. The intracorneal blood was washed out with balanced saline solution following deep corneal incision and lamellar dissection. Descemet′s membrane was reattached with air injection into the anterior chamber. Two months later, visual acuity improved to 20/50, intraocular pressure was 16 mm Hg without medication and confocal microscopy showed deep stromal folds and limited endothelial cell loss. Viscoelastic entering the cornea at Schwalbe′s line and reflux of blood from the collector channels to Schlemm′s canal can account for corneal hematoma. Even six weeks after canaloplasty, successful blood removal could be fulfilled without rupturing the Descemet′s membrane.

  17. Vehicle Technologies’ Fact of the Week 2013

    Energy Technology Data Exchange (ETDEWEB)

    Davis, Stacy Cagle [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Diegel, Susan W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Moore, Sheila A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Boundy, Robert Gary [Roltek, Inc., Clinton, TN (United States)

    2014-04-01

    Each week the U.S. Department of Energy’s Vehicle Technology Office (VTO) posts a Fact of the Week on their website: http://www1.eere.energy.gov/vehiclesandfuels/ . These Facts provide statistical information, usually in the form of charts and tables, on vehicle sales, fuel economy, gasoline prices, and other transportation-related trends. Each Fact is a stand-alone page that includes a graph, text explaining the significance of the data, the supporting information on which the graph was based, and the source of the data. A link to the current week’s Fact is available on the VTO homepage, but older Facts are archived and still available at: http://www1.eere.energy.gov/vehiclesandfuels/facts/. This report is a compilation of the Facts that were posted during calendar year 2013. The Facts were written and prepared by staff in Oak Ridge National Laboratory's Center for Transportation Analysis.

  18. First week nutrition for broiler chickens

    OpenAIRE

    Lamot, David

    2017-01-01

    During the first week of life, broiler chickens undergo various developmental changes that are already initiated during incubation. Ongoing development of organs such as the gastro- intestinal tract and the immune system may affect the nutritional requirements during this age period. Despite the residual yolk that is available at hatch and that may provide nutritional support during the first days after hatch, the growth performance may be affected by the time in between hatch and first feed ...

  19. Golden Week Tourism and Beijing City

    OpenAIRE

    Zhao, Jian-Tong; Zhu, Wen-Yi

    2012-01-01

    Tourist Industry plays an important role in Beijing’s national economy and social development. After the Beijing Olympic Games, the urban space of Beijing has turned into a new development stage, and the city’s tourist attractiveness has been further improved. Beijing has been the hottest tourist city nationwide in National Day Golden Week for years running, and the new characteristics and problems of its urban space are concentratedly shown during the holiday. Through a brief summary of the ...

  20. One week ahead short term load forecasting

    Energy Technology Data Exchange (ETDEWEB)

    Baharudin, Z.; Kamel, N. [Petronas Technology Univ., Perak (Malaysia). Dept. of Electrical and Electronics

    2007-07-01

    Autoregressive (AR) Burg techniques were used to optimize week-ahead short-term load forecasting for Malaysia's electricity grid. The digital signal processing method used historical data signals to predict performance over future intervals. The predicted value was hourly to a maximum of 168 hours. The AR model provided an improved mean absolute percentage error (MAPE) values for short term load forecasts (STLF). The model was then compared with other models of the electricity grids of both Malaysia and New South Wales (NSW). A time series model was used to simulate discrete-time stochastic progresses using linear difference equations of complex coefficients. An autoregressive moving average (ARMA) model was generated by filtering unit variance white noise with a causal linear shift-invariant filter. The Burg's spectrum estimation method computed reflection coefficients sequentially by minimizing mean-squares of the forward and backward prediction errors. The performance of the different parametric techniques on week-ahead forecasts were investigated using both the ARMA and AR models. Results of the evaluation demonstrated that the average value of MAPE over a 7-day period was 54 per cent less for the AR models than for the ARMA model. Fourteen weeks of data were used to develop the 1-week forecasts. It was concluded that removing periods of load variation and weekends from the data improve the accuracy of the ARMA model by 50 per cent, while the accuracy of the AR model was improved by only 40 per cent. 20 refs., 8 tabs., 7 figs.

  1. Medical image of the week: empyema necessitans

    Directory of Open Access Journals (Sweden)

    Tey KR

    2015-12-01

    Full Text Available No abstract available. Article truncated after 150 words. A previously healthy 46-year-woman was evaluated for two week history of right shoulder pain, associated pleuritic chest pain and dyspnea. Chest radiograph showed right apical mass (Figure 1A. Imaging showed loculated fluid collection with extension into the soft tissues of the adjacent right chest wall suggestive of empyema necessitans (Figure 1B. Chest Tube placement was done along with broad spectrum antibiotics. Blood and pleural fluid cultures showed methicillin-resistant Staphylococcus aureus (MRSA. Due to persistence of loculation despite antibiotics, she underwent a video-assisted-thoracoscopic surgery (VATS for decortication and further drainage of the effusion. Symptoms and radiologic findings improved and she was discharged with intravenous antibiotics to complete a six week course. Chest imaging at six week period showed complete resolution (Figure 2. Empyema necessitans, defined by the extension of an empyema through the parietal pleura, into surrounding tissue is becoming rare with the routine drainage of empyema and antibiotics use. Common ...

  2. A busy week for Arts@CERN

    CERN Document Server

    Antonella Del Rosso

    2015-01-01

    Last week, Semiconductor – the winners of the Collide@CERN Ars Electronica award for 2015 – and artists Francesco Mariotti and José­-Carlos Mariátegui visited CERN and met the scientists.   Ruth Jarman (left) and Joe Gerhardt (right) of Semiconductor with Peter Jenni, one of the scientists they met during their visit to ATLAS.   Just a few weeks ago, Ruth Jarman and Joe Gerhardt, two English artists collaborating under the name Semiconductor, were awarded the Collide@CERN Ars Electronica prize for 2015. Last week, they came on their first visit to CERN to meet the scientists and select their scientific partner in preparation for their residency. They will soon begin a two-month residency at CERN before going to Linz (Austria), where they will spend a month at the Ars Electronica Futurelab. During their residency, the artists aim to create a digital artwork elaborating on the n...

  3. A phase IB dose-escalation study of the safety and pharmacokinetics of pictilisib in combination with either paclitaxel and carboplatin (with or without bevacizumab) or pemetrexed and cisplatin (with or without bevacizumab) in patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Soria, Jean-Charles; Adjei, Alex A; Bahleda, Rastilav; Besse, Benjamin; Ferte, Charles; Planchard, David; Zhou, Jing; Ware, Joseph; Morrissey, Kari; Shankar, Geetha; Lin, Wei; Schutzman, Jennifer L; Dy, Grace K; Groen, Harry J M

    2017-11-01

    The phosphatidylinositol 3-kinase (PI3K) pathway is a potential therapeutic target in non-small cell lung cancer (NSCLC). This study aimed to evaluate the pan-PI3K inhibitor pictilisib in combination with first-line treatment regimens that were the standard of care at the time of study, in patients with NSCLC. A 3 + 3 dose-escalation study was performed using a starting daily dose of 60 mg pictilisib on days 1-14 of a 21-day cycle. Depending on bevacizumab eligibility and NSCLC histology, patients also received either paclitaxel + carboplatin or pemetrexed + cisplatin, ± bevacizumab every 3 weeks. The primary objectives of the study were to assess safety and tolerability and to identify dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD) and a recommended phase II dose (RP2D), for each combination. All 66 treated patients experienced at least one adverse event (AE). Grade ≥III AEs, serious AEs and deaths occurred in 57 (86.4%), 56 (84.8%) and 9 (13.6%) patients, respectively. Three patients reported DLTs across the four arms of the study. The MTD was not reached in any arm and the RP2D of pictilisib was determined to be 330 mg (capsules) or 340 mg (tablets) on a '14 days on, 7 days off' schedule. The best confirmed response was partial response in 29 (43.9%) patients and stable disease in 20 (30.9%) patients. Combining pictilisib with various standard-of-care first-line treatment regimens is feasible from a safety perspective in patients with NSCLC, and encouraging preliminary anti-tumour activity was observed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Phase II randomized trial of carboplatin, paclitaxel, bevacizumab with or without cixutumumab (IMC-A12) in patients with advanced non-squamous, non-small cell lung cancer: A trial of the ECOG-ACRIN Cancer Research Group (E3508).

    Science.gov (United States)

    Argiris, A; Lee, J W; Stevenson, J; Sulecki, M G; Hugec, V; Choong, N W; Saltzman, J N; Song, W; Hansen, R M; Evans, T L; Ramalingam, S S; Schiller, J H

    2017-09-18

    Cixutumumab is a fully human IgG1 monoclonal antibody to the insulin-like growth factor type I receptor (IGF-IR) that can potentially reverse resistance and enhance the efficacy of chemotherapy. Bevacizumab-eligible patients with stage IV or recurrent non-squamous, non-small cell lung cancer (NSCLC) and good performance status were randomized to receive standard doses of paclitaxel, carboplatin, and bevacizumab to a maximum of 6 cycles followed by bevacizumab maintenance (CPB) until progression (arm A) or CPB plus cixutumumab 6 mg/kg IV weekly (arm B). Of 175 patients randomized, 153 were eligible and treated (78 in arm A; 75 in arm B). The median progression-free survival was 5.8 months (95% CI, 5.4-7.1) in arm A vs. 7 months (95% CI, 5.7-7.6) in arm B (p = 0.33); hazard ratio 0.92 (95% CI, 0.65-1.31). Objective response was 46.2% vs. 58.7% in arm A vs. arm B (p = 0.15). The median overall survival was 16.2 months in arm A vs. 16.1 months in arm B (p = 0.95). Grade 3/4 neutropenia and febrile neutropenia, thrombocytopenia, fatigue, and hyperglycemia were increased with cixutumumab. The addition of cixutumumab to CPB increased toxicity without improving efficacy and is not recommended for further development in NSCLC. Both treatment groups had longer OS than historical controls which may be attributed to several factors, and emphasizes the value of a comparator arm in phase II trials. NCT00955305.

  5. Weekly cycle of minor air gases in Moscow

    Science.gov (United States)

    Lokoshchenko, Mikhail A.; Elansky, Nikolay F.; Trifanova, Alexandra V.

    2017-04-01

    effect' is a result of the gradual contamination of the urban air after week-end. Any other changes from one working day to another are occasional and non-regular in time, so the average differences between working days are usually insignificant. Usually there is no gradual accumulation of air pollutants during working days in Moscow except only for specific conditions of fires during extremely hot weather (e.g., heat wave in summer of 2010). Weekly and annual cycles of NO, NO2 and CO surface concentrations have nearly the same amplitudes whereas the weekly variability of O3 is less than the annual one for this gas. Average differences between working days and weekend days (Saturday and Sunday), i.e. an amplitude of the weekly cycle, has a tendency to be reduced in time during nine years, but statistical significance of these inter-annual changes remains doubtful due to insufficient length of the row. Unlike other trace gases, sulphur dioxide doesn't demonstrate clear weekly cycle because the urban heating, the main source of it, has the same intensity on any day of the week.

  6. [The motivational week: A new approach in smoking cessation].

    Science.gov (United States)

    Hanssens, L; Lustygier, V; Ansseau, M; Thiebaut, I; Thimpont, J

    2017-03-01

    Smoking cessation is complex and challenging. The motivational week is a multidisciplinary approach that has been established in order to increase the chances of quitting smoking. The purpose of this study was to determine the rates of abstinence achieved and the predictive factors for quitting. Clinical data, smoking status, levels of dependence and motivation as well as rates of continuous abstinence in the short and long-term of all patients who participated in the motivational week were analysed. Two hundred and thirteen patients were included. The mean age was 49.8 years (10.6). The rates of continuous abstinence were 40.4% at 6 months, 29.1% at 12 months and 21.6% at 2 years. Using logistic regression, having depression or a history of depression was associated with reduced likelihood of smoking cessation: OR: 0.32 [95%CI: 0.16-0.76; P=0.003] at 6 months, OR: 0.35 [95%CI: 0.16-0.77; P=0.009] at 12 months and OR: 0.27 [95%CI: 0.11-0.65; P=0.004] at 2 years. The motivational week seems to be an approach which is effective long-term and could be used in smoking cessation. This study confirms that depression is an unfavourable factor for quitting. Copyright © 2016 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  7. Dichorionic twin ultrasound surveillance: sonography every 4 weeks significantly underperforms sonography every 2 weeks: results of the Prospective Multicenter ESPRiT Study.

    Science.gov (United States)

    Corcoran, Siobhan; Breathnach, Fionnuala; Burke, Gerard; McAuliffe, Fionnuala; Geary, Michael; Daly, Sean; Higgins, John; Hunter, Alyson; Morrison, John J; Higgins, Shane; Mahony, Rhona; Dicker, Patrick; Tully, Elizabeth; Malone, Fergal D

    2015-10-01

    A 2-week ultrasound scanning schedule for monochorionic twins is endorsed widely. There is a lack of robust data to inform a schedule for the surveillance of dichorionic gestations. We aimed to determine how ultrasound scanning that is performed at 2- or 4-week intervals (or every 4 weeks before 32 weeks' gestation and every 2 weeks thereafter) may impact the prenatal detection of fetal growth restriction (FGR) and ultimately influence timing of delivery. In a consecutive cohort of 789 dichorionic twin pregnancies that were recruited prospectively for the multicenter Evaluation of Sonographic Predictors of Restricted Growth in Twins study, ultrasound determination of fetal growth and interrogation of umbilical and middle cerebral artery Doppler scans were performed every 2 weeks from 24 weeks' gestation until delivery. Complete delivery and perinatal outcome data were recorded for all pregnancies. Where delivery was prompted by FGR, abnormal umbilical artery Doppler examination or poor biophysical profile and in the absence of ruptured membranes, onset of labor, preeclampsia, or antepartum hemorrhage, the delivery was considered "ultrasound-indicated." For ultrasound-indicated deliveries, detection probabilities for FGR/abnormal umbilical artery Doppler scans/poor biophysical were determined according to the interval between examinations, by the suppression if alternate examination data. Among 789 dichorionic twin pregnancies, 66 pairs (8%) had an "ultrasound indicated" delivery. Detection of FGR was reduced from 88-69%, and detection of abnormal umbilical artery Doppler was reduced from 82-62% when a 4-week ultrasound schedule was simulated. Both of these reductions reached statistical significance. There was a nonsignificant trend toward a reduction in the recording of oligohydramnios with a 4-week interval between examinations. This study suggests that the ultrasound surveillance program of every 2 weeks that is recommended currently for monochorionic twins

  8. Closing a temporary ileostomy within two weeks.

    Science.gov (United States)

    Hindenburg, Tommy; Rosenberg, Jacob

    2010-06-01

    Temporary ileostomy is frequently constructed to relieve a rectal anastomosis and avoid peritonitis if the anastomosis is leaking. Ostomy is a burden for both the patient and society and early closure is therefore desirable to counteract increased morbidity. Several prospective studies and a single randomized controlled trial have shown that closure in less than two weeks was associated with lower or equal morbidity compared with later closure. Thus, current data support early closure of temporary ileostomy performed to cover rectal anastomosis in routine clinical practice.

  9. Designing the eatwell week: the application of eatwell plate advice to weekly food intake

    National Research Council Canada - National Science Library

    Leslie, Wilma S; Comrie, Fiona; Lean, Michael E J; Hankey, Catherine R

    2013-01-01

    .... Development and analysis of an illustrative 7 d 'eatwell week' menu to meet current UK recommendations for nutrients with a Dietary Reference Value, with a daily energy base of 8368 kJ (2000 kcal...

  10. A clean environmental week: Let the nature breathe.

    Science.gov (United States)

    Moustafa, Khaled

    2017-11-15

    High levels of CO 2 emissions in the atmosphere and toxic pollutants in air, water and food have serious repercussions on all life's systems, including living beings, environment and economy. Everyone on the Earth is concerned by pollution in some way or another, no matter where and how the pollution is produced as airborne and foodborne pollutants could circulate around the world in different ways, through for example climate components (wind, rain) and/or import and export of foodstuffs. Similarly to living beings that take advantage of day-night circadian rhythms to recover after diurnal hardships, the environment in its entirety could also be seen as a complex living system that needs regular breaks to assimilate or ingest toxic pollutants produced during intensive and continuous industrial processes. If greenhouses gas emissions and pollution rates continue to increase at the same rates as they are nowadays, uncontrollable climate effects might be inevitable and the air quality in some crowded cities in the world might be hardly respirable in the future. A global "Clean Environmental Week" is discussed as an attempt toward reducing air pollution and CO 2 emissions through the interruption or reduction of industrial polluting activities regularly, for a week or so per year, to let the nature 'breathe' and recover from environmentally challenging pollutions. A clean environmental period of 10 days per year could reduce CO 2 emissions by about one billion tons of CO 2 per annum. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Resource Utilization and Toxicities After Carboplatin/Etoposide/Melphalan and Busulfan/Melphalan for Autologous Stem Cell Rescue in High-Risk Neuroblastoma Using a National Administrative Database.

    Science.gov (United States)

    Desai, Ami V; Seif, Alix E; Li, Yimei; Getz, Kelly; Fisher, Brian T; Huang, Vera; Mante, Adjoa; Aplenc, Richard; Bagatell, Rochelle

    2016-05-01

    High-dose chemotherapy with autologous stem cell rescue (ASCR) is a key component of high-risk neuroblastoma therapy. Resources required to support patients treated with ASCR conditioning regimens [carboplatin/etoposide/melphalan (CEM) and busulfan/melphalan (BuMel)] have not been directly compared. An administrative database was used to analyze resource utilization and outcomes in a cohort of high-risk neuroblastoma patients. Patients were followed for 60 days from start of conditioning or until death. Length of hospitalization, length of intensive care unit (ICU) level of care, incidence of sepsis and sinusoidal obstruction syndrome (SOS), and duration of use of specific supportive care resources were analyzed. Six of 171 CEM patients and zero of 59 BuMel patients died during the study period (P = 0.34). Duration of hospitalization was longer following BuMel (median 35 vs. 31 days; P = 0.01); however, there was no difference in duration of ICU-level care. Antibiotic use was longer following CEM (median 19 vs. 15 days; P = 0.01), as was antihypertensive use (median 5 vs. 1.6 days; P = 0.0024). Duration of opiate and nonnarcotic analgesic use was longer following CEM early in the study period. Resources consistent with a diagnosis of SOS were used in a higher proportion of BuMel patients. A higher proportion of BuMel treated patients required mechanical ventilation (17% vs. 6%; P = 0.03). We used administrative billing data to compare resources associated with ASCR conditioning regimens. CEM patients required more extended use of analgesics, antibiotics, and antihypertensives, while duration of hospitalization was longer, and SOS and the use of mechanical ventilation were more frequent following BuMel. © 2016 Wiley Periodicals, Inc.

  12. Subsidence at the Weeks Island SPR Facility

    Energy Technology Data Exchange (ETDEWEB)

    Bauer, S.J.

    1999-01-01

    The elevation change data measured at the Weeks Island SPR site over the last 16+ years has been studied and analyzed. The subsidence rate is not constant with time and while the subsidence rate may have increased slightly during the past several years, recently the rate has increased more dramatically. The most recent increase comes at a time when the Strategic Petroleum Reserve (SPR) storage mine had been emptied of oil and was in the process of being refilled with brine. Damage to surface structures that has been observed during the past 12-18 months is attributed to the continued subsidence and dtierential subsidence across structures. The recent greater subsidence rates were unanticipated according to analysis results and will be used to aid further subsidence model development.

  13. Medical image of the week: empyema

    Directory of Open Access Journals (Sweden)

    Young JR

    2013-11-01

    Full Text Available A 71 year-old man with chronic obstructive pulmonary disease (COPD presents to the emergency department complaining of dyspnea after recent admission for pneumonia. Chest CT shows a low density collection in the right lung suggesting necrosis (Figure 1. A CT obtained 1 week after admission (Figure 2 shows progression to empyema. Management of empyema can be difficult. If the fluid cannot be removed with a therapeutic thoracentesis, a chest tube should be inserted and consideration be given to the intrapleural instillation of fibrinolytics (1. If the loculated effusion persists, the patient should be subjected to video-assisted thoracoscopic surgery. If the lung cannot be expanded with this procedure, a full thoracotomy with decortication should be performed. The definitive procedure should be performed within fourteen days.

  14. Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma of the oropharynx: a single-arm, phase 2 study.

    Science.gov (United States)

    Chen, Allen M; Felix, Carol; Wang, Pin-Chieh; Hsu, Sophia; Basehart, Vincent; Garst, Jordan; Beron, Phillip; Wong, Deborah; Rosove, Michael H; Rao, Shyam; Melanson, Heather; Kim, Edward; Palmer, Daphne; Qi, Lihong; Kelly, Karen; Steinberg, Michael L; Kupelian, Patrick A; Daly, Megan E

    2017-06-01

    Head and neck cancers positive for human papillomavirus (HPV) are exquisitely radiosensitive. We investigated whether chemoradiotherapy with reduced-dose radiation would maintain survival outcomes while improving tolerability for patients with HPV-positive oropharyngeal carcinoma. We did a single-arm, phase 2 trial at two academic hospitals in the USA, enrolling patients with newly diagnosed, biopsy-proven stage III or IV squamous-cell carcinoma of the oropharynx, positive for HPV by p16 testing, and with Zubrod performance status scores of 0 or 1. Patients received two cycles of induction chemotherapy with 175 mg/m2 paclitaxel and carboplatin (target area under the curve of 6) given 21 days apart, followed by intensity-modulated radiotherapy with daily image guidance plus 30 mg/m2 paclitaxel per week concomitantly. Complete or partial responders to induction chemotherapy received 54 Gy in 27 fractions, and those with less than partial or no responses received 60 Gy in 30 fractions. The primary endpoint was progression-free survival at 2 years, assessed in all eligible patients who completed protocol treatment. This study is registered with ClinicalTrials.gov, numbers NCT02048020 and NCT01716195. Between Oct 4, 2012, and March 3, 2015, 45 patients were enrolled with a median age of 60 years (IQR 54-67). One patient did not receive treatment and 44 were included in the analysis. 24 (55%) patients with complete or partial responses to induction chemotherapy received 54 Gy radiation, and 20 (45%) with less than partial responses received 60 Gy. Median follow-up was 30 months (IQR 26-37). Three (7%) patients had locoregional recurrence and one (2%) had distant metastasis; 2-year progression-free survival was 92% (95% CI 77-97). 26 (39%) of 44 patients had grade 3 adverse events, but no grade 4 events were reported. The most common grade 3 events during induction chemotherapy were leucopenia (17 [39%]) and neutropenia (five [11%]), and during chemoradiotherapy were

  15. A randomized phase II study investigating the addition of the specific COX-2 inhibitor celecoxib to docetaxel plus carboplatin as first-line chemotherapy for stage IC to IV epithelial ovarian cancer, Fallopian tube or primary peritoneal carcinomas : the DoCaCel study

    NARCIS (Netherlands)

    Reyners, A. K. L.; de Munck, L.; Erdkamp, F. L. G.; Smit, W. M.; Hoekman, K.; Lalisang, R. I.; de Graaf, H.; Wymenga, A. N. M.; Polee, M.; Hollema, H.; van Vugt, M. A. T. M.; Schaapveld, M.; Willemse, P. H. B.

    2012-01-01

    In ovarian cancer, cyclooxygenase-2 (COX-2) overexpression is prognostic for poor survival. We investigated the efficacy of celecoxib (C), a selective COX-2 inhibitor, added to docetaxel (Taxotere)/carboplatin (DC) in advanced ovarian cancer. In a phase II, randomized study, 400 mg celecoxib b.i.d.

  16. The new Bulletin arrives in two weeks

    CERN Multimedia

    2006-01-01

    In May, you will discover a redesigned CERN Bulletin. Starting with the first May issue (No. 19-20/2006), the format of the CERN Bulletin will change completely. The page layout will be more attractive, reminiscent of a proper newspaper, with pictograms to identify the different sections. The information provided will also be more visible. The Bulletin was much in need of a makeover as its current layout dates back to 1976! The introduction of the new format will coincide with the introduction of a new means of distribution. You will still receive the elctronic version of the Bulletin every week directly on your computer. However, in order to avoid the waste from the dozens of copies that linger unread in people's mailboxes, the paper version will be available at a series of distribution points around the Laboratory. You will find the Bulletin along with the Staff Association newsletter at the cafeteria closest to your office. The Bulletin will be available from the following distribution points: On the M...

  17. Medical image of the week: leptomeningeal carcinomatosis

    Directory of Open Access Journals (Sweden)

    Bernardo R

    2014-03-01

    Full Text Available No abstract available. Article truncated at 150 words. A 65 year old woman with a history of breast cancer presented to the emergency department (ED with dizziness and disequilibrium, which started a week prior to admission. A year ago, she was diagnosed with locally advanced lobular carcinoma confined to the left breast (Figure 1. She underwent mastectomy followed by chemoradiation including taxol, sunitinib, cyclophosphamide and doxorubicin with remarkable response, and achieved complete remission. In the ED, her neurologic status deteriorated rapidly, she developed tonic-clonic seizures and became unresponsive to verbal and painful stimuli. CT of the head showed no evidence of acute intracranial abnormality or metastatic lesion, however, a brain MRI brain showed contrast enhancement and increased fluid attenuated inversion recovery (FLAIR signal of the leptomeninges in cranial nerves III, V, VII and VIII as well as cerebellar surface, suggesting meningeal carcinomatosis (Figure 2B and 2C. A lumbar puncture demonstrated malignant cells in the cerebospinal fluid confirming the ...

  18. Medical image of the week: bullous emphysema

    Directory of Open Access Journals (Sweden)

    Tey KR

    2016-04-01

    Full Text Available No abstract available. Article truncated at 150 words. A 63-year-old gentleman, with a history of 90-pack-years of smoking and stage IV chronic obstructive pulmonary disease was receiving home oxygen at 2 L/min at baseline. He has had multiple prior hospital admissions for respiratory failure. Over the past 2 weeks he has had increased production of sputum, associated with worsening shortness of breath. He is on fluticasone-salmeterol inhaler, albuterol inhaler, and tiotropium as an outpatient. On examination, he was hemodynamically stable, SpO2 was 92% on 4L/min of oxygen. He was in obvious respiratory distress, in a tripod position with tachypnea and using respiratory accessory muscles. Lung examination revealed diffuse expiratory wheezing. Chest radiograph shows severe emphysema (Figure 1. Chest computed tomography showed diffuse centrilobular and bullous emphysema (Figure 2. He was treated as an acute severe exacerbation of COPD and was eventually discharged to follow-up with the pulmonary clinic. Emphysema is defined as alveolar destruction and airspace enlargement distal ...

  19. Medical image of the week: aspergilloma

    Directory of Open Access Journals (Sweden)

    Hsu W

    2014-05-01

    Full Text Available No abstract available. Article truncated after 150 words. A 69-year-old woman, a current smoker, with very severe chronic obstructive pulmonary disease and prior atypical mycobacterium, was found unresponsive by her family and intubated in the field by emergency medical services for respiratory distress. Her CT thorax showed severe emphysematous disease, apical bullous disease, and a large left upper lobe cavitation with debris (Figure 1. She was treated with broad-spectrum antibiotics and anti-fungal medications. Hemoptysis was never seen. Sputum cultures over a span of two weeks repeatedly showed Aspergillus fumigatus and outside medical records confirmed the patient had a known history of stable aspergilloma not requiring therapy. Aspergillomas usually arises in cavitary areas of the lung damaged by previous infections. The fungus ball is a combination of colonization by Aspergillus hyphae and cellular debris. Individuals with aspergillomas are usually asymptomatic or have mild symptoms (chronic cough and do not require treatment unless it begins to invade into the cavity ...

  20. Bevacizumab and paclitaxel–carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial

    Science.gov (United States)

    Coleman, Robert L; Brady, Mark F; Herzog, Thomas J; Sabbatini, Paul; Armstrong, Deborah K; Walker, Joan L; Kim, Byoung-Gie; Fujiwara, Keiichi; Tewari, Krishnansu S; O'Malley, David M; Davidson, Susan A; Rubin, Stephen C; DiSilvestro, Paul; Basen-Engquist, Karen; Huang, Helen; Chan, John K; Spirtos, Nick M; Ashfaq, Raheela; Mannel, Robert S

    2017-01-01

    Summary Background Platinum-based chemotherapy doublets are a standard of care for women with ovarian cancer recurring 6 months after completion of initial therapy. In this study, we aimed to explore the roles of secondary surgical cytoreduction and bevacizumab in this population, and report the results of the bevacizumab component here. Methods The multicentre, open-label, randomised phase 3 GOG-0213 trial was done in 67 predominantly academic centres in the USA (65 centres), Japan (one centre), and South Korea (one centre). Eligible patients were adult women (aged ≥18 years) with recurrent measurable or evaluable epithelial ovarian, primary peritoneal, or fallopian tube cancer, and a clinical complete response to primary platinum-based chemotherapy, who had been disease-free for at least 6 months following last infused cycle of platinum. Patients were randomly assigned (1:1) to standard chemotherapy (six 3-weekly cycles of paclitaxel [175 mg/m2 of body surface area] and carboplatin [area under the curve 5]) or the same chemotherapy regimen plus bevacizumab (15 mg/kg of bodyweight) every 3 weeks and continued as maintenance every 3 weeks until disease progression or unacceptable toxicity. Individuals who participated in both the bevacizumab objective and surgical objective (which is ongoing) were randomly assigned (1:1:1:1) to receive either of these two chemotherapy regimens with or without prior secondary cytoreductive surgery. Randomisation for the bevacizumab objective was stratified by treatment-free interval and participation in the surgical objective. The primary endpoint was overall survival, analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00565851. Findings Between Dec 10, 2007, and Aug 26, 2011, 674 women were enrolled and randomly assigned to standard chemotherapy (n=337) or chemotherapy plus bevacizumab (n=377). Median follow-up at the end of the trial on Nov 5, 2014, was 49·6 months in each treatment

  1. Weekly Paclitaxel plus Capecitabine versus Docetaxel Every 3 Weeks plus Capecitabine in Metastatic Breast Cancer

    Directory of Open Access Journals (Sweden)

    E. A. Wist

    2012-01-01

    Full Text Available Background. We performed a randomized phase II study comparing efficacy and toxicity of weekly paclitaxel 80 mg/m2 (Weetax with three weekly docetaxel 75 mg/m2 (Threetax, both in combination with oral capecitabine 1000 mg/m2 twice daily for 2 weeks followed by a 1-week break. Patients. Thirty-seven women with confirmed metastatic breast cancer were randomized. Results. Median TTF was 174 (Weetax versus 147 days (Threetax (=0.472. Median OS was 933 (Weetax versus 464 days (Threetax (=0.191. Reasons for TTF were PD 8/18 (Weetax, 9/19 (Threetax; and toxicity: 8/18 (Weetax, 8/19 (Threetax. ORR was 72% (Weetax versus 26% (Threetax (=0.01. The Threetax-combination resulted in a higher incidence of leuco-/neutropenia compared to Weetax. Grade II anemia was more pronounced in the Weetax group. No difference was found in quality of life. Conclusion. Taxanes in combination with capecitabine resulted in a high level of toxicity. Taxanes and capecitabine should be considered given sequentially and not in combination.

  2. Designing the eatwell week: the application of eatwell plate advice to weekly food intake.

    Science.gov (United States)

    Leslie, Wilma S; Comrie, Fiona; Lean, Michael E J; Hankey, Catherine R

    2013-05-01

    To develop a menu and resource to illustrate to consumers and health professionals what a healthy balanced diet looks like over the course of a week. Development and analysis of an illustrative 7 d 'eatwell week' menu to meet current UK recommendations for nutrients with a Dietary Reference Value, with a daily energy base of 8368 kJ (2000 kcal). Foods were selected using market research data on meals and snacks commonly consumed by UK adults. Analysis used the food composition data set from year 1 (2008) of the UK National Diet and Nutrition Survey rolling programme. The eatwell week menu was developed using an iterative process of nutritional analysis with adjustments made to portion sizes and the inclusion/exclusion of foods in order to achieve the target macronutrient composition. Three main meals and two snacks were presented as interchangeable within the weekdays and two weekend days to achieve adult food and nutrient recommendations. Main meals were based on potatoes, rice or pasta with fish (two meals; one oily), red meat (two meals), poultry or vegetarian accompaniments. The 5-a-day target for fruit and vegetables (range 5-6·7 portions) was achieved daily. Mean salt content was below recommended maximum levels (foods, and those widely consumed by British adults, can be incorporated within a 7 d healthy balanced menu. Future research should investigate the effect of using the eatwell week on adults' dietary habits and health-related outcomes.

  3. One Week, Many Ripples: Measuring the Impacts of the Fall Reading Week on Student Stress

    Science.gov (United States)

    Poole, Heather; Khan, Ayesha; Agnew, Michael

    2017-01-01

    More and more Canadian post-secondary institutions are introducing a fall break into their term calendars. In 2015, a full week fall break was introduced at our university in order to enhance academic performance and improve mental health amongst students. Our interdisciplinary team surveyed undergraduate students at our university about their…

  4. 75 FR 2049 - National Influenza Vaccination Week, 2010

    Science.gov (United States)

    2010-01-13

    ... Influenza Vaccination Week. I encourage all Americans to observe this week by getting the H1N1 flu vaccine... Proclamation 8472--National Influenza Vaccination Week, 2010 #0; #0; #0; Presidential Documents #0; #0; #0;#0...;Title 3-- #0;The President ] Proclamation 8472 of January 8, 2010 National Influenza Vaccination Week...

  5. WE-G-BRE-06: New Potential for Enhancing External Beam Radiotherapy for Lung Cancer Using FDA-Approved Concentrations of Cisplatin Or Carboplatin Nanoparticles Administered Via Inhalation

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Y; Altundal, Y; Sajo, E [University Massachusetts Lowell, Lowell, MA (United States); Detappe, A [Brigham ' Woman' s Hospital, Boston, MA (United States); Dana Farber Cancer Institute, Boston, MA (United States); Harvard Medical School, Boston, MA (United States); University of Lyon, Lyon (France); Makrigiorgos, G; Berbeco, R [Brigham ' Woman' s Hospital, Boston, MA (United States); Dana Farber Cancer Institute, Boston, MA (United States); Harvard Medical School, Boston, MA (United States); Ngwa, W [University Massachusetts Lowell, Lowell, MA (United States); Brigham ' Woman' s Hospital, Boston, MA (United States); Dana Farber Cancer Institute, Boston, MA (United States); Harvard Medical School, Boston, MA (United States)

    2014-06-15

    Purpose: This study investigates, for the first time, the dose enhancement to lung tumors due to cisplatin nanoparticles (CNPs) and carboplatin nanoparticles (CBNPs) administered via inhalation route (IR) during external beam radiotherapy. Methods: Using Monte Carlo generated 6 MV energy fluence spectra, a previously employed analytic method was used to estimate dose enhancement to lung tumor due to radiation-induced photoelectrons from CNPs administered via IR in comparison to intravenous (IV) administration. Previous studies have indicated about 5% of FDA-approved cisplatin concentrations reach the lung tumor via IV. Meanwhile recent experimental studies indicate that 3.5–14.6 times higher concentrations of CNPs can reach the lung tumors by IR compared to IV. Taking these into account, the dose enhancement factor (DEF) defined as the ratio of the dose with and without CNPs was calculated for field size of 10 cm × 10 cm (sweeping gap), for a range of tumor depths and tumor sizes. Similar calculations were done for CBNPs. Results: For IR with 3.5 times higher concentrations than IV, and 2 cm diameter tumor, clinically significant DEF values of 1.19–1.30 were obtained for CNPs at 3–10 cm depth, respectively, in comparison to 1.06–1.09 for IV. For CBNPs, DEF values of 1.26–1.41 were obtained in comparison to 1.07–1.12 for IV. For IR with 14.6 times higher concentrations, higher DEF values were obtained e.g. 1.81–2.27 for CNPs. DEF increased with increasing field size or decreasing tumor size. Conclusions: Our preliminary results indicate that major dose enhancement to lung tumors can be achieved using CNPs/CBNPs administered via IR, in contrast to IV administration during external beam radiotherapy. These findings highlight a potential new approach for radiation boosting to lung tumors using CNPs/CBNPs administered via IR. This would, especially, be applicable during concomitant chemoradiotherapy, potentially allowing for dose enhancement while

  6. Dose Estimation from Daily and Weekly Dosimetry Data

    Energy Technology Data Exchange (ETDEWEB)

    Ostrouchov, G.

    2001-11-16

    Statistical analyses of data from epidemiologic studies of workers exposed to radiation have been based on recorded annual radiation doses (yearly dose of record). It is usually assumed that the dose values are known exactly, although it is generally recognized that the data contain uncertainty due to measurement error and bias. In our previous work with weekly data, a probability distribution was used to describe an individual's dose during a specific period of time and statistical methods were developed for estimating it from weekly film dosimetry data. This study showed that the yearly dose of record systematically underestimates doses for Oak Ridge National Laboratory (ORNL) workers. This could result in biased estimates of dose-response coefficients and their standard errors. The results of this evaluation raise serious questions about the suitability of the yearly dose of record for direct use in low-dose studies of nuclear industry workers. Here, we extend our previous work to use full information in Pocket meter data and develop the Data Synthesis for Individual Dose Estimation (DSIDE) methodology. Although the DSIDE methodology in this study is developed in the context of daily and weekly data to produce a cumulative yearly dose estimate, in principle it is completely general and can be extended to other time period and measurement combinations. The new methodology takes into account the ''measurement error'' that is produced by the film and pocket-meter dosimetry systems, the biases introduced by policies that lead to recording left-censored doses as zeros, and other measurement and recording practices. The DSIDE method is applied to a sample of dose histories obtained from hard copy dosimetry records at ORNL for the years 1945 to 1955. First, the rigorous addition of daily pocket-meter information shows that the negative bias is generally more severe than was reported in our work based on weekly film data only, however, the

  7. Intracranial Hemorrhage Following a 3-week Headache

    Directory of Open Access Journals (Sweden)

    John Jiao

    2017-01-01

    Full Text Available History of present illness: A 35-year-old female presented to the ED with a Glasgow Coma Scale (GCS of 11. Per her boyfriend, the patient was having headaches for the past 3 weeks. She was initially taken to an outside hospital where her GCS was reported as 13. A non-contrast head computed tomography (CT revealed a large lobar intraparenchymal hemorrhage within the left frontal parietal lobe with midline shift. Upon examination, vitals were notable for blood pressure of 209/88mmHg, and her left pupil was fixed and dilated. The patient had extension of her right arm to noxious stimuli, paralysis of her right leg, and purposeful movement of the left arm and left leg. The patient was started on a nicardipine drip in the ED and subsequently taken to the operating room for a decompressive craniectomy. Significant findings: The patient’s head CT showed a significant area of hyperdensity consistent with an intracranial hemorrhage located within the left frontal parietal lobe (red arrow. Additionally, there is rightward midline shift up to 1.1cm (green arrow and entrapment of the right lateral ventricle (blue arrow. Discussion: Intraparenchymal hemorrhage (IPH is associated with high morbidity and mortality. Although the mortality for subarachnoid hemorrhage (SAH has declined steadily over the past several decades, the mortality for IPH mortality has not significantly.1 One of the most serious considerations when treating a patient with IPH is the management of intracranial pressure (ICP.2 Once an IPH is identified, immediate steps should be taken to bring ICP within acceptable levels including elevating the head of the bed to 30 degrees, sedation, and controlling hypertension with medications.2-3 Even with early and aggressive care, the prognosis for IPH remains poor; the 30-day mortality rate for IPH is estimated to be less than 50%, and a 2010 systematic review estimated only 12-39% of IPH patients achieve independent function.4-5 Predictors of

  8. Reduced Tillage

    OpenAIRE

    Hegglin, Django; Clerc, Maurice; Dierauer, Hansueli

    2014-01-01

    Reduced tillage can significantly contribute to soil quality and fertility. By avoiding a deep and intense loosening of the soil, the soil structure and soil biology is better conserved and humus decomposition is slowed down. Furthermore, the load capacity, erosion sensitivity and water household of the soil are improved. However, avoiding the use of a plough brings certain challenges, especially in organic farming. For example, weed pressure can increase or nutrient supply can becom...

  9. Cortical Reorganisation during a 30-Week Tinnitus Treatment Program.

    Directory of Open Access Journals (Sweden)

    Catherine M McMahon

    the tinnitus treatment, and may result from the hearing loss per se. On the other hand, the shifts in the tonotopic map towards the non-tinnitus participants' source location suggests that the tinnitus treatment might reduce the disruptions in the map, presumably produced by the tinnitus percept directly or indirectly. Further, the similarity in the trajectory of change across the objective and subjective parameters after time-shifting the perceptual changes by 5 weeks suggests that during or following treatment, perceptual changes in the tinnitus percept may precede neurophysiological changes. Subgroup analyses conducted by magnitude of hearing loss suggest that there were no differences in the 500 Hz and 1000 Hz source strength amplitudes for the mild-moderate compared with the mild-severe hearing loss subgroup, although the mean source strength was consistently higher for the mild-severe subgroup. Further, the mild-severe subgroup had 500 Hz and 1000 Hz source locations located more anteriorly (i.e., more disrupted compared to the control group compared to the mild-moderate group, although this was trending towards significance only for the 500Hz left hemisphere source. While the small numbers of participants within the subgroup analyses reduce the statistical power, this study suggests that those with greater magnitudes of hearing loss show greater cortical disruptions with tinnitus and that tinnitus treatment appears to reduce the tonotopic map disruptions but not the source strength (or central gain.

  10. Cortical Reorganisation during a 30-Week Tinnitus Treatment Program

    Science.gov (United States)

    McMahon, Catherine M.; Ibrahim, Ronny K.; Mathur, Ankit

    2016-01-01

    tinnitus treatment, and may result from the hearing loss per se. On the other hand, the shifts in the tonotopic map towards the non-tinnitus participants’ source location suggests that the tinnitus treatment might reduce the disruptions in the map, presumably produced by the tinnitus percept directly or indirectly. Further, the similarity in the trajectory of change across the objective and subjective parameters after time-shifting the perceptual changes by 5 weeks suggests that during or following treatment, perceptual changes in the tinnitus percept may precede neurophysiological changes. Subgroup analyses conducted by magnitude of hearing loss suggest that there were no differences in the 500 Hz and 1000 Hz source strength amplitudes for the mild-moderate compared with the mild-severe hearing loss subgroup, although the mean source strength was consistently higher for the mild-severe subgroup. Further, the mild-severe subgroup had 500 Hz and 1000 Hz source locations located more anteriorly (i.e., more disrupted compared to the control group) compared to the mild-moderate group, although this was trending towards significance only for the 500Hz left hemisphere source. While the small numbers of participants within the subgroup analyses reduce the statistical power, this study suggests that those with greater magnitudes of hearing loss show greater cortical disruptions with tinnitus and that tinnitus treatment appears to reduce the tonotopic map disruptions but not the source strength (or central gain). PMID:26901425

  11. Medical image of the week: arachnoid cyst

    Directory of Open Access Journals (Sweden)

    Erisman M

    2016-10-01

    Full Text Available No abstract available. Article truncated at 150 words. A 40 year-old woman with adult attention deficit hyperactive and bipolar 1 disorder presents with an altered mental status. Per her family, she had been non-verbal, with reduced oral intake, confusion and sedated for the past three days. Per her husband, she had episodes of diarrhea and abdominal discomfort. She was on multiple medications including ramelteon 8mg nightly, atomoxetine 40mg daily, hydroxyzine 25mg twice daily, bupropion 75mg twice daily and risperidone 2mg daily with recent addition of lithium ER 1200mg/daily started one month prior to presentation with unknown adherence. Upon arrival, vital signs were within normal limits. Physical exam revealed an overweight Caucasian woman with a significant coarse tremor visible at rest, restlessness and diaphoresis. Neurological examination was limited by patient hesitancy, however, it did not demonstrate focal deficits except for altered consciousness with Glasgow Coma Scale of 10. Notable laboratory findings were Na+ 134 mEq/L, K+ 3.2 mEq/L, and ...

  12. Medical image of the week: panloubular emphysema

    Directory of Open Access Journals (Sweden)

    Mathur A

    2015-08-01

    Full Text Available No abstract available. Article truncated after 150 words. A 60 year old female, non-smoker with a past medical history of chronic rhinosinusitis with nasal polyps presented with an eight year history of productive cough and dyspnea. Previous treatment with inhaled corticosteroids, courses of systemic corticosteroids and antibiotics provided modest improvement in her symptoms. Pulmonary function testing revealed a severe obstructive ventilatory defect without significant bronchodilator response and reduced diffusing capacity (DLCO. Chest x-ray surprisingly revealed lower lobe predominant emphysematous changes (Figure 1. Alpha-1-antitrypsin level was within normal range at 137 mg/dL. Panlobular emphysema represents permanent destruction of the entire acinus distal to the respiratory bronchioles and is more likely to affect the lower lobes compared to centrilobular emphysema (1. Panlobular emphysema is associated with alpha-1-antitrypsin deficiency, intravenous drug abuse specifically with methylphenidate and methadone, Swyer-James syndrome, and obliterative bronchiolitis. Whether this pattern is seen as part of normal senescence in non-smoking individuals remains controversial (2. Panlobular emphysema may ...

  13. Medical image of the week: bronchiectasis

    Directory of Open Access Journals (Sweden)

    Jaffer F

    2016-06-01

    Full Text Available No abstract available. Article truncated at 150 words. A 49-year old Native American woman with chronic hypoxic and hypercarbic respiratory failure requiring 3 liters continuous via nasal cannula and nocturnal non-invasive bi-level ventilation presented with acute shortness of breath for 5 days. She has history of recurrent respiratory infections since early childhood, however over the past five years has been treated multiple times for presumed COPD exacerbation with last such treatment one month prior to admission. Upon arrival, vitals displayed elevated blood pressure 183/96. Clinical examination demonstrated morbidly obese patient in mild somnolence and has diffuse expiratory wheezing, basal crackles with reduced air entry bilaterally. Laboratory examination showed leukocytosis (13,800 cells/uL with neutrophilic predominance, thrombocytopenia (85,000 cells/uL, and elevated bicarbonate (31 mg/dL. Arterial blood gas showed pH=7.29, pCO2 756 mm Hg, and pO2 73 mm Hg. Thoracic computed tomography (CT with contrast ruled out pulmonary embolism, however demonstrated extensive cystic bronchiectasis in left upper and lower lobes, right ...

  14. Medical image of the week: pulmonary mycetoma

    Directory of Open Access Journals (Sweden)

    Khan S

    2017-10-01

    Full Text Available No abstract available. Article truncated at 150 words. A 59 year-old woman presented with right sided chest pain and worsening shortness of breath. On CT of the chest she was found to have cavitary lesions in her right lung with one of them having a distinct opacity within the lesion concerning for a pulmonary mycetoma (Figure 1, arrow. Most literature describes pulmonary mycetomas occurring due to Aspergillus species. However, in our patient, neither the bronchoscopy with bronchoalveolar lavage (BAL nor serological studies tested positive for Aspergillus. Cultures did however grow Candida albicans in 2 of the samples from the BAL. Mycetoma due to Candida has been described in the urinary tract in immunocompromised patients and, uncommonly, in the lung (1-3. Our patient had been treated for Stage III ovarian cancer with chemotherapy and at presentation her absolute neutrophil count was reduced at 860. In the hospital, she was treated for her shortness of breath with albuterol-ipratropium nebulizations to …

  15. Medical image of the week: Pott's disease

    Directory of Open Access Journals (Sweden)

    Thao C

    2015-07-01

    Full Text Available No abstract available. Article truncated at 150 words. A 22 year-old man with a history of asthma presented with a two-month history of progressive right upper extremity weakness with back pain, weight loss, and night sweats. CT scan of the chest revealed mass-like infiltrative mass in the right lung apex with mediastinal and hilar lymphadenopathy (Figure 1. An MRI cervical spine showed a large infiltrating process at the right medial lung apex with vertebral body compression (Figure 2. A CT-guided lung biopsy was performed and it showed necrotizing granulomatous inflammation (Figure 3. Pott’s disease was diagnosed and the patient started on anti-tuberculous treatment with a good recovery. Pott’s disease is a common cause of spinal infection and its clinical presentations are nonspecific. Early findings on imaging may reveal loss of vertebral body height, bone sequestration, sclerosis, and paraspinal mass with calcification (1. A diagnosis of this condition must be made early as prompt treatment may reduce significant morbidity ...

  16. Medical image of the week: Kartagener syndrome

    Directory of Open Access Journals (Sweden)

    Das D

    2015-06-01

    Full Text Available No abstract available. Article truncated at 150 words. A 65-year-old woman presented with 7 days of productive cough and the new onset sharp central chest pain. She has a known history of chronic sinusitis and COPD after being a 50 pack-year smoker. On examination, her blood pressure was 116/70 with a heart rate of 86 (sinus rhythm and oxygen saturations were 93% on 4L/min by nasal cannula. She had bilateral expiratory wheezes with reduced air entry on the left side. An AP chest x-ray revealed dextrocardia with a left sided tension pneumothorax (Figure 1A. Our patient was stabilized with an urgent chest tube insertion and taken for a CT chest and abdomen. CT chest indicated diffuse bronchiectasis (Figure 1B, arrow with a CT of the abdomen showing reversal of major abdominal organs (Figure 1C. First described in 1933, the triad of chronic sinusitis, bronchiectasis, and situs inversus is classic for Kartagener syndrome (1. Otherwise known as primary ciliary ...

  17. Physical activity initiated by employer and its health effects; an eight week follow-up study

    Directory of Open Access Journals (Sweden)

    Marit Skogstad

    2016-05-01

    Full Text Available Abstract Background While the health benefits of physical activity are well established, little is known about health effects of physical activity programs initiated by employer. Methods Background data and level of physical activity were collected by questionnaire among 78 men and 43 women working in road maintenance pre and post an 8-week physical activity motivational program. As a part of the program steps measured by accelerometer were registered online where team and individual performances could be continuously monitored. The physical activity levels were registered as 1 those physical active ≤1 time per week, 2 2–3 times per week and 3 ≥4 times a week. Maximal oxygen uptake (VO2max, blood pressure, resting heart rate (RHR and blood samples (glycosylated hemoglobin, lipids and C-reactive protein were obtained at baseline and after eight weeks. Mixed models were applied to evaluate associations between physical activity and health parameters. Results With ≤1 time per week as reference, exercising 2–3 times per week at baseline was associated with higher levels of VO2max. During follow-up, VO2max increased with 2.8 mL ∙ kg−1∙ min−1 (95 % CI = 1.4, 4.3. Women had more favorable body mass index (BMI, blood pressure, RHR and lipid profile than men. Total cholesterol, low density lipoprotein (LDL, RHR and diastolic blood pressure (dBP were lower among participants who exercised 2–3 times per week or ≥4 times a week, compared with those with ≤1 time per week. Half of the participants reported increased daily PA during follow-up, with high intensity PA such as jogging by 8.6 min (SD 14.6 and 8.3 min (SD 18.2, among women and men, respectively. During follow-up dBP increased among men. Further, total cholesterol and LDL were reduced by 0.12 mmol/L and 0.13 mmol/L, respectively (95 % CI = −022, –0.01 and −0.22,–0.04. Conclusions Exercise several times a week was associated with lower blood pressure and a

  18. Effect of Prolonged Exposure Therapy Delivered Over 2 Weeks vs 8 Weeks vs Present-Centered Therapy on PTSD Symptom Severity in Military Personnel: A Randomized Clinical Trial.

    Science.gov (United States)

    Foa, Edna B; McLean, Carmen P; Zang, Yinyin; Rosenfield, David; Yadin, Elna; Yarvis, Jeffrey S; Mintz, Jim; Young-McCaughan, Stacey; Borah, Elisa V; Dondanville, Katherine A; Fina, Brooke A; Hall-Clark, Brittany N; Lichner, Tracey; Litz, Brett T; Roache, John; Wright, Edward C; Peterson, Alan L

    2018-01-23

    ). At 2 weeks posttreatment, mean PSS-I score was 18.03 for spaced therapy (decrease, 7.29; difference in means vs massed therapy, 0.79 [1-sided 95% CI, -∞ to 2.29; P = .049 for noninferiority]) and at 12 weeks posttreatment was 18.88 for massed therapy (decrease, 6.32) and 18.34 for spaced therapy (decrease, 6.97; difference, 0.55 [1-sided 95% CI, -∞ to 2.05; P = .03 for noninferiority]). At posttreatment, PSS-I scores for PCT were 18.65 (decrease, 7.31; difference in decrease vs spaced therapy, 0.10 [95% CI, -2.48 to 2.27]; P = .93). Among active duty military personnel with PTSD, massed therapy (10 sessions over 2 weeks) reduced PTSD symptom severity more than MCC at 2-week follow-up and was noninferior to spaced therapy (10 sessions over 8 weeks), and there was no significant difference between spaced therapy and PCT. The reductions in PTSD symptom severity with all treatments were relatively modest, suggesting that further research is needed to determine the clinical importance of these findings. clinicaltrials.gov Identifier: NCT01049516.

  19. Trichophyton rubrum onychomycosis in an 8-week-old infant

    Directory of Open Access Journals (Sweden)

    Vinod K Khurana

    2011-01-01

    Full Text Available An 8-week-old infant presented with 7 weeks history of nail involvement and discoloration. Lesions started over the middle fingernail of right hand at 1 week of age, spreading over to other nails within 2 weeks. Only two nails of the feet were spared. On KOH examination, fungal hyphae were seen and culture showed growth of Trichophyton rubrum. The purpose is to report the earliest case of onychomycosis having multiple nail involvement of fingers and toes (18 nails.

  20. Reducing Resistance

    DEFF Research Database (Denmark)

    Lindell, Johanna

    care may influence decisions on antibiotic use. Based on video-and audio recordings of physician-patient consultations it is investigated how treatment recommendations are presented, can be changed, are forecast and explained, and finally, how they seemingly meet resistance and how this resistance......Antibiotic resistance is a growing public health problem both nationally and internationally, and efficient strategies are needed to reduce unnecessary use. This dissertation presents four research studies, which examine how communication between general practitioners and patients in Danish primary...... is responded to.The first study in the dissertation suggests that treatment recommendations on antibiotics are often done in a way that encourages patient acceptance. In extension of this, the second study of the dissertation examines a case, where acceptance of such a recommendation is changed into a shared...

  1. 20 CFR 617.13 - Weekly amounts of TRA.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Weekly amounts of TRA. 617.13 Section 617.13... FOR WORKERS UNDER THE TRADE ACT OF 1974 Trade Readjustment Allowances (TRA) § 617.13 Weekly amounts of TRA. (a) Regular allowance. The amount of TRA payable for a week of total unemployment (including a...

  2. Open Data poster for Open Access Week - AI file

    OpenAIRE

    Briney, Kristin

    2013-0