The Experts below are selected from a list of 60 Experts worldwide ranked by ideXlab platform
H A Burris - One of the best experts on this subject based on the ideXlab platform.
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patients rescued by crossover to Rubitecan in phase iii study of Rubitecan capsules versus 5 fu in pancreatic cancer
Journal of Clinical Oncology, 2005Co-Authors: S W Papish, R K Ramanathan, J Pincus, M Hirmand, H A BurrisAbstract:4165 Background: Rubitecan (Orathecin) is a novel oral inhibitor of topoisomerase I in the camptothecin class. Methods: A Phase III randomized multinational open-label study of Rubitecan versus 5-FU in pancreatic cancer patients who had progressive disease following gemcitabine treatment was undertaken. The primary endpoint was overall survival. Key patient eligibility criteria included pathologic diagnosis of pancreatic cancer, progressive disease on gemcitabine, Karnofsky Performance Status of ≥50 and life expectancy of ≥2 months. Rubitecan was administered at 1.5 mg/m2 orally 5 days/week. 5-FU was administered at 600 mg/m2 intravenously once weekly. Patients who progressed or experienced intolerable toxicity could crossover to the alternate treatment arm. Results: 93 of 224 (41%) 5-FU patients crossed over to Rubitecan rescue. Only 1 of 224 Rubitecan patients crossed over to 5-FU. Main reasons for rescue with Rubitecan were radiologic (75%) and symptomatic (12%) progression on 5-FU. Median survival fro...
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phase ii trial of oral Rubitecan in previously treated pancreatic cancer patients
Oncologist, 2005Co-Authors: H A Burris, Saul Rivkin, Robert Reynolds, Jules Harris, Arnold Wax, Hal Gerstein, Karl L Mettinger, Arthur StaddonAbstract:Background. Additional systemic treatments for locally advanced or metastatic pancreatic cancer are needed, as current treatment options produce only modest survival benefits. Rubitecan (Orathecin ™ ; Supergen Inc., Dublin, CA, http://www.supergen.com) is an orally active camptothecin derivative with demonstrated responses in patients with pancreatic cancer in early clinical trials. This phase II, open-label trial was developed to assess the safety and efficacy of Rubitecan in patients with locally advanced or metastatic pancreatic cancer refractory to conventional chemotherapy. Methods. Fifty-eight patients with failed or relapsed advanced pancreatic cancer after receiving at least one prior chemotherapy regimen were enrolled to receive eight consecutive weeks of treatment with Rubitecan at a dose of 1.5 mg/m 2 orally on five consecutive days per week, followed by 2 days off therapy, repeatedly. The primary end point was response rate. Time to progression, overall survival, changes in CA19-9 levels, and the composite measure of clinical benefit response were evaluated as secondary end points. Results. Among 43 patients with measurable disease, 7% (3/43) achieved partial responses and 16% (7/43)
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a randomized phase iii study of Rubitecan ora vs best choice bc in 409 patients with refractory pancreatic cancer report from a north american multi center study
Journal of Clinical Oncology, 2004Co-Authors: A D Jacobs, H A Burris, S Rivkin, Paul S Ritch, P Eisenberg, K L MettingerAbstract:4013 Background: Rubitecan (Orathecin), an oral topoisomerase I inhibitor, showed promising activity in pancreatic cancer in previous single-center Phase 2 studies in US and Europe. Our objective was to compare ORA with BC (physicians' best choice of treatment or care). Primary end-point: Median survival (MS) . Secondary endpoints: Response rate (RR), progression- free survival (PFS) and safety. Methods: ORA was administered orally at a dose of 1.5 mg/m2 for 5 consecutive days each week for 8 or more weeks. BC consisted of standard regimens of best alternative chemotherapy (89%) or supportive care (11%). CT scans were followed every 8 weeks. Results: 198 patients (pts) were randomized to ORA and 211 to BC. More than 90% were resistant to prior chemotherapy and 70% were refractory to 2 or more prior regimens. 49% of BC patients crossed over to rescue therapy with ORA at time of failure. No significant difference was noted in MS time (ORA: 108 days, BC 94 days, p =0.626), whereas a significant survival adva...
Patrick Schoffski - One of the best experts on this subject based on the ideXlab platform.
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development of an optimal pharmacokinetic sampling schedule for Rubitecan administered orally in a daily times five schedule
Cancer Chemotherapy and Pharmacology, 2002Co-Authors: Nadja E Schoemaker, Ron A A Mathot, Patrick Schoffski, Hilde Rosing, Jan H M Schellens, Jos H BeijnenAbstract:Abstract Purpose. Our aim was to develop an optimal sampling strategy for the description of the pharmacokinetics of Rubitecan and its active metabolite 9-aminocamptothecin (9-AC) for use in phase II/III studies with oral Rubitecan administered in a daily times five schedule. Methods. Concentration-time data of Rubitecan and 9-AC were obtained from 14 patients who had received 1.5 mg/m2 per day Rubitecan orally. Population pharmacokinetic analysis of both the parent and the metabolite was performed using the nonlinear mixed effect modelling program (NONMEM). Optimal sampling points were selected on the basis of the assessed population pharmacokinetic parameters using a D-optimality algorithm. Results. The pharmacokinetics of both Rubitecan and 9-AC were adequately described with a one-compartment model. The absorption rate constant, apparent volume of distribution and apparent clearance of Rubitecan were 0.81 h–1, 50 l and 1.7 l/h, respectively. For 9-AC the corresponding values of the apparent volume of distribution and the elimination rate constant were 51 l and 0.102 h–1. Interindividual variability of the pharmacokinetic parameters ranged from 38% to 49%. For the first dose, optimal sampling points were 1, 3, 5, 8 and 24 h after dosing. Monte Carlo simulations indicated that the sampling schedule produced parameter estimates which were unbiased and precise. Conclusions. An optimal sampling schedule was derived which allowed assessment of the pharmacokinetic parameters of both the parent compound and its metabolite 9-AC after oral administration of Rubitecan.
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clinical phase ii study and pharmacological evaluation of Rubitecan in non pretreated patients with metastatic colorectal cancer significant effect of food intake on the bioavailability of the oral camptothecin analogue
European Journal of Cancer, 2002Co-Authors: Patrick Schoffski, Hilde Rosing, A Herr, J B Vermorken, J Van Den Brande, J H Beijnen, J Volk, Arnold Ganser, S Adank, H J BotmaAbstract:Abstract A randomised, open label phase II study was performed in patients with advanced colorectal cancer to evaluate the safety, toxicity and antineoplastic activity of the topoisomerase I-inhibitor Rubitecan. A cross-over design was chosen to determine the intrapatient variation of the bioavailability and pharmacokinetics of the anticancer agent depending on the timing of food intake in relation to the oral drug administration. Patients with previously untreated metastatic disease received two single oral doses of Rubitecan 1.5 mg/m2 for assessment of the pharmacokinetics. They were randomised to have the first administration either after an overnight fasting period or immediately after a high calorie breakfast, and crossed over to the alternative schedule after a one-week washout period. After completion of the pharmacokinetic sampling, treatment continued with Rubitecan given orally at a dose of 1.5 mg/m2/day, to be increased up to 2.0 mg/m2/day, under fasting conditions for 5 consecutive days per week until disease progression. 19 patients entered the trial after informed consent was obtained. A total number of 35 treatment cycles (median 2, range 1–4) were administered. All patients were evaluable for safety. The toxicity profile of Rubitecan was generally mild to moderate, with sporadic cases of grade 4 toxicities (Common Toxicity Criteria (CTC) version 2.0) diarrhoea, leucopenia and neutropenia. None of 15 evaluable patients achieved an objective response. The majority had early disease progression. 14 patients were evaluable for pharmacokinetic analysis. The bioavailability of Rubitecan was found to be strongly dependent on the timing of food intake with a fasted-to-fed ratio for Cmax of 1.98 (two-tailed P
Hilde Rosing - One of the best experts on this subject based on the ideXlab platform.
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development of an optimal pharmacokinetic sampling schedule for Rubitecan administered orally in a daily times five schedule
Cancer Chemotherapy and Pharmacology, 2002Co-Authors: Nadja E Schoemaker, Ron A A Mathot, Patrick Schoffski, Hilde Rosing, Jan H M Schellens, Jos H BeijnenAbstract:Abstract Purpose. Our aim was to develop an optimal sampling strategy for the description of the pharmacokinetics of Rubitecan and its active metabolite 9-aminocamptothecin (9-AC) for use in phase II/III studies with oral Rubitecan administered in a daily times five schedule. Methods. Concentration-time data of Rubitecan and 9-AC were obtained from 14 patients who had received 1.5 mg/m2 per day Rubitecan orally. Population pharmacokinetic analysis of both the parent and the metabolite was performed using the nonlinear mixed effect modelling program (NONMEM). Optimal sampling points were selected on the basis of the assessed population pharmacokinetic parameters using a D-optimality algorithm. Results. The pharmacokinetics of both Rubitecan and 9-AC were adequately described with a one-compartment model. The absorption rate constant, apparent volume of distribution and apparent clearance of Rubitecan were 0.81 h–1, 50 l and 1.7 l/h, respectively. For 9-AC the corresponding values of the apparent volume of distribution and the elimination rate constant were 51 l and 0.102 h–1. Interindividual variability of the pharmacokinetic parameters ranged from 38% to 49%. For the first dose, optimal sampling points were 1, 3, 5, 8 and 24 h after dosing. Monte Carlo simulations indicated that the sampling schedule produced parameter estimates which were unbiased and precise. Conclusions. An optimal sampling schedule was derived which allowed assessment of the pharmacokinetic parameters of both the parent compound and its metabolite 9-AC after oral administration of Rubitecan.
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clinical phase ii study and pharmacological evaluation of Rubitecan in non pretreated patients with metastatic colorectal cancer significant effect of food intake on the bioavailability of the oral camptothecin analogue
European Journal of Cancer, 2002Co-Authors: Patrick Schoffski, Hilde Rosing, A Herr, J B Vermorken, J Van Den Brande, J H Beijnen, J Volk, Arnold Ganser, S Adank, H J BotmaAbstract:Abstract A randomised, open label phase II study was performed in patients with advanced colorectal cancer to evaluate the safety, toxicity and antineoplastic activity of the topoisomerase I-inhibitor Rubitecan. A cross-over design was chosen to determine the intrapatient variation of the bioavailability and pharmacokinetics of the anticancer agent depending on the timing of food intake in relation to the oral drug administration. Patients with previously untreated metastatic disease received two single oral doses of Rubitecan 1.5 mg/m2 for assessment of the pharmacokinetics. They were randomised to have the first administration either after an overnight fasting period or immediately after a high calorie breakfast, and crossed over to the alternative schedule after a one-week washout period. After completion of the pharmacokinetic sampling, treatment continued with Rubitecan given orally at a dose of 1.5 mg/m2/day, to be increased up to 2.0 mg/m2/day, under fasting conditions for 5 consecutive days per week until disease progression. 19 patients entered the trial after informed consent was obtained. A total number of 35 treatment cycles (median 2, range 1–4) were administered. All patients were evaluable for safety. The toxicity profile of Rubitecan was generally mild to moderate, with sporadic cases of grade 4 toxicities (Common Toxicity Criteria (CTC) version 2.0) diarrhoea, leucopenia and neutropenia. None of 15 evaluable patients achieved an objective response. The majority had early disease progression. 14 patients were evaluable for pharmacokinetic analysis. The bioavailability of Rubitecan was found to be strongly dependent on the timing of food intake with a fasted-to-fed ratio for Cmax of 1.98 (two-tailed P
Ramesh K Ramanathan - One of the best experts on this subject based on the ideXlab platform.
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phase ii study of Rubitecan an oral camptothecin in patients with advanced colorectal cancer who have failed previous 5 fluorouracil based chemotherapy
Investigational New Drugs, 2006Co-Authors: Hitendra Patel, Ronald G Stoller, Miklos L Auber, Douglas M Potter, Chao Cai, William C Zamboni, Gauri J Kiefer, Khalid Matin, Amy Schmotzer, Ramesh K RamanathanAbstract:Background: Rubitecan (RFS-2000, 9NC, Orathecin™ is an orally bioavailable camptothecin analogue, with evidence of preclinical activity in colon cancer cell lines. We evaluated oral Rubitecan (5 days on, 2 days rest per week) on a continuous schedule, in patients with advanced colorectal cancer (CRC), who progressed after 5-flurouracil based chemotherapy. Patients and results: Fourteen eligible patients were treated with Rubitecan at 1.5 mg/m2/day on a 5 day/week continuous schedule. Therapy was well tolerated with most adverse events in the mild to moderate category. Grade 3/4 toxicity consisting of anemia, diarrhea and elevated bilirubin was seen in 4 patients. No responses were seen in 13 evaluable patients. Overall median survival (95% confidence interval) was 10.1 (range 3.1–12.6) months, and median time to progression was 2.1 months. Conclusions: Administration of Rubitecan was well tolerated, but this schedule does not appear to have clinical activity in patients with advanced previously treated CRC.
H J Botma - One of the best experts on this subject based on the ideXlab platform.
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clinical phase ii study and pharmacological evaluation of Rubitecan in non pretreated patients with metastatic colorectal cancer significant effect of food intake on the bioavailability of the oral camptothecin analogue
European Journal of Cancer, 2002Co-Authors: Patrick Schoffski, Hilde Rosing, A Herr, J B Vermorken, J Van Den Brande, J H Beijnen, J Volk, Arnold Ganser, S Adank, H J BotmaAbstract:Abstract A randomised, open label phase II study was performed in patients with advanced colorectal cancer to evaluate the safety, toxicity and antineoplastic activity of the topoisomerase I-inhibitor Rubitecan. A cross-over design was chosen to determine the intrapatient variation of the bioavailability and pharmacokinetics of the anticancer agent depending on the timing of food intake in relation to the oral drug administration. Patients with previously untreated metastatic disease received two single oral doses of Rubitecan 1.5 mg/m2 for assessment of the pharmacokinetics. They were randomised to have the first administration either after an overnight fasting period or immediately after a high calorie breakfast, and crossed over to the alternative schedule after a one-week washout period. After completion of the pharmacokinetic sampling, treatment continued with Rubitecan given orally at a dose of 1.5 mg/m2/day, to be increased up to 2.0 mg/m2/day, under fasting conditions for 5 consecutive days per week until disease progression. 19 patients entered the trial after informed consent was obtained. A total number of 35 treatment cycles (median 2, range 1–4) were administered. All patients were evaluable for safety. The toxicity profile of Rubitecan was generally mild to moderate, with sporadic cases of grade 4 toxicities (Common Toxicity Criteria (CTC) version 2.0) diarrhoea, leucopenia and neutropenia. None of 15 evaluable patients achieved an objective response. The majority had early disease progression. 14 patients were evaluable for pharmacokinetic analysis. The bioavailability of Rubitecan was found to be strongly dependent on the timing of food intake with a fasted-to-fed ratio for Cmax of 1.98 (two-tailed P
