التفاصيل البيبلوغرافية
| العنوان: |
A dose regimen-finding study to evaluate the safety, tolerability, pharmacokinetics, and activity of oratecan in subjects with advanced malignancies. |
| المؤلفون: |
Boland, Patrick M., Fountzilas, Christos, Fakih, Marwan, Opyrchal, Mateusz, Diamond, Jennifer R., Corr, Bradley, Ma, Wen Wee, Redman, Michelle, Chan, Wing-Kai, Wang, Hui, Kramer, Doug, Kwan, Rudolf, Cutler, David, Zhi, Jay, Jimeno, Antonio |
| المصدر: |
Cancer Chemotherapy & Pharmacology; Aug2022, Vol. 90 Issue 2, p175-187, 13p |
| مصطلحات موضوعية: |
RESEARCH, DRUG dosage, CLINICAL trials, RESEARCH methodology, CAMPTOTHECIN, ANTINEOPLASTIC agents, EVALUATION research, COMPARATIVE studies, ALKANES, TUMORS, ENZYME inhibitors, DRUG toxicity |
| مستخلص: |
Purpose: Irinotecan is a commonly used chemotherapeutic in solid tumor malignancies. Oratecan is an investigational product comprised of encequidar methanesulfonate, a novel minimally absorbed P-glycoprotein pump inhibitor, and irinotecan. This study sought to determine the maximum tolerated dose (MTD) of oratecan in patients with advanced malignancies.Methods: Using a "3 + 3″ dose-escalation design, patients were treated with oratecan on day 1 every 21 days. The irinotecan dose was escalated from 20 to 320 mg/m2. The encequidar methanesulfonate dose was fixed at 15 mg (12.9 mg free base). PK sampling for irinotecan, encequidar and its major metabolites was performed following a single dose of oratecan during cycle 1. Patients were treated until disease progression or unacceptable toxicity.Results: Thirty-five patients were treated. The MTD was determined to be 280 mg/m2 every 21 days. Irinotecan and SN-38 plasma concentration-time profile showed that irinotecan exposure increased with dose and followed biexponential decay. Nine of 17 patients at oratecan dose levels 200 mg/m2 and above had SN-38 exposures comparable to those with intravenous irinotecan at standard dosing. None of the 35 patients achieved a radiologic response, ten patients had SD for > 8 weeks; the median progression-free survival for all treated patients was 9 weeks (95% CI 8.6-13.9).Conclusions: The MTD of oratecan was encequidar methanesulfonate 15 mg plus irinotecan 280 mg/m2. Exposure for irinotecan and SN-38 increased with increased dose. Potential antitumor activity was observed at the 280 and 320 mg/m2 dose levels. The safety profile of oratecan was comparable to that of intravenous irinotecan. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
