Phase I trial of fixed dose-rate gemcitabine in combination with carboplatin in chemonaive advanced non-small-cell lung cancer: a Cancer Therapeutics Research Group study
Phase I trial of fixed dose-rate gemcitabine in combination with carboplatin in chemonaive advanced non-small-cell lung cancer: a Cancer Therapeutics Research Group study
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DOI：
10.1007/s00280-003-0637-5
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发表时间：
2003-08-01
影响因子：
3
通讯作者：
Goh, BC
中科院分区：
文献类型：
--
作者：
Soo, RA;Lim, HL;Goh, BC
目的。测定吉西他滨以10 mg/m(2)/min的固定剂量率与固定剂量卡铂联合给药的最大耐受量(MTD)，评价该方案的毒性，并测定血浆吉西他滨的药代动力学。方法：研究方法。晚期非小细胞肺癌(NSCLC)患者先用卡铂(AuC5)第1天给药，然后吉西他滨以10 mg/m(2)/min的剂量剂量递增，第1、8天每21天给药一次。于治疗第1天、第1周期采集药代动力学数据。结果。共有15名患者接受了卡铂和吉西他滨的治疗，队列中有3至6名患者，剂量为3个水平。吉西他滨的剂量分别为600、750和900 mg/m(2)。MTD为900 mg/m(2)。剂量限制毒副反应为血小板减少和肝功能衰竭，反复给药常可观察到中性粒细胞减少。吉西他滨第二阶段的推荐剂量为750 mg/m(2)。吉西他滨在600 mg/m~2和750 mg/m~(2)剂量时出现部分反应。血浆吉西他滨未达到稳定状态，只有一名患者的输注时间被研究过。但在20-90分钟内，所有患者的血药浓度均在10摩尔/L以上。结论。吉西他滨以10 mg/m(2)/min的固定剂量速率静脉滴注，第1天和第8天，联合卡铂第1天，每21天一次，75分钟静脉滴注，对非小细胞肺癌是耐受性和有效的。药代动力学研究表明，吉西他滨的血药浓度达到了10 mumol/L以上。有必要进行进一步的研究，将该方案与卡铂和吉西他滨的标准方案进行比较。
Purpose. To determine the maximally tolerated dose (MTD) of gemcitabine administered at a fixed dose-rate of 10 mg/m(2) per min in combination with fixed dose carboplatin, to evaluate the toxicity of this regimen and to determine the pharmacokinetics of plasma gemcitabine. Methods. Patients with advanced stage non-small-cell lung cancer (NSCLC) received carboplatin (AUC 5) on day 1 followed by gemcitabine at a fixed dose rate of 10 mg/m(2) per min in escalating durations of infusion on days 1 and 8 every 21 days. Pharmacokinetic sampling was obtained on day 1, cycle 1 of treatment. Results. A total of 15 patients received carboplatin and gemcitabine in cohorts of three to six patients at three dose levels. The doses of gemcitabine studied were 600, 750, and 900 mg/m(2). The MTD was reached at 900 mg/m(2). Dose-limiting toxicities were thrombocytopenia and liver failure, and with repeated dosing neutropenia was commonly observed. The recommended phase II dose of gemcitabine was 750 mg/m(2). Partial responses were observed at 600 and 750 mg/m(2) of gemcitabine. Plasma gemcitabine did not reach steady state except in one patient with the durations of infusion studied. Plasma concentrations, however, were above 10 mumol/l between 20 and 90 min in all patients. Conclusions. Gemcitabine administered as a 75-min infusion at a fixed dose rate of 10 mg/m(2)/min on days 1 and 8 in combination with carboplatin on day 1 every 21 days is tolerable and active in NSCLC. Pharmacokinetic studies demonstrated that the target plasma gemcitabine concentration above 10 mumol/l was achieved. Further studies are warranted to compare this regimen against standard regimens of carboplatin and gemcitabine.