Department of Medical Oncology, University General Hospital of Heraklion, Heraklion, Crete, Greece.
Cancer Chemother Pharmacol. 2011 Aug;68(2):415-22. doi: 10.1007/s00280-010-1508-5. Epub 2010 Nov 11.
A phase I study was conducted to determine the maximum tolerated doses (MTD) and the dose-limiting toxicities (DLT) of pemetrexed and docetaxel in patients with advanced unresectable or metastatic non-small-cell lung cancer (NSCLC). Patients were treated with escalating doses of pemetrexed (400-600 mg/m(2) as a 10-min intravenous infusion) and docetaxel (65-85 mg/m(2) as a 1-h intravenous infusion) on day 1, every 3 weeks. An expanded accrual at the level of the recommended dose (RD) had been scheduled. Forty-two patients with metastatic NSCLC were enrolled in the phase I study and 20 additional patients at the RD level. The MTD could not be reached even at the doses of 550 and 85 mg/m(2) for pemetrexed and docetaxel, respectively, which are higher than the recommended dose for each drug given as a single agent. Therefore, the RD was defined at 500 mg/m(2) pemetrexed and 75 mg/m(2) docetaxel. Among the 164 administered chemotherapy cycles (phase I part), there were three episodes of febrile neutropenia whereas 13 (7.9%) and 11 (6.7%) cycles were complicated with grade III and IV neutropenia, respectively. Three patients developed grade III/IV thrombocytopenia. Non-hematologic toxicity was mild with grade III fatigue occurring in three (6.7%) patients. There was no toxic death. The favorable toxicity profile of the regimen was confirmed in patients treated at the RD level. Overall, one complete (CR) and 13 partial responses (PR) (overall response rate = 23; 95% C.I:12.4-33.5%] were documented. The combination of pemetrexed and docetaxel seems to be an effective regimen in NSCLC with acceptable and manageable toxicity, which merits further investigation.
一项 I 期研究旨在确定晚期不可切除或转移性非小细胞肺癌（NSCLC）患者中培美曲塞和多西他赛的最大耐受剂量（MTD）和剂量限制毒性（DLT）。患者接受培美曲塞（400-600mg/m²，静脉输注 10 分钟）和多西他赛（65-85mg/m²，静脉输注 1 小时）递增剂量治疗，每 3 周 1 次。已计划在推荐剂量（RD）水平上扩大入组。42 例转移性 NSCLC 患者入组 I 期研究，20 例患者在 RD 水平入组。即使培美曲塞和多西他赛的剂量分别达到 550mg/m²和 85mg/m²，MTD 仍未达到，这高于每种药物作为单药的推荐剂量。因此，RD 定义为培美曲塞 500mg/m²和多西他赛 75mg/m²。在 164 个化疗周期（I 期部分）中，有 3 例发热性中性粒细胞减少症，分别有 13（7.9%）和 11（6.7%）个周期并发 3 级和 4 级中性粒细胞减少症。3 例患者发生 3/4 级血小板减少症。非血液学毒性较轻，3 例（6.7%）患者出现 3 级疲劳。无毒性死亡。在 RD 水平治疗的患者中证实了该方案具有良好的毒性特征。总的来说，13 例患者（CR1，PR12）获得了完全缓解（CR）和部分缓解（PR）（总缓解率=23%；95%置信区间：12.4-33.5%）。培美曲塞和多西他赛联合方案在 NSCLC 中具有较好的疗效和可接受的毒性，值得进一步研究。
