Phase I/II study of docetaxel and S-1, an oral fluorinated pyrimidine, for untreated advanced non-small cell lung cancer
Phase I/II study of docetaxel and S-1, an oral fluorinated pyrimidine, for untreated advanced non-small cell lung cancer
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多西他赛和 S-1（一种口服氟化嘧啶）治疗未经治疗的晚期非小细胞肺癌的 I/II 期研究
DOI：
10.1016/j.lungcan.2009.08.009
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发表时间：
2010
期刊：
影响因子：
5.3
通讯作者：
Niitani H
中科院分区：
文献类型：
--
作者：
Takiguchi Y;Tada Y;Gemma A;Kudoh S;Hino M;Yoshimori K;Yoshimura A;Nagao K;Niitani H
本项I/II期研究的目的是评价一种由多西他赛和S-1组成的新型联合化疗方案作为未经治疗的晚期非小细胞肺癌（NSCLC）患者的一线治疗。治疗包括多西他赛（第1天）和口服S-1（固定剂量40 mg/m2，每日2次，第1-14天），每3周重复一次。在I期，从水平1开始，多西他赛剂量递增至40（水平0）、50（水平1）和60 mg/m2（水平2）。由于水平1的6例患者队列中仅1例患者和水平2的3例患者队列中无患者发生定义的剂量限制性毒性（DLT），因此将水平2确定为推荐剂量。在II期，60例患者接受了中位3个周期的推荐剂量治疗，总缓解率为30%（95%置信区间[CI]，18.9-43.2%），中位总生存期和无进展生存期分别为15.2（95% CI：10.5-17.7）和4.9（95% CI：3.5-5.6）个月。最常见的毒性反应为中性粒细胞减少症、发热性中性粒细胞减少症和食欲不振;但所有毒性反应均可良好管理。本方案在未经治疗的NSCLC中显示出强效活性和轻度毒性。
The purpose of this phase I/II study is to evaluate a new combination chemotherapy consisting of docetaxel and S-1 as front-line therapy for patients with untreated advanced non-small cell lung cancer (NSCLC). The treatment included docetaxel on day 1 and oral S-1 at a fixed dose of 40mg/m2administered twice daily on days 1–14 and repeated every 3 weeks. In phase I, docetaxel at escalating doses of 40 (level 0), 50 (level 1) and 60mg/m2(level 2) was administered starting from level 1. Because only one patient among the 6-patient cohort at level 1 and no patient among the 3-patient cohort at level 2 experienced defined dose-limiting toxicity (DLT), level 2 was determined as the recommended dose. In phase II, 60 patients were treated at the recommended dose for median 3 cycles, and the overall response rate was 30% (95% confidence interval [CI], 18.9–43.2%), and the median overall and progression-free survival times were 15.2 (95% CI: 10.5–17.7) and 4.9 (95% CI: 3.5–5.6) months, respectively. The most frequent toxicities experienced were neutropenia, febrile neutropenia and appetite loss; all toxicities were however well manageable. The present regimen showed a potent activity with mild toxicity in untreated NSCLC.