多西他赛、吉西他滨和顺铂给药顺序改变对晚期非小细胞肺癌患者的影响。

Influence of altering administration sequence of docetaxel, gemcitabine and cisplatin in patients with advanced non-small cell lung cancer.

作者信息

Harita Shingo, Watanabe Youichi, Kiura Katsuyuki, Tabata Masahiro, Takigawa Nagio, Kuyama Shoichi, Kozuki Toshiyuki, Kamei Haruhito, Tada Atsuhiko, Okimoto Niro, Genba Kenichi, Tada Shinichi, Ueoka Hiroshi, Hiraki Shunkichi, Tanimoto Mitsune

机构信息

Department of Internal Medicine, Chugoku Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuyama, Japan.

出版信息

Anticancer Res. 2006 Mar-Apr;26(2B):1637-41.

PMID:16619585

Abstract

BACKGROUND

A phase II study of a triplet chemotherapy with the administration sequence of gemcitabine (GEM), docetaxel (DCT) and cisplatin (CDDP) (OLCSG9908) was previously conducted in patients with advanced non-small cell lung cancer (NSCLC). The objective response rate was 34% and the median survival time (MST) and 1-year survival rate were 11.7 months and 49%, respectively. In an in vitro study of different sequence exposures to GEM and DCT, it was reported that the synergistic effect was more prominent using the administration sequence of DCT followed by GEM compared with the reverse sequence. In order to estimate the effects of the administration sequence, a phase II study of the same triplet chemotherapy was conducted with the administration sequence of DCT, CDDP and GEM.

PATIENTS AND METHODS

Patients with unresectable stage IIIB/IV NSCLC were eligible. All drugs were given intravenously on days 1 and 8, and repeated every 4 weeks for up to 4 cycles. DCT (30 mg/m2) was given first, followed by CDDP (40 mg/m2) and GEM (800 mg/m2).

RESULTS

Thirty-four patients were enrolled on this study (OLCSG0101). The objective response rate was 38% (95% CI: 22-56%). As grade 3/4 hematological toxicities, neutropenia, thrombocytopenia and anemia were observed in 70%, 41% and 21%, respectively, and febrile neutropenia was observed in 12%. As grade 3/4 non-hematological toxicities, vomiting and liver dysfunction were observed in 15% and 18%, respectively. These toxicities were manageable by conventional therapy. The MST and 1-year survival rate were 13.3 months (95% CI: 7.8-18.7 months) and 55% (95% CI: 38-73%), respectively. These results were similar to those of OLCSG9908.

CONCLUSION

This triplet chemotherapy is well tolerated and effective in patients with advanced NSCLC, however, the treatment outcome was not significantly influenced by the administration sequence of DCT and GEM.

摘要

背景

先前对晚期非小细胞肺癌（NSCLC）患者进行了一项吉西他滨（GEM）、多西他赛（DCT）和顺铂（CDDP）三联化疗的II期研究（OLCSG9908）。客观缓解率为34%，中位生存时间（MST）和1年生存率分别为11.7个月和49%。在一项关于GEM和DCT不同给药顺序的体外研究中，据报道与相反顺序相比，采用DCT后接GEM的给药顺序时协同效应更为显著。为了评估给药顺序的影响，对相同的三联化疗进行了II期研究，给药顺序为DCT、CDDP和GEM。

患者与方法

不可切除的IIIB/IV期NSCLC患者符合条件。所有药物均在第1天和第8天静脉给药，每4周重复一次，最多进行4个周期。先给予DCT（30mg/m²），随后给予CDDP（40mg/m²）和GEM（800mg/m²）。

结果

34例患者纳入本研究（OLCSG0101）。客观缓解率为38%（95%CI：22 - 56%）。作为3/4级血液学毒性，中性粒细胞减少、血小板减少和贫血的发生率分别为70%、41%和21%，发热性中性粒细胞减少的发生率为12%。作为3/4级非血液学毒性，呕吐和肝功能障碍的发生率分别为15%和18%。这些毒性可通过常规治疗控制。MST和1年生存率分别为13.3个月（95%CI：7.8 - 18.7个月）和55%（95%CI：38 - 73%）。这些结果与OLCSG9908的结果相似。