依托泊苷、顺铂和伊立替康三联方案用于晚期小细胞肺癌患者的Ⅰ期研究

Phase I study of etoposide, cisplatin and irinotecan triplet in patients with advanced-stage small-cell lung cancer.

作者信息

Briasoulis E, Samantas E, Kalofonos H, Skarlos D, Makatsoris T, Christodoulou C, Fountzilas G, Bamias A, Dimopoulos M A, Kosmidis P, Pavlidis N

机构信息

Medical Oncology Department, University Hospital, Ioannina, Greece.

出版信息

Cancer Chemother Pharmacol. 2005 Nov;56(5):521-8. doi: 10.1007/s00280-004-0994-8. Epub 2005 Jun 15.

DOI:10.1007/s00280-004-0994-8

PMID:15959778

Abstract

AIM

The irinotecan-cisplatin combination has emerged as a new standard for the treatment of advanced-stage small-cell lung cancer (AS-SCLC). To move forward we developed a 3-day regimen of cisplatin, etoposide and irinotecan.

METHODS

Successive cohorts of AS-SCLC patients were treated with irinotecan administered as a single 1-h infusion in combination with fixed doses of cisplatin (20 mg/m(2)) and etoposide (75 mg/m(2)), both given for three consecutive days (ECI regimen). Irinotecan dose was escalated from 60 mg/m(2) by 40-mg/m(2) increments. At mid-step between the maximum tolerated dose (MTD) and the previous dose level, patients were randomized for the day of administration of irinotecan (day 1 vs day 3).

RESULTS

A total of 36 AS-SCLC patients received 166 courses of treatment at four dose levels. The MTD of irinotecan was 140 mg/m(2) (three dose-limiting toxicities, DLTs), and the recommended optimal dose (ROD) 120 mg/m(2) (two DLTs). DLTs were febrile neutropenia and grade 3 diarrhea. Other toxicities were mild. No difference in toxicity was seen between the two time schedules. A 77% (95% CI 63.25-90.75%) response rate was recorded among 31 evaluable patients and the median survival was 12 months.

CONCLUSIONS

The ECI regimen was well tolerated and showed considerable activity in patients with AS-SCLC. Phase II/III evaluation is ongoing.

摘要

目的

伊立替康联合顺铂已成为晚期小细胞肺癌（AS-SCLC）治疗的新标准。为进一步推进治疗，我们制定了一种顺铂、依托泊苷和伊立替康的3天治疗方案。

方法

连续多组AS-SCLC患者接受伊立替康治疗，静脉滴注1小时，联合固定剂量的顺铂（20mg/m²）和依托泊苷（75mg/m²），均连续给药3天（ECI方案）。伊立替康剂量从60mg/m²开始，每次递增40mg/m²。在最大耐受剂量（MTD）和前一剂量水平之间的中间步骤，患者被随机分配伊立替康的给药日（第1天与第3天）。

结果

共有36例AS-SCLC患者在四个剂量水平接受了166个疗程的治疗。伊立替康的MTD为140mg/m²（3例剂量限制性毒性，DLTs），推荐最佳剂量（ROD）为120mg/m²（2例DLTs）。DLTs为发热性中性粒细胞减少和3级腹泻。其他毒性较轻。两种给药时间方案之间的毒性无差异。31例可评估患者的缓解率为77%（95%CI 63.25-90.75%），中位生存期为12个月。