伊立替康和顺铂同步分程放疗用于不可切除的局部晚期非小细胞肺癌的I期研究

Phase I study of irinotecan and cisplatin with concurrent split-course radiotherapy in unresectable and locally advanced non-small cell lung cancer.

作者信息

Oka M, Fukuda M, Fukuda M, Kinoshita A, Kuba M, Ichiki M, Rikimaru T, Soda H, Takatani H, Narasaki F, Nagashima S, Nakamura Y, Hayashi N, Kohno S

机构信息

Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.

出版信息

Eur J Cancer. 2001 Jul;37(11):1359-65. doi: 10.1016/s0959-8049(01)00099-5.

DOI:10.1016/s0959-8049(01)00099-5

PMID:11435065

Abstract

We conducted a phase I study of irinotecan (CPT-11) and cisplatin with concurrent split-course radiotherapy in locally advanced stage III non-small cell lung cancer (NSCLC). This study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of this therapy. Two chemotherapy cycles of CPT-11 (days 1, 8 and 15) and cisplatin (day 1) were repeated with a 28-day interval. Radiotherapy of 2 Gy/day commenced on day 2 of each chemotherapy cycle, with 24 Gy and 36 Gy administered for the first and second cycle, respectively. 24 eligible patients were enrolled at five dose levels (CPT-11/cisplatin: 40/60, 50/60, 60/60, 60/70 and 60/80 mg/m(2)), and 23 patients were evaluated for toxicity and clinical outcome. Only 1 patient experienced a DLT with neutropenia and diarrhoea at 60/60 mg/m(2). Dose escalation was limited to 60/80 mg/m(2) which was the recommended dose for CPT-11/cisplatin alone in NSCLC. Tumour responses included one complete response (CR), 15 partial response (PR), and 7 no change (NC), and the overall response rate was 69.6% (95% confidence interval (CI) 47.1-86.8%). This combined modality is tolerable, and CPT-11/cisplatin of 60/80 mg/m(2) in this modality is recommended for phase II study.

摘要

我们开展了一项针对局部晚期 III 期非小细胞肺癌（NSCLC）患者的伊立替康（CPT-11）与顺铂同步分程放疗的 I 期研究。本研究旨在确定该治疗方案的最大耐受剂量（MTD）和剂量限制毒性（DLT）。CPT-11（第 1、8 和 15 天）和顺铂（第 1 天）的两个化疗周期以 28 天的间隔重复进行。每个化疗周期的第 2 天开始每天 2 Gy 的放疗，第一个周期和第二个周期分别给予 24 Gy 和 36 Gy。在五个剂量水平（CPT-11/顺铂：40/60、50/60、60/60、60/70 和 60/80 mg/m²）纳入了 24 例符合条件的患者，23 例患者接受了毒性和临床结局评估。仅 1 例患者在 60/60 mg/m²剂量时出现了中性粒细胞减少和腹泻的 DLT。剂量递增限于 60/80 mg/m²，这是 NSCLC 中单独使用 CPT-11/顺铂的推荐剂量。肿瘤反应包括 1 例完全缓解（CR）、15 例部分缓解（PR）和 7 例病情稳定（NC），总缓解率为 69.6%（95%置信区间（CI）47.1 - 86.8%）。这种联合治疗方式是可耐受的，推荐采用 60/80 mg/m²的 CPT-11/顺铂进行 II 期研究。