Ueoka H, Tabata M, Kiura K, Shibayama T, Gemba K, Segawa Y, Chikamori K, Yonei T, Hiraki S, Harada M
Second Department of Medicine, Okayama University Medical School, Japan.
Br J Cancer. 1999 Feb;79(5-6):984-90. doi: 10.1038/sj.bjc.6690157.
A combination chemotherapy of irinotecan (CPT-11) and cisplatin (CDDP) has been reported to be active for lung cancer. In the previous trial, however, diarrhoea and leucopenia became the major obstacle for sufficient dose escalation of CPT-11 to improve the treatment outcome. We conducted a phase I study to investigate whether the fractionated administration of CDDP and CPT-11 at escalated dose was feasible and could improve the treatment outcome. Twenty-four previously untreated patients with unresectable non-small-cell lung cancer (NSCLC) or extensive disease of small-cell lung cancer (SCLC) were eligible. Both CDDP and CPT-11 were given on days 1 and 8, and repeated every 4 weeks. The dose of CDDP was fixed at 60 mg m(-2) and given by 1-h infusion before CPT-11 administration. The starting dose of CPT-11 was 40 mg m(-2), and the dose was escalated by an increase of 10 mg m(-2). The maximally tolerated dose of CPT-11 was determined as 60 mg m(-2) because grade 4 haematological or grade 3 or 4 non-haematological toxicities developed in six patients out of 11 patients evaluated. Diarrhoea became a dose-limiting toxicity. The objective response rates were 76% for NSCLC and 100% for SCLC. The recommended dose of CPT-11 and CDDP in a phase II study will be 50 mg m(-2) and 60 mg m(-2) respectively.
据报道，伊立替康（CPT-11）和顺铂（CDDP）联合化疗对肺癌有效。然而，在之前的试验中，腹泻和白细胞减少成为了将CPT-11剂量充分增加以改善治疗效果的主要障碍。我们进行了一项I期研究，以调查递增剂量的CDDP和CPT-11分阶段给药是否可行以及能否改善治疗效果。24例既往未接受过治疗的不可切除非小细胞肺癌（NSCLC）或广泛期小细胞肺癌（SCLC）患者符合条件。CDDP和CPT-11均在第1天和第8天给药，每4周重复一次。CDDP剂量固定为60 mg/m²，在CPT-11给药前通过1小时输注给药。CPT-11起始剂量为40 mg/m²，剂量以每次增加10 mg/m²的幅度递增。由于在11例评估患者中有6例出现4级血液学毒性或3级或4级非血液学毒性，因此CPT-11的最大耐受剂量确定为60 mg/m²。腹泻成为剂量限制性毒性。NSCLC的客观缓解率为76%，SCLC为100%。II期研究中CPT-11和CDDP的推荐剂量将分别为50 mg/m²和60 mg/m²。
