Japanese Journal of Clinical Oncology 30:122-127 (2000)
© 2000 Foundation for Promotion of Cancer Research
Phase I Study of a Weekly Infusion of Irinotecan Hydrochloride (CPT-11) and a 14-day Continuous Infusion of Etoposide in Patients with Lung Cancer: Japan Clinical Oncology Group 9408
1Division of Medical Oncology, National Cancer Center Hospital, Tokyo, 2Division of Medical Oncology, National Cancer Center Hospital East, Kashiwa, 3Pathological Division, National Cancer Center Research Institute, Tokyo and 4Japan Clinical Oncology Group Data Center, National Cancer Center Research Institute, Tokyo, Japan
Background: To determine the maximum-tolerated dose (MTD) and acceptable dose level of CPT-11 in combination with a 14-day continuous infusion of etoposide in patients with refractory advanced lung cancer (LC), especially small cell lung cancer (SCLC).
Methods: Etoposide was administered continuously at 25 mg/m2/day for 14 days. The initial dose of CPT-11 was 40 mg/m2 given as a 90-min intravenous infusion on days 1, 8 and 15 and the dose escalation of CPT-11 was planned in increments of 20 mg/m2 until severe or life-threatening toxic effects were observed.
Results: Eight refractory advanced LC patients entered this study, of whom two were not assessable for toxicity because of patient’s refusal and progressive disease. One treatment-related death due to pulmonary toxicity and one patient with hypotension who needed catecholamine for more than 48 h were observed at a CPT-11 dose of 40 mg/m2. The MTD of CPT-11 was 40 mg/m2. Therapeutic efficacy could be assessed in six patients, of whom two achieved a partial response.
Conclusions: This regimen was too toxic and the recommended dose was outside this study. One has to consider pulmonary toxicity when using CPT-11, especially for patients previously treated with cytotoxic agents for which pulmonary toxicity has been reported.
+ For reprints and all correspondence: Tetsu Shinkai, Division of Medical Oncology, National Cancer Center Hospital, 1–1, Tsukiji 5-chome, Chuo-ku, Tokyo, Japan. E-mail: tshinkai@ncc.go.jpAbbreviations: JCOG, Japan Clinical Oncology Group; CPT-11, irinotecan hydrochloride; MTD, maximum tolerated dose; LC, lung cancer; SCLC, small cell lung cancer; LD, limited disease; ED, extensive disease; NSCLC, non-small cell lung cancer; ECOG, Eastern Cooperative Oncology Group; PS, performance status; WBC, white blood cell; Hb, hemoglobin; CBC, complete blood cell; ECG, electrocardiogram; CT, computerized tomography; DLT, dose-limiting toxicity; WHO, World Health Organization; TRT, treatment-related death; GOT, glutamic–oxaloacetic transaminase; GPT, glutamic–pyruvic transaminase; LDH, lactate dehydrogenase; ALP, alkaline phosphatase; BUN, blood urea nitrogen; G-CSF, granulocyte colony-stimulating factor; MMC, mitomycin C; MVP, combination therapy of mitomycin C, vindesine and cisplatin; CODE, combination therapy of cisplatin, vincristine, doxorubicin and etoposide; PR, partial response; SD, stable disease; PD, progressive disease; NE, not evaluable