Phase I study of irinotecan and cisplatin with concurrent split-course radiotherapy in unresectable and locally advanced non-small cell lung cancer.
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.
Oka
M
M
Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan. okamikio@net.nagasaki-u.ac.jp
Fukuda
M
M
Fukuda
M
M
Kinoshita
A
A
Kuba
M
M
Ichiki
M
M
Rikimaru
T
T
Soda
H
H
Takatani
H
H
Narasaki
F
F
Nagashima
S
S
Nakamura
Y
Y
Hayashi
N
N
Kohno
S
S
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin