Phase I study of a combination of irinotecan and ifosfamide in advanced primary lung cancer.
We sought to investigate cisplatin-free chemotherapy for patients with primary lung cancer. We therefore conducted a Phase II study to identify; a) the maximum tolerated dose (MTD) of irinotecan (CPT-11) given with a fixed dose of ifosfamide (IFM), and b) the principal toxic effects associated with this regimen in a Phase I study. A total of 27 patients with previously treated or untreated primary lung cancer received CPT-11 on days 1, 8 and 15 in combination with a fixed dose of IFM, 1.5 g/m2/day, on days 1 through 3, given every 4 weeks. The starting dose of CPT-11 was 30 mg/m2, which was increased by amounts of 10 mg/m2. Four patients were assigned to different dosage levels, and drug toxicity was evaluated for the first 2 cycles. The MTD of CPT-11 was 90 mg/m2, with leukopenia being the dose-limiting effect. The response rate was 43% (6/14; 1 complete response) in non-small cell lung cancer, and 78% (7/9; no complete response) in small cell lung cancer. The recommended dose of CPT-11 for a Phase II study is thus 80 mg/m2 on days 1, 8 and 15 with IFM 1.5 g/m2 given on days 1 through 3. This regimen appears particularly encouraging, because of its low toxicity. Phase II trials of the combination are indicated.
Department of Medicine, Kurume University School of Medicine, Japan.
M
M
Ichiki
T
T
Rikimaru
Y
Y
Okubo
R
R
Gohara
T
T
Mitui
T
T
Kawayama
M
M
Kinoshita
K
K
Oizumi
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged
D000077146:Irinotecan; D007069:Ifosfamide; D002166:Camptothecin