Phase I and pharmacologic study of irinotecan in combination with cisplatin for advanced lung cancer.
We have conducted a Phase I trial to determine the maximum tolerated dose of CPT-11 together with a fixed dose of cisplatin in patients with advanced lung cancer, and the dose-limiting toxicities of this combination. Fourteen previously untreated patients with stage IIIB or IV disease were treated with CPT-11 (90-min intravenous infusion on days 1, 8, and 15) plus cisplatin (60 mg m-2, intravenously on day 1). The starting dose of CPT-11 was 60 mg m-2, and diarrhea was the dose-limiting toxicity at the 90 mg m-2 dose level. All three patients (all four cycles) given 90 mg m-2 of CPT-11 experienced grade 3 diarrhea. Hematologic toxicity was relatively mild. Elimination of CPT-11 was biphasic with a mean (+/- s.d.) beta half-life of 11.36 +/- 7.26 h. The mean terminal half-life of the major metabolite (7-ethyl-10-hydroxycamptothecin; SN-38) was 22.13 +/- 13.28 (s.d.) h, and modest escalation of the CPT-11 dose from 80 mg m-2 to 90 mg m-2 resulted in a statistically significant apparent increase in the plasma concentrations of SN-38. There were one complete response (7%) and five partial responses (36%) among the 14 patients for an overall response rate of 43%. The recommended dose for Phase II studies is 80 mg m-2 of CPT-11 and 60 mg m-2 of cisplatin.
Department of Internal Medicine, Osaka Prefectural Habikino Hospital, Osaka, Japan.
N
N
Masuda
M
M
Fukuoka
S
S
Kudoh
Y
Y
Kusunoki
K
K
Matsui
N
N
Takifuji
K
K
Nakagawa
M
M
Tamanoi
T
T
Nitta
T
T
Hirashima
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077146:Irinotecan; D007970:Leukopenia / Q000139:chemically induced; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging
D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin