Phase I study of daily S-1 combined with weekly irinotecan in patients with advanced non-small cell lung cancer.
BACKGROUND
S-1 is a novel oral fluorouracil prodrug active against non-small cell lung cancer (NSCLC). To determine the feasibility of S-1 combined with weekly irinotecan for patients with advanced NSCLC, we performed a phase I study to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of irinotecan.


METHODS
Patients with advanced NSCLC received S-1 (80 mg/m(2)) on days 1-14 and irinotecan (50-80 mg/m(2)) on days 1, 8, and 15 of each 28-day cycle. Three to six patients were treated with each dose of irinotecan, with the MTD defined as the dose at which dose-limiting toxicity (DLT) appeared in 33% of patients.


RESULTS
At doses of 50-70 mg/m(2), no patients experienced any DLT, whereas, at a dose of 80 mg/m(2), two of four patients experienced DLTs. Two patients experienced grade 3 toxicities - neutropenia and diarrhea.


CONCLUSIONS
The MTD of weekly irinotecan was 80 mg/m(2), making its RD for phase II trials 70 mg/m(2).
Ishimoto
Osamu
O
Department of Pulmonary Medicine, Sendai Kousei Hospital, Aoba-ku, Sendai, Miyagi, Japan.
Ishida
Takashi
T
Honda
Yoshihiro
Y
Munakata
Mitsuru
M
Sugawara
Shunichi
S
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000008:administration & dosage; D005641:Tegafur / Q000008:administration & dosage; D016896:Treatment Outcome
D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000077146:Irinotecan; D002166:Camptothecin