Phase I-II study of irinotecan in combination with mitomycin C in patients with advanced gastrointestinal cancer.
This phase I-II study was conducted to determine the maximum tolerated dose and optimal schedule of a combination of irinotecan (CPT 11) and mitomycin C (MMC) in a population of previously treated patients with gastrointestinal malignancies. Four cohorts of patients were recruited with MMC given at 8 mg/m2 for the first 3 levels together with irinotecan at 300 mg/m2, 325 mg/m2, and 350 mg/m2; the fourth dose level was given with MMC at 10 mg/m2 and irinotecan at 325 mg/m2. All treatment was repeated at 21-day intervals. The dose-limiting toxicity was hematologic (thrombocytopenia at level 4), and the recommended doses for subsequent phase II studies are MMC 8 mg/m2 with irinotecan 325 mg/m2. Evidence of efficacy was seen at all dose levels examined and justifies further exploration of this combination in a less heavily pretreated patient population.
Gil-Delgado
M A
MA
Department of Medical Oncology, Salpêtrière Hospital, Paris, France.
Antoine
E C
EC
Guinet
F
F
Bassot
V
V
Grapin
J P
JP
Benhammonda
A
A
Adam
R
R
Castaing
D
D
Bismuth
H
H
Khayat
D
D
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009367:Neoplasm Staging
D016685:Mitomycin; D000077146:Irinotecan; D002166:Camptothecin