Prospective phase II trial of iriontecan, 5-fluorouracil, and leucovorin in combination as salvage therapy for advanced colorectal cancer.
Irinotecan (CPT11) has established activity in the treatment of advanced colorectal cancer without cross-resistance with established 5-fluorouracil/folinic acid-based therapy. This phase II study was conducted to establish the efficacy and tolerance of combination treatment with irinotecan and 5-fluorouracil as salvage treatment for this disease. Open phase II trial of CPT11 180 mg/m2 on day 1, leucovorin 200 mg/m2 on days 1 and 2, and 5-fluorouracil 400 mg/m2 loading dose followed by 600 mg/m2 infusion on days 1 and 2. Treatment was continued until progression or limiting toxicity. Responders could proceed to surgical resection of residual disease. Thirty-nine patients from 2 institutions received a total of 287 cycles of therapy (median 7 cycles/patient). Eight patients achieved an objective response (7 for liver metastasis and 1 for lung metastasis), and an additional 12 obtained stabilization of disease or minor responses (MR); of these patients, 8 with liver metastasis (7 partial response and 1 MR) underwent hepatic resection of metastases and all them obtained a complete response. The median duration of response was 14 months, and the median survival was 11 months. Hematologic toxicity (neutropenia) was the most common serious side effect (29% of patients in 2% of cycles), but significant fever developed in only 4 patients. Grade III diarrhea was experienced in at least 1 cycle by 10% of patients. The results of this schedule compare favorably with previously reported experience of a phase I study designed to establish the dose of CPT11. Efficacy in this poor prognosis group of patients is very encouraging, and the schedule is well tolerated by even previously treated patients.
Department of Medical Oncology, Pitié Salpêtrière Hospital, Paris, France.
M A
MA
Gil-Delgado
F
F
Guinet
D
D
Castaing
R
R
Adam
D
D
Coeffic
A K
AK
Durrani
H
H
Bismuth
D
D
Khayat
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011446:Prospective Studies; D016879:Salvage Therapy
D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin