A phase II study of irinotecan alternated with a weekly schedule of high-dose leucovorin and 48-hour 5-fluorouracil infusion in patients with metastatic colorectal cancer.
OBJECTIVE
To evaluate the activity and safety of an alternating schedule of irinotecan (CPT-11) with high-dose 5-fluorouracil (5-FU) given as a weekly 48-hour infusion in combination with leucovorin (LV) in the first-line treatment of metastatic colorectal cancer (MCRC) patients.


METHODS
We tested the activity of a regimen consisting of a four times per week schedule of high-dose LV (150 mg/m2) followed by a 48-hour 5-FU infusion (2,600 mg/m2) alternated with CPT-11 (350 mg/m2). An alternating cycle was to be performed every 8 weeks. Treatment was administered until disease progression, unacceptable toxicity or patient refusal occurred. Thirty-five consecutive patients with measurable MCRC, aged 18-80, with a performance status < or =2, were entered into our study from May 1998 to January 2000.


RESULTS
Four complete and 9 partial responses were observed (objective response rate was 37%; 95% confidence interval, CI: 21.5-55.1%); an additional 46% of the patients had stable disease. The median duration of response was 6.2 months, median time to progression 8 months (95% CI: 5.9-10.1%), and overall survival was 18.5 months (95% CI: 15.1-21.9%). The 1-year survival was 68%. No toxic deaths occurred. The incidence of grade 3-4 toxicity per patient in any cycle was: mucositis 9% and diarrhea 11% for the infusional 5-FU part, nausea/vomiting 3%, diarrhea 14%, and neutropenia 43% for the CPT-11 part of regimen.


CONCLUSIONS
Our alternating schedule of 5-FU/LV and CPT-11 is a well-tolerated outpatient treatment as front-line therapy for MCRC with comparable efficacy to regimens with both drugs given together.
Rosati
Gerardo
G
Medical Oncology Unit, 'S. Carlo' Hospital, Potenza, Italy. rosatiger@yahoo.com
Rossi
Antonio
A
Reggiardo
Giorgio
G
Manzione
Luigi
L
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018395:CA-19-9 Antigen / Q000378:metabolism; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D016896:Treatment Outcome
D018395:CA-19-9 Antigen; D002272:Carcinoembryonic Antigen; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin