Phase I trial of weekly irinotecan combined with UFT as second-line treatment for advanced colorectal cancer.
The aim of this study was to determine the maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT) of weekly Irinotecan (CPT-11) plus UFT, and to assess the antitumour activity of this combination as second-line chemotherapy in patients with advanced colorectal carcinoma, 31 patients with measurable advanced colorectal carcinoma were treated. Cohorts of 3 patients received increasing dose levels of the combination. Levels 1 to 4 included a fixed dose of oral (p.o.) UFT (250 mg/m(2)/day) for 21 days of a 28-day cycle combined with increasing intravenous (i.v.) doses of CPT-11 (80, 100, 110 and 120 mg/m(2)) on days 1, 8 and 15. Levels 5 and 6 included a higher fixed dose of oral UFT (300 mg/m(2)) combined with increasing i.v. doses of CPT-11 (100 and 110 mg/m(2)) on days 1, 8 and 15. 147 courses were administered. MTD were reached at level 4 (2 cases of grade 4 diarrhoea and 1 grade 3 asthenia), and level 6 (1 grade 4 diarrhoea, 1 grade 3 diarrhoea and 1 grade 3 febrile neutropenia). Responses in 30 evaluable patients were: 3 partial responses (10%), 15 stable disease (50%) and progressive disease in 12 patients (40%). Median time to progression was 4.5 months (95% Confidence Interval (CI): 3.4-6.6 months) and median survival was 11 months (95% CI: 7.9-14.1 months). The recommended doses for phase II trials are: (a) CPT-11 110 mg/m(2) i.v. on days 1, 8 and 15 every 28 days plus UFT 250 mg/m(2) p.o. on days 1 through to 21 or (b) CPT-11 100 mg/m(2) and UFT 300 mg/m(2).
Alonso
V
V
Division of Medical Oncology, Miguel Servet Hospital, Zaragoza, Spain. valonsoo@ene.es
Escudero
P
P
Zorrilla
M
M
Isla
M D
MD
Herrero
A
A
Mayordomo
J I
JI
Martinez-Trufero
J
J
Sáenz
A
A
Tres
A
A
Antón
A
A
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003967:Diarrhea / Q000139:chemically induced; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D014498:Uracil / Q000008:administration & dosage / Q000009:adverse effects
D005641:Tegafur; D014498:Uracil; D000077146:Irinotecan; D002166:Camptothecin