Multicenter phase II trial of dose-fractionated irinotecan in patients with advanced colorectal cancer failing oxaliplatin-based first-line combination chemotherapy

Background: A multicenter phase II trial was initiated to investigate the e fficacy and tolerance of a dose-fractionated administration schedule of iri notecan in patients with advanced colorectal cancer pre-treated with fluoro pyrimidine/oxaliplatin-based first-line combination chemotherapy. Patients and methods: 38 patients with metastatic colorectal cancer, who pr ogressed while receiving or within six months after withholding systemic ch emotherapy with oxaliplatin in combination with 5-fluorouracil/leucovorin o r the specific thymidilate synthase inhibitor raltitrexed were enrolled in this study. Treatment consisted of irinotecan 175 mg/m(2) given on days 1 a nd 10. Courses were repeated every three weeks for a total of six courses u nless prior evidence of progressive disease. Results: The overall objective response rate was 21% for all 38 patients (9 5% confidence interval (95% CI): 9.6% to 37.4%). Stable disease was noted i n 19 patients (50%), whereas the tumour progressed in 11 (29%). The median progression-free survival was 4.8 months (range 1.5 to 10.5). After a media n follow-up time of 10 months, 21 patients (55%) are still alive. Treatment was fairly well tolerated with only 9 of 38 patients (24%) experiencing gr ade 3 or 4 neutropenia. Similarly, nonhaematologic adverse reactions were g enerally mild; grade 3 toxicities included late-onset diarrhoea in 2 (5%), alopecia in 5 (13%), and infection in 1 case (3%), respectively. Conclusions: Our data suggest that this dose-fractionated irinotecan monoth erapy schedule has substantial antitumour activity in patients with fluprop yrimidine/oxaliplatin-based pre-treated colorectal cancer. Because of its f avourable toxicity profile when compared to previous experiences with the E uropean standard schedule of 350 mg/m(2) every three weeks, further evaluat ion of this modified regimen seems warranted.