Background: A multicenter phase II trial was initiated to investigate the efficacy and tolerance of a dose-fractionated administration schedule of irinotecan in patients with advanced colorectal cancer pre-treated with fluoropyrimidine/ oxaliplatin-based first-line combination chemotherapy.
Patients and methods: 38 patients with metastatic colorectal cancer, who progressed while receiving or within six months after withholding systemic chemotherapy with oxaliplatin in combination with 5-fluorouracil/leucovorin or the specific thymidilate synthase inhibitor raltitrexed were enrolled in this study. Treatment consisted of irinotecan 175 mg/m2 given on days 1 and 10. Courses were repeated every three weeks for a total of six courses unless prior evidence of progressive disease.
Results: The overall objective response rate was 21% for all 38 patients (95% confidence interval (95% CI): 9.6% to 37.4%). Stable disease was noted in 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 median 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 grade 3 or 4 neutropenia. Similarly, nonhaematologic adverse reactions were generally 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 monotherapy schedule has substantial antitumour activity in patients with flupropyrimidine/oxaliplatin-based pre-treated colorectal cancer. Because of its favourable toxicity profile when compared to previous experiences with the European standard schedule of 350 mg/m2 every three weeks, further evaluation of this modified regimen seems warranted.