A prospective randomised trial of protracted venous infusion 5-fluorouracil with or without mitomycin C in advanced colorectal cancer

Background: To compare protracted venous infusion (PVI) 5-fluorouracil (5-FU) with and without mitomycin C (MMC) in a prospectively randomised study and analyse for tumour response, survival, toxicity and quality of life (QL). Patients and methods. Two hundred patients with advanced colorectal cancer received PVI 5-FU 300 mg/m(2)/day for a maximum of 24 weeks and were randomised to PVI 5-FU alone or PVI 5-FU + MMC 10 mg/m(2) (7 mg/m(2) from June 1995) 6 weekly for 4 courses. Results. Overall response was 54% (95% confidence interval [CI] 44.1%-63.9%) with PVI 5-FU + MMC compared to 38% (95% CI: 28.3%-47.7%) for PVI 5-FU alone (P = 0.024). The median failure free survival was 7.9 months in PVI 5-FU plus MMC and 5.4 months with PVI 5-FU alone (P = 0.033) and at one year 31.9% for the combination compared to 17.7% for PVI 5-FU alone. Median survival was 14 months with MMC and 15 months in 5-FU alone; one-year survival 51.7% vs. 57.2%. PVI 5-FU + MMC caused more overall haematological toxicity but CTC grades 3/4 was increased only for thrombocytopaenia. Two patients treated with a cumulative dose of MMC of 40 mg/m(2) developed haemolytic uraemic syndrome warranting the reduction in cumulative MMC dose to 28 mg/m(2). The global QL scores were better for PVI 5-FU + MMC arm at 24 weeks, but the remaining QL data showed no differences. Conclusions. PVI 5-FU + MMC results in failure-free survival and response advantage, tolerable toxicity and better QL when compared to PVI 5-FU alone but no Overall survival advantage. There is no irreversible toxicity with MMC at a cumulative dose of 28 mg/m(2).