Protracted infusional 5-fluorouracil (5-FU) with bolus mitomycin in 5-FU-resistant colorectal cancer

Background: MF (protracted infusion 5-fluorouracil (5-FU), 300 mg/m(2)/24 hours plus bolus mitomycin, 7 mg/m(2) every 6 weeks, maximum 4 doses), was recently shown in a randomised trial to be superior to protracted 5-FU alone, as first-line chemotherapy for metastatic colorectal cancer (Ross et al. Ann Oncol 1997; 8: 995-1001 [5]). We have examined the same regimen in patients with 5-FU-resistant disease. Patients and methods: MF was given to 24 patients with metastatic colorectal cancer, median age 63 years. Two had progressed within four months of adjuvant 5-FU; the rest had already received palliative 5-FU, with progression during (11 patients), within four months (5 patients) or after four months of completion (6 patients). The prior 5-FU regimens were bolus 5-FU/FA (8 patients); 48 hour bolus + infusion 5-FU/FA (18 patients) or protracted 5-FU alone (3 patients). Five patients had received more than one prior 5-FU regimen. Results: Three patients, 12.5%, achieved WHO partial response; seven others had minor response or stable disease (SD or better = 42%, 95% confidence interval (95% CI): 22%-64%). Median failure-free survival (FFS) was 15 weeks; median overall survival was 9.0 months. No grade 3 or 4 drug toxicity occurred, but dose reduction and/or interruption for persistent grade 2 toxicity was required in eight patients (33%). Three patients (12.5%) had venous line problems (2 thrombosis; 1 dislodged). There were no toxic deaths. 12 patients (50%) went on to receive third-line therapy after MF, including irinotecan or oxaliplatin. Conclusions: MF is a low-cost, well-tolerated regimen in second-line treatment of metastatic colorectal cancer. The response rate and FFS obtained in this small group are similar to those reported for single agent irinotecan. Half our patients obtained a useful period of control with MF before moving on to further treatment with new agents such as irinotecan and oxaliplatin.