CONTINUOUS-INFUSION FLUOROURACIL LEUCOVORIN AND BOLUS MITOMYCIN-C AS A SALVAGE REGIMEN FOR PATIENTS WITH ADVANCED COLORECTAL-CANCER

Background. No effective systemic salvage therapy exists for patients with advanced colorectal cancer who progress after receiving bolus flu orouracil (FU) and leucovorin (LV) chemotherapy. In vitro data suggest that bolus FU resistance can be overcome by continuous infusion (CI) FU, and that the cytotoxic effects of Mitomycin-C (MMC) and FU are syn ergistic. Based on this data, a Phase II trial of CI FU and LV with bo lus MMC in patients with advanced colorectal carcinoma who progressed on only one previous chemotherapy regimen was performed.Methods. Twent y-eight patients with advanced colorectal carcinoma who had progressed after one previous chemotherapy regimen of bolus FU/LV were treated w ith bolus MMC 10 mg/m(2) every 6 weeks and CI FU 200 mg/m(2)/day admir ed with LV 10 mg/m(2)/day given 14 days on/7 days off. Results. The pa rtial response rate in 24 evaluable patients was 17% (95% confidence i nterval, 2-32%) with a median response duration of 9.5 months (range, 4.2-12.0 months). Twelve (50%) additional patients achieved disease st abilization. Median survival was 9.9 months in the whole group (28 pat ients) and 11.5 months in the 24 evaluable patients. The major toxicit ies were grade 4 diarrhea occurring in two patients and grade 3 mucosi tis occurring in five patients. There was minimal myelosuppression (gr ade 3 thrombocytopenia in one patient) and no occurrences of hand-foot syndrome or cardiotoxicity. Conclusions. This regimen demonstrates mo dest activity with acceptable toxicity in colorectal cancer patients w ho have failed a single-bolus FU/LV regimen. Modifications of this and other infusional FU-based chemotherapy regimens should be explored as potential salvage chemotherapy regimens in advanced colorectal cancer .