Addition of either irinotecan or methotrexate to bolus 5-fluorouracil and high-dose folinic acid every 2 weeks in advanced colorectal carcinoma: a randomised study by the Southern Italy Cooperative Oncology Group

Purpose: The purpose of this study was to compare the activity and toxicity of the combination of irinotecan (IRI) plus folinic acid (FA)- modulated 5-fluorouracil (5-FU)i.v. bolus with a regimen of double modulation of 5-FU with methotrexate (MTX) and FA in patients with advanced colorectal carcinoma, Patients and methods: Two-hundred and thirty-four patients were enrolled: 118 patients received IRI 200 mg/m(2) (90-min i.v. infusion) on day 1, followed by levo-FA 250 mg/m(2) (2-h i.v. infusion) and 5-FU 850 mg/m(2) (i.v. bolus) on day 2 (IRIFAFU), and 116 patients received MTX 750 mg/m(2) (2-h i.v, infusion) on day 1, followed by levo-FA 250 mg/m(2) (2-h i.v. infusion) and FU 800 mg/m(2) (i.v. bolus) on day 2 (MTXFAFU). Both cycles were repeated every 2 weeks until progression or to a maximum of 16 cycles. Response rate (RR) was the main end point of the study; responses were assessed every four cycles and confirmed after 2 additional month of treatment. Results: RR was significantly greater with IRIFAFU (36%) than with MTXFAFU (20%) (P <0.001). Multivariate analysis showed that IRIFAFU was significantly associated with a greater activity (P = 0.028). Median progression-free survival was longer with IRIFAFU than with MTXFAFU (7.2 months compared with 4.8 months; P = 0.048). Median survival time (MST) did not differ between the two arms (14.7 months compared with 14.8 months, respectively). Patients not receiving second-line chemotherapy, however, lived longer when treated in the first-line with IRIFAFU (MST 11.9 months compared with 6.4 months; P = 0.038). IRIFAFU caused a significantly greater occurrence of grade 3 or 4 neutropenia (40% compared with 9%; P = 0.001) and diarrhoea (13% compared with 4%; P = 0.024), but a significantly lower incidence of stomatitis (3% compared with 12%; P = 0.007), than the comparative regimen. Conclusions: IRIFAFU appeared comparable in terms of activity and toxicity with other weekly or biweekly bolus or infusional combination regimens. IRIFAFU, however, seems easier to administer, because it does not require infusional catheter or pump devices, and it is less expensive. It may represent a new option for treating advanced colorectal carcinoma.