5-fluorouracil and folinic acid with or without CPT-11 in advanced colorectal cancer patients: A multicenter randomised phase II study of the Southern Italy Oncology Group

Purpose: The combination regimen CPT-11 plus bolus and infusion 5-fluoroura cil (5-FU) with high-dose leucovorin (hybrid regimen LV5FU2) has been teste d for activity and toxicity against advanced colorectal carcinoma in a rand omised, multicenter phase II trial. Patients and methods: A total of 102 chemotherapy-naive patients were rando mised in a 1 : 2 fashion to receive: leucovorin 100 mg/m(2) administered as a two-hour infusion before 5-FU 400 mg/m(2) as an intravenous bolus, and F U 600 mg/m(2) as a 22-hour infusion immediately after 5-FU bolus injection repeated on days 1 and 2 (LV5FU2 regimen, arm A, 34 patients) or CPT-11 at 180 mg/m(2) (150 mg/m(2) for patients of age greater than or equal to 70 an d < 75 years) only on day 1 immediately before LV5FU2 therapy (LV5FU2 + CPT -11 regimen, arm B 68 patients). Both treatments were repeated every two we eks. The presence of a calibration arm assured consistency and more realist ic evaluation of results achieved with the LV5FU2 + CTP-11 regimen. Results: Thirty-three and sixty-four patients were evaluable in arm A and B , respectively. The overall response rate was 18% in arm A (95% CI: 7%-34%) and 40% in arm B (95% CI: 28%-52%). Median time to progression, median dur ation of response and survival were similar in both groups. Responders (CR + PR) survived statistically longer than non-responders only in arm B (20 v s. 10 months, P = 0.0016). All patients were evaluable for toxicity which w as mild in both groups; gastrointestinal disturbances were the most common. There were no treatment-related deaths. Grade 3-4 toxicity was uncommon in both arms. Conclusions: The addition of CPT-11 to the hybrid LV5FU2 regimen provided a significant overall response rate (40%) with relatively mild toxicity. The overall response rate was 18% in patients treated with LV5FU2 alone in the calibration arm. Thus, considering other encouraging data from the literat ure, the CPT-11 + FU-LV combination therapy can be regarded as a new, very effective treatment option for first-line treatment of advanced colorectal cancer patients.