Multiple-target Chemotherapy (Lv-modulated 5-FU Bolus and Continuous Infusion,Oxaliplatin,CPT-11) in Advanced 5-Fu-refractory Colorectal Cancer: Mtd Definition and Efficacy Evaluation. A Phase I-II Study

Abstract

Aims and Background

To identify the maximum tolerated doses and to define the activity of a regimen incorporating leucovorin (LV)-modulated 5-fluorouracil (5-FU) bolus and continuous infusion, oxaliplatin (I-OHP) and irinotecan (CPT-11) in patients with advanced, 5-FU-refractory colorectal cancer (CRC).

Patients and Methods

Starting doses: LV 100 mg/m² as a 2-hour infusion followed by 5-FU 300 mg/m² bolus administration followed by 5-FU 500 mg/m² as a 22-hour infusion on days 1 and 2; I-OHP 65 mg/m² as a 2-hour infusion concomitantly with LV on day 1; CPT-11 90 mg/m² concomitantly with LV on day 2. Planned cycle interval: 2 weeks.

Results

Two hundred twenty-six cycles were administered to 27 patients. Recommended doses were 5-FU bolus 300 mg/m², 5-FU protracted infusion 500 mg/m², l-OHP 75 mg/m², and CPT-11 150 mg/m². Among 25 patients evaluable for response we observed 13 disease stabilizations (52%; 95% CI: 33-71%), 6 instances of disease progression and 6 responses (24%; 95% CI: 7-41%). Median time to progression and overall survival were 24 and 60 weeks, respectively. A cycle delay >3 days was observed in 134/199 cycles (67%).

Conclusions

This study confirms the feasibility of triplet chemotherapy in patients with advanced 5-FU-refractory CRC.