A phase II study of irinotecan plus chronomodulated oxaliplatin, 5-fluorouracil and folinic acid in advanced colorectal cancer patients

The combination of irinotecan (CPT-11), oxaliplatin (L-OHP), 5- fluorouracil (5-FU) and folinic acid ( FA) is one of the possibilities to overcome chemoresistance in advanced colorectal cancer (ACRC) patients. The aim of this study was to determine the tolerability and activity of CPT-11 plus chronomodulated infusion of L-OHP, 5-FU and FA in ACRC patients. A total of 35 patients (91% pretreated, 77% with CPT-11, 54% with L-OHP, 42% with both) were treated every 3 weeks with CPT-11, 180 mg m(-2) day 1 i. v., plus L-OHP, 20 mg m(-2) day(-1), 5-FU, 700 mg m(-2) day(-1) and FA, 150 mg m(-2) day(-1), all three drugs from day 2 to day 5 by chronomodulated infusion. The patients' (pt) data were as follows: male/female 21/14; median age 58 years ( range: 38 - 70); PS 0: 26 pts (74%), PS 1: 8 pts (23%), PS 2: 1 pt (3%); primary tumour colon/rectum 26/9; involved organs: 1, 14 pts (40%); 2, 17 pts (48%); greater than or equal to3: 4 pts (11%); previous chemotherapy lines 1: 12 pts (34%), 2: 10 pts (28%), greater than or equal to3: 10 pts (28%). A total of 221 courses (c) were performed; no grade 4 toxicity was observed with only one grade 3 (G3) neutropenia and thrombocytopenia ( 3%) in one out of 221 courses (<1%). Maximal toxicity (G3) was nausea and diarrhoea in 10 pts (28%), occurring in 14 out of 221 c (6%) and 12 out of 221 c (5%) respectively. Seven patients achieved a partial response (20%, confidence interval (c. i.) 6.8 - 33.3) and one patient a complete response (2.9%, c. i. 0 - 8.4), for a total overall response rate of 22.9% (c. i. 9 - 36.8); 15 out of 35 (42.9%, c. i. 26.5 - 59.3) had stable disease and 12 out of 35 (34.3%, c. i. 18.6 - 50) patients underwent a progression. In conclusion, this four-drug regimen is feasible in advanced pretreated ACRC patients with no significant haematological toxicity and acceptable diarrhoea. The activity of this combination is currently studied in EORTC 05011 study.