Chronomodulated infusion of 5-fluorouracil, folinic acid and carboplatin in colorectal cancer: a pilot study.

We investigated if chronomodulated infusion of fluorouracil, folinic acid in combination with carboplatin shows antitumor efficacy in patients advanced metastatic colorectal cancer. Thirteen patients entered into the study. Each treatment cycle consisted of a 5 day course of continuous venous infusion of 5-fluorouracil (5-FU; 500 mg/m2/die), folinic acid (FA; L-form, 150 mg/m2/die) and carboplatin (CBDCA; the dose being calculated according to the Calvert's formula). Patients received the drugs according to the circadian-modified infusion schedule with a sinusoidally modulated delivery with peak flow rate at 4.00 AM for 5-FU and FA and 4.00 PM for CBDCA. Overall a total number of 54 cycles were administered. Two partial responses and one minor response were observed among the 5 untreated patients. Five patients had progression of disease. Stabilization of previously progressive disease was obtained in the 5 remaining patients. These preliminary results show that the combination of 5-FU, FA and CBCDA infused at circadian-modulated rate has moderate activity in colorectal cancer, specially in previously untreated patients, with a mild and acceptable toxicity.