Chronomodulated irinotecan, oxaliplatin, and leucovorin-modulated 5-Fluorouracil as ambulatory salvage therapy in patients with irinotecan- and oxaliplatin-resistant metastatic colorectal cancer.

PURPOSE: To evaluate the activity and tolerability of salvage chronomodulated chemotherapy combining irinotecan (I), 5-fluorouracil/leucovorin (5-FU/LV), and oxaliplatin (O) (chronoIFLO) in patients with metastatic colorectal cancer (MCRC) and prior progression on four drugs. PATIENTS AND METHODS: Seventy-seven nonhospitalized MCRC patients received chronoIFLO every 3 weeks, with day 1: I (180 mg/m2 over 6 hours, with peak infusion rate at 05:00) and days 2-5: 5-FU/LV (700/300 mg/m2 per day over 12 hours, with peak flow rate at 04:00), and O (20 mg/m2 per day over 12 hours, with peak flow rate at 16:00). Toxicity and response were assessed every 3 weeks and every 2 months, respectively. RESULTS. Three or more prior chemotherapy lines were given to 75% of the patients. Two or more organs had metastatic disease in 65% of the patients. A median number of six courses of chronoIFLO was given. The main grade 3-4 toxicities were diarrhea (39% of the patients, 9% of the courses) and neutropenia (30% of the patients and 7% of the courses). Grade 3 peripheral sensory neuropathy occurred in 14% of the patients. Two patients achieved a partial response and 61 had stable disease, resulting in disease control for 82% of the patients. The median time to progression (TTP) was 5.5 months (95% confidence interval, 3.7-6.0). The median overall survival time was 14.2 months (9.8-17.3). Baseline performance status, serum carcinoembryonic antigen (CEA) level, and CEA doubling time were independent prognostic factors of TTP.
CONCLUSIONS: ChronoIFLO safely and durably halted tumor progression in most extensively pretreated MCRC patients.