IFLUX for advanced bowel cancer

Abstract

IFLUX, a chemotherapy regimen that combines irinotecan, 5-fl uorodeoxyuridine (FUdR), and folinic acid, might increase the median survival of patients with advanced colorectal cancer (Anticancer Drugs, 2007; 18: 955–61). In a phase II study of IFLUX, Bach Ardalan (University of Miami, FL, USA) and colleagues report that median patient survival was 31·3 months (95% CI 20·9– 38·0); in comparison, median survival with the widely used regimen of folinic acid, fl uorouracil, oxaliplatin (FOLFOX) is 19·5 months. Fluorouracil kills tumours partly through its activation, via FUdR, to fl uorodeoxyuridine monophosphate. This inhibits thymidylate synthase, which causes DNA damage and cell death. “Fluorouracil’s conversion to FUdR requires the addition of a deoxyribose sugar, which is often rate-limiting in cancer cells”, explains Ardalan, “so giving FUdR should bypass the ratelimiting step in fl uorouracil activation”. 38 patients with untreated, advan ced colorectal cancer received fi ve 6-week cycles (on average) of IFLUX. Each cycle comprised four weekly intravenous infusions of 110 mg/m irinotecan followed by a 24 h continuous intravenous infusion of 120 mg/kg FUdR and 500 mg/m folinic acid, and 2 weeks’ rest. Median time to tumour progression was 11·5 months (6·8–12·9). IFLUX was well-tolerated; toxic eff ects included vomiting (24%) and diarrhoea (16%). “Although this is a small study, it’s exciting to see the survival fi gures reported here”, comments Anne Thomas (University of Leicester, Leicester, UK). “However, I think it’s unlikely that the average patient with colorectal cancer could tolerate the toxicity associated with this regimen, which might also make it diffi cult to combine IFLUX with targeted agents. We await with interest the outcome of a phase II study combining IFLUX with bevacizumab that Ardalan is currently recruiting to.” Initial toxicity studies, notes Ardalan, indicate that this combination is acceptable to patients.