Sinusoidal circadian continuous infusion with a maximal flow rate in the afternoon (3-9 pm) reduces Fudr toxicity. In order to estimate if the reported lower toxicity is merely due to the quasi-intermittence of the daily dose or to the circadian rhythm of infusion. Ten patients with widespread cancer (9 colorectal and 1 renal) underwent sinusoidal continuous iv Fudr infusion with the peak level in antiphase (ie 68% of the dose from 3 to 9 am) as compared with the Römeling shape. An initial dose of 0.15 mg/kg/d for 14 days monthly has been given, escalating it every cycle by 0.025 mg/kg/d increments until toxicity. Mean (+/- SD) number of cycles has been 4.1 +/- 2.1 (range 2-8), maximal dose given has been 0.2 mg/kg/die in 5 patient and mean dose intensity of 0.570 +/- 0.04. Gastrointestinal toxicity consisted of nausea/vomiting WHO grade 1 in one patient and diarrhoea grade 1 in two, grade 2 and 3 in one and one case. Toxicity and dose intensity of both sinusoidal infusion seem to be similar and allow higher dose of Fudr than continuous constant infusion. Some other studies have to be done to include pharmacokinetics evaluation in order to estimate chronobiologic implication in continuous Fudr infusion
