No effect of dose, hepatic function, or nutritional status on 5-fu clearance following continuous (5-day), 5-fu infusion

Abstract

One hundred and eighty seven patients (155 males, 32 females) with histologically proven and previously untreated head and neck cancer were entered in the study. A total of 222 cycles of therapy were analyzed (cisplatin 100 mg m-2 on day 1 and 5-day continuous intravenous infusion of 5-FU 550-1069 mg m-2 day-1, mean 875. 5 mg m-2 day-1). Significant interpatient variability for various 5-FU pharmacokinetic parameters was observed including an almost ten-fold range in 5-FU clearance (5-FU Cl, ml min-1 m-2 = 791-7769, mean 2820. 7). Log 5-FU Cl was not modified by 5-FU dose (r=-0. 1034, P = 0. 124, n = 222). Poor linear correlations between log 5-FU Cl and hepatic function tests were observed (respective r and P values for 222 cycles, log AST: 0. 0526, 0. 4365; Log ALT: -0. 1167, 0. 0842; Log AIK. Phos.: 0. 154, 0. 0214; Log GGT: 0. 0652, 0. 3436; Log LDH: - 0. 0984, 0. 1563; Log bilirubin: 0. 1278, 0. 0601). The log 5-FU Cl was also poorly correlated with the serum concentration of various nutritional proteins (respective r and P values for 222 cycles, Albumin: 0. 0110, 0. 8714; prealbumin: — 0. 1067, 0. 1129; transferrin: 0. 0439, 0. 5226). Laboratory data including indices of hepatic function and nutritional status cannot account for the interpatient variability in 5-FU disposition. © Macmillan Press Ltd., 1992.