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Correlation between Dihydropyrimidine Dehydrogenase Activity in Peripheral Mononuclear Cells and Systemic Clearance of Fluorouracil in Cancer Patients¹

Centre Antoine Lacassagne, Nice 06054, France

Dihydropyrimidine dehydrogenase (DPD) is the initial key enzyme in the catabolism of 5-fluorouracil (5-FU). We measured DPD activity in lymphocytes from 57 consecutive head and neck cancer patients while simultaneously monitoring 5-FU pharmacokinetics during 5-day, continuous infusion (1000 mg/m²/day) 5-FU therapy (82 cycles in total). The mean value for DPD activity was 0.186 ± 0.068 (SD) nmol/min/mg of protein (range, 0.058 to 0.357). The mean value for 5-FU clearance was 2522.6 ± 684.2 ml/min/m² (range, 1052 to 4029). A significant linear correlation was observed between DPD activity and 5-FU clearance (r = 0.716, P < 0.0001). DPD activity was poorly correlated to plasma uracil concentrations (r = –0.260, P = 0.0215). Likewise, plasma uracil concentrations were poorly correlated to 5-FU clearance (r = -0.214, P = 0.0595). In patients evaluated for more than one cycle (n = 18), there was large intrapatient variability in both DPD activity and 5-FU clearance. No significant difference was noted between cycles for DPD activity or 5-FU clearance (Kruskal-Wallis test). Monitoring DPD activity in lymphocytes may be useful in identifying patients at risk for altered 5-FU disposition.

¹ Funded by the Ligue Nationale Francaise contre le Cancer.

² Recipient of a Chateaubriand Scholarship from the Mission Scientifique, Ambassade de France. Present address: Comprehensive Cancer Center of Wake Forest University, Bowman Gray School of Medicine, Winston-Salem, NC 27609.

³ To whom requests for reprints should be addressed, at Laboratoire d'Oncopharmacologie, Centre Antoine Lacassagne, 36 voie Romaine, 06054 Nice Cedex, France.

Received 10/16/91. Accepted 3/10/92.

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