Role of dihydropyrimidine dehydrogenase activity in patients with esophageal cancer

Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme involved in the degradation of 5-FU. DPD activity in peripheral blood mononuclear cells of 30 esophageal cancer patients treated with 5-FU and low-dose CDDP with irradiation was determined at the beginning of each cytostatic cycle, the objective being to determine if DPD activity is related to the occurrence of side-effects and responses to therapy. The DPD activity showed interpatient variability (mean: 325.5 pmol/min/mg protein). 5-FU-related side-effects tended to be registered more frequently in patients with low DPD activity. In particular, nausea occurred in 30.8 % of patients in the high DPD activity group but, in 70.6 % in those with low DPD activity (p < 0.05). The relationship between the histological response to therapy and DPD activity was nil. We propose that determination of DPD activity prior to initiation of 5-FU-based chemotherapy for patients with esophageal cancer could aid in identifying those at risk for toxicity.