Tumor dihydropyrimidine dehydrogenase activity in advanced cervical carcinoma

Patients with advanced cervical carcinoma were treated with oral fluoropyrimidine (UFT) as neoadjuvant chemotherapy and its antitumor effect was examined. The relationship between thymidylate synthase (TS) or dihydropyrimidine dehydrogenase (DPD) activity in tumor tissue and apoptosis was also investigated. The subjects were 56 patients with advanced cervical carcinoma. The patients received two courses of therapy consisting of UFT at a dose of 600 mg/day for 5 days and 2 days off treatment. The TS and DPD activity in tumor tissue was measured before and after UFT administration by the FdUMP binding assay and a catalytic assay in 38 patients, respectively. Apoptosis was detected by the TUNEL method, and the apoptotic index (AI) was calculated. Tumor tissue activity of TS or DPD was unrelated to clinicopathologic factors or to the activity of the other enzyme. The mean tumor TS and DPD activity before UFT administration was 5.42+/-3.92 pmol/g tissue and 206.54+/-128.58 pmol/mg/min, respectively, and the levels of these enzymes in two patients showing an antitumor effect were below the mean values. The AI increased from 1.10+/-0.57% before UFT to 1.27+/-0.81% afterwards, and the DPD activity before UFT showed an inverse relationship with the AI after UFT (r=-0.6938). In patients with DPD activity below the median value (186.92 pmol/mg/min), UFT administration significantly caused an increase of the AI (p=0.0002). These results indicate that the DPD activity of advanced cervical carcinoma is a determinant of sensitivity to UFT, suggesting an association between UFT therapy and the induction of apoptosis.