Phase II clinical trial of capecitabine in ovarian carcinoma recurrent 6-12 months after completion of primary chemotherapy, with exploratory TS, DPD, and TP correlates: a Gynecologic Oncology Group study.

Purpose: A phase II trial was conducted to evaluate the anti-tumor activity and adverse effects of capecitabine in women with measurable platinum-sensitive ovarian cancer or platinum-sensitive primary peritoneal cancer and to explore the ability of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and thymidine phosphorylase (TP) to predict response and toxicities.

Experimental Design: Patients were treated with a daily starting dose of 2500 mg/m2/day (divided in two doses given every 12 h) for 14 days of each 21-day cycle. Genotyping in the 5' and 3' ends of TS was performed in DNA from 23/23 pre-treatment blood specimens. Relative gene expression of TS, DPD, and TP was quantified in 18/21 paraffin-embedded tumor specimens.

Results: Of the 27 patients enrolled on study, 2 were never treated leaving 25 patients evaluable. Two patients (8.0%) achieved a partial response, 13 (52%) exhibited stable disease, 5 (20%) displayed increasing disease, and response could not be assessed in 5 (20%). The median time to progression and survival was 3.9 and 21.2 months, respectively. The most common serious toxicities were nausea/vomiting, gastrointestinal, and dermatological. There was one treatment-related death. TS expression was associated with severe nausea/vomiting (P = 0.039), but not with other severe toxicities. TS genotype or expression of DPD or TP was not associated with any of the severe toxicities.

Conclusions: Based on the low response rate, this trial was closed after the first stage of accrual, the drug was not selected for further study in this patient population, and biomarker associations with response could not be assessed.