Epirubicin-carboplatin-capecitabine (ECarboX) in relapsed ovarian cancer: A phase I/II trial

Abstract

5109 Background: We have previously shown the combination of epirubicin, cisplatin, and prolonged infusional 5-fluorouracil (5-FU) is active in relapsed epithelial ovarian cancer (EOC). Capecitabine (Xeloda, X) is an orally bioavailable tumour selective fluoropyrimidine, it has proven efficacy and is more convenient than infusional 5-FU. We have performed a phase I/II study of ECarboX in relapsed EOC. Methods: Patients (pts) with relapsed EOC with an interval of at least 6 months from platinum-based first line treatment, received bolus iv epirubicin 50mg/m2 and iv carboplatin AUC 5 on day 1, and capecitabine either 750mg/m2 (level 1) or 1000mg/m2 (level 2) daily in two divided doses throughout a 21-day cycle, or 1000mg/m2 daily for days 1–14 of a 21-day cycle (level 3). Pts were planned to receive 6 cycles. The primary endpoint was the maximum tolerated dose (MTD) of ECarboX. Tumour response was a secondary endpoint. Results: Eleven pts have entered the study and eight have received ≥3 cycles of ECarboX and are evaluable. At level 1 two pts completed 6 cycles and one pt 4 cycles of treatment. Seven cycles were delayed, and 50% dose reductions in epirubicin and capecitabine were required in two pts: one pt had recurrent grade 3 neutropenia, the other had grade 3 neutropenia, lethargy and diarrhoea, and was subsequently withdrawn for prolonged (>2 week) grade 2 neutropenia despite dose reduction. At level 2 four out of five pts completed 6 cycles, the fifth received 2 cycles. There were 11 treatment delays: 2 pts had 25% dose reductions and 1 pt was withdrawn from the study due to prolonged grade 3 neutropenia. Four pts experienced grade ≥2 haematological toxicity and one pt grade 3 lethargy. At level 3, three pts have received 2 cycles each, one cycle has been delayed. Six pts have obtained a partial or complete response and one has stable disease. Only one pt progressed. Conclusions: ECarboX results in haematological toxicity. The MTD was level 2, capecitabine 1000mg/m2 for 21 days of a 21-day cycle. Capecitabine on days 1–14 of a 21-day cycle is likely to be better tolerated. As expected, ECarboX is highly active in relapsed EOC. No significant financial relationships to disclose.