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Objective This retrospective study is to evaluate the efficacy and toxicity of combination chemotherapy with etoposide andifosfamide (ETI) in the management of pretreated recurrent or persistent epithelial ovarian cancer (EOC). Methods Patients with recurrent or persistent EOC who had measurable disease and at least one chemotherapy regimen wereto receive etoposide at a dose of 100 mg/m2/day intravenous (IV) on days 1 to 3 in combination with ifosfamide 1 g/m2/dayIV on days 1 to 5, every 21 days. Results From August 2008 to August 2016, 66 patients were treated with ETI regimen. Most patients were heavily pretreatedprior to ETI: 53 (80.3%) patients had received 3 or more chemotherapy regimens. The response rate (RR) of ETIchemotherapy was 18.2% and median duration of response was 6.8 months (range, 0–30). Median survival of allpatients was 5 months at a median follow up of 7.2 months. Platinum-free interval (PFI) more than 6 months prior toETI has statistically significant correlation with overall survival (OS; 9.2 vs. 5.6 months; P=0.029) and RR (34.5% vs. 5.4%;P<0.010). However, treatment free interval before ETI, number of prior chemotherapy regimen, and optimality ofprimary surgery did not show significant difference for RR or OS. Grade 3 or 4 hematologic toxicities were observed in7 cases (3%) of the 232 cycles of ETI. Conclusion The ETI combination regimen shows comparatively low toxicity and modest activity in heavily pretreated recurrent orpersistent EOC patients with more than 6 months of PFI after last platinum treatment.