An escalating dose finding study of liposomal doxorubicin and vinorelbine for the treatment of refractory or resistant epithelial ovarian cancer

Background: The aim of this study was to determine the maximum tolerated dose (MTD) of liposomal doxorubicin (LD)-vinorelbine (V) in patients with refractory or resistant ovarian cancer. Patients and methods: Thirty patients were eligible. Seven levels were studied [LD 25-V20 (three patients enrolled); LD 30-V20 (three); LD 35-V20 (three); LD 20-V25 (three); LD 25-V25 (three); LD 30-V25 (10); LD 35-V25 (five)]. LD was given on day 1, while V was given on days I and 8 every 21 days. Cohorts of three patients were enrolled at each level, and another three patients were planned, if one dose-limiting toxicity (DLT) was registered. Results: DLT was observed in four patients: two febrile neutropenia, one grade 4 thrombocytopenia and one grade 3 palmar-plantar erythrodysesthesia (PPE) at level 7 (LD35-V25). Thus, liposomal doxorubicin 30 mg/m 2 plus vinorelbine 25 mg/m 2 was the MTD. The most frequent toxicity was neutropenia. Fifteen patients (50%) experienced grade 3 neutropenia and 10 (33.3%) grade 4 neutropenia. Non-hematological toxicity was mild. Mucositis and PPE were the most frequent toxicities, but in most cases were grade I. Out of 29 assessable patients, six (20.7%; 95% confidence interval 10%-39%) experienced an objective response, with one complete response. Conclusions: In patients with refractory or resistant ovarian cancer, the recommended doses for the combination studied are liposomal doxorubicin 30 mg/m 2 (day 1) plus vinorelbine 25 mg/m 2 (day I and 8). Neutropenia is the most frequent toxicity, while non-hematological toxicity is mild. Substantial activity was recorded and a phase II study is justified.