Phase I study of liposomal doxorubicin and oxaliplatin as salvage chemotherapy in advanced ovarian cancer.

Oxaliplatin (L-OHP) and stealth pegylated liposomal doxorubicin (PLD) have been shown to be active in pre-treated advanced ovarian cancer (PAOC). The aim of this phase I study was to determine the maximum tolerated dose (MTD) of L-OHP, combined with fixed doses of PLD as salvage treatment of PAOC. Twenty patients with recurrent ovarian cancer previously treated with two (30%) or three lines (70%) of chemotherapy were entered into the trial. Patients had a median age of 64 years (52-77) and a median platinum-free interval of 13 months (range 6-35). Patients received a fixed dose of PLD 40 mg/m2, combined with escalating doses of L-OHP from 80 to 130 mg/m2 administered in 1 day, every 3 weeks. Dose escalation was interrupted if 30% or more patients of a given cohort (three patients) exhibited dose-limiting toxicity in the first treatment cycle. The MTD of L-OHP was 130 mg/m2 as two out of three patients of this cohort showed dose-limiting thrombocytopenia and/or neutropenia during the first cycle of treatment. Amongst 20 evaluable patients, we observed an overall response rate of 55% (95% confidence interval 31.5-76.9%). With a median follow-up of 12 months (3.4+/-19.2), median time to progression was 9.7 months, while median survival was not reached yet. We conclude that a combination of PLD and L-OHP has a manageable toxicity profile, and can be safely administered as outpatient chemotherapy for heavily pre-treated patients with relapsed ovarian cancer. Promising anti-tumor activity was observed.