A phase II study of combination chemotherapy in early relapsed epithelial ovarian cancer using gemcitabine and pegylated liposomal doxorubicin

ObjectiveTreatment of epithelial ovarian cancer patients relapsing with a short treatment-free interval (TFI) after prior chemotherapy is unsatisfactory. This phase II trial evaluated the activity and feasibility of pegylated liposomal doxorubicin (PLD) plus gemcitabine in this setting.MethodsPatients who had received prior platinum and paclitaxel with a TFI 0–12 months received PLD 25 mg/m2 day 1 plus gemcitabine 800 mg/m2 day 1, 8 every 21 days. Gemcitabine was dose escalated to 1000 mg/m2 day 1, 8 from course 2 in the absence of grade 3/4 toxicity. The primary endpoint was progression-free survival (PFS). Patients were stratified according to response to primary chemotherapy.ResultsSeventy-nine patients (n = 26 with CR on prior chemotherapy and TFI 6–12 months; n = 20 with CR and TFI 0–6 months; n = 33 with PR/SD and TFI 0–12 months) were enrolled. The median age was 59 years (range 31–77 years), and 33 patients had received ≥ 2 prior treatments. A median of five courses was delivered per patient (total 389 courses). Gemcitabine was dose escalated in 124 courses and reduced in 105 courses. No PLD dose reductions occurred. Grade 3/4 toxicities were febrile neutropenia (n = 4), PPE (n = 2), and mucositis (n = 2). One toxic death occurred (pneumonitis/alveolitis). Responses were complete in 5.1%, partial in 27.9%, and stable disease in 55.7%. Median OS and PFS were 12.5 and 6.4 months, respectively.ConclusionsThe PLD–gemcitabine combination is an effective and well-tolerated salvage treatment for relapsed epithelial ovarian cancer and is a valid candidate for evaluation in a phase III trial.