Biweekly pegylated liposomal doxorubicin in patients with relapsed ovarian cancer: results of a multicenter phase-II trial.
BACKGROUND: The obvious benefit of pegylated liposomal doxorubicin (PLD) for tumour control in recurrent ovarian cancer is frequently offset by severe palmar-plantar erythrodysesthesia (PPE). There is evidence that dose reduction from 50 to 40 mg/m(2) reduces the incidence of PPE without compromising cytotoxic activity. We set out to investigate whether biweekly application further improves the therapeutic index of PLD. PATIENTS AND METHODS: Patients with recurrent ovarian cancer after surgery and adjuvant chemotherapy with platinum and taxane compounds were eligible to participate in this multi-institutional phase II study. PLD was administered at a dose of 20 mg/m(2) every two weeks. Eligible patients had ECOG performance status of< or =2, and sufficient organ function. We employed an optimized two-stage design to test the hypothesis that biweekly application of PLD reduces the frequency of grade III and IV PPE from 25% to 10%. Response and survival were addressed descriptively. RESULTS: Between October 2001 and February 2004, 64 patients with median age of 59 (range 38-81) years were recruited onto this trial. We evaluated 553 (median 7, range 1-25) courses of PLD treatment. Most patients were in their third or fourth line of chemotherapy. PPE was noted in 30 patients (47.6%), but only three participants progressed to grade 3 severity (4.7%, 95% confidence interval 1.0-13.1%). Partial response, stable disease, and tumour progression were observed in 5, 13, and 24 patients, respectively. Median overall and progression-free survival were 18.2 (range, 1.4-34.0) and 4.3 (range 0.5-22.3) months. CONCLUSIONS: Biweekly PLD may reduce the incidence of PPE while retaining efficacy in relapsed ovarian cancer. Our data support the need for a randomized trial to strengthen these assumptions.