Randomized Phase Iii Trial Comparing Pegylated Liposomal Doxorubicin (Pld) At 50 Mg/M(2) Versus 40 Mg/M(2) In Patients With Platinum-Refractory And -Resistant Ovarian Carcinoma: The Jgog 3018 Trial

Objective: The standard dose for pegylated liposomal doxorubicin (PLD) is 50 mg/m 2 every 4 weeks. While 40 mg/m 2 has recently been used in clinical practice, evidence supporting this use remains lacking.Methods: This phase III randomized, non-inferiority study compared progression-free survival (PFS) for patients with platinum-resistant ovarian carcinoma between an experimental arm (40 mg/m(2) PLD) and a standard arm (50 mg/m(2) PLD) until 10 courses, disease progression or unacceptable toxicity. Eligible patients had received <= 2 prior lines. Stratification was by performance status and PFS of prior chemotherapy (<3 months versus >= 3 months). The primary endpoint was PFS and secondary endpoints were overall survival (OS), toxicity profile, clinical response and tolerability. The total number of patients was 470.Results: The trial was prematurely closed due to slow recruitment, with 272 patients randomized to the experimental arm (n=137) and standard arm (n=135). Final analysis was performed with 234 deaths and 269 events for PFS. In the experimental arm vs. standard arm, median PFS was 4.0 months vs. 4.0 months (hazard ratio [HR)=1.065; 95% confidence interval [CI)=0.830-1.366) and median OS was 14.0 months vs. 14.0 months (HR=1.078; 95% CI=0.831-1.397). Hematologic toxicity and oral cavity mucositis (>= grade 2) were more frequent in the standard arm than in the experimental arm, but no difference was seen in >= grade 2 hand-foot skin reaction.Conclusion: Non-inferiority of 2 PLD dosing schedule was not confirmed because the trial was closed prematurely. However, recommendation of dose reduction of PLD should be based both on efficacy and safety.