Tolerability, Efficacy, and Safety of Pegylated Liposomal Doxorubicin in Combination with Carboplatin Versus Gemcitabine-Carboplatin for the Treatment of Platinum-Sensitive Recurrent Ovarian Cancer: A Systematic Review
Review
Holloway, Robert W., Grendys, Edward C., Lefebvre, Patrick, Vekeman, Francis, McMeekin, Scott
funding text
This research was supported by Centocor Ortho Biotech Services, LLC.
abstract
Objective. To compare the tolerability, efficacy, and safety profiles of pegylated liposomal doxorubicin in combination with carboplatin (PLD-Carbo) with those of gemcitabine carboplatin (Gem Carbo) for the treatment of patients with platinum-sensitive recurrent ovarian cancer (PSROC) by reviewing the published literature. Methods. Using the PubMed database, a systematic review of peer-reviewed literature published between January 2000 and September 2009 was undertaken to identify studies related to the treatment of patients with PSROC with PLD-Carbo or Gem Carbo. Studies reporting either response rate, progression-free survival (PFS), and/or overall survival (OS) were included. Treatment regimens, efficacy endpoints, and safety profiles were compared between the two combination therapies. Results. Ten studies evaluating 608 patients (PLD-Carbo: 5 studies, 278 patients; Gem Carbo: 5 studies, 330 patients) were identified. The mean planned doses were: PLD, 34.8 mg/m(2) and Gem, 993 mg/m(2). The dose intensity reported in Gem trials was lower (75% of the planned dose) than the dose intensity reported in PLD trials (93.7% of the planned dose), suggesting better tolerability for the PLD Carbo regimen. Among patients receiving PLD-Carbo, 60.2% achieved a response (complete, 27.0%; partial, 33.2%), versus 51.4% of patients treated with Gem-Carbo (complete, 19.2%; partial, 32.2%). The median PFS times were 10.6 months and 8.9 months in the PLD-Carbo and the Gem Carbo populations, respectively. The median OS was longer for the PLD Carbo regimen (27.1 months) than for the Gem Carbo regimen (19.7 months). The hematological safety profiles were comparable in the two groups, although grade III or IV anemia (PLD-Carbo, 13.6%; Gem Carbo, 24.5%) and neutropenia (PLD-Carbo, 45.5%; Gem Carbo, 62.9%) were more common in patients receiving Gem-Carbo. Conclusion. Results from this systematic analysis of peer-reviewed literature suggest that PLD-Carbo therapy is a rational alternative to Gem Carbo for the treatment of patients with PSROC. The Oncologist 2010;15: 1073-1082