J Gynecol Oncol.  2021 Jan;32(1):e9. 10.3802/jgo.2021.32.e9.

Randomized phase III trial comparing pegylated liposomal doxorubicin (PLD) at 50 mg/m2 versus 40 mg/m2 in patients with platinum-refractory and -resistant ovarian carcinoma: the JGOG 3018 Trial

Affiliations
  • 1Department of Obstetrics and Gynecology, Tokyo Women's Medical University, Tokyo, Japan
  • 2Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Tokyo, Japan
  • 3Kitasato University School of Pharmacy, Tokyo, Japan
  • 4Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago, Japan
  • 5Global Clinical Research Coordinating Center Division of Clinical Research Kitasato University Hospital, Tokyo, Japan
  • 6Department of Clinical Oncology, National Defense Medical College Hospital, Tokorozawa, Japan
  • 7Department of Obstetrics and Gynecology, Kurume University School of Medicine, Kurume, Japan
  • 8Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi, Japan
  • 9Department of Obstetrics and Gynecology, Mie University School of Medicine, Mie, Japan
  • 10Department of Obstetrics and Gynecology, St. Mary's Hospital, Kurume, Japan

Abstract


Objective
The standard dose for pegylated liposomal doxorubicin (PLD) is 50 mg/m2 every 4 weeks. While 40 mg/m2 has recently been used in clinical practice, evidence supporting this use remains lacking.
Methods
This phase III randomized, non-inferiority study compared progressionfree survival (PFS) for patients with platinum-resistant ovarian carcinoma between an experimental arm (40 mg/m2 PLD) and a standard arm (50 mg/m2 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.

Keyword

Chemotherapy; Ovarian Neoplasms; Doxorubicin; Recurrence
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