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
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
Takashi Motohashi(Tokyo Women's Medical University); Akira Yabuno(Saitama Medical University International Medical Center); Hiroshi Michimae(Kitasato University School of Pharmacy); Tetsuro Ohishi(Tottori University School of Medicine); Miwa Nonaka(Global Clinical Research Coordinating Center Division of Clinical Research Kitasato University Hospi); Masashi Takano(National Defense Medical College Hospita); Shin Nishio(Kurume University School of Medicine); Hiroyuki Fujiwara(Jichi Medical University); Keiichi Fujiwara(Saitama Medical University International Medical Center); Eiji Kondo(Mie University School of medicine); Toru Sugiyama(St. Mary's Hospital); Tsutomu Tabata(Tokyo Women's Medical University)
32권 1호, 1~11쪽
초록
Objective: The standard dose for pegylated liposomal doxorubicin (PLD) is 50 mg/m2every 4weeks. While 40 mg/m2has recently been used in clinical practice, evidence supporting thisuse remains lacking. Methods: This phase III randomized, non-inferiority study compared progression free survival (PFS) for patients with platinum-resistant ovarian carcinoma between anexperimental arm (40 mg/m2PLD) and a standard arm (50 mg/m2PLD) 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 ≥3months). 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 randomizedto the experimental arm (n=137) and standard arm (n=135). Final analysis was performed with234 deaths and 269 events for PFS. In the experimental arm vs. standard arm, median PFS was4.0 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). Hematologictoxicity and oral cavity mucositis (≥grade 2) were more frequent in the standard arm than in theexperimental 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 trialwas closed prematurely. However, recommendation of dose reduction of PLD should bebased both on efficacy and safety. Trial Registration: UMIN Clinical Trials Registry Identifier: UMIN000003130
Abstract
Objective: The standard dose for pegylated liposomal doxorubicin (PLD) is 50 mg/m2every 4weeks. While 40 mg/m2has recently been used in clinical practice, evidence supporting thisuse remains lacking. Methods: This phase III randomized, non-inferiority study compared progression free survival (PFS) for patients with platinum-resistant ovarian carcinoma between anexperimental arm (40 mg/m2PLD) and a standard arm (50 mg/m2PLD) 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 ≥3months). 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 randomizedto the experimental arm (n=137) and standard arm (n=135). Final analysis was performed with234 deaths and 269 events for PFS. In the experimental arm vs. standard arm, median PFS was4.0 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). Hematologictoxicity and oral cavity mucositis (≥grade 2) were more frequent in the standard arm than in theexperimental 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 trialwas closed prematurely. However, recommendation of dose reduction of PLD should bebased both on efficacy and safety. Trial Registration: UMIN Clinical Trials Registry Identifier: UMIN000003130
- 발행기관:
- 대한부인종양학회
- 분류:
- 부인종양학/부인암