A phase II randomized controlled study of pegylated liposomal doxorubicin and carboplatin vs. gemcitabine and carboplatin for platinum-sensitive recurrent ovarian cancer (GOTIC003/intergroup study)
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To compare the efficacy, safety, and tolerability profiles of pegylated liposomal doxorubicin and carboplatin (PLDC) with those of gemcitabine and carboplatin (GC) for the treatment of patients with platinum-sensitive recurrent ovarian cancer.
Ovarian cancer patients with recurrence > 6 months after first-line platinum and taxane-based therapies were randomly assigned to PLDC [pegylated liposomal doxorubicin 30 mg/m2 plus carboplatin area under the curve (AUC) 5 mg/mL/min on day 1] every 4 weeks or GC (gemcitabine 1000 mg/m2 on days 1 and 8 plus carboplatin AUC 4 mg/mL/min on day 1) every 3 weeks for at least 6 cycles. The primary endpoint was progression-free survival, and overall response rate, overall survival, toxicity, and dose administration were secondary endpoints.
One-hundred patients (49 PLDC; 51 GC) were randomly assigned. Over a median follow-up of 24 months, the median progression-free survival was 12.0 months (95% CI 9.2–15.0) for PLDC and 9.8 months (8.9–12.3) for GC [HR 0.69 (0.455–1.047)] with a difference of 2.2 months. The response rate was 57.1% (41.0–72.3) for PLDC and 56.4% (39.6–72.2) for GC. No obvious differences in toxicity (G3/4) were noted between arms. The median relative dose intensity of planned dose per week was 88.9% for pegylated liposomal doxorubicin and 53.1% for gemcitabine (p < 0.0001).
PLDC and GC are both good treatment candidates for platinum-sensitive recurrent ovarian cancer patients; however, the dose intensity was lower for GC than for PLDC. PLDC had a more favorable risk–benefit profile than that of GC for patients.
KeywordsPlatinum-sensitive recurrent ovarian cancer Pegylated liposomal doxorubicin Gemcitabine Randomized clinical trial
We thank Izumi Kohara, Yoshie Ueki and staff of Global Clinical Research Coordinating Center of Kitasato University Hospital for general support of this trial, and Toshiharu Yamashita and Takaaki Takenaga for statistical support. We also gratefully acknowledge the participation of 100 women in this trial. This study was presented in part at the 20th Biennial meeting of the European Society of Gynaecological Oncology (ESGO2017), November 4–7, 2017, Vienna, Austria and the 17th biennial meeting of the international gynecologic cancer society (IGCS2018), September 14–16, 2018, Kyoto, Japan.
This study was supported by Janssen Pharmaceutical K.K. and the Japan Society of Clinical Oncology Clinical Research Program Grant. The study was performed and analyzed independently by the study groups (GOTIC and Intergroup in Japan).
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
Jichi Medical University, Kurume University School of Medicine, Saitama Medical University International Medical Center, Tottori University School of Medicine, National Defense Medical College Hospital, Osaka University Graduate School of Medicine, Kyushu University, Shizuoka Cancer Center Hospital, Yamagata University School of Medicine, Kansai Rosai Hospital, Iwate Medical University, Kosei Hospital, The Jikei University School of Medicine, Kashiwa Hospital, Hirosaki University School of Medicine & Hospital, Nara Medical University Hospital, Niigata University Medical and Dental Hospital, Mie University Hospital, Ehime University Hospital, Hyogo Medical College Hospital, Miyoshi Central Hospital, Nagaoka Red Cross Hospital, NHO Shikoku Cancer Center, Niigata Cancer Center Hospital, Tottori Municipal Hospital.
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