An Open-Label, Randomized, Parallel, Phase II Trial to Evaluate the Efficacy and Safety of a Cremophor-Free Polymeric Micelle Formulation of Paclitaxel as First-Line Treatment for Ovarian Cancer: A Korean Gynecologic Oncology Group Study (KGOG-3021).
OBJECTIVE
Genexol-PM is a biodegradable cremophor EL-free polymeric micelle formulation of paclitaxel. Here,we compared efficacy and safety of Genexol-PM plus carboplatin versus Genexol plus carboplatin for ovarian cancer treatment.


METHODS
In this multicenter, randomized, phase II study, patients with International Federation of Gynecology and Obstetrics IC-IV epithelial ovarian cancer were randomly assigned (1:1) to receive Genexol-PM 260 mg/m2or Genexol 175 mg/m2with 5 area under the curve carboplatin every 3weeks (6 cycles). The primary endpointwas the carbohydrate antigen 125 and Response Evaluation Criteria In Solid Tumor composite overall response rate (ORR).


RESULTS
Of 131 enrolled patients, 98 were included in intention-to-treat analysis. Mean dosages were 260.00±0.00 mg/m2Genexol-PM or 174.24±3.81 mg/m2Genexol. Median followup was 18.0 months (range, 6.1 to 33.8 months). ORR was 88.0% (95% confidence interval [CI], 80.4 to 95.6) with Genexol-PM, and 77.1% (95% CI, 67.1 to 87.1) with Genexol (noninferiority threshold, 16.3%). Median time to progression was 14.8 months (95% CI, 11.3 to 20.2) with Genexol-PM and 15.4 months (95% CI, 13.2 to 29.6) with Genexol (p=0.550). Overall, six patients died. Neutropenia was the most common toxicity (incidences of 86.0% vs. 77.1%, p=0.120). Peripheral neuropathy incidences were 84.0% versus 64.6% (p= 0.148). Peripheral neuropathy of ≥ grade 3 occurred in one patient receiving Genexol. All toxicities were manageable.


CONCLUSIONS
Genexol-PM plus carboplatin as first-line treatment in patients with epithelial ovarian cancer demonstrated non-inferior efficacy and well-tolerated toxicities compared with the standard paclitaxel regimen. Further studies are warranted to optimize the dose and schedule, and to investigate long-term outcomes.
Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Shin-Wha
SW
Lee
Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Yong-Man
YM
Kim
Department of Obstetrics and Gynecology, Keimyung University School of Medicine, Daegu, Korea.
Chi Heum
CH
Cho
Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Young Tae
YT
Kim
Department of Obstetrics and Gynecology, Chonnam National University Medical School, Gwangju, Korea.
Seok Mo
SM
Kim
Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Soo Young
SY
Hur
Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Jae-Hoon
JH
Kim
Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University, Seoul, Korea.
Byoung-Gie
BG
Kim
Department of Obstetrics and Gynecology, Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Korea.
Seung-Cheol
SC
Kim
Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon, Korea.
Hee-Sug
HS
Ryu
Department of Obstetrics and Gynecology, Konkuk University Medical Center, Seoul, Korea.
Soon Beom
SB
Kang
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008823:Micelles; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011108:Polymers; D056910:Republic of Korea
D000972:Antineoplastic Agents, Phytogenic; D008823:Micelles; D011108:Polymers; D017239:Paclitaxel
Carboplatin; Genexol; Genexol-PM; Ovarian neoplasms; Phase II trial