title: An open-label, multicenter, phase I trial of a cremophor-free, polymeric micelle formulation of paclitaxel combined with carboplatin as a first-line treatment for advanced ovarian cancer: a Korean Gynecologic Oncology Group study (KGOG-3016).
abstract: OBJECTIVE
  This phase I study aimed to determine the maximum tolerated dose (MTD) of Genexol-PM, when combined with carboplatin, as a first-line treatment in patients with advanced ovarian cancer.
  
  
  METHODS
  This open-label, multicenter, phase I, dose-escalation study included 18 patients (median age: 59.0 years, range: 40-75 years) diagnosed with advanced epithelial ovarian cancer. All patients had measurable residual disease after debulking surgery. Patients were assigned to groups (n=6 each group) that received different doses of Genexol-PM (220, 260, and 300 mg/m², once every 3 weeks) and 5 area under the curve (AUC) carboplatin. Safety and efficacy were analyzed for each dose group.
  
  
  RESULTS
  In this intention-to-treat population, 3 out of 18 patients dropped out of the study: 1 due to dose-limiting toxicity (DLT), 1 due to hypersensitivity, and 1 was lost during follow-up. DLTs were not reported at 220 mg/m² or 260 mg/m², but at 300 mg/m², 1 patient experienced DLT (grade 3 general pain). The MTD of Genexol-PM was not determined, but a dose of 300 mg/m² or less could be recommended for the phase II study. Most patients (73.9%) with adverse events recovered without sequelae, and no death occurred that was related to the disease or treatment. The best overall response rate was 94.1%.
  
  
  CONCLUSIONS
  Genexol-PM combined with carboplatin was well tolerated as a first-line treatment, and good responses were observed in patients with advanced ovarian cancer. Based on these results, we recommended a dose of 300 mg/m² or less for a phase II study.
authors.affiliation: Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: Shin Wha
authors.identifier: http://orcid.org/0000-0002-5088-1905
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea. ymkim@amc.seoul.kr.
authors.forename: Yong Man
authors.identifier: http://orcid.org/0000-0003-3225-5748
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University, Seoul, Korea.
authors.forename: Young Tae
authors.identifier: http://orcid.org/0000-0002-7347-1052
authors.initials: YT
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and Gynecology, Konkuk University Medical Center, Seoul, Korea.
authors.forename: Soon Beom
authors.identifier: http://orcid.org/0000-0001-7084-8080
authors.initials: SB
authors.lastname: Kang
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage*; D000077216:Carcinoma, Ovarian Epithelial; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008823:Micelles; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D011092:Polyethylene Glycols / Q000009:adverse effects; D056910:Republic of Korea
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008823:Micelles; C022131:cremophor; D011092:Polyethylene Glycols; D016190:Carboplatin; D017239:Paclitaxel
keywords: Carboplatin; Clinical Trial, Phase I; Genexol-PM; Maximum Tolerated Dose; Ovarian Neoplasms; Toxicity Tests