J Gynecol Oncol.  2017 May;28(3):e26. 10.3802/jgo.2017.28.e26.

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)

• Lee SW
• Kim YM
• Kim YT
• Kang SB

• KMID: 2413442
• DOI: http://doi.org/10.3802/jgo.2017.28.e26

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%.
CONCLUSION
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.

Keyword

Genexol-PM; Carboplatin; Clinical Trial, Phase I; Maximum Tolerated Dose; Toxicity Tests; Ovarian Neoplasms

MeSH Terms

Adult
Aged
Antineoplastic Agents, Phytogenic/*administration & dosage/adverse effects
Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
Carboplatin/*administration & dosage
Dose-Response Relationship, Drug
Drug Administration Schedule
Female
Humans
Micelles
Middle Aged
Neoplasms, Glandular and Epithelial/*drug therapy
Ovarian Neoplasms/*drug therapy
Paclitaxel/*administration & dosage/adverse effects
Polyethylene Glycols/adverse effects
Republic of Korea
Antineoplastic Agents, Phytogenic
Micelles
Polyethylene Glycols
Carboplatin
Paclitaxel