Cancer Res Treat.  2023 Oct;55(4):1346-1354. 10.4143/crt.2022.1436.

Safety and Tolerability of Weekly Genexol-PM, a Cremophor-Free Polymeric Micelle Formulation of Paclitaxel, with Carboplatin in Gynecologic Cancer: A Phase I Study

• Nam SH
• Lee SW
• Lee YJ
• Kim YM

• KMID: 2547808
• DOI: http://doi.org/10.4143/crt.2022.1436

Abstract

Purpose
This phase I study was conducted to determine the maximum tolerated dose and the recommended phase II dose of weekly administered Genexol-PM combined with carboplatin in patients with gynecologic cancer.
Materials and Methods
This open-label, phase I, dose-escalation study of weekly Genexol-PM included 18 patients with gynecologic cancer, who were equally divided into three cohorts of dose levels. Cohort 1 received 100 mg/m² Genexol-PM and 5 area under the curve (AUC) carboplatin, cohort 2 received 120 mg/m² Genexol-PM and 5 AUC carboplatin, and cohort 3 received 120 mg/m² Genexol-PM and 6 AUC carboplatin. The safety and efficacy of each dose were analyzed for each cohort.
Results
Of the 18 patients, 11 patients were newly diagnosed and seven patients were recurrent cases. No dose-limiting toxicity was observed. The maximum tolerated dose was not defined, but a dose up to 120 mg/m² of Genexol-PM in combination with AUC 5-6 of carboplatin could be recommended for a phase II study. In this intention-to-treat population, five patients dropped out of the study (carboplatin-related hypersensitivity, n=1; refusal of consent, n=4). Most patients (88.9%) with adverse events recovered without sequelae, and no treatment-related death occurred. The overall response rate of weekly Genexol-PM in combination with carboplatin was 72.2%.
Conclusion
Weekly administered Genexol-PM with carboplatin demonstrated an acceptable safety profile in gynecologic cancer pati-ents. The recommended phase II dose of weekly Genexol-PM is up to 120 mg/m² when combined with carboplatin.

Keyword

Genexol-PM; Carboplatin; Ovarian neoplasms; Fallopian tube neoplasms; Uterine neoplasms

Figure

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  Fig. 1 Study design during dose escalation steps. AUC, area under the curve; DLT, dose-limiting toxicity; MTD, maximum tolerated dose.

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  Fig. 2 Kaplan-Meier estimates of progression-free survival (A) and overall survival (B).

Reference

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