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

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/m<sup>2</sup> Genexol-PM and 5 area under the curve (AUC) carboplatin, cohort 2 received 120 mg/m<sup>2</sup> Genexol-PM and 5 AUC carboplatin, and cohort 3 received 120 mg/m<sup>2</sup> 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/m<sup>2</sup> 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/m<sup>2</sup> when combined with carboplatin.

Redox-responsive polymer micelles co-encapsulating immune checkpoint inhibitors and chemotherapeutic agents for glioblastoma therapy

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Therapeutic impacts of GNE‑477‑loaded H2O2 stimulus‑responsive dodecanoic acid‑phenylborate ester‑dextran polymeric micelles on osteosarcoma

“…A variety of polymers are currently undergoing pre-clinical scrutiny to investigate potential in micelle formation, carrying chemotherapeutic agents, and anti-tumor effects in both in vitro cell experiments and in vivo animal models ( 29 - 32 ). Several polymeric micelles have progressed to clinical trials and have proved their efficacy in human subjects ( 33 , 34 ). Notably, GNE-477 has special amino and methanesulfonyl ( Fig.…”