Onapristone Extended Release: Safety Evaluation from Phase I-II Studies with an Emphasis on Hepatotoxicity.

ABSTRACT:

Introduction

Antiprogestins have demonstrated promising activity against breast and gynecological cancers, but liver-related safety concerns limited the advancement of this therapeutic class. Onapristone is a full progesterone receptor antagonist originally developed as an oral contraceptive and later evaluated in phase II studies for metastatic breast cancer. Because of liver enzyme elevations identified during clinical studies, further development was halted. Evaluation of antiprogestin pharmacology and pharmacokinetic data suggested that liver enzyme elevations might be related to off-target or metabolic effects associated with clinical drug exposure.

Objective

We explored whether the use of a pharmaceutic strategy targeting efficacious systemic dose concentrations, but w

SUBMITTER: Lewis JH 

PROVIDER: S-EPMC7497701 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature