ASCO 2021: An Open-Label, Pharmacokinetic Study to Determine the Bioavailability, Safety and Tolerability of Single Dose Oral Docetaxel in Metastatic Prostate Cancer Patients Treated with IV Docetaxel

( Following androgen deprivation therapy (ADT) which was introduced decades prior, the TAX-327 trial of docetaxel for patients with metastatic castration-resistant prostate cancer was the first to demonstrate a survival advantage for systemic treatment in prostate cancer. Since then, docetaxel has proven survival benefit for men with metastatic castration-sensitive disease. However, docetaxel requires the non-ionic surfactant polysorbate 80 which is associated with hypersensitivity to allow for IV solubility, necessitating steroid pre-medication. While oral treatment may improve tolerability and improve convenience, docetaxel has poor oral bioavailability due to extrusion by intestinal p-glycoprotein. In the Prostate, Testicular, Penile Poster session at the 2021 American Society of Clinical Oncology Annual Meeting, Dr. Christopher Jackson presented an assessment of Oradoxel, a new combination of oral docetaxel capsules plus the novel gut-selective P-glycoprotein inhibitor encequidar (HM30181A). This agent has already been used in combination with oral paclitaxel.


The authors performed a one-sequence cross-over study to assess the absolute bioavailability and pharmacokinetics or oral docetaxel and encequidar, compared to IV docetaxel. This study enrolled patients with metastatic prostate cancer who were receiving IV docetaxel into three different cohorts with Oradoxel dose-escalation: 75 mg/m2 in Cohort 1, 150 mg/m2 in Cohort 2, and 300mg/m2 in Cohort 3. Oradoxel was given 3 weeks before or after IV docetaxel treatment. Intensive pharmacokinetic samples were taken on days 1-5 for Oradoxel and days 1-4 for IV docetaxel. Dose-limiting toxicity (DLT) or serious adverse events (SAE) were assessed per CTCAE v4.03.

While 11 men were initially included, each cohort included three evaluable patients (n=9). Pharmacokinetic parameters of Oradoxel vs IV docetaxel are summarized in the table below.


The mean absolute bioavailability of Oradoxel was 15.9% (range 8-25%) while pharmacokinetics became nonlinear at 300mg/m2. The authors identified no DLT, MTD, or drug-related SAE.

The authors conclude that Oradoxel was well tolerated. Further, oral dosing may be able to achieve equivalent exposure to intravenous administration of docetaxel. These data form the basis of further evaluation in phase 2 studies.

Presented by: Christopher G. Jackson, FRACP, University of Otago, Dunedin, New Zealand

Written by: Christopher J.D. Wallis, MD, Ph.D., Urologic Oncology Fellow, Vanderbilt University Medical Center, Twitter: @WallisCJD at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting #ASCO21, June, 4-8, 2021

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