Oral docetaxel plus encequidar - a phase 1 clinical trial

Area of Science:

• Pharmacology
• Oncology
• Clinical Trials

Background:

• Docetaxel, a taxane anti-neoplastic agent, has limited oral bioavailability due to P-glycoprotein (P-gp) efflux.
• Oral docetaxel with encequidar (oDox + E), a gut-specific P-gp inhibitor, offers a potential alternative to intravenous administration.
• This study aimed to assess the pharmacokinetic exposure of oDox + E compared to IV docetaxel.

Purpose of the Study:

• To determine the bioavailability, safety, and tolerability of a single oral dose of docetaxel plus encequidar (oDox + E).
• To compare the pharmacokinetic exposure of oDox + E with standard intravenous (IV) docetaxel.
• To evaluate oDox + E in patients with metastatic prostate cancer (mPC).

Main Methods:

• A multicenter, phase I, open-label pharmacokinetic trial.
• Single doses of oDox + E (75, 150, or 300 mg/m2 + 15 mg) were administered to mPC patients.
• Encequidar (15 mg) was given one hour prior to oral docetaxel; pharmacokinetic exposure was compared to IV docetaxel.

Main Results:

• Oral docetaxel exposure increased with dose, becoming non-linear at 300 mg/m2 oDox + E.
• Mean absolute bioavailability of oDox + E ranged from 8.19% to 25.09% (mean 16.14%).
• No deaths, dose-limiting toxicities, serious adverse events, or Grade 4 toxicities were observed; maximum tolerated dose was not reached.

Conclusions:

• oDox + E demonstrated a safe and tolerable adverse event profile in mPC patients.
• Increased oral bioavailability suggests potential for multi-dose oDox + E to achieve exposures comparable to IV docetaxel.
• Further research into optimal multi-dose regimens of oDox + E is warranted.