A Phase I study of the safety, pharmacokinetics and efficacy of navitoclax plus docetaxel in patients with advanced solid tumors

Aim: This Phase I study investigated safety of navitoclax and docetaxel in patients (n = 41) with advanced solid tumors. Patients & methods: Two navitoclax plus docetaxel dosing schedules (21 and 28 days) were evaluated. Maximum tolerated dose, dose-limiting toxicities and preliminary antitumor activity were assessed. Results: Ten (24%) patients experienced dose-limiting toxicities; dose-escalation cohorts: n = 7 (21-day schedule: n = 5; 28-day schedule: n = 2) and 21-day expanded safety cohort: n = 3. Navitoclax 150-mg days 1-5 every 21 days with docetaxel 75 mg/m(2) day 1 was the maximum tolerated dose and optimal schedule. Adverse events included thrombocytopenia (63%), fatigue (61%), nausea (59%) and neutropenia (51%). Four confirmed partial responses occurred. Conclusion: Navitoclax 150-mg orally once/day was safely administered with docetaxel. Myelosuppression limited dose escalation; antitumor activity was observed.

Automated summary

This Phase I study explored the safety and efficacy of navitoclax and docetaxel in patients with advanced solid tumors. The maximum tolerated dose was determined to be navitoclax 150mg orally once/day in combination with docetaxel. Despite dose-limiting toxicities, there were observed instances of antitumor activity, including four confirmed partial responses.