Open AccessA Phase I study of the safety, pharmacokinetics and efficacy of navitoclax plus docetaxel in patients with advanced solid tumors
Author(s) -
Martina Puglisi,
L. Rhoda Molife,
Maja J. De Jonge,
Khurum Khan,
Leni van Doorn,
Martin Förster,
Montserrat Blanco,
Martin Gutierrez,
Catherine Franklin,
Todd Busman,
Jianke Yang,
Ferry A.L.M. Eskens
Publication year - 2021
Publication title -
future oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.857
H-Index - 72
eISSN - 1744-8301
pISSN - 1479-6694
DOI - 10.2217/fon-2021-0140
Subject(s) - docetaxel , medicine , maximum tolerated dose , nausea , neutropenia , dosing , adverse effect , pharmacokinetics , limiting , pharmacology , oncology , chemotherapy , mechanical engineering , engineering
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. Clinical trial registration: NCT00888108 (ClinicalTrials.gov)