Sunitinib in combination with docetaxel in patients with advanced solid tumors: a phase I dose-escalation study
Open Access
- 31 December 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cancer Chemotherapy and Pharmacology
- Vol. 66 (4), 669-680
- https://doi.org/10.1007/s00280-009-1209-0
Abstract
Purpose Sunitinib in combination with docetaxel enhances antitumor activity in xenograft models of human breast and non-small cell lung cancer. We assessed the maximum tolerated doses (MTDs), safety, pharmacokinetic profiles, and preliminary efficacy of sunitinib plus docetaxel in patients with advanced solid tumors. Methods In this phase I study, successive patient cohorts received sunitinib 25, 37.5, or 50 mg/day for 4 weeks of a 6-week cycle (Schedule 4/2, 4 weeks on, 2 weeks off) or for 2 weeks of a 3-week cycle (Schedule 2/1, 2 weeks on, 1 week off) with docetaxel 60 or 75 mg/m2 IV q21d to determine the MTDs of this treatment combination. Results Fifty patients enrolled: 10 on Schedule 4/2 and 40 on Schedule 2/1. MTDs were established as sunitinib 25 mg on Schedule 4/2 with docetaxel 60 mg/m2 q21d, and as sunitinib 37.5 mg on Schedule 2/1 with docetaxel 75 mg/m2 q21d. On Schedule 2/1, the most frequent dose-limiting toxicity was neutropenia (±fever; grade [G]3/4, n = 5) and the most common G3/4 non-hematologic adverse event (AE) was fatigue (G3, n = 8). Hematologic AEs were managed with growth factor support in 11 of 23 (48%) patients treated at Schedule 2/1 MTD. Three patients achieved a partial response at the Schedule 2/1 MTD. There were no pharmacokinetic drug–drug interactions with either schedule. Conclusions Oral sunitinib 37.5 mg/day on Schedule 2/1 with docetaxel 75 mg/m2 IV q21d is a clinically feasible regimen with a manageable safety profile, no pharmacokinetic drug–drug interactions, and shows antitumor activity in patients with advanced solid tumors.This publication has 25 references indexed in Scilit:
- Activity of Sunitinib in Patients With Advanced Neuroendocrine TumorsJournal of Clinical Oncology, 2008
- Phase II Study of Sunitinib Malate, an Oral Multitargeted Tyrosine Kinase Inhibitor, in Patients With Metastatic Breast Cancer Previously Treated With an Anthracycline and a TaxaneJournal of Clinical Oncology, 2008
- Multicenter, Phase II Trial of Sunitinib in Previously Treated, Advanced Non–Small-Cell Lung CancerJournal of Clinical Oncology, 2008
- Identification of a subset of pericytes that respond to combination therapy targeting PDGF and VEGF signalingInternational Journal of Cancer, 2007
- Phase III Trial Comparing Three Doses of Docetaxel for Second-Line Treatment of Advanced Breast CancerJournal of Clinical Oncology, 2006
- Contribution of individual targets to the antitumor efficacy of the multitargeted receptor tyrosine kinase inhibitor SU11248Molecular Cancer Therapeutics, 2006
- Emerging role of tyrosine kinase inhibitors in the treatment of advanced renal cell cancer: a reviewAnnals of Oncology, 2006
- Activity of SU11248, a Multitargeted Inhibitor of Vascular Endothelial Growth Factor Receptor and Platelet-Derived Growth Factor Receptor, in Patients With Metastatic Renal Cell CarcinomaJournal of Clinical Oncology, 2006
- Randomized Phase III Trial of Pemetrexed Versus Docetaxel in Patients With Non–Small-Cell Lung Cancer Previously Treated With ChemotherapyJournal of Clinical Oncology, 2004
- New Guidelines to Evaluate the Response to Treatment in Solid TumorsJNCI Journal of the National Cancer Institute, 2000