Feasibility study of two schedules of sunitinib in combination with pemetrexed in patients with advanced solid tumors

Abstract

Background: Sunitinib is an oral multitargeted tyrosine kinase inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptors, as well as of other receptor types. We have performed a feasibility study to investigate the safety of sunitinib in combination with pemetrexed for treatment of advanced refractory solid tumors.

Methods: Sunitinib was administered once daily on a continuous daily dosing (CDD) schedule (37.5 mg/day) or a 2-weeks-on, 1-week-off treatment schedule (50 mg/day, Schedule 2/1) in combination with pemetrexed at 500 mg/m(2) on day 1 of repeated 21-day cycles.

Results: Twelve patients were enrolled in the study: six on the CDD schedule and six on Schedule 2/1. None of the treated patients experienced a dose-limiting toxicity. Toxicities were manageable and similar in type to those observed in monotherapy studies of sunitinib and pemetrexed. Pharmacokinetic analysis did not reveal any substantial drug-drug interaction. One patient with squamous cell lung cancer showed a partial response and five patients had stable disease.

Conclusions: Combination therapy with sunitinib administered on Schedule 2/1 (50 mg/day) or a CDD schedule (37.5 mg/day) together with standard-dose pemetrexed (500 mg/m(2)) was well tolerated in previously treated patients with advanced solid tumors.

Trial registration: ClinicalTrials.gov NCT00732992.

Fig. 1

Plasma concentration-time profiles for sunitinib, SU12662, total drug (sunitinib + SU12662), and pemetrexed on day 1 of cycle 2 for the CDD schedule. Data are means ± standard deviation (SD) for three patients

Fig. 2

Tumor response. a maximum percentage change in the size of the target lesion in the eight evaluable patients. PD progressive disease, PR partial response, ^†stable disease due to a new bone lesion. b computed tomography of a solid tumor in the right lung of a patient indicated by ^† in part a at baseline (left panel) and on day 14 of cycle 2 for the CDD schedule. The tumor showed marked central cavitation after treatment