Sunitinib in combination with gemcitabine for advanced solid tumours: a phase I dose-finding study

Background: This phase I, dose-finding study determined the maximum tolerated dose (MTD), safety, and pharmacokinetics of sunitinib plus gemcitabine in patients with advanced solid tumours. Methods: Two schedules with sunitinib (25–50 mg per day) and IV gemcitabine (750–1250 mg m −2 ) in escalating doses were studied. First, patients received sunitinib on a 4-weeks-on-2-weeks-off schedule (Schedule 4/2) plus gemcitabine on days 1, 8, 22, and 29. Second, patients received sunitinib on a 2-weeks-on-1-week-off schedule (Schedule 2/1) plus gemcitabine on days 1 and 8. The primary endpoint was determination of MTD and tolerability. Results: Forty-four patients received the combination (Schedule 4/2, n =8; Schedule 2/1, n =36). With no dose-limiting toxicities (DLTs) at maximum dose levels on Schedule 2/1, MTD was not reached. Grade 4 treatment-related AEs and laboratory abnormalities included cerebrovascular accident, hypertension, and pulmonary embolism ( n =1 each), and neutropenia ( n =3), thrombocytopenia and increased uric acid (both n =2), and lymphopenia ( n =1). There were no clinically significant drug–drug interactions. Antitumor activity occurred across dose levels and tumour types. In poor-risk and/or high-grade renal cell carcinoma patients ( n =12), 5 had partial responses and 7 stable disease ⩾6 weeks. Conclusion: Sunitinib plus gemcitabine on Schedule 2/1 with growth factor support was well tolerated and safely administered at maximum doses of each drug, without significant drug–drug interactions.