A phase II study of sunitinib administered in a continuous daily regimen in patients with cytokine-refractory metastatic renal cell carcinoma (mRCC)

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Abstract
4529 Background: Renal cell carcinomas are known for their vascularity and production of high levels of VEGF. Sunitinib malate (SU11248), an oral, multitargeted tyrosine kinase inhibitor of multiple receptors including VEGFR, PDGFR, KIT, RET, and FLT3, has previously demonstrated significant efficacy in 168 patients (pts) with mRCC, with a 42% objective response rate (ORR) at 50 mg/day in 6-week (wk) cycles of 4 wks on treatment followed by 2 wks off. This study sought to determine the efficacy and safety of single-agent sunitinib in mRCC when administered in a continuous 37.5 mg/day regimen. Methods: Pts with histologically proven mRCC, refractory to a cytokine-based regimen, were enrolled in this open-label, multicenter, phase II study. Eligibility criteria included measurable disease, ECOG PS 0/1, and adequate organ function. Pts were randomized to receive sunitinib in the morning (AM) or in the evening (PM) at a dose of 37.5 mg/day, with individual doses subsequently titrated based on tolerability. The primary endpoint was RECIST-defined ORR. Secondary endpoints includedprogression-free survival, adverse events (AEs) and quality of life measures. Results: A total of 88/100 planned pts have been randomized to date: AM (43) and PM (45), and enrollment will be completed by end January 2006. 44 pts have been on continuous sunitinib treatment at 37.5 mg/day for >16 wks (3), >12 wks (9), >8 wks (12), and >4 wks (20). 2 pts (2.3%) discontinued (colon perforation and renal insufficiency) and 9 (10.2%) dose reduced to 25 mg/day due to grade 2/3 AEs: mucositis (2), hand-foot syndrome (2), thrombocytopenia (2), asthenia (1), nausea/diarrhea (1), and neutropenia (1). Preliminary efficacy data show some tumor shrinkage in the majority of patients evaluated at 4 wks, with 3 initial partial responses. There has been no significant difference between pts who received AM or PM doses. The most commonly reported AEs were mucositis, fatigue, hair/skin discoloration, and hand-foot syndrome. Conclusions: Sunitinib administered at a continuous dose of 37.5 mg/day was generally well tolerated; only a few patients required treatment breaks and/or dose reduction. Preliminary efficacy data are encouraging. Mature data will be presented. [Table: see text]

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