Phase II trial of continuous once-daily dosing of sunitinib as first-line treatment in patients with metastatic renal cell carcinoma.

BACKGROUND: Sunitinib at 50 mg/day on the 4-weeks-on-2-weeks-off schedule is the current approved regimen for advanced/metastatic renal cell carcinoma (mRCC). Escudier et al reported that continuous, once-daily dosing with sunitinib 37.5 mg had a manageable safety profile and significant antitumor activity as second-line mRCC therapy. In this prospective, multicenter, phase II study, we evaluated the activity of continuous once-daily dosing with sunitinib 37.5 mg as first-line mRCC treatment. METHODS: One hundred nineteen treatment-naive patients with measurable mRCC received sunitinib. The primary endpoint was objective response; secondary endpoints included progression-free survival (PFS), safety, pharmacokinetic measurements, exploration of response biomarkers, and patient reported outcomes (PRO). RESULTS: Objective response rate (ORR) was 35.3%; median response duration was 10.4 months; 36% of patients had stable disease ≥12 weeks. Median PFS at 1 year was 9 months, and 1-year survival probability was 67.8%. The most common any-grade treatment-related adverse events (AEs) were diarrhea (50%) and hand-foot syndrome (43%); the most common grade 3-4 treatment-related AEs were hand-foot syndrome (13%), neutropenia (11%), and diarrhea (9%). Steady-state pharmacokinetics were reached within 3 weeks, with no disproportionate accumulation of sunitinib or its active metabolite throughout the study. No significant correlations between trough drug, active metabolite, or soluble protein levels and clinical response were observed. PRO was largely maintained, although fatigue appeared to worsen after treatment started, with improvement over time. CONCLUSIONS: Continuous once-daily dosing with sunitinib 37.5 mg was active with a manageable safety profile as first-line mRCC therapy, making this a feasible alternative dosing regimen.ope