A 2 weeks on and 1 week off schedule of sunitinib is associated with decreased toxicity in metastatic renal cell carcinoma.

Treatment of metastatic renal cell carcinoma (mRCC) with sunitinib is often associated with toxicity necessitating dose reduction. Maintaining adequate dosing and drug levels are essential for optimising clinical efficacy. Standard sunitinib schedule is 4 weeks of treatment and 2 weeks of rest (schedule 4/2). Empirically, several mRCC patients at The Cleveland Clinic (CCF) have been changed from schedule 4/2 to 2 weeks of treatment/1 week off (schedule 2/1) after experiencing toxicity, in an attempt to maintain daily dosing. The medical records of 30 mRCC patients on sunitinib who were changed from schedule 4/2 to schedule 2/1 at CCF were retrospectively reviewed. Toxicity on each schedule was recorded during routine clinic visits and graded using Common Toxicity Criteria, version 4.0. 97% of patients on schedule 4/2 had grade 3 or 4 toxicity that led to changing to schedule 2/1. There were no grade 4 toxicities on schedule 2/1, and 27% of patients experienced grade 3 toxicity (p=0.0001). Two of the most common toxicities, fatigue and hand-foot syndrome (HFS), were significantly less frequent on schedule 2/1 than on schedule 4/2 (p=0.0003; p=0.0004, respectively). Median overall treatment duration on schedule 4/2 was 12.6 months (range 1.2 months-5.1 years) and median overall treatment duration on schedule 2/1 was 11.9 months (range 0.9+ to 73.3+ months). Treatment with sunitinib on schedule 2/1 is associated with significantly decreased toxicity in patients who experience grade 3 or greater toxicity on schedule 4/2, and can extend treatment duration considerably. Prospective clinical trials are required to define the optimal sunitinib schedule to balance efficacy and toxicity.