Abstract

Conventional sunitinib dosing in metastatic renal cell carcinoma (mRCC) administers 50 mg daily on a 4 weeks on/2 weeks off (4/2) schedule. Not all patients tolerate this regimen and many undergo modifications to schedule, dose, or both. All patients with mRCC treated with sunitinib by the Saskatchewan Cancer Agency between January 1, 2006, and January 1, 2013, were included. Regimens were categorized as standard intermittent dosing (SID), modified intermittent schedule (MIS), modified intermittent dosing (MID), combination of modified schedule and dosing (MSD), or continuous dosing (CD). The primary objective was to compare overall survival (OS) between regimens. Secondary outcomes included progression-free survival (PFS), discontinuation due to adverse effects (AE), and medication cost. Among 161 patients, 18.0%, 51.6%, and 30.4% had favorable, intermediate, and poor Heng risk prognoses, respectively. A total of 140 (87.0%) received sunitinib as first-line therapy. MID was associated with longer OS compared with SID (estimated median 28.4 vs. 11.2 months). PFS was longer for MID, MSD, and CD compared with SID (estimated median 12.0, 9.0, and 8.0 months vs. 3.0 months, respectively). Adjustment for potential confounders did not negate these associations. SID also had higher average monthly drug costs than MIS, MID, and MSD. Overall discontinuation rate due to AE was high (24%). An adjusted-dose sunitinib regimen is associated with improved OS and PFS over SID, with lower costs. The development of toxicities requiring dose reductions serves as a predictive biomarker for better outcomes.

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