Visceral Adiposity as a Significant Predictor of Sunitinib-Induced Dose-Limiting Toxicities and Survival in Patients with Metastatic Clear Cell Renal Cell Carcinoma

SIMPLE SUMMARY: Although sunitinib is a standard first-line treatment for metastatic renal cell carcinoma, little is known about the predictive factors of sunitinib-induced dose-limiting toxicity in Asian populations. Thus, the aim of this study was to determine whether body composition features significantly associated with sunitinib toxicity in Western populations might predict early dose-limiting toxicity in Korean patients with metastatic renal cell carcinoma. The administration of sunitinib at a fixed dose has the advantage of simplicity but does not consider inter-individual variations, resulting in a high drug toxicity. As high-resolution computed tomography images of patients with cancer are readily available using the body composition, mainly visceral adipose tissue, individualized sunitinib dosage could be feasible in real-world clinical practice, according to this study. Using the appropriate sunitinib dosage based on body composition, visceral adipose tissue index, would reduce sunitinib toxicity. ABSTRACT: Sunitinib is a first-line treatment for metastatic renal cell carcinoma (mRCC). Little is known about the predictive factors of sunitinib-induced dose-limiting toxicity (DLT) in Asian populations. We investigated whether body composition predicts sunitinib-induced DLT. We retrospectively reviewed sunitinib-treated Korean patients with clear cell mRCC from eight institutions. Body composition was measured using computed tomography. DLT was defined as any adverse event leading to dose reduction or treatment discontinuation. Univariate analysis was used to compare body composition indices, and logistic regression analyses were performed for factors predicting early DLT. Overall, 111/311 (32.5%) of patients experienced DLT. Significant differences were observed in the subcutaneous adipose tissue index (SATI; p = 0.001) and visceral adipose tissue index (VATI; p < 0.001) between patients with and without DLT. Multivariate analyses revealed that VATI (odds ratio: 1.013; p = 0.029) was significantly associated with early DLT. Additionally, 20% of patients who had a body mass index (BMI) greater than 23 kg/m(2) and a low VATI experienced DLT, whereas 34.3% of the remaining groups had DLT (p = 0.034). Significant differences were observed for median progression-free survival (13.0 vs. 26.0 months, respectively; p = 0.006) between patients with low and high VATI. Visceral adiposity was a significant predictor of sunitinib-associated DLT and survival. Patients with a low VATI and a BMI greater than 23 kg/m(2) experienced lower DLTs.