Risk of Hand-Foot Skin Reaction with the Multitargeted Kinase Inhibitor Sunitinib in Patients with Renal Cell and Non–Renal Cell Carcinoma: A Meta-analysis

Hand-foot skin reaction (HFSR) is an emerging issue in cancer treatment with multitargeted tyrosine kinase inhibitors (TKIs), leading to morbidity, suboptimal dosing, and poor compliance. The overall risk of HFSR is not clear for sunitinib, a TKI effective for metastatic renal cell carcinoma (RCC) and gastrointestinal stromal tumor. We therefore conducted a systematic review and a meta-analysis to determine the risk of developing HFSR with sunitinib. Databases from PubMed and Web of Science for articles from July 1966 until July 2007 and abstracts presented at the American Society of Clinical Oncology conferences were searched to identify relevant studies. Eligible studies were prospective clinical trials that had described events of HFSR for patients who received singleagent sunitinib. Incidence and relative risk (RR) were calculated using a random-effects or fixed-effects model. A total of 5005 patients with RCC and other cancers from 10 clinical trials were included for analysis. Among patients receiving sunitinib, the summary incidences of all-grade and high-grade HFSR were 18.9% (95% CI, 14.1%–24.8%) and 5.5% (95% CI, 3.9%–7.9%), respectively. Interestingly, patients with RCC have significantly decreased risk of HFSR compared with patients with non-RCC malignancy (RR, 0.56; 95% CI, 0.50–0.64; P < .001). In addition, sunitinib was associated with a significantly increased risk of all-grade HFSR (RR, 9.86; 95% CI, 3.1–31.31; P < .001) in comparison with controls. There is a significant risk of developing HFSR in patients with cancer receiving sunitinib. Adequate monitoring and intervention are recommended for reducing the toxicity.