Long-term use of sunitinib in metastatic renal cell carcinoma: no unpleasant surprises about tolerability

Metastatic relapse occurs in approximately 30% of patients who have previously undergone nephrectomy for renal cell carcinoma (1). Anti-angiogenic agents, such as tyrosine kinase inhibitors (TKI), have played a leading role in the treatment of metastatic renal cell carcinoma (mRCC) because it is highly resistant to chemotherapy. Sunitinib is a first-line TKI targeting both the vascular endothelial growth factor receptor (VEGFR) and the platelet-derived growth factor receptor (PDGFR). Treatment of mRCC with sunitinib has been shown to increase progression-free survival (PFS) to 11 months (95% confidence interval 0.32–0.54) versus 5 months with baseline interferon alpha treatment (P<0.001) (1), and to improve overall survival (OS) and quality of life. However, patients receiving sunitinib experience specific treatment-related adverse events, including hypertension, epistaxis, hypothyroidism, hand-foot syndrome, hair color changes, fatigue, diarrhea and hematological toxicity. Although almost all patients will develop secondary resistance to sunitinib, 10% remain progression free during >24 months’ therapy (2). This chronic use of sunitinib raises the question of long-term safety for patients treated for more than 2 years (3).