Sunitinib Does Not Accelerate Tumor Growth in Patients with Metastatic Renal Cell Carcinoma

• Published in: Cell reports (Cambridge) Vol. 3; no. 2; pp. 277 - 281
• Main Authors: Blagoev, Krastan B., Wilkerson, Julia, Stein, Wilfred D., Motzer, Robert J., Bates, Susan E., Fojo, A. Tito
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.02.2013; Elsevier
• Subjects: Antineoplastic Agents - therapeutic use; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - mortality; Carcinoma, Renal Cell - secondary; Cell Proliferation; Humans; Indoles - therapeutic use; Interferon-alpha - therapeutic use; Kidney Neoplasms - drug therapy; Kidney Neoplasms - mortality; Kidney Neoplasms - secondary; Pyrroles - therapeutic use; Sunitinib; Survival Analysis
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2013.01.015

Preclinical studies have suggested that sunitinib accelerates metastases in animals, ascribing this to inhibition of the vascular endothelial growth factor receptor or the tumor’s adaptation. To address whether sunitinib accelerates tumors in humans, we analyzed data from the pivotal randomized phase III trial comparing sunitinib and interferon alfa in patients with metastatic renal cell carcinoma. The evidence clearly shows that sunitinib was not harmful, did not accelerate tumor growth, and did not shorten survival. Specifically, neither longer sunitinib treatment nor a greater effect of sunitinib on tumors reduced survival. Sunitinib did reduce the tumor’s growth rate while administered, thereby improving survival, without appearing to alter tumor biology after discontinuation. Concerns arising from animal models do not apply to patients receiving sunitinib and likely will not apply to similar agents. [Display omitted] ► Drugs targeting the tumor vasculature are under investigation for cancer treatment ► However, changes in tumor vasculature may promote tumor growth and/or tumor spread ► Our analysis shows that sunitinib does not accelerate tumor growth in humans ► Sunitinib administration has positive effects and no negative effects when stopped Drugs putatively targeting tumor vasculature are approved or under investigation in cancer treatment. There are concerns that tumor vasculature changes induced by these drugs may promote tumor growth and/or spread. Indeed, animal experiments have been interpreted as suggesting that such therapies may accelerate metastases. Blagoev, Fojo, and colleagues' analysis of a clinical trial in humans with metastatic renal cell carcinoma shows that one such drug, sunitinib, has a positive effect when administered, does not accelerate tumor growth, and does not appear to have negative effects after discontinuation.