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Genitourinary Cancer

Targeted Therapies for Metastatic Renal Cell Carcinoma: An Overview of Toxicity and Dosing Strategies

^aBaylor University Medical Center, Sammons Cancer Center, Dallas, Texas, USA; ^bCity of Hope National Medical Center, Duarte, California, USA; ^cUniversity of Texas Health Science Center, San Antonio, Texas, USA; ^dMemorial Sloan-Kettering Cancer Center, New York, New York, USA

Key Words. Renal cell carcinoma • Temsirolimus • Sunitinib • Sorafenib • Safety • Dosing

Correspondence: Thomas E. Hutson, D.O., Pharm.D., Baylor University Medical Center, GU Oncology Program, Texas Oncology, PA, Sammons Cancer Center, 3535 Worth Street, Dallas, Texas 75246, USA. Telephone: 214-370-1069; Fax: 214-370-1190; e-mail: thomas.hutson{at}usoncology.com

Received May 21, 2008; accepted for publication September 3, 2008; first published online in THE ONCOLOGIST Express on October 6, 2008.

Disclosure: Employment/leadership position: None; Intellectual property rights/inventor/patent holder: None; Consultant/advisory role: Thomas E. Hutson, Pfizer, Bayer, GlaxoSmithKline, Wyeth; Robert A. Figlin, Wyeth, Novartis, Pfizer, Kely, Aveo Pharmaceuticals, Innate Pharmaceuticals; Honoraria: Thomas E. Hutson, Pfizer, Bayer, Wyeth; Research funding/contracted research: Thomas E. Hutson, Pfizer, Bayer, Wyeth, GlaxoSmithKline, Genentech; Robert A. Figlin, Wyeth, Novartis, Keryx, Amgen, Pfizer, Argos Pharmaceuticals; Robert J. Motzer, Pfizer, Wyeth, Genentech; Ownership interest: None; Expert testimony: None; Fees for non-CME services: Robert J. Motzer, Bayer/Onyx.

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the authors, planners, independent peer reviewers, or staff managers.

The targeted therapies sunitinib, sorafenib, temsirolimus, and bevacizumab (when used in combination with interferon-2a) have dramatically improved outcomes for patients with advanced renal cell carcinoma (RCC). Clinical application of these novel agents outside the trial setting, however, may present some challenges for treating individual patients with unique needs. In some patients, dose modifications may be considered for potential drug interactions and for management of severe cases of hematologic or nonhematologic toxicities. The more common grade 3 or 4 side effects with sunitinib and sorafenib include hypertension, fatigue, hand–foot syndrome, elevated lipase, lymphopenia, and neutropenia. Congestive heart failure is a less common but serious side effect that warrants treatment discontinuation. Temsirolimus exhibits a different side-effect profile, with the more common grade 3 or 4 side effects being metabolic in nature (i.e., elevated triglycerides, elevated glucose, hypophosphatemia) as a result of its inhibitory effects on the mammalian target of rapamycin–regulated lipid and glucose pathways. Asthenia, rash, and dyspnea also occur in patients receiving temsirolimus. Virtually all of the side effects associated with these agents can be managed effectively in the majority of patients with medical treatment or supportive interventions. Recognition and prompt management of side effects are important to avoid unnecessary dose reductions that may result in suboptimal efficacy.