Targeted therapies for metastatic renal cell carcinoma: an overview of toxicity and dosing strategies.
The targeted therapies sunitinib, sorafenib, temsirolimus, and bevacizumab (when used in combination with interferon-alpha2a) 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.
Hutson
Thomas E
TE
Baylor University Medical Center, Sammons Cancer Center, Dallas, Texas 75246, USA. thomas.hutson@usoncology.com
Figlin
Robert A
RA
Kuhn
John G
JG
Motzer
Robert J
RJ
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000009:adverse effects; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects; D011994:Recombinant Proteins; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077157:Sorafenib; D000077210:Sunitinib
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001557:Benzenesulfonates; D007211:Indoles; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D010671:Phenylurea Compounds; D011725:Pyridines; D011758:Pyrroles; D011994:Recombinant Proteins; D009536:Niacinamide; D000068258:Bevacizumab; C401859:temsirolimus; D000077157:Sorafenib; D000077210:Sunitinib; D020123:Sirolimus