Toxicities associated with the administration of sorafenib, sunitinib, and temsirolimus and their management in patients with metastatic renal cell carcinoma.
OBJECTIVE
To provide a systematic review of the side effects associated with sorafenib, sunitinib, and temsirolimus and to provide an outline of possible preventive or therapeutic measures.


METHODS
We performed a PubMed-based systematic review of side effects associated with the three agents and relied on product monographs and prescribing information to provide an outline of treatments aimed at reducing these toxicities.


RESULTS
Side effects range from <1% to 72%. Grade 3/4 side effects are less common and range from <1% to 13% for sorafenib, <1% to 16% for sunitinib, and 1% to 20% for temsirolimus. Overall, sunitinib causes the most grade 3/4 side effects and sorafenib causes the fewest grade 3/4 side effects, although head-to-head trials are required to compare safety profiles of all three kinase inhibitors. Virtually all side effects can be managed effectively.


CONCLUSIONS
Prevention, recognition, and prompt management of side effects are of key importance and avoid unnecessary dose reductions, which may undermine treatment efficacy.
Bhojani
Naeem
N
Cancer Prognostics and Health Outcomes Unit, University of Montreal, Montreal, QC, Canada.
Jeldres
Claudio
C
Patard
Jean-Jacques
JJ
Perrotte
Paul
P
Suardi
Nazareno
N
Hutterer
Georg
G
Patenaude
François
F
Oudard
Stéphane
S
Karakiewicz
Pierre I
PI
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000009:adverse effects*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000556:secondary*; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011379:Prognosis; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects*; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects*; D040262:Receptors, Vascular Endothelial Growth Factor; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077157:Sorafenib; D000077210:Sunitinib
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D007211:Indoles; D010671:Phenylurea Compounds; D011725:Pyridines; D011758:Pyrroles; D009536:Niacinamide; C401859:temsirolimus; D000077157:Sorafenib; D040262:Receptors, Vascular Endothelial Growth Factor; D000077210:Sunitinib; D020123:Sirolimus