Axitinib for the treatment of metastatic renal cell carcinoma: recommendations for therapy management to optimize outcomes.
Axitinib is a novel, oral, multitargeted tyrosine kinase inhibitor, which inhibits vascular endothelial growth factor receptors 1, 2, and 3 at subnanomolar concentrations in vitro. In the phase III clinical trial in patients with metastatic renal cell carcinoma, axitinib showed a high objective response rate, and significantly prolonged progression-free survival compared with sorafenib. Thus, it is the first drug that has proven the concept of sequencing tyrosine kinase inhibitors in second-line treatment in a phase III prospective randomized trial. Although generally well tolerated and associated with a low incidence of grade 3 or 4 toxicities, axitinib shows a distinct pattern of adverse events that require monitoring and management. The most common adverse events observed with axitinib include diarrhea, hypertension, fatigue, nausea, and vomiting. This article summarizes the most important adverse events observed and proposes recommendations for their monitoring, prevention, and treatment. The recommendations are based on the existing literature and discussion by an expert group of international physicians and nurses specialized in oncologic treatment of metastatic renal cell carcinoma, which gathered in July 2011 in London, UK. Proactive assessment and management of adverse events during axitinib therapy can minimize treatment interruptions and ensure optimal effect of treatment.
*Renal Cancer Unit, Department of Medicine, Royal Marsden, London, UK †H. Lee Moffitt Cancer Center, Tampa, FL ‡Cleveland Clinic Cancer Institute, Cleveland, OH §Massachusetts General Hospital, Boston, MA ∥N.N. Blokhin Russian Cancer Research Center, Moscow, Russia ¶M.D. Anderson Cancer Center, Houston #Texas Oncology PA Sammons Cancer Center/Baylor, Dallas, TX **Department of Urology, University of Munich, Munich, Germany.
James
J
Larkin
Mayer
M
Fishman
Laura
L
Wood
Sylvie
S
Negrier
Kara
K
Olivier
Linda
L
Pyle
Vera
V
Gorbunova
Eric
E
Jonasch
Lori
L
Andrews
Michael
M
Staehler
D000077784:Axitinib; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D003967:Diarrhea / Q000139:chemically induced / Q000628:therapy; D055154:Dysphonia / Q000139:chemically induced; D005221:Fatigue / Q000139:chemically induced; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D007191:Indazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy*; D009325:Nausea / Q000139:chemically induced / Q000628:therapy; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011507:Proteinuria / Q000139:chemically induced / Q000188:drug therapy; D014839:Vomiting / Q000139:chemically induced / Q000628:therapy
D007093:Imidazoles; D007191:Indazoles; D047428:Protein Kinase Inhibitors; D000077784:Axitinib