Comprehensive overview of axitinib development in solid malignancies: focus on metastatic renal cell carcinoma.
The landscape of treatment for metastatic renal cell carcinoma (mRCC) continues to evolve. Although several new drugs have been approved for the treatment of this disease in recent years, mRCC remains incurable. Thus, the search continues for new effective therapies. One such novel compound is axitinib (Inlyta, Pfizer), a potent vascular endothelial growth factor receptor tyrosine kinase inhibitor. Following phase I testing in advanced solid tumors (where hypertension, stomatitis, and diarrhea were the dose-limiting toxicities), use of axitinib has been further developed through phase II testing in thyroid, breast, lung, and renal cancers. Recently, the phase III AXIS (Axitinib [AG 013736] as Second Line Therapy for Metastatic Renal Cell Cancer) trial demonstrated an improvement in progression-free survival for patients with mRCC who were treated with axitinib versus sorafenib (Nexavar, Bayer) as second-line therapy. This article describes the preclinical and clinical evolution of axitinib, with an emphasis on its development and role in mRCC.
City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA. ccarmichael@coh.org
Courtney
C
Carmichael
Clayton
C
Lau
David Y
DY
Josephson
Sumanta K
SK
Pal
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D000077784:Axitinib; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D002986:Clinical Trials as Topic; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000627:therapeutic use*; D007191:Indazoles / Q000737:chemistry / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use
D000970:Antineoplastic Agents; D007093:Imidazoles; D007191:Indazoles; D047428:Protein Kinase Inhibitors; D000077784:Axitinib