|Systematic (IUPAC) name|
|Licence data||US FDA:|
|Pregnancy cat.||D (US)|
|Legal status||℞-only (US)|
|Mol. mass||386.469 g/mol|
| (what is this?)
Axitinib (AG013736; trade name Inlyta) is a small molecule tyrosine kinase inhibitor developed by Pfizer. It inhibits multiple targets, including VEGFR-1, VEGFR-2, VEGFR-3, platelet derived growth factor receptor (PDGFR), and cKIT (CD117). It has been shown to significantly inhibit growth of breast cancer in xenograft models and has been successful in trials with renal cell carcinoma (RCC) and several other tumor types.
A Phase II clinical trial showed good response in combination chemotherapy with gemcitabine for advanced pancreatic cancer. However, Pfizer reported on January 30, 2009 that Phase III clinical trials of the drug when used in combination with gemcitabine showed no evidence of improved survival rates over treatments using gemcitabine alone for advanced pancreatic cancer and halted the trial.
In December 2011, the Oncologic Drugs Advisory Committee (ODAC) voted unanimously to recommend the approval of axitinib for the second-line treatment of patients with advanced renal cell carcinoma (RCC), based on the results of the Phase III trial comparing axitinib and sorafenib.
The FDA approved the drug for advanced renal cell carcinoma after the failure of one prior systemic therapy. It is to be given orally, twice daily in 5 mg doses. Dose adjustment should be made on an individual basis. The doses can be given with or without food every 12 hours and needs to be swallowed with a full glass of water.
Patients receiving a strong CYP3A4/5 inhibitor may require a weaker dose of the drug, for these patients decrease the dose size by half. Those with hepatic impairment should receive a half dose. 
Diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphonia, hand-foot syndrome, weight decreased, vomiting, asthenia, and constipation were the most common side effects occurring in greater than 20% of patients.
- Wilmes LJ, Pallavicini MG, Fleming LM, Gibbs J, Wang D, Li KL, Partridge SC, Henry RG, Shalinsky DR, Hu-Lowe D, Park JW, McShane TM, Lu Y, Brasch RC, Hylton NM. (2007) AG-013736, a novel inhibitor of VEGF receptor tyrosine kinases, inhibits breast cancer growth and decreases vascular permeability as detected by dynamic contrast-enhanced magnetic resonance imaging. Magn Reson Imaging 25(3):319-27
- Rini B, Rixe O, Bukowski R, Michaelson MD, Wilding G, Hudes G, Bolte O, Steinfeldt H, Reich SD, Motzer R. (2005) AG-013736, a multi-target tyrosine kinase receptor inhibitor, demonstrates anti-tumor activity in a Phase 2 study of cytokine-refractory, metastatic renal cell cancer (RCC). ASCO Proceedings Abstract 4509
- Rugo HS, Herbst RS, Liu G, Park JW, Kies MS, Steinfeldt HM, Pithavala YK, Reich SD, Freddo JL, Wilding G. (2005) Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with advanced solid tumors: pharmacokinetic and clinical results. J Clin Oncol. 23(24):5474-83
- Spano JP, Chodkiewicz C, Maurel J, Wong R, Wasan H, Barone C, Létourneau R, Bajetta E, Pithavala Y, Bycott P, Trask P, Liau K, Ricart AD, Kim S, Rixe O. (2008) Efficacy of gemcitabine plus axitinib compared with gemcitabine alone in patients with advanced pancreatic cancer: an open-label randomised phase II study. Lancet. [Epub ahead of print]
- "Pfizer pancreatic cancer drug fails, trial halted". Reuters. January 30, 2009.
- "Pfizer’s Phase III Trial in mRCC Turns Up Positive Results". 19 Nov 2010.
- "ODAC Unanimously Supports Axitinib for Renal Cell Carcinoma". 7 Dec 2011.
- "FDA Approves Axitinib for Advanced Kidney Cancer Patients". 27 Jan 2012.
- "FDA Prescribing Information". 30 Jan 2012.