Axitinib, sold under the brand name Inlyta, is a small molecule tyrosine kinase inhibitor developed by Pfizer. It has been shown to significantly inhibit growth of breast cancer in animal (xenograft) models[3] and has shown partial responses in clinical trials with renal cell carcinoma (RCC)[4] and several other tumour types.[5]
It was approved to treat renal cell carcinoma by the U.S. Food and Drug Administration after showing a modest increase in progression-free survival,[6] though there have been reports of fatal adverse effects.[7]
A Phase II clinical trial showed good response in combination chemotherapy with gemcitabine for advanced pancreatic cancer.[11] 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.[12]
In 2010, a Phase III trial for previously treated metastatic renal cell carcinoma (mRCC) showed significantly extended progression-free survival when compared to sorafenib.[13] In December 2011, the Oncologic Drugs Advisory Committee (ODAC) voted unanimously to recommend that US FDA approve 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.[14]
It has also been studied in combination with the ALK1 inhibitor dalantercept.[15]
Diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphonia, hand-foot syndrome, weight decreased, vomiting, asthenia, and constipation are the most common side effects occurring in more than 20% of patients.[17]
Coadministration with strong CYP3A4/CYP3A5 inhibitors and inducers should be avoided where possible as they may increase or reduce plasma exposure of axitinib, respectively. [18]
It was also proposed that it might act by inducing autophagy, as some other tyrosine kinase inhibitors, like sorafenib.[20]
It has also been shown[16] to bind (in a different conformation from the VEGF binding) to the BCR-ABL fusion protein, specifically inhibiting the drug-resistant T315I mutant isoform.
^Wilmes LJ, Pallavicini MG, Fleming LM, Gibbs J, Wang D, Li KL, et al. (April 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". Magnetic Resonance Imaging. 25 (3): 319–327. doi:10.1016/j.mri.2006.09.041. PMID17371720.
^Spano JP, Chodkiewicz C, Maurel J, Wong R, Wasan H, Barone C, et al. (June 2008). "Efficacy of gemcitabine plus axitinib compared with gemcitabine alone in patients with advanced pancreatic cancer: an open-label randomised phase II study". Lancet. 371 (9630): 2101–2108. doi:10.1016/S0140-6736(08)60661-3. PMID18514303. S2CID11062859.
^AHFS Patient Medication Information [Internet]. Bethesda (MD): American Society of Health-System Pharmacists, Inc.; c2022. Axitinib; [last revised 2020 August 15; cited 2022 March 28]; [about 5 p.]. Available from: https://medlineplus.gov/druginfo/meds/a612017.html
^"Axitinib". PubChem. U.S. National Library of Medicine. Retrieved 2022-03-28.
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