Axitinib, sold under the brand nameInlyta, is a small moleculetyrosine kinase inhibitor developed byPfizer. It has been shown to significantly inhibit growth of breast cancer in animal (xenograft) models[4] and has shown partial responses in clinical trials withrenal cell carcinoma (RCC)[5] and several other tumour types.[6]
It was approved to treat renal cell carcinoma by the U.S. Food and Drug Administration after showing a modest increase inprogression-free survival,[7] though there have been reports of fatal adverse effects.[8]
A Phase IIclinical trial showed good response in combination chemotherapy withgemcitabine for advancedpancreatic cancer.[12] However, Pfizer reported on 30 January 2009, that Phase IIIclinical 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.[13]
In 2010, a Phase III trial for previously treated metastaticrenal cell carcinoma (mRCC) showed significantly extended progression-free survival when compared tosorafenib.[14] In December 2011, theOncologic Drugs Advisory Committee (ODAC) voted unanimously to recommend thatUS 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.[15]
It has also been studied in combination with theALK1 inhibitor dalantercept.[16]
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.[18]
Coadministration with strongCYP3A4/CYP3A5 inhibitors and inducers should be avoided where possible as they may increase or reduce plasma exposure of axitinib, respectively.[19]
It was also proposed that it might act by inducingautophagy, as some other tyrosine kinase inhibitors, likesorafenib.[21]
It has also been shown[17] to bind (in a different conformation from the VEGF binding) to theBCR-ABL fusion protein, specifically inhibiting the drug-resistant T315I mutant isoform.
In July 2024, theCommittee for Medicinal Products for Human Use of theEuropean Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Axitinib Accord, intended for the treatment of adults with renal cell carcinoma.[22] The applicant for this medicinal product is Accord Healthcare S.L.U.[22]
^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.{{cite journal}}: CS1 maint: overridden setting (link)
^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.{{cite journal}}: CS1 maint: overridden setting (link)
^ab"Axitinib Accord EPAR".European Medicines Agency. 25 July 2024. Retrieved27 July 2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
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