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]
Interactions
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.
External links
"Axitinib". Drug Information Portal. U.S. National Library of Medicine.