cediranib
{{Short description|Chemical compound}}
{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 449572361
| IUPAC_name = 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline
| image = Cediranib.svg
| tradename =
| pregnancy_AU =
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| legal_AU =
| legal_CA =
| legal_UK =
| legal_US =
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| routes_of_administration = Oral
| bioavailability =
| protein_bound =
| metabolism =
| elimination_half-life = 12 to 35 hours
| excretion =
| IUPHAR_ligand = 5664
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 288383-20-0
| ATC_prefix = L01
| ATC_suffix = EK02
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank =
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = NQU9IPY4K9
| PubChem = 9933475
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 491473
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 8109103
| KEGG = D08881
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C25H27FN4O3/c1-16-12-17-19(29-16)6-7-21(24(17)26)33-25-18-13-22(31-2)23(14-20(18)27-15-28-25)32-11-5-10-30-8-3-4-9-30/h6-7,12-15,29H,3-5,8-11H2,1-2H3
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = XXJWYDDUDKYVKI-UHFFFAOYSA-N
| C=25 | H=27 | F=1 | N=4 | O=3
| smiles = COc4cc3c(Oc2ccc1[nH]c(C)cc1c2F)ncnc3cc4OCCCN5CCCC5
}}
Cediranib (AZD-2171; tentative trade name Recentin) is a potent inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases.{{cite journal | vauthors = Wedge SR, Kendrew J, Hennequin LF, Valentine PJ, Barry ST, Brave SR, Smith NR, James NH, Dukes M, Curwen JO, Chester R, Jackson JA, Boffey SJ, Kilburn LL, Barnett S, Richmond GH, Wadsworth PF, Walker M, Bigley AL, Taylor ST, Cooper L, Beck S, Jürgensmeier JM, Ogilvie DJ | display-authors = 6 | title = AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer | journal = Cancer Research | volume = 65 | issue = 10 | pages = 4389–400 | date = May 2005 | pmid = 15899831 | doi = 10.1158/0008-5472.CAN-04-4409 | doi-access = free }}{{cite journal | vauthors = Goss G, Shepherd FA, Laurie S, Gauthier I, Leighl N, Chen E, Feld R, Powers J, Seymour L | display-authors = 6 | title = A phase I and pharmacokinetic study of daily oral cediranib, an inhibitor of vascular endothelial growth factor tyrosine kinases, in combination with cisplatin and gemcitabine in patients with advanced non-small cell lung cancer: a study of the National Cancer Institute of Canada Clinical Trials Group | journal = European Journal of Cancer | volume = 45 | issue = 5 | pages = 782–8 | date = March 2009 | pmid = 19091548 | doi = 10.1016/j.ejca.2008.10.022 }}{{cite journal | vauthors = Nikolinakos P, Heymach JV | title = The tyrosine kinase inhibitor cediranib for non-small cell lung cancer and other thoracic malignancies | journal = Journal of Thoracic Oncology | volume = 3 | issue = 6 Suppl 2 | pages = S131-4 | date = June 2008 | pmid = 18520296 | doi = 10.1097/JTO.0b013e318174e910 | doi-access = free }}
The drug is being developed by AstraZeneca as a possible anti-cancer chemotherapeutic agent for oral administration.
Clinical trials
Beginning in 2007, it underwent phase I clinical trials for the treatment of non-small cell lung cancer, kidney cancer, and colorectal cancer in adults, as well as tumors of the central nervous system in children. Phase I trials of interactions with other drugs used in cancer treatment were also undertaken.{{cn|date=February 2023}}
On February 27, 2008, AstraZeneca announced that the use of cediranib in non-small cell lung cancer will not progress into phase III after failing to meet its main goal. On 8 March 2010, AstraZeneca issued a press-release stating that cediranib had failed Phase III clinical trials for use in first-line metastatic colorectal cancer when it was compared clinically with the market-leader bevacizumab.{{cite web|title=AstraZeneca - RECENTIN did not meet primary endpoint in Horizon III study in metastatic colorectal cancer|url=http://www.astrazeneca.com/Media/Press-releases/Article/20100308--RECENTIN-did-not-meet-primary-endpoint-in-Horizon-III|access-date=17 March 2014}}
In 2016, AstraZeneca completed a phase III trial comparing the efficacy of cediranib alone and cediranib with lomustine to the efficacy of lomustine alone in patients with recurrent glioblastoma. The trial failed to meet its primary endpoint and survival was not extended with cediranib.{{cite journal | vauthors = Batchelor TT, Mulholland P, Neyns B, Nabors LB, Campone M, Wick A, Mason W, Mikkelsen T, Phuphanich S, Ashby LS, Degroot J, Gattamaneni R, Cher L, Rosenthal M, Payer F, Jürgensmeier JM, Jain RK, Sorensen AG, Xu J, Liu Q, van den Bent M | display-authors = 6 | title = Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma | journal = Journal of Clinical Oncology | volume = 31 | issue = 26 | pages = 3212–8 | date = September 2013 | pmid = 23940216 | pmc = 4021043 | doi = 10.1200/JCO.2012.47.2464 | authorlink8 = Tom Mikkelsen }}
Combination trials
Findings from a federally funded, NCI-sponsored phase II clinical trial{{ClinicalTrialsGov|NCT01116648|Cediranib Maleate and Olaparib in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Peritoneal Cancer or Recurrent Triple-Negative Breast Cancer}} presented at the 50th Annual Meeting of the American Society of Clinical Oncology (May 30 - June 3, 2014, Chicago, Ill; Abstract No: LBA5500),{{cite journal | vauthors = Liu JF, Barry WT, Birrer M, Lee JM, Buckanovich RJ, Fleming GF, Rimel B, Buss MK, Nattam S, Hurteau J, Luo W, Quy P, Whalen C, Obermayer L, Lee H, Winer EP, Kohn EC, Ivy SP, Matulonis UA | display-authors = 6 | title = Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study | journal = The Lancet. Oncology | volume = 15 | issue = 11 | pages = 1207–14 | date = October 2014 | pmid = 25218906 | pmc = 4294183 | doi = 10.1016/S1470-2045(14)70391-2 }} show that the combination of two investigational oral drugs, olaparib, a PARP inhibitor, and cediranib is significantly more active against recurrent, platinum chemotherapy-sensitive disease or ovarian cancer related to mutations in BRCA genes than olaparib alone.{{Cite web |url=http://oncozine.com/profiles/blogs/combination-of-targeted-drugs-may-significantly-increase-pfs |title=Combination of Targeted Drugs May Significantly Increase Progression-Free Survival in Women with Recurrent Ovarian Cancer, Study Shows - Onco'Zine - The International Oncology Network; June 2, 2014 |access-date=June 12, 2014 |archive-url=https://web.archive.org/web/20150221153623/http://oncozine.com/profiles/blogs/combination-of-targeted-drugs-may-significantly-increase-pfs |archive-date=February 21, 2015 |url-status=dead }}
References
{{reflist}}
External links
- [https://web.archive.org/web/20070310202726/http://www.cancerline.com/cancerlinehcp/15602_15632_9_3_1.aspx AZD2171—AstraZeneca Pipeline]
{{Extracellular chemotherapeutic agents}}
{{Growth factor receptor modulators}}
Category:Receptor tyrosine kinase inhibitors
Category:Indole ethers at the benzene ring
Category:Drugs developed by AstraZeneca