Cediranib

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Cediranib
Cediranib.svg
Clinical data
Routes of
administration
Oral
ATC code L01XE32 (WHO)
Pharmacokinetic data
Biological half-life 12 to 35 hours
Identifiers
CAS Number 288383-20-0 YesY
PubChem (CID) 9933475
IUPHAR/BPS 5664
ChemSpider 8109103 N
UNII NQU9IPY4K9 YesY
ChEMBL CHEMBL491473 N
ECHA InfoCard 100.196.628
Chemical and physical data
Formula C25H27FN4O3
Molar mass 450.505 g/mol
3D model (Jmol) Interactive image
 NYesY (what is this?)  (verify)

Cediranib (AZD-2171; tentative trade name Recentin) is a potent inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases.[1][2][3]

The drug is being developed by AstraZeneca as a possible anti-cancer chemotherapeutic agent for oral administration.

Clinical trials[edit]

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.

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.[4] 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.[5]

Combination trials[edit]

Findings from a federally funded, NCI-sponsored phase II clinical trial[6] presented at the 50th Annual Meeting of the American Society of Clinical Oncology (May 30 - June 3, 2014, Chicago, Ill; Abstract No: LBA5500),[7] 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.[8]

References[edit]

  1. ^ Wedge, S. R.; Kendrew, J; Hennequin, L. F.; Valentine, P. J.; Barry, S. T.; Brave, S. R.; Smith, N. R.; James, N. H.; Dukes, M; Curwen, J. O.; Chester, R; Jackson, J. A.; Boffey, S. J.; Kilburn, L. L.; Barnett, S; Richmond, G. H.; Wadsworth, P. F.; Walker, M; Bigley, A. L.; Taylor, S. T.; Cooper, L; Beck, S; Jürgensmeier, J. M.; Ogilvie, D. J. (2005). "AZD2171: A Highly Potent, Orally Bioavailable, Vascular Endothelial Growth Factor Receptor-2 Tyrosine Kinase Inhibitor for the Treatment of Cancer". Cancer Research. 65 (10): 4389–400. doi:10.1158/0008-5472.CAN-04-4409. PMID 15899831. 
  2. ^ Goss, Glenwood; Shepherd, Frances A.; Laurie, Scott; Gauthier, Isabelle; Leighl, N.; Chen, Eric; Feld, Ronald; Powers, Jean; Seymour, Lesley (2009). "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". European Journal of Cancer. 45 (5): 782–8. doi:10.1016/j.ejca.2008.10.022. PMID 19091548. 
  3. ^ Nikolinakos, Petros; Heymach, John V. (2008). "The Tyrosine Kinase Inhibitor Cediranib for Non-small Cell Lung Cancer and Other Thoracic Malignancies". Journal of Thoracic Oncology. 3 (6): S131–4. doi:10.1097/JTO.0b013e318174e910. PMID 18520296. 
  4. ^ "AstraZeneca - RECENTIN did not meet primary endpoint in Horizon III study in metastatic colorectal cancer". Retrieved 17 March 2014. 
  5. ^ Batchelor, T. T.; Mulholland, P.; Neyns, B.; Nabors, L. B.; Campone, M.; Wick, A.; Mason, W.; Mikkelsen, T.; Phuphanich, S.; Ashby, L. S.; Degroot, J.; Gattamaneni, R.; Cher, L.; Rosenthal, M.; Payer, F.; Jurgensmeier, J. M.; Jain, R. K.; Sorensen, A. G.; Xu, J.; Liu, Q.; Van Den Bent, M. (2013). "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 of Clinical Oncology. 31 (26): 3212–8. doi:10.1200/JCO.2012.47.2464. PMC 4021043Freely accessible. PMID 23940216. 
  6. ^ Clinical trial number NCT01116648 for "Cediranib Maleate and Olaparib in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Peritoneal Cancer or Recurrent Triple-Negative Breast Cancer" at ClinicalTrials.gov
  7. ^ Liu, Joyce F; Barry, William T; Birrer, Michael; Lee, Jung-Min; Buckanovich, Ronald J; Fleming, Gini F; Rimel, BJ; Buss, Mary K; Nattam, Sreenivasa; Hurteau, Jean; Luo, Weixiu; Quy, Philippa; Whalen, Christin; Obermayer, Lisa; Lee, Hang; Winer, Eric P; Kohn, Elise C; Ivy, S Percy; Matulonis, Ursula A (2014). "Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: A randomised phase 2 study". The Lancet Oncology. 15 (11): 1207–14. doi:10.1016/S1470-2045(14)70391-2. PMC 4294183Freely accessible. PMID 25218906. 
  8. ^ 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

External links[edit]