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bevacizumab (Avastin, Altuzan)

Tradename: Avastin (FDA approved 2004), Altuzan not approved by FDA for use in the United States (it is an approved drug in Turkey) [15] Indications: 1) metastatic colorectal cancer a) in combination with conventional chemotherapy b) improves survival by about 5 months) [2] c) no benefit as maintenance monotherapy [20] 2) lung cancer, ovarian cancer, breast cancer [13] 3) malignant brain tumor [13] 4) metastatic renal cell carcinoma, in combination with interferon alpha-2a [12,18] 5) advanced cervical cancer [18] 6) intravitreal treatment of exudative macular degeneration (ophthalmic) - diabetic macular edema 7) intravitreal treatment of proliferative diabetic retinopathy* [21] * off label use Contraindications: - in combination with paclitaxel for treatment of metastatic breast cancer [11]; FDA approval revoked Nov 2011 [14]; not safe & effective for this indication Adverse effects: 1) infusion reaction [13] 2) hypertension (most common adverse effect) 3) severe hemorrhage is most common serious adverse event - pulmonary hemorrhage & hemoptysis - gastrointestinal bleeding 4) thrombosis, arterial thrombosis 5) increase in treatment-related mortality 6) reversible posterior leukoencephalopathy syndrome [7] 7) nasal septum perforation 8) tracheo-esophageal (TE) fistula in contex of persistent esophagitis [8] 9) intestinal perforation, pneumoperitoneum [13,16] - perforation of previously asymptomatic peptic ulcers or colonic diverticula [13] 10) enterovaginal fistula [18] 11) dehiscence of recent (< 3 years) surgical wounds 12) poor wound healing 13) nephrotic syndrome [13] 14) thrombosis, thrombotic microangiopathy [13] Drug interactions: - several reports of microangiopathic hemolytic anemia in patients with solid tumors receiving Avastin in combination with sunitinib malate; this combination is not recommended [9] Mechanism of action: 1) angiogenesis inhibitor, binds to & inhibits VEGF 2) reduces blood supply to tumors Notes: - according to the Washington Post, this is the same drug as ranibizumab (Lucentis) both produced by Genentech [17] - initially FDA-approved on the basis of progression-free surivival, but later revealed there is no overall survival benefit.

Interactions

drug adverse effects of pharmaceutical monoclonal antibodies

Specific

bevacizumab ophthalmic (Avastin)

General

vascular endothelial growth factor (VEGF) inhibitor antineoplastic monoclonal antibody

References

  1. Prescriber's Letter 10(6):35 2003
  2. Prescriber's Letter 11(3):16 2004 Detail-Document#: 200311 (subscription needed) http://www.prescribersletter.com
  3. Genentech, Inc. 1 DNA Way South San Francisco, California 94080-4990 USA Phone: 650-225-1000 Fax: 650-225-6000 http://www.genentech.com
  4. Bevacizumab (Avastin) for Metastatic Colorectal Cancer http://www.cancer.gov/newscenter/pressreleases/bevacizumab
  5. Journal Watch 25(14):112, 2005
  6. Grand Rounds UC Davis
  7. FDA Medwatch http://www.fda.gov/medwatch/safety/2006/safety06.htm#Avastin
  8. FDA Medwatch http://www.fda.gov/medwatch/safety/2007/safety07.htm#Avastin
  9. FDA Medwatch http://www.fda.gov/medwatch/safety/2008/safety08.htm#Avastin
  10. PubMed Search PubMed search: bevacizumab+OR+Avastin
  11. Miller K et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 2007 Dec 27; 357:2666. PMID: 18160686 - FDA advisory committee does not recommend approval for Avastin for breast cancer. http://ecancertrials.com/Default.aspx?DocumentID=40958 - Miller R. The biotech bottleneck. Wall Street Journal Dec 28 , 2007:A13 http://online.wsj.com/article/SB119880414063654409.html - FDA MedWatch Avastin (bevacizumab): Process for Removal of Breast Cancer Indication Begun http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm237280.htm
  12. Escudier BJ et al Final results of the phase III, randomized, double-blind AVOREN trial of first-line bevacizumab (BEV) + interferon-alpha 2a (IFN) in metastatic renal cell carcinoma (mRCC). J Clin Oncol 27:15s, 2009 (suppl; abstr 5020) http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=65&abstractID=32687
  13. Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 18. American College of Physicians, Philadelphia 2009, 2012, 2018.
  14. MedScape Oncology, Nov 18, 2011 FDA MedWatch Pending
  15. FDA MedWatch Altuzan (bevacizumab): Counterfeit Product - Contains no Active Ingredient http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm298583.htm - Health Care Provider Alert: Feb 5, 2013 nother Counterfeit Cancer Medicine Found in United States. Purchasing Unapproved Drugs is Risky Business. http://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/CounterfeitMedicine/ucm338283.htm
  16. Keefe D, Bowen J, Gibson R, Tan T, Okera M, Stringer A. Noncardiac vascular toxicities of vascular endothelial growth factor inhibitors in advanced cancer: a review. Oncologist. 2011;16(4):432-44 PMID: 21441297
  17. Kliff S This $2,000 drug says everything about our messed up health- care system. Washington Post Dec 9, 2013 http://www.washingtonpost.com/blogs/wonkblog/wp/2013/12/09/this-2000-drug-says-everything-about-our-messed-up-health-care-system/
  18. Tewari KS et al. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med 2014 Feb 20; 370:734 PMID: 24552320 http://www.nejm.org/doi/full/10.1056/NEJMoa1309748 - Kelly KJ, Sadoughi S, Sofair A Bevacizumab Approved for Late-Stage Cervical Cancer. Physician's First Watch, Aug 18, 2014 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org - FDA News Release/ August 14, 2014 FDA approves Avastin to treat patients with aggressive and late-stage cervical cancer. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm410121.htm
  19. Kim C, Prasad V Cancer Drugs Approved on the Basis of a Surrogate End Point and Subsequent Overall SurvivalAn Analysis of 5 Years of US Food and Drug Administration Approvals. JAMA Intern Med. Published online October 19, 2015. PMID: 26502403 http://archinte.jamanetwork.com/article.aspx?articleID=2463590
  20. Jenkins K. No Survival Benefit with Bevacizumab Maintenance in CRC. Monotherapy no better than observation after induction chemo. MedPage Today. January 28, 2018 https://www.medpagetoday.com/hematologyoncology/coloncancer/70800 - Aparicio T, Ghiringhelli F, Boige V et al Bevacizumab Maintenance Versus No Maintenance During Chemotherapy- Free Intervals in Metastatic Colorectal Cancer: A Randomized Phase III Trial (PRODIGE 9). J Clin Oncol 2018; Jan 18:JCO2017752931 PMID: 29346040
  21. NEJM Knowledge+ Ophthalmology