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Bevacizumab (Avastin)

Bevacizumab is a recombinant humanized monoclonal antibody directed against the vascular endothelial growth factor-A  (VEGF-A), a pro-angiogenic cytokine.    Bevacizumab works by attaching to and inactivating molecules of VEGF-A in the bloodstream.  [In contrast, some other angiogenesis inhibitors act by inhibiting the tumor cell-surface receptors for VEGF, rather than VEGF itself.] Bevacizumab binds to VEGF and inhibits VEGF receptor binding, thereby preventing the growth and maintenance of tumor blood vessels. 

Bevacizumab is usually given intravenously through the arm every 14 days.

It is manufactured by Genetech/Roche, who have posted details at these links:
Avastin.com   and  Gene.com

FDA approval  has been granted  for the use of Bevacizumab in the treatment of metastatic cancers,  first in 2004 for use in combination with standard chemotherapy for metastatic colon cancer and non-small cell lung cancer.  In 2008 it was approved for breast cancer.

The FDA issued has drug warnings about Bevacizumab, which may cause serious, but uncommon, side effects.  These include:

  • formation of holes in the colon (gastrointestinal perforation),  generally requiring surgery, and sometimes leading to intra-abdominal infections
  • impaired wound healing, and
  • bleeding from the lungs or internally.

Other more common and less serious side effects are:

  • high blood pressure
  • tiredness
  • blood clots
  • diarrhea
  • decreased white blood cells (lowering immunity to diseases)
  • headache
  • appetite loss
  • mouth sores

The FDA warnings can be seen at this link, alongside the details of the FDA approval for its use. 

Summary Table of Results in Other Cancers

You can link here for a table showing the effect of adding bevacizumab to standard treatments for several different types of cancer (not GIST).  Although the duration of progression-free survival or overall survival was longer with the addition of bevacizumab in many cases, the differences were a matter of months. This table is from the following paper:

Targeting angiogenesis: progress with anti-VEGF treatment with large molecules
Axel Grothey & Evanthia Galanis
Nature Reviews Clinical Oncology advance online publication Published online 28 July 2009
doi:10.1038/nrclinonc.2009.110

Trials for GIST Patients

Bevacizumab is in the following current clinical trials relevant to GIST:

Trials currently recruiting:

A Phase III Randomized Study of Imatinib Mesylate With Versus Without Bevacizumab in Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumor
             

Phase I Partially Randomized Study of Dasatinib and Bevacizumab in Patients With Metastatic or Unresectable Solid Tumors

Phase I Bevacizumab and Sunitinib in Treating Patients With Solid Tumors
 

Trials no longer recruiting due to adverse events:

Sorafenib and Bevacizumab in Treating Patients With Refractory, Metastatic, or Unresectable Solid Tumors

Publications

1. Rini BI (February 2007). "Vascular endothelial growth factor-targeted therapy in renal cell carcinoma: current status and future directions". Clin Cancer Res 13 (4): 1098–106.
Open resource: http://clincancerres.aacrjournals.org/cgi/content/abstract/13/4/1098

2. Konner JA et al. Proc ASCO 2007 (May 2008). A phase II study of intravenous (IV) and intraperitoneal (IP) paclitaxel (Tax), IP cisplatin (Cis), and IV bevacizumab (Bev) as first-line chemotherapy for optimal stage II or III ovarian, primary peritoneal, and fallopian tube cancer..
http://www.asco.org/ASCO/Abstracts+&+Virtual+Meeting/Abstracts?&vmview=abst_detail_view&confID=47&abstractID=310963.

3.  Saif MW (2008). "New developments in the treatment of pancreatic cancer. Highlights from the "44th ASCO Annual Meeting". Chicago, IL, USA. May 30 - June 3, 2008    http://www.joplink.net/prev/200807/27.html

4.  Rocha-Lima CM (June 2008). "New directions in the management of advanced pancreatic cancer: a review". Anticancer Drugs 19 (5): 435–46. doi:10.1097/CAD.0b013e3282fc9d11. http://www.ncbi.nlm.nih.gov/pubmed/18418211

5.  Riess H (2008). "Antiangiogenic strategies in pancreatic cancer". Recent Results Cancer Res 177: 123–9.  PunMed:  http://www.ncbi.nlm.nih.gov/pubmed/18084954

6.  Gregg L. Semenza  “Clinical Implications of Basic Research: A New Weapon for Attacking Tumor Blood Vessels”, New England Journal of Medicine, 8 May 2008, 358(19):2066.

7.  Maki, RG  “Targeting angiogenesis in sarcomas, Doxorubicin + bevacizumab. Phase II study, Simon 2-stage design”  CTOS 2007.
www.esmo.org/fileadmin/media/presentations/757/LCT13050936.ppt




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