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Bevacizumab (Vascular Endothelial Growth Factor Inhibitor)

Bevacizumab

Bevacizumab is a monoclonal antibody that inhibits vascular endothelial growth factor (VEGF). The inhibition of VEGF prevents the angiogenic switch in micrometastases, which is a key factor in malignancy. Bevacizumab has also been shown to have inhibitory effects on VEGF receptor activation and vascular permeability, and induces apoptosis in tumour cells.1

Indications

Colorectal cancer (CRC)

It is licensed for treating metastatic colorectal cancer with combinations either of fluorouracil and folinic acid, or of fluorouracil, folinic acid, and irinotecan. Bevacizumab is given by intravenous infusion.

  • Bevacizumab (Avastin®), is the first approved therapy designed to inhibit tumour angiogenesis
  • It has significant clinical benefits in the management of colorectal cancer.
  • When bevacizumab is added to IFL (irinotecan / fluorocil / leucovorin)(Camptosar™) as first-line therapy for metastatic CRC, significant benefits are obtained.2 People live on average 5 months longer with this treatment.
  • Similar survival benefits may be achieved when bevacizumab is added to 5-FU/ leucovorin alone.
  • Clinical data show that bevacizumab is the only agent in addition to chemotherapy that has demonstrated survival benefit in the first and second-line settings.
  • Further trials e.g. QUASAR 2,3 will define its role in adjuvant therapy.

NICE are currently appraising the role of Bevacizumab in carcinoma of the colon. This is due for publication in November 2006.4

Breast cancer

Bevacizumab is also used as first-line chemotherapy in patients with recurrent breast cancer, in combination with paclitaxel.5 The addition of bevacizumab to standard chemotherapy improves progression-free survival in breast cancer patients.6

Lung cancer

Last, but not least among the big killers, after breast cancer and colorectal cancer, non-small cell lung cancer (NSCLC) can now benefit from the addition of bevacizumab to standard first-line chemotherapy.

  • Bevacizumab, in combination with carboplatin and paclitaxel, improved overall response and time to progression, in patients with advanced or recurrent non-small-cell lung cancer.
  • Patients with nonsquamous cell histology appear to be a subpopulation with improved outcome and acceptable safety risks.7
  • Careful patient selection is mandatory to avoid fatal bleeding following bevacizumab administration.8

Other metastatic disease

Bevacizumab also offers the potential to increase survival without substantially altering the toxicity profile in other tumour types.

  • Bevacizumab has shown activity in patients with refractory metastatic renal cell carcinoma. Progression-free survival (PFS) was significantly longer in patients treated with bevacizumab (10 mg/kg every 2 weeks) than those treated with placebo. In addition, combining bevacizumab with erlotinib (Tarceva) has shown a median time to progression of more than 11 months.9
  • Pancreatic cancer and other tumour types may also benefit when used first line in combination with standard therapy.


Document references
  1. Wedam SB, Low JA, Yang SX, et al; Antiangiogenic and antitumor effects of bevacizumab in patients with inflammatory and locally advanced breast cancer. J Clin Oncol. 2006 Feb 10;24(5):769-77. Epub 2006 Jan 3. [abstract]
  2. Diaz-Rubio E, Schmoll HJ; The future development of bevacizumab in colorectal cancer. Oncology. 2005;69 Suppl 3:34-45. Epub 2005 Nov 21. [abstract]
  3. QUASAR; Cancer Research UK; Capecitabine with or without bevacizumab for colon cancer (Quasar 2)
  4. Colorectal cancer (metastatic) - bevacizumab and cetuximab, NICE Technology Appraisal (Jan 2007); Bevacizumab and cetuximab for the treatment of metastatic colorectal cancer
  5. National Comprehensive Cancer Network Guidelines - Breast Cancer
  6. Miller KD; E2100: a phase III trial of paclitaxel versus paclitaxel/bevacizumab for metastatic breast cancer. Clin Breast Cancer. 2003 Feb;3(6):421-2.
  7. Johnson DH, Fehrenbacher L, Novotny WF, et al; Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2004 Jun 1;22(11):2184-91. [abstract]
  8. Belvedere O, Grossi F; Lung Cancer Highlights from ASCO 2005. Oncologist. 2006 Jan;11(1):39-50. [abstract]
  9. de Gramont A, Van Cutsem E; Investigating the potential of bevacizumab in other indications: metastatic renal cell, non-small cell lung, pancreatic and breast cancer. Oncology. 2005;69 Suppl 3:46-56. Epub 2005 Nov 21. [abstract]

Internet and further reading AcknowledgementsEMIS is grateful to Dr Hayley Willacy for writing this article. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2008.
DocID: 286
Document Version: 2
DocRef: bgp25226
Last Updated: 24 Sep 2007
Review Date: 23 Sep 2008

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PS - Health and Poverty

Perhaps the biggest cause of ill health in the world is poverty. Help to Make Poverty History. For example, why not lend some of your money to disadvantaged communities to enable them to trade their way out of poverty through schemes such as Shared Interest.

See also MAKEPOVERTYHISTORY North East for details and links to campaigns against poverty.

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