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The Use of Anti-angiogenic Factors in the Treatment of Oncologic Disease. Kyle Treesh, PA-S Bob Hadley, Ph.D., PA-C, Advisor University of Kentucky. Learning Objectives. Why do we need new cancer treatments? What is angiogenesis? What are the anti-angiogenesis agents?
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The Use of Anti-angiogenic Factors in the Treatment of Oncologic Disease Kyle Treesh, PA-S Bob Hadley, Ph.D., PA-C, Advisor University of Kentucky
Learning Objectives • Why do we need new cancer treatments? • What is angiogenesis? • What are the anti-angiogenesis agents? • What agents are FDA-approved? • What combinations of treatment are best? • What does the future hold for these therapies?
U.S. Cancer Statistics • Cancer is a major public health problem! • One in four deaths is due to cancer (570,280 deaths in 2005) • 1,372,910 new cancer cases in 2005 • Lung and bronchus, and colon and rectum equal 25% of total cancer deaths • Breast and Prostate cancers are prevalent in their respective sexes
What is angiogenesis? • Think way back to pathophysiology… • Angiogenesis is the formation of blood vessels in a tissue initiated by VEGF and bfGF • Angiogenesis aids in the healing of wounds, proliferates the endometrium, and is a vital part of pregnancy • Tumors can also cause angiogenesis to occur in order to bring oxygen and nutrients to the tumor for growth • These new blood vessels are the vehicle for metastasis
Anti-angiogenesis factors • Protein anti-angiogenic agents • Monoclonal antibody anti-angiogenic agents • Metronomic chemotherapy
Bevacizumab/Avastin • 1st FDA-approved Angiogenesis Inhibitor • Approved for use with chemotherapy in the treatment of colorectal cancer • Prolonged lives 5 months compared to standard treatment • No additional side effects! • Not expected to be a cure, but provides hope for a longer life
Combination Therapies with Anti-angiogenesis agents: • With Chemotherapy • With Radiation • With other anti-angiogenesis agents • With Vascular Disrupting Agents • Metronomic Chemotherapy • Trimodal Therapy
Into the Future… • What are the limitations of these therapies? • Can these agents work in all cancer sites? • Could these agents be used for prevention of a recurrent cancer (e.g. Breast CA)? • Will clinicians use these therapies? • Over 50 angiogenesis inhibitors in ongoing clinical trials
The bottom line… • Angiogenesis inhibitors have the potential to prolong cancer patients’ quantity of life without diminishing their quality of life
For more information: • The American Cancer Society www.cancer.org • The National Cancer Institute www.cancer.gov
References:1. Jemal A, Murray T, Ward E, Samuels A, Tiwari R, Ghafoor A, et al. Cancer Statistics, 2005. 2005; CA: A Cancer Journal for Clinicians 55: 10-30.2. Wittekind C, and Neid N. Cancer Invasion and Metastasis. 2005; Oncology 69: 14-16.3. ACS, What is antiangiogenesis therapy? 2 April 2005, available at: http://www.cancer.org/docroot/ETO/content/ETO_1_4X_What_Is_Antiangiogenesis_Therapy.asp?sitearea=ETO. Accessed 3 Nov 2005.4. Isayeva T, Kumar S, and Ponnazhagan S. Anti-angiogenic gene therapy for cancer (review). 2004: International Journal of Oncology 25: 335-343.5. ACS, Why do tumors need their own blood supply? 2 April 2005, available at: http://www.cancer.org/docroot/ETO/content/ETO_1_4X_Why_Do_Tumors_Need_Their_Own_Blood_Supply.asp?sitearea=ETO. Accessed 3 Nov 2005.6. ACS, How different antiangiogenesis drugs work. 2 April 2005, available at: http://www.cancer.org/docroot/ETO/content/ETO_1_4X_The_Details_How_Antiangiogenesis_Drugs_Work.asp?sitearea=ETO. Accessed 3 Nov 2005.7. NCI, Understanding cancer series: angiogenesis. 28 Jan 2005, available at: http://www.cancer.gov/cancertopics/understandingcancer/angiogenesis. Accessed 3 Nov 2005.8. ACS, Possible pros and cons of antiangiogenesis drugs. 2 April 2005, available at: http://www.cancer.org/docroot/ETO/content/ETO_1_4X_Advantages_of_Antiangiogenesis_Drugs.asp?sitearea=ETO. Accessed 3 Nov 2005.9. Ma L, Giulio F, Viloria-Petit A, Hicklin DJ, du Manior J, Rak J, et al. In vitro procoagulant activity induced in endotelial calls by chemotherapy and antiangiogenic drug combinations: modulation by lower-dose chemotherapy. 2005; Cancer Research 65: 5365-5373.10. Hurwitz H, and Kabbinavar F. Bevacizumab combined with standard fluoropyrimidine-based chemotherapy regimens to treat colorectal cancer. 2005; Oncology 69: 17-24.11. ACS, Recent research in antiangiogenesis therapy. 2 April 2005, available at: http://www.cancer.org/docroot/ETO/content/ETO_1_4X_Recent_and_Current_Research_in_Antiangiogenesis_Therapy.asp?sitearea=ETO. Accessed 3 Nov 2005.12. ACS, The future of antiangiogenesis. 2 April 2005, available at: http://www.cancer.org/docroot/ETO/content/ETO_1_4x_The_Future_of_Antiangiogenesis.asp?sitearea=ETO. Accessed 3 Nov 2005.13. Huber PE, Bischof M, Jenne J, Heiland S, Peschke P, Saffrich R, et al. Trimodal cancer treatment: beneficial effects of combined antiangiogenesis, radiation, and chemotherapy. 2005; Cancer Research 65: 3645-3655.14. Siemann DW and Shi W. Efficacy of combined antiangiogenic and vascular disrupting agents in treatment of solid tumors. 2004. International Journal of Radiation Oncology*Biology*Physics 60: 1233-1240.15. Klement G, Huang P, Mayer B, Green SK, Man S, Bohlen P, et al. Differences in therapeutic indexes of combination metronomic chemotherapy and an anti-VEGFR-2 antibody in multidrug-resistant human breast cancer xenografts. 2002; Clinical Cancer Research 8: 221-232.16. NCI, Angiogenesis inhibitors in the treatment of cancer. 20 May 2002, available at: http://www.cancer.gov/cancertopics/factsheet/Therapy/angiogenesis-inhibitors. Accessed 3 Nov 2005.