Seminars in Oncology
Volume 33 , Pages S35-S40 , October 2006

Combined Vascular Endothelial Growth Factor–Targeted Therapy and Radiotherapy for Rectal Cancer: Theory and Clinical Practice

  • Christopher G. Willett

      Affiliations

    • Department of Radiation Oncology, Duke University Medical Center, Durham, NC.
    • Corresponding Author InformationAddress reprint requests to Christopher G. Willett, MD, Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
  • ,
  • Sergey V. Kozin

      Affiliations

    • Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
  • ,
  • Dan G. Duda

      Affiliations

    • Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
  • ,
  • Emmanuelle di Tomaso

      Affiliations

    • Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
  • ,
  • Kevin R. Kozak

      Affiliations

    • Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
  • ,
  • Yves Boucher

      Affiliations

    • Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
  • ,
  • Rakesh K. Jain

      Affiliations

    • Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
    • Dr Jain is a consultant to AstraZeneca Pharmaceuticals, GLG, Nektar Therapeutics, and ThromboGenics.

References 

  1. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines: Colon Cancer—v.2.2006. http://www.nccn.org/professionals/physician_gls/default.asp (accessed July 17, 2006).
  2. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines: Rectal Cancer—v.2.2006. http://www.nccn.org/professionals/physician_gls/default.asp (accessed July 17, 2006).
  3. Kapiteijn E, Marijnen CA, Nagtegaal ID, et al. Preoperative radiotherapy combined with total mesorectal excision for respectable rectal cancer. N Engl J Med. 2001;345:638–646
  4. Willett CG, Lewandrowski K, Donnelly S, et al. Are there patients with stage I rectal carcinoma at risk for failure after abdominoperineal resection?. Cancer. 1992;69:1651–1655
  5. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin. 2006;56:106–130
  6. Rich T, Gunderson LL, Lew R, et al. Patterns of recurrence of rectal cancer after potentially curative surgery. Cancer. 1983;34:1317–1329
  7. Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351:1731–1740
  8. Wolmark N, Wieand HS, Hyams DM, et al. Randomized trial of postoperative adjuvant chemotherapy with or without radiotherapy for carcinoma of the rectum: National Surgical Adjuvant Breast and Bowel Project Protocol R-02. J Natl Cancer Inst. 2000;95:388–396
  9. Wachsberger P, Burd R, Dicker AP. Tumor response to ionizing radiation combined with antiangiogenesis or vascular targeting agents: Exploring mechanisms of interaction. Clin Cancer Res. 2003;9:1957–1971
  10. O’Reilly MS. Radiation combined with antiangiogenic and antivascular agents. Semin Radiat Oncol. 2006;16:45–50
  11. Teicher BA, Holden SA, Ara G, et al. Comparison of several antiangiogenic regimens alone and with cytotoxic therapies in the Lewis lung carcinoma. Cancer Chemother Pharmacol. 1996;38:169–177
  12. Mauceri HJ, Hanna NN, Beckett MA, et al. Combined effects of angiostatin and ionizing radiation in antitumor therapy. Nature. 1998;394:287–291
  13. Murata R, Nishimura Y, Hiraoka M. An antiangiogenic agent (TNP-470) inhibited reoxygenation during fractionated radiotherapy of murine mammary carcinoma. Int J Radiat Oncol Biol Phys. 1997;37:1107–1113
  14. Gorski DH, Beckett MA, Jaskowiak NT, et al. Blockage of the vascular endothelial growth factor stress response increases the antitumor effects of ionizing radiation. Cancer Res. 1999;59:3374–3378
  15. Lee CG, Heijn M, di Tomaso E, et al. Anti-vascular endothelial growth factor treatment augments tumor radiation response under normoxic or hypoxic conditions. Cancer Res. 2000;60:5565–5570
  16. Kozin SV, Boucher Y, Hicklin DJ, et al. Vascular endothelial growth factor receptor-2-blocking antibody potentiates radiation-induced long-term control of human tumor xenografts. Cancer Res. 2001;61:39–44
  17. Winkler F, Kozin SV, Tong RT, et al. Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: Role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell. 2004;6:553–563
  18. Li J, Huang S, Armstrong EA, et al. Angiogenesis and radiation response modulation after vascular endothelial growth factor receptor-2 (VEGFR2) blockade. Int J Radiat Oncol Biol Phys. 2005;62:1477–1485
  19. Ansiaux R, Baudelet C, Jordan BF, et al. Thalidomide radiosensitizes tumors through early changes in the tumor microenvironment. Clin Cancer Res. 2005;11:743–750
  20. Jain RK, Duda DG, Clark JW, et al. Lessons from phase III clinical trials on anti-VEGF therapy for cancer. Nat Clin Pract Oncol. 2006;3:24–40
  21. Carmeliet P. Angiogenesis in life, disease and medicine. Nature. 2005;438:932–936
  22. Garcia-Barros M, Paris F, Cordon-Cardo C, et al. Tumor response to radiotherapy regulated by endothelial cell apoptosis. Science. 2003;300:1155–1159
  23. Willett CG, Boucher Y, di Tomaso E, et al. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med. 2004;10:145–147
  24. Willett CG, Boucher Y, Duda DG, et al. Surrogate markers for antiangiogenic therapy and dose-limiting toxicities for bevacizumab with radiation and chemotherapy: Continued experience of a phase I trial in rectal cancer patients. J Clin Oncol. 2005;23:8136–8139
  25. Clinicaltrials.gov. 2006. http://www.clinicaltrials.gov/ct/show/NCT00321685?order=1 (accessed June 12, 2006).
  26. Clinicaltrials.gov. 2006. http://www.clinicaltrials.gov/ct/show/NCT00113230?order=7 (accessed June 12, 2006).

 This work was supported by grants from the National Institutes of Health-National Cancer Institute (R21-CA 99237 to C.G.W. and P01-CA80124 and R01-CA115767 to R.K.J.), the National Foundation for Cancer Research (to R.K.J. and C.G.W.), and the American Association for Cancer Research (to D.G.D.).

PII: S0093-7754(06)00318-6

doi: 10.1053/j.seminoncol.2006.08.007

Seminars in Oncology
Volume 33 , Pages S35-S40 , October 2006