International Journal of Radiation Oncology * Biology * Physics
Volume 71, Issue 1 , Pages 79-86 , 1 May 2008

A Phase III Study of Conventional Radiation Therapy Plus Thalidomide Versus Conventional Radiation Therapy for Multiple Brain Metastases (RTOG 0118)

  • Jonathan P.S. Knisely, M.D., F.R.C.P.C.

      Affiliations

    • Department of Therapeutic Radiology, Yale University School of Medicine and Yale Cancer Center, New Haven, CT
    • Corresponding Author InformationReprint requests to: Jonathan P. S. Knisely, M.D., F.R.C.P.C., Yale University School of Medicine and Yale Cancer Center, 333 Cedar Street, 133 HRT, P.O. Box 208040, New Haven, CT 06520-8040. Tel: (203) 785-2960; Fax: (203) 785-4622
    • ,
  • Brian Berkey, M.S.

      Affiliations

    • Radiation Therapy Oncology Group, Philadelphia, PA
    • ,
  • Arnab Chakravarti, M.D.

      Affiliations

    • Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA
    • ,
  • Al W.K. Yung, M.D.

      Affiliations

    • Department of Neuro-Oncology and Brain Tumor Center, The University of Texas M.D. Anderson Cancer Center, Houston, TX
    • ,
  • Walter J. Curran Jr., M.D.

      Affiliations

    • Department of Radiation Oncology, Emory University, Atlanta, GA
    • ,
  • H. Ian Robins, M.D., Ph.D.

      Affiliations

    • Department of Human Oncology, University of Wisconsin Medical School, Madison, WI
    • Department of Medicine, University of Wisconsin Medical School, Madison, WI
    • ,
  • Benjamin Movsas, M.D.

      Affiliations

    • Department of Radiation Oncology, Henry Ford Health System, Detroit, MI
    • ,
  • David G. Brachman, M.D.

      Affiliations

    • Department of Radiation Oncology, AZ Oncology Services and St. Joseph's Hospital, Phoenix, AZ
    • ,
  • Randall H. Henderson, M.D., M.B.A.

      Affiliations

    • University of Florida Proton Therapy Institute, Jacksonville, FL
    • ,
  • Minesh P. Mehta, M.D.

      Affiliations

    • Department of Medicine, University of Wisconsin Medical School, Madison, WI

Received 18 June 2007 ,Revised 23 August 2007 ,Accepted 24 September 2007.

References 

  1. Posner JB. Neurologic complications of cancer. Philadelphia: F.A. Davis; 1995;
  2. Cairncross G, Kim JH, Posner J. Radiation therapy for brain metastases. Ann Neurol. 1979;7:529–541
  3. Chao J, Phillips R, Nickson J. Roentgen-ray therapy of cerebral metastases. Cancer. 1954;7:682–689
  4. Andrews DW, Scott CB, Sperduto PW, et al. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: Phase III results of the RTOG 9508 randomised trial. Lancet. 2004;363:1665–1672
  5. Patchell RA, Tibbs PA, Walsh JW, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med. 1990;22(322):494–500
  6. Folkman J. Angiogenesis and angiogenesis inhibition: An overview. EXS. 1997;79:1–8
  7. Folkman J. New perspectives in clinical oncology from angiogenesis research. Eur J Cancer. 1996;32:2534–2539
  8. Klagsbrun M, Amore PA. Regulators of angiogenesis. Ann Rev Physiol. 1991;53:217–239
  9. Rockwell S, Knisely JPS. Hypoxia and angiogenesis in experimental tumor models: Therapeutic implications. In:  Goldberg ID,  Rosen EM editor. Regulation of angiogenesis. Switzerland: Birkhauser Verlag; 1997;p. 335–360
  10. D'Amato RJ, Loughnan MS, Flynn E, et al. Thalidomide is an inhibitor of angiogenesis. Proc Nat Acad Sci U S A. 1994;91:4082–4085
  11. Geitz H, Handt S, Zwingenberger K. Thalidomide selectively modulates the density of cell surface molecules involved in the adhesion cascade. Immunopharmacology. 1996;31:213–221
  12. Haslett PA, Corral LG, Albert M, et al. Thalidomide costimulates primary human T lymphocytes, preferentially inducing proliferation, cytokine production, and cytotoxic responses in the CD8+ subset. J Exp Med. 1998;187:1885–1892
  13. Fine HA, Figg WD, Jaeckle K, et al. Phase II trial of the antiangiogenic agent thalidomide in patients with recurrent high-grade gliomas. J Clin Oncol. 2000;18:708–715
  14. Yung WKA, Seiferheld W, Donahue B, et al. A RTOG (Radiation Therapy Oncology Group) Phase II study of conventional radiation therapy plus thalidomide followed by thalidomide post XRT for supratentorial glioblastoma. Proc Am Soc Clin Oncol. 2001;20;(abstract 206)
  15. Sotomayor EA, Teicher BA, Schwartz GN, et al. Minocycline in combination with chemotherapy or radiation therapy in vitro and in vivo. Cancer Chemother Pharmacol. 1992;30:377–384
  16. Kakeji Y, Teicher BA. Preclinical studies of the combination of angiogenic inhibitors with cytotoxic agents. Invest New Drugs. 1997;15:39–48
  17. Gorski DH, Mauceri HJ, Salloum RM, et al. Potentiation of the antitumor effect of ionizing radiation by brief concomitant exposures to angiostatin. Cancer Res. 1998;58:5686–5689
  18. Gaspar LE, Scott C, Murray K, et al. Validation of the RTOG recursive partitioning analysis (RPA) classification for brain metastases. Int J Radiat Oncol Biol Phys. 2000;47:1001–1006
  19. Fox S, Berkey B, Knisely J, et al. Prospective neurocognitive effects and quality of life (QOL) in patients with multiple brain metastases receiving whole brain radiation (WBRT) ± thalidomide on RTOG Trial 0118. (2006 ASCO Annual Meeting Proceedings Part I.). J Clin Oncol. 2006;24(Suppl):8589
  20. Tobin DA, Vermund H. A randomized study of hyperbaric oxygen as an adjunct to regularly fractionated radiation therapy for clinical treatment of advanced neoplastic disease. Am J Roentgenol Radium Ther Nucl Med. 1971;111:613–621
  21. Khuntia D, Brown P, Li J, Mehta MP. Whole-brain radiotherapy in the management of brain metastasis. J Clin Oncol. 2006;24:1295–1304
  22. Tsao M, Lloyd N, Wong R, et al. Whole brain radiotherapy for the treatment of multiple brain metastases. Cochrane Database Syst Rev. 2006;3:CD003869
  23. Jain RK. Antiangiogenic therapy for cancer: Current and emerging concepts. Oncology (Williston Park). 2005;19(4 Suppl 3):7–16
  24. Presta M, Dell'Era P, Mitola S, et al. Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis. Cytokine Growth Factor Rev. 2005;16:159–178
  25. Aigner A, Butscheid M, Kunkel P, et al. An FGF-binding protein (FGF-BP) exerts its biological function by parallel paracrine stimulation of tumor cell and endothelial cell proliferation through FGF-2 release. Int J Cancer. 2001;92:510–517
  26. Sampaio EP, Sarno EN, Galilly R, et al. Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes. J Exp Med. 1991;173:699–703
  27. Kedar I, Mermershtain W, Ivgi H. Thalidomide reduces serum C-reactive protein and interleukin-6 and induces response to IL-2 in a fraction of metastatic renal cell cancer patients who failed IL-2-based therapy. Int J Cancer. 2004;110:260–265
  28. Fujita J, Mestre JR, Zeldis JB, et al. Thalidomide and its analogues inhibit lipopolysaccharide-mediated induction of cyclooxygenase-2. Clin Cancer Res. 2001;7:3349–3355
  29. Davies FE, Raje N, Hideshima T, et al. Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood. 2001;98:210–216
  30. Marriott JB, Clarke IA, Czajka A, et al. A novel subclass of thalidomide analogue with anti-solid tumor activity in which caspase-dependent apoptosis is associated with altered expression of bcl-2 family proteins. Cancer Res. 2003;63:593–599
  31. Mitsiades N, Mitsiades CS, Poulaki V, et al. Intracellular regulation of tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in human multiple myeloma cells. Blood. 2002;99:2162–2171
  32. Ansiaux R, Baudelet C, Jordan BF, et al. Thalidomide radiosensitizes tumors through early changes in the tumor microenvironment. Cancer Res Clin Cancer Res. 2005;11:743–750
  33. Wu JJ, Huang DB, Pang KR, et al. Thalidomide: Dermatological indications, mechanisms of action and side-effects. Br J Dermatol. 2005;153:254–273
  34. Clark TE, Edom N, Larson J, et al. Thalomid (thalidomide) capsules: A review of the first 18 months of spontaneous postmarketing adverse event surveillance, including off-label prescribing. Drug Saf. 2001;24:87–117
  35. Zeldis JB, Williams BA, Thomas SD, et al. S.T.E.P.S.: A comprehensive program for controlling and monitoring access to thalidomide. Clin Ther. 1990;21:319–330
  36. Teicher BA. A systems approach to cancer therapy. Cancer Metastasis Rev. 1996;15:247–272
  37. Folkman J. Angiogenesis inhibitors: a new class of drugs. Cancer Biol Ther. 2003;2:S127–S133
  38. Nieder C, Wiedenmann N, Andratschke N, et al. Current status of angiogenesis inhibitors combined with radiation therapy. Cancer Treat Rev. 2006;32:348–364
  39. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–2342
  40. Bevacizumab (Avastin™) for Treatment of Solid Tumors: NCI Fact Sheet. Available at: http://www.cancer.gov/cancertopics/factsheet/AvastinFactSheet. Accessed on August 6, 2006.
  41. 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
  42. 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
  43. Crane CH, Ellis LM, Abbruzzese JL, et al. Phase I trial evaluating the safety of bevacizumab with concurrent radiotherapy and capecitabine in locally advanced pancreatic cancer. J Clin Oncol. 2006;24:1145–1151
  44. Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 2005;23:1011–1027
  45. Mehta MP, Carrie C, Mahe MA, et al. Motexafin gadolinium (MGd) combined with prompt whole brain radiation therapy prolongs time to neurologic progression in non–small cell lung cancer (NSCLC) patients with brain metastases: Results of a randomized phase 3 trial. Int J Radiat Oncol Biol Phys. 2006;66(Suppl):S23
  46. Suh JH, Stea B, Nabid A, et al. Phase III study of efaproxiral as an adjunct to whole-brain radiation therapy for brain metastases. J Clin Oncol. 2006;24:106–114

 Conflict of interest: none.

PII: S0360-3016(07)04231-9

doi: 10.1016/j.ijrobp.2007.09.016

International Journal of Radiation Oncology * Biology * Physics
Volume 71, Issue 1 , Pages 79-86 , 1 May 2008

Article Tools

* Image Usage & Resolution