International Journal of Radiation Oncology * Biology * Physics
Volume 70, Issue 4 , Pages 993-1001 , 15 March 2008

A Phase I Dose-Escalation Study of Fractionated Stereotactic Radiosurgery in Combination With Gefitinib in Patients With Recurrent Malignant Gliomas

  • Amanda L. Schwer, M.D.

      Affiliations

    • Department of Radiation Oncology, University of Colorado Health Sciences Center, Aurora, CO
    • ,
  • Denise M. Damek, M.D.

      Affiliations

    • Department of Medical Oncology, University of Colorado Health Sciences Center, Aurora, CO
    • ,
  • Brian D. Kavanagh, M.D., M.P.H.

      Affiliations

    • Department of Radiation Oncology, University of Colorado Health Sciences Center, Aurora, CO
    • ,
  • Laurie. E. Gaspar, M.D., M.B.A.

      Affiliations

    • Department of Radiation Oncology, University of Colorado Health Sciences Center, Aurora, CO
    • ,
  • Kevin Lillehei, M.D.

      Affiliations

    • Department of Neurosurgery, University of Colorado Health Sciences Center, Aurora, CO
    • ,
  • Kelly Stuhr, M.S.

      Affiliations

    • Department of Radiation Oncology, University of Colorado Health Sciences Center, Aurora, CO
    • ,
  • Changhu Chen, M.D.

      Affiliations

    • Department of Radiation Oncology, University of Colorado Health Sciences Center, Aurora, CO
    • Corresponding Author InformationReprint requests to Changhu Chen, M.D., Department of Radiation Oncology, University of Colorado Health Sciences Center, 1665 North Ursula Street, Suite 1032, Mail Stop F-706, P.O. Box 6510, Aurora, CO 80045-0508; Tel: (720)-848-0116; Fax: (720)-848-0222

Received 20 June 2007 ,Revised 23 July 2007 ,Accepted 27 July 2007.

References 

  1. Glioma Meta-analysis Trialists (GMT) Group . Chemotherapy in adult high-grade glioma: A systematic review and meta-analysis of individual patient data from 12 randomized trials. Lancet. 2002;359:1011–1018
  2. Wong ET, Hess KR, Gleason MJ, et al. Outcomes and prognostic factors in recurrent glioma patients enrolled onto Phase II clinical trials. J Clin Oncol. 1999;17:2572–2579
  3. Hess CF, Schaaf JC, Kortmann RD, et al. Malignant glioma: Patterns of failure following individually tailored limited volume irradiation. Radiother Oncol. 1994;30:146–149
  4. Brem H, Piantadosi S, Burger PC, et al. Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas: The Polymer-brain tumor treatment group. Lancet. 1995;345:1008–1012
  5. Schrieve DC, Alexander E, Wen PY, et al. Comparison of stereotactic radiosurgery and brachytherapy in the treatment of recurrent glioblastoma multiforme. Neurosurgery. 1995;36:275–282
  6. Cho KH, Hall WA, Gerbi BJ, et al. Single dose versus fractionated stereotactic radiosurgery for recurrent high-grade gliomas. Int J Radiat Oncol Biol Phys. 1999;45:1133–1141
  7. Hudes RS, Corn BW, Werner-Wasik M, et al. A Phase I dose escalation study of hypofractionated stereotactic radiosurgery as salvage therapy for persistent or recurrent malignant glioma. Int J Radiat Oncol Biol Phys. 1999;43:293–298
  8. Shepherd SF, Laing RW, Cosgrove VP, et al. Hypofractionated stereotactic radiosurgery in the management of recurrent glioma. Int J Radiat Oncol Biol Phys. 1997;37:393–398
  9. Glass J, Silverman CL, Axelrod R, et al. Fractionated stereotactic radiosurgery with cis-platinum radiosensitization in the treatment of recurrent, progressive, or persistent malignant astrocytoma. Am J Clin Oncol. 1997;20:226–229
  10. Lederman G, Wronski M, Arbit E, et al. Treatment of recurrent glioblastoma multiforme using fractionated stereotactic radiosurgery and concurrent paclitaxel. Amer J Clin Oncol. 2000;23:155–159
  11. Laing RW, Warrington AP, Graham J, et al. Efficacy and toxicity of fractionated stereotactic radiosurgery in the treatment of recurrent gliomas (Phase I/II study). Radiother Oncol. 1993;27:22–29
  12. Vordermark D, Kolbl O, Ruprecht K, et al. Hypofractionated stereotactic re-irradiation: Treatment option in recurrent malignant glioma. BMC Cancer. 2005;5:55
  13. Wurm RE, Kuczer DA, Schlenger L, et al. Hypofractionated stereotactic radiosurgery combined with topotecan in recurrent malignant glioma. Int J Radiat Oncol Biol Phys. 2006;66(Suppl. 4):S26–S32
  14. Liebermann T, Nussbaum H, Razon N, et al. Amplification, enhanced expression and possible rearrangement of EGF-receptor gene in primary human tumors of glial origin. Nature. 1985;313:144–147
  15. Ekstrand AJ, Longo N, Hamid ML, et al. Functional characterization of a EGF receptor with a truncated extracellular domain expressed in glioblastomas with EGF-R gene amplification. Oncogene. 1994;9:2313–2320
  16. Naruse I, Ohmori T, Ao Y, et al. Antitumor activity of the selective epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) Iressa (GEFITINIB) in an EGFR-expressing multidrug-resistant cell line in vitro and in vivo. Int J Cancer. 2002;98:310–315
  17. Anderson NG, Ahmad T, Chan K, et al. Gefinitib (Iressa), a novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, potently inhibits the growth of EGFR-positive cancer cell lines with or without erbB2 overexpression. Int J Cancer. 2001;94:774–782
  18. Heimberger AB, Learn CA, Archer GE, et al. Brain tumors in mice are susceptible to blockade of epidermal growth factor receptor (EGFR) with the oral, specific, EGFR-tyrosine kinase inhibitor ZD1839 (iressa). Clin Cancer Res. 2002;8:3496–3502
  19. Bianco C, Tortora G, Bianco R, et al. Enhancement of antitumor activity of ionizing radiation by combined treatment with the selective epidermal growth factor receptor-tyrosine kinase inhibitor ZD1839 (Iressa). Clin Cancer Res. 2002;8:3250–3258
  20. Rich JN, Reardon DA, Peery T, et al. Phase II trial of gefitinib in recurrent glioblastoma. J Clin Oncol. 2004;22:133–142
  21. Mellinghoff IK, Wang MY, Vivanco I, et al. Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. N Engl J Med. 2005;353:2012–2024
  22. Shaw E, Kline R, Gillin M, et al. Radiation Therapy Oncology Group: Radiosurgery quality assurance guidelines. Int J Radiat Oncol Biol Phys. 1993;27:1231–1239
  23. Available at: http://ctep.cancer.gov/forms/CTCAEv3.pdf. Accessed April 20, 2007.
  24. Brown PD, Buckner JC, O'Fallon JR, et al. Effects of radiotherapy on cognitive function in patients with low-grade glioma measured by the Folstein Mini-Mental State Examination. J Clin Oncol. 2003;21:2519–2524
  25. Brown PD, Jensen AW, Felten SJ, et al. Detrimental effects of tumor progression on cognitive function of patients with high-grade glioma. J Clin Oncol. 2006;24:5427–5433
  26. Guerrero M, Li XA. Extending the linear-quadratic model for large fraction doses pertinent to stereotactic radiotherapy. Phys Med Biol. 2004;49:4825–4835
  27. Shaw E, Scott C, Souhami L, et al. Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: Final report of RTOG protocol 90-05. Int J Radiat Oncol Biol Phys. 2000;47:291–298
  28. Van der Kogel AJ. Radiation response and tolerance of normal tissues. In:  Steel GG editors. Basic clinical radiobiology. 2nd ed.. London: Arnold; 1997;p. 30–39
  29. Mullins ME, Barest GD, Schaefer PW, et al. Radiation necrosis versus glioma recurrence: conventional MR imaging clues to diagnosis. Am J Neuroradiol. 2005;26:1967–1972
  30. Rabinov JD, Lee PL, Barker FG, et al. In vivo 3-T MR spectroscopy in the distinction of recurrent glioma versus radiation effects: Initial experience. Radiology. 2002;225:871–879
  31. McGirt MJ, Bulsara KR, Cummings TJ, et al. Prognostic value of magnetic resonance imaging-guided stereotactic biopsy in the evaluation of recurrent malignant astrocytoma compared with a lesion due to radiation effect. J Neurosurg. 2003;98:14–20

 The preliminary results of this study were presented at the 48th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO), November 5–9, 2006, Philadelphia, PA

 AstraZeneca Pharmaceuticals Inc. provided study drug gefitinib and partial funding.

 Conflict of interest: none.

PII: S0360-3016(07)03912-0

doi: 10.1016/j.ijrobp.2007.07.2382

International Journal of Radiation Oncology * Biology * Physics
Volume 70, Issue 4 , Pages 993-1001 , 15 March 2008

Article Tools

* Image Usage & Resolution