Phase II study of high central dose Gamma Knife radiosurgery and marimastat in patients with recurrent malignant glioma

Larson, David A; Prados, Michael; Lamborn, Kathleen R; Smith, Vernon; Sneed, Penny K; Chang, Susan; Nicholas, Kelly M; Wara, William M; Devriendt, Daniel; Kunwar, Sandeep; Berger, Mitch; McDermott, Michael W

doi:10.1016/S0360-3016(02)03743-4

« Previous Next »International Journal of Radiation Oncology * Biology * Physics
Volume 54, Issue 5 , Pages 1397-1404, 1 December 2002

Phase II study of high central dose Gamma Knife radiosurgery and marimastat in patients with recurrent malignant glioma☆

David A Larson, M.D., Ph.D.
- Reprint requests to: David A. Larson, M.D., Ph.D., Department of Radiation Oncology, University of California, San Francisco, School of Medicine, 505 Parnassus Ave., L-08, San Francisco, CA 94143-0226 USA. Tel: 415-476-4815; Fax: 415-476-8734
- Department of Radiation Oncology, University of California, San Francisco, School of Medicine, San Francisco, CA, USA
- Department of Neurological Surgery, University of California, San Francisco, School of Medicine, San Francisco, CA, USA
Michael Prados, M.D.
- Department of Neurological Surgery, University of California, San Francisco, School of Medicine, San Francisco, CA, USA
Kathleen R Lamborn, Ph.D.
- Department of Neurological Surgery, University of California, San Francisco, School of Medicine, San Francisco, CA, USA
Vernon Smith, Ph.D.
- Department of Radiation Oncology, University of California, San Francisco, School of Medicine, San Francisco, CA, USA
Penny K Sneed, M.D.
- Department of Radiation Oncology, University of California, San Francisco, School of Medicine, San Francisco, CA, USA
Susan Chang, M.D.
- Department of Neurological Surgery, University of California, San Francisco, School of Medicine, San Francisco, CA, USA
Kelly M Nicholas, M.D.
- Department of Neurological Surgery, University of California, San Francisco, School of Medicine, San Francisco, CA, USA
William M Wara, M.D.
- Department of Radiation Oncology, University of California, San Francisco, School of Medicine, San Francisco, CA, USA
Daniel Devriendt, M.D.
- Department of Radiation Oncology, University of California, San Francisco, School of Medicine, San Francisco, CA, USA
Sandeep Kunwar, M.D.
- Department of Neurological Surgery, University of California, San Francisco, School of Medicine, San Francisco, CA, USA
Mitch Berger, M.D.
- Department of Neurological Surgery, University of California, San Francisco, School of Medicine, San Francisco, CA, USA
Michael W McDermott, M.D.
- Department of Radiation Oncology, University of California, San Francisco, School of Medicine, San Francisco, CA, USA
- Department of Neurological Surgery, University of California, San Francisco, School of Medicine, San Francisco, CA, USA

Received 7 March 2002; received in revised form 10 July 2002; accepted 17 July 2002.

Abstract

: To assess the outcome of high central dose Gamma Knife radiosurgery plus marimastat in patients with recurrent malignant glioma.

: Twenty-six patients with recurrent malignant glioma were enrolled in a prospective Phase II study between November 1996 and January 1999. The radiosurgery dose was prescribed at the 25–30% isodose surface to increase the dose substantially within the tumor’s presumably hypoxic core. Marimastat was administered after radiosurgery to restrict regional tumor progression. Survival was compared with that of historical patients treated at our institution with standard radiosurgery.

: The median times to progression after radiosurgery for Grade 3 and 4 patients was 31 and 15 weeks, respectively. The corresponding median survival time after radiosurgery was 68 and 38 weeks. The median survival time after radiosurgery in the historical patients was 59 and 44 weeks.

: The dual strategies of using high central dose radiosurgery to overcome tumor hypoxia together with marimastat to inhibit local tumor invasion may offer a small survival advantage for recurrent Grade 3 tumors; they do not offer an advantage for recurrent Grade 4 tumors.