Journal of Neuro-Oncology

, Volume 110, Issue 2, pp 265–270

Chemosensitized radiosurgery for recurrent brain metastases

  • David Roberge
  • Luis Souhami
  • Marie-Andrée Fortin
  • Jean-François Pouliot
Clinical Study

DOI: 10.1007/s11060-012-0965-6

Cite this article as:
Roberge, D., Souhami, L., Fortin, MA. et al. J Neurooncol (2012) 110: 265. doi:10.1007/s11060-012-0965-6

Abstract

Temozolomide is known to penetrate the blood–brain barrier and sensitize brain tumors to radiation and has been used clinically to sensitize fractionated external beam radiotherapy. However, there are limited prospective clinical data available on the safety of temozolomide as a chemosensitizing agent administered with stereotactic radiosurgery. This is a phase I trial of previously irradiated patients with one to four progressive brain metastases and Karnofsky performance scale score ≥60 % enrolled in three sequential cohorts: temozolomide 100, 150 or 200 mg/(m2 day) administered for 5 days. Stereotactic radiosurgery (SRS) was administered on day 5. The SRS dose was dependent on target diameter: 15 Gy (31–40 mm), 18 Gy (21–30 mm) or 21 Gy (<20 mm). The primary endpoint was safety of increasing temozolomide doses. Secondary endpoints included local control and survival. 26 subjects were enrolled and 49 total metastatic lesions were treated. The median number of brain metastases was 1.5, with a median target diameter of 21 mm. The most common grade 1–2 adverse events irrespective of causality were vomiting (23 %), nausea (23 %), edema (12 %), seizure (8 %), psychosis (4 %) and thrombocytopenia (4 %). The frequency of nausea and vomiting did not appear to be dose-dependent. Grade 3–4 toxicities were not observed. Median overall survival was 10.2 months. Crude local control was 87.5 %, with a radiological response seen in eight of 24 evaluable patients (33.3 %), and stable disease >6 months in 13 of 24 patients (54.2 %). Temozolomide, at doses up to 200 mg/(m2 day) × 5 days, prior to SRS is well tolerated, with no dose-limiting toxicities in patients with recurrent brain metastases. Local control of target lesions was >80 %.

Keywords

Brain Neoplasms/secondary Radiosurgery Radiation-Sensitizing Agents/administration & dosage Radiation-Sensitizing Agents/therapeutic use Temozolomide 

Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • David Roberge
    • 1
    • 2
  • Luis Souhami
    • 1
  • Marie-Andrée Fortin
    • 2
  • Jean-François Pouliot
    • 3
  1. 1.Department of Radiation OncologyMontreal General HospitalMontrealCanada
  2. 2.Departement de Radio-OncologieHôpital Notre-Dame de MontrealMontrealCanada
  3. 3.Merck CanadaKirklandCanada