Safety and feasibility of motexafin gadolinium administration with whole brain radiation therapy and stereotactic radiosurgery boost in the treatment of ≤6 brain metastases: A multi-institutional phase II trial

Derek R. McHaffie, Pierre Chabot, Anne Dagnault, John H. Suh, Marie Andrée Fortin, Eric Chang, Robert Timmerman, Luis Souhami, John Grecula, Abdenour Nabid, Chris Schultz, Maria Werner-Wasik, Laurie E. Gaspar, David Brachman, Tarak Mody, Minesh P. Mehta

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

To determine the safety, tolerability, and report on secondary efficacy endpoints of motexafin gadolinium (MGd) in combination with whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) for patients with ≤6 brain metastases. We conducted an international study of WBRT (37.5 Gy in 15 fractions) and SRS (15-21 Gy) with the addition of MGd (5 mg/kg preceding each fraction beginning week 2). The primary endpoint was to evaluate the rate of irreversible grade 3 or any grade ≥4 neurotoxicity and establish feasibility in preparation for a phase III trial. Sixty-five patients were enrolled from 14 institutions, of which 45 (69%) received SRS with MGd as intended and were available for evaluation. Grade ≥3 neurotoxicity attributable to radiation therapy within 3 months of SRS was seen in 2 patients (4.4%), including generalized weakness and radionecrosis requiring surgical management. Immediately following the course of MGd plus WBRT, new brain metastases were detected in 11 patients (24.4%) at the time of the SRS treatment planning MRI. The actuarial incidence of neurologic progression at 6 months and 1 year was 17 and 20%, respectively. The median investigator-determined neurologic progression free survival and overall survival times were 8 (95% CI: 5-14) and 9 months (95% CI: 6-not reached), respectively. We observed a low rate of neurotoxicity, demonstrating that the addition of MGd does not increase the incidence or severity of neurologic complications from WBRT with SRS boost.

Original languageEnglish (US)
Pages (from-to)301-308
Number of pages8
JournalJournal of Neuro-Oncology
Volume105
Issue number2
DOIs
Publication statusPublished - Nov 2011

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Keywords

  • Brain metastases
  • Motexafin gadolinium
  • Stereotactic radiosurgery
  • Whole-brain radiotherapy

ASJC Scopus subject areas

  • Clinical Neurology
  • Cancer Research
  • Oncology
  • Neurology

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