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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

  • Clinical Study – Patient Study
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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.

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Acknowledgments

Trial was sponsored and supported by Pharmacyclics Inc., Sunnyvale, CA.

Conflict of interest

1. Minesh Mehta serves on the Board of Directors of Pharmacyclics (paid, including stock options), Inc. and is a consultant for Schering-Plough, Genentech, Tomotherapy (including stock options), Bayer, and Adnexus. 2. Tarak Mody is a Senior Director for Development for Pharmacyclics, Inc. All additional authors report no conflicts of interests.

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Authors and Affiliations

  1. Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave, K4/B100, Madison, WI, 53792, USA

    Derek R. McHaffie

  2. Maisonneuve-Rosemont Hospital, Montreal, QC, Canada

    Pierre Chabot

  3. Hôtel-Dieu de Québec du CHUQ, Quebec City, QC, Canada

    Anne Dagnault

  4. Department of Radiation Oncology, The Cleveland Clinic Foundation, Cleveland, OH, USA

    John H. Suh

  5. Departement de Radio-Oncologie, Notre-Dame Hospital, Montreal, QC, Canada

    Marie-Andrée Fortin

  6. Department of Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA

    Eric Chang

  7. Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, TX, USA

    Robert Timmerman

  8. Department of Radiation Oncology, McGill University, Montreal, QC, Canada

    Luis Souhami

  9. Department of Radiation Oncology, The Ohio State University, Columbus, OH, USA

    John Grecula

  10. CHUS Hôpital Fleurimont, Sherbrooke, QC, Canada

    Abdenour Nabid

  11. Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA

    Chris Schultz

  12. Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, USA

    Maria Werner-Wasik

  13. Department of Radiation Oncology, University of Colorado Denver, Aurora, CO, USA

    Laurie E. Gaspar

  14. Department of Radiation Oncology, St. Joseph’s Hospital, Phoenix, AZ, USA

    David Brachman

  15. Clinical Development, Pharmacyclics Inc, Sunnyvale, CA, USA

    Tarak Mody

  16. Department of Radiation Oncology, Northwestern University, Chicago, IL, USA

    Minesh P. Mehta

Authors
  1. Derek R. McHaffie
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  2. Pierre Chabot
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  3. Anne Dagnault
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  4. John H. Suh
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  5. Marie-Andrée Fortin
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  6. Eric Chang
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  7. Robert Timmerman
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  8. Luis Souhami
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  9. John Grecula
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  10. Abdenour Nabid
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  11. Chris Schultz
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  12. Maria Werner-Wasik
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  13. Laurie E. Gaspar
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  14. David Brachman
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  15. Tarak Mody
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  16. Minesh P. Mehta
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Corresponding author

Correspondence to Derek R. McHaffie.

Additional information

This trial, PCYC-0224, is registered through the NIH at http://clinicaltrials.gov with an identifier of NCT00121420.

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McHaffie, D.R., Chabot, P., Dagnault, A. et al. 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. J Neurooncol 105, 301–308 (2011). https://doi.org/10.1007/s11060-011-0590-9

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  • DOI: https://doi.org/10.1007/s11060-011-0590-9

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