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Survival and Neurologic Outcomes in a Randomized Trial of Motexafin Gadolinium and Whole-Brain Radiation Therapy in Brain Metastases

Minesh P. Mehta, Patrick Rodrigus, C.H.J. Terhaard, Aroor Rao, John Suh, Wilson Roa, Luis Souhami, Andrea Bezjak, Mark Leibenhaut, Ritsuko Komaki, Christopher Schultz, Robert Timmerman, Walter Curran, Jennifer Smith, See-Chun Phan, Richard A. Miller, Markus F. Renschler

From the University of Wisconsin Medical School, Madison; Froedtert Memorial Hospital at Medical College of Wisconsin, Milwaukee, WI; Kaiser Permanente, Los Angeles; Sutter Hospital, Radiological Associates of Sacramento, Sacramento; Pharmacyclics, Inc, Sunnyvale, CA; Cleveland Clinic, Cleveland, OH; University of Texas M.D. Anderson Cancer Center, Houston, TX; Indiana University Medical Center, Indianapolis, IN; Thomas Jefferson University, Philadelphia, PA; Dr Bernard Verbeeten Institut, Tilburg; Academisch Ziekenhuis Utrecht, Utrecht, the Netherlands; Cross Cancer Institute, Alberta; Montreal General Hospital, Quebec; and Princess Margaret Hospital, Toronto, Canada.

Address reprint requests to Minesh Mehta, MD, Department Human Oncology Radiation Oncology, University of Wisconsin—Madison, K4/B100, 600 Highland Ave, Madison, WI 53792; email: mehta{at}mail.humonc.wisc.edu.

Purpose: This phase III randomized trial evaluated survival as well as neurologic and neurocognitive function in patients with brain metastases from solid tumors receiving whole-brain radiation therapy (WBRT) with or without motexafin gadolinium (MGd).

Patients and Methods: Patients were randomly assigned to 30 Gy of WBRT ± 5 mg/kg/d MGd. Survival and time to neurologic progression determined by a blinded events review committee (ERC) were coprimary end points. Standardized investigator neurologic assessment and neurocognitive testing were evaluated.

Results: Four hundred one (251 non–small-cell lung cancer) patients were enrolled. There was no significant difference by treatment arm in survival (median, 5.2 months for MGd v 4.9 months for WBRT; P = .48) or time to neurologic progression (median, 9.5 months for MGd v 8.3 months for WBRT; P = .95). Treatment with MGd improved time to neurologic progression in patients with lung cancer (median, not reached for MGd v 7.4 months for WBRT; P = .048, unadjusted). By investigator, MGd improved time to neurologic progression in all patients (median, 4.3 months for MGd v 3.8 months for WBRT; P = .018) and in lung cancer patients (median, 5.5 months for MGd v 3.7 months for WBRT; P = .025). MGd improved neurocognitive function in lung cancer patients.

Conclusion: The overall results did not demonstrate significant differences by treatment arm for survival and ERC time to neurologic progression. Investigator neurologic assessments demonstrated an MGd treatment benefit in all patients. In lung cancer patients, ERC- and investigator-determined time to neurologic progression demonstrated an MGd treatment benefit. MGd may improve time to neurologic and neurocognitive progression in lung cancer.

Supported by and study drug provided by Pharmacyclics, Inc, Sunnyvale, CA.

This study has been presented in part at the 2002 Annual Meetings of the American Society of Clinical Oncology, May 18–21, 2002, Orlando, FL; the American Society of Therapeutic Radiology and Oncology, October 6–10, 2002, New Orleans, La; and the Society of Neuro-Oncology, November 21–24, 2002, San Diego, CA.

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