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Neurocognitive Function and Progression
in Patients With Brain Metastases Treated With Whole-Brain Radiation and
Motexafin Gadolinium: Results of a Randomized Phase III Trial
Christina A. Meyers, Jennifer A. Smith, Andrea
Bezjak, Minesh P. Mehta, James Liebmann, Tim
Illidge, Ian Kunkler, Jean-Michel Caudrelier, Peter
D. Eisenberg, Jacobus Meerwaldt, Ross Siemers, Christian
Carrie, Laurie E. Gaspar, Walter Curran, See-Chun
Phan, Richard A. Miller, Markus F. Renschler
From the M.D. Anderson Cancer Center, Houston, TX;
Pharmacyclics Inc, Sunnyvale; California Cancer Care, Greenbrae, CA; University
of Wisconsin Medical School, Madison, WI; New Mexico Hematology-Oncology
Consultants, Albuquerque, NM; North Memorial Research Center, Robbinsdale, MN;
University of Colorado, Denver, CO; Thomas Jefferson University, Philadelphia,
PA; Princess Margaret Hospital, Toronto; Ottawa Regional Cancer Centre, Ottawa,
Canada; Wessex Cancer Centre, Southampton, United Kingdom; Western General
Hospital, Edinburgh, Scotland; Medisch Spectrum Twente, Enschede, The
Netherlands; and Centre Léon Bérard, Lyon, France.
Address reprint requests to Christina A. Meyers, PhD, M.D. Anderson Cancer
Center, Department of Neuro-Oncology, Unit 431, 1515 Holcombe Blvd, Houston, TX
77030; e-mail: cameyers@mdanderson.org
Purpose. To report the neurocognitive findings in a phase III
randomized trial evaluating survival and 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 receive WBRT
30 Gy in 10 fractions with or without MGd 5 mg/kg/d.
Monthly neurocognitive testing for memory, executive function, and
fine motor skill was performed.
Results. Four hundred one patients were enrolled (251 with
non–small-cell lung cancer, 75 with breast cancer, and 75 with
other cancers); 90.5% patients had impairment of one or more
neurocognitive tests at baseline.
Neurocognitive test scores of memory, fine motor speed, executive
function, and global neurocognitive impairment at baseline were
correlated with brain tumor volume and predictive of survival.
There was no statistically significant difference between treatment
arms in time to neurocognitive progression.
Patients with lung cancer (but not other types of cancer) who were
treated with MGd tended to have improved memory and executive function
(P = .062) and improved neurologic function as assessed by a
blinded events review committee (P = .048).
Conclusion. Neurocognitive tests are a relatively sensitive measure of
brain functioning; a combination of tumor prognostic variables and
brain function assessments seems to predict survival better than
tumor variables alone.
Although the addition of MGd to WBRT did not produce a significant
overall improvement between treatment arms, MGd may improve memory
and executive function and prolong time to neurocognitive and
neurologic progression in patients with brain metastases from lung
cancer.
The study drug and funding for this research were provided by
Pharmacyclics Inc.
This study was presented in part at the 38th Annual Meeting of
the American Society of Clinical Oncology, May 18–21, 2002,
Orlando, FL; 44th Annual Meeting of the American Society for
Therapeutic Radiology and Oncology, October 6–10, 2002, New
Orleans, LA; and 7th Annual Meeting of the Society of
Neuro-Oncology, November 21–24, 2002, San Diego, CA. C.A.M and J.A.S. contributed equally to this manuscript.
© 2004 American Society for Clinical Oncology
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