This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Meyers, C. A. Articles by Renschler, M. F. Search for Related Content PubMed PubMed Citation Articles by Meyers, C. A. Articles by Renschler, M. F. Social Bookmarking                            What's this?

Neurocognitive Function and Progression in Patients With Brain Metastases Treated With Whole-Brain Radiation and Motexafin Gadolinium: Results of a Randomized Phase III Trial

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{at}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 38^th Annual Meeting of the American Society of Clinical Oncology, May 18–21, 2002, Orlando, FL; 44^th Annual Meeting of the American Society for Therapeutic Radiology and Oncology, October 6–10, 2002, New Orleans, LA; and 7^th 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.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				A. M. Evens, W. G. Spies, I. B. Helenowski, D. Patton, S. Spies, B. D. Jovanovic, S. Miyata, E. Hamilton, D. Variakojis, J. Chen, et al. The Novel Expanded Porphyrin, Motexafin Gadolinium, Combined with [90Y]Ibritumomab Tiuxetan for Relapsed/Refractory Non-Hodgkin's Lymphoma: Preclinical Findings and Results of a Phase I Trial Clin. Cancer Res., October 15, 2009; 15(20): 6462 - 6471. [Abstract] [Full Text] [PDF]

				D. Schiff and R. Cavaliere Role of Fractionated Radiotherapy and Radiosurgery in Newly Diagnosed Brain Metastases ASCO Educational Book, January 1, 2009; 2009(1): 95 - 99. [Abstract] [Full Text] [PDF]

				K. A. Bradley, I. F. Pollack, J. M. Reid, P. C. Adamson, M. M. Ames, G. Vezina, S. Blaney, P. Ivy, T. Zhou, M. Krailo, et al. Motexafin gadolinium and involved field radiation therapy for intrinsic pontine glioma of childhood: A Children's Oncology Group phase I study Neuro-oncol, January 1, 2008; 10(5): 752 - 758. [Abstract] [Full Text] [PDF]

				C. A. Meyers, K. R. Lamborn, and M. D. Prados In Reference to Lamborn et al. (Neuro-Oncology. 2008;10:162-170) Neuro-oncol, January 1, 2008; 10(6): 1171 - 1172. [Full Text] [PDF]

				J. Li, S. M. Bentzen, M. P. Mehta, and M. Renschler In Reply J. Clin. Oncol., September 1, 2007; 25(25): 4024 - 4025. [Full Text] [PDF]

				D. Correa, L Maron, H Harder, M Klein, C. Armstrong, P Calabrese, J. Bromberg, L. Abrey, T. Batchelor, and D Schiff Cognitive functions in primary central nervous system lymphoma: literature review and assessment guidelines Ann. Onc., July 1, 2007; 18(7): 1145 - 1151. [Abstract] [Full Text] [PDF]

				A. F. Eichler and J. S. Loeffler Multidisciplinary Management of Brain Metastases Oncologist, July 1, 2007; 12(7): 884 - 898. [Abstract] [Full Text] [PDF]

				J. Li, S. M. Bentzen, M. Renschler, and M. P. Mehta Regression After Whole-Brain Radiation Therapy for Brain Metastases Correlates With Survival and Improved Neurocognitive Function J. Clin. Oncol., April 1, 2007; 25(10): 1260 - 1266. [Abstract] [Full Text] [PDF]

				R. R. Patel and M. P. Mehta Targeted Therapy for Brain Metastases: Improving the Therapeutic Ratio Clin. Cancer Res., March 15, 2007; 13(6): 1675 - 1683. [Abstract] [Full Text] [PDF]

				J. P. Evans, F. Xu, M. Sirisawad, R. Miller, L. Naumovski, and P. R. O. de Montellano Motexafin Gadolinium-Induced Cell Death Correlates with Heme oxygenase-1 Expression and Inhibition of P450 Reductase-Dependent Activities Mol. Pharmacol., January 1, 2007; 71(1): 193 - 200. [Abstract] [Full Text] [PDF]

				P. D. Brown, A. W. Jensen, S. J. Felten, K. V. Ballman, P. L. Schaefer, K. A. Jaeckle, J. H. Cerhan, and J. C. Buckner Detrimental Effects of Tumor Progression on Cognitive Function of Patients With High-Grade Glioma J. Clin. Oncol., December 1, 2006; 24(34): 5427 - 5433. [Abstract] [Full Text] [PDF]

				M. P. Mehta Models Support Prophylactic Cranial Irradiation J. Clin. Oncol., August 1, 2006; 24(22): 3524 - 3526. [Full Text] [PDF]

				J. Raizer Radiosurgery and whole-brain radiation therapy for brain metastases: either or both as the optimal treatment. JAMA, June 7, 2006; 295(21): 2535 - 2536. [Full Text] [PDF]

				S. I. Hashemy, J. S. Ungerstedt, F. Z. Avval, and A. Holmgren Motexafin Gadolinium, a Tumor-selective Drug Targeting Thioredoxin Reductase and Ribonucleotide Reductase J. Biol. Chem., April 21, 2006; 281(16): 10691 - 10697. [Abstract] [Full Text] [PDF]

				E. G. Shaw, R. Rosdhal, R. B. D'Agostino Jr, J. Lovato, M. J. Naughton, M. E. Robbins, and S. R. Rapp Phase II Study of Donepezil in Irradiated Brain Tumor Patients: Effect on Cognitive Function, Mood, and Quality of Life J. Clin. Oncol., March 20, 2006; 24(9): 1415 - 1420. [Abstract] [Full Text] [PDF]

				M. A. Vogelbaum and J. H. Suh Resectable Brain Metastases J. Clin. Oncol., March 10, 2006; 24(8): 1289 - 1294. [Abstract] [Full Text] [PDF]

				D. Khuntia, P. Brown, J. Li, and M. P. Mehta Whole-Brain Radiotherapy in the Management of Brain Metastasis J. Clin. Oncol., March 10, 2006; 24(8): 1295 - 1304. [Abstract] [Full Text] [PDF]

				C. A. Meyers and P. D. Brown Role and Relevance of Neurocognitive Assessment in Clinical Trials of Patients With CNS Tumors J. Clin. Oncol., March 10, 2006; 24(8): 1305 - 1309. [Abstract] [Full Text] [PDF]

				R. Manon, A. O'Neill, J. Knisely, M. Werner-Wasik, H. M. Lazarus, H. Wagner, M. Gilbert, and M. Mehta Phase II Trial of Radiosurgery for One to Three Newly Diagnosed Brain Metastases From Renal Cell Carcinoma, Melanoma, and Sarcoma: An Eastern Cooperative Oncology Group Study (E 6397) J. Clin. Oncol., December 1, 2005; 23(34): 8870 - 8876. [Abstract] [Full Text] [PDF]

				K. F. Hofland, A. V. Thougaard, M. Dejligbjerg, L. H. Jensen, P. E.G. Kristjansen, P. Rengtved, M. Sehested, and P. B. Jensen Combining Etoposide and Dexrazoxane Synergizes with Radiotherapy and Improves Survival in Mice with Central Nervous System Tumors Clin. Cancer Res., September 15, 2005; 11(18): 6722 - 6729. [Abstract] [Full Text] [PDF]

				C. J. Langer and M. P. Mehta Current Management of Brain Metastases, With a Focus on Systemic Options J. Clin. Oncol., September 1, 2005; 23(25): 6207 - 6219. [Abstract] [Full Text] [PDF]