© 2003 by Society
© 2003 by the Society forNeuro-Oncology
Multifaceted end points in brain tumor clinical trials: Cognitivedeterioration precedes MRI progression
Departments of Neuro-Oncology (C.A.M.) and Biostatistics (K.R.H.), The University of Texas M. D.Anderson Cancer Center, Houston, TX 77030, USA
1 Address correspondence and reprint requests to Christina A. Meyers, Departmentof Neuro-Oncology, Box 431, The University of Texas M. D. Anderson CancerCenter, 1515 Holcombe Boulevard, Houston, TX 77030(cameyers{at}mdanderson.org).
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Abstract |
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Current treatments for brain cancer have, for the most part, equivocalsurvival benefit. However, clinical trials of new anticancer agents do notadequately assess potential clinical benefits for patient function other thansurvival and time to tumor progression.We evaluated 56 patients with recurrentbrain tumors who were recruited on phase 1 and phase 2 clinical trials andgiven assessments of cognitive function, quality of life (QOL), and ability toperform activities of daily living (ADL) prior to receiving treatment and atintervals coinciding with MRI scans, generally monthly. Meaningful change onthe cognitive and functional assessments was determined by the reliable changeindex. Cognitive or functional deterioration was then used as a time-dependentcovariate in a Cox proportional hazards regression model with tumorprogression, as defined by standard criteria, as the end point. Cognitivedeterioration occurred 6 weeks prior to radiographic failure (median 7.4 weeksvs. 13.4 weeks). In contrast, median time for QOL to deteriorate was notachieved. Median time for instrumental ADL to decline was 43 weeks, long aftertumor progression. For patients with brain cancer, brain function began toworsen before MRI evidence of tumor progression. QOL and ADL function were notstrongly tied to cognitive decline or to time to tumor progression, suggestingthat these measures may not be sufficiently sensitive to change in clinicaltrials of new anticancer agents, although they are important measures in termsof patient care. This study also demonstrates the feasibility of performingneurocognitive testing in this patient population. New drugs that slow thecognitive decline of brain tumor patients may be of clinical benefitregardless of the impact on overall survival.
Received July 8, 2002; Accepted December 20, 2002
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