Neurotoxicity of CI-980, a novel mitotic inhibitor.

CI-980 is a chemotherapeutic agent currently in Phase II trials that arrests cellular division by binding to tubulin. It is structurally and functionally similar to colchicine, a potent nonreversible neurotoxin, and is able to cross the blood-brain barrier. In Phase I studies, neurotoxicity was noted. The neurotoxicity of CI-980 was prospectively evaluated in two Phase II studies by neurological evaluation, quantitative sensory testing, and neuropsychological assessment of cognitive functioning. The results revealed a significant but reversible decline in recent memory functioning after each course of CI-980, with no effect on overall mental status or neurological function. Sixty-seven percent of patients performed in the impaired range on the memory test after their first infusion, whereas only one exhibited a decline on a brief cognitive screen. The results are consistent with the known effects of colchicine on the brain. Colchicine selectively blocks choline acetyltransferase in the hippocampus and basal forebrain, the area of the brain responsible for memory consolidation. Although the effect of CI-980 was reversible at the dose and schedule used, this study suggests that careful monitoring of cognitive function in patients receiving this agent should be performed if dose or schedule parameters are changed. In addition, this study demonstrates the feasibility of incorporating neuropsychological assessment in clinical trials of new anticancer agents having potential neurotoxic side effects.

The Functional Assessment of Cancer Therapy (FACT) scale. Development of a brain subscale and revalidation of the general version (FACT-G) in patients with primary brain tumors.

BACKGROUND: This report describes the development and validation of a brain subscale for the Functional Assessment of Cancer Therapy (FACT) scale, and the revalidation of the subscales of the general version (FACT-G), which measure physical, social, family, emotional, and functional well-being and the quality of the relationship with the physician. METHODS: 101 patients with primary brain tumors, after giving informed consent, participated in the last two phases of a four-phase validation process: item generation, item reduction, validation, and reliability testing. In the validation phase, FACT-G subscale and total scores as well as the brain subscale scores were correlated with other tests of mood, response, bias, and quality of life (QOL). Test-retest reliability testing was performed with 46 patients who had primary brain tumors. RESULTS: Validity and reliability coefficients were high for the FACT-G and brain subscale, except for the comparison with a second QOL measure (FP-QLI) and the Karnofsky Performance Status (KPS). The lower scores were the result of inherent differences in the two QOL instruments and the relatively high performance status of the brain tumor patients, which restricted the KPS score range. CONCLUSION: The FACT-G has good psychometric properties supporting its broad generalizability and the brain subscale tests substantially different QOL issues than the core instrument. Use of this scale with the addition of the brain subscale provides a well rounded view of the various aspects of QOL from the patient's perspective. With modifications and further psychometric testing, the brain subscale may have broader applicability to subpopulations of patients with other brain disorders.