Evaluation of multiple neurotoxic outcomes in cancer chemotherapy.

Although it is now clear that cognitive dysfunction is a common accompaniment of cancer chemotherapy, its implications await further research and direction. Most of the clinical research relies on standard neuropsychological tests that were developed to diagnose stable traits. Cognitive dysfunction in patients undergoing treatment varies with time, however. Its dimensions will vary during the course of treatment, which generally consists of cycles of drug administration followed by recovery periods. To effectively determine the connection between chemotherapy and cognitive function requires neuropsychological tests based on performance, so that they can be administered repeatedly at specified times during the entire course of treatment and beyond. A number of computerized test batteries, many of which have been developed for environmental neurotoxicology, are now available that fit such criteria. Moreover, cognitive impairment is only one aspect of chemotherapy-induced neurotoxicity. A full appreciation of its scope requires assessment of sensory functions such as vision, audition and somatosensory properties and assessment of motor function. A program of research based on animal models is also essential. Only with animal models is it possible to determine dose-response relationships and to couple behavioral with mechanistic indices such as neuroplasticity. Animal behavior models play a vital role in environmental toxicology because, from them, it is possible to derive some index of exposure that limits adverse effects. However, as in human testing, it is critical to choose situations whose properties remain stable over long periods of time so as to trace the time course of neurotoxicity. Schedule-controlled operant behavior offers the most promising source of animal models.