The major objectives of this proposal are as follows: To define the acute toxicities of new anticancer agents in patients with advanced cancer; to redefine the acute toxicities and pharmacokinetics of existing anticancer agents administered in combination with colony-stimulating factors and other toxicity ameliorating agents which may facilitate the exploration of more effective doses and schedules; to provide information on the pharmacologic characteristics of selected antitumor agents; to define treatment regimens for evaluation of antitumor activity in Phase II trials; based on pharmacologic characteristics, to establish appropriate Phase II doses in special patient populations, such as those with impaired end-organ function or with heavy pretreatment, geriatric function or with heavy pretreatment, geriatric populations, and to explore pharmacokinetic and pharmacodynamic differences based on gender, race or ethnic group; to obtain preliminary information on pharmacokinetic/pharmacodynamic correlations which can then be extended in Phase II trials; to incorporate ancillary basic laboratory studies, when possible and appropriate, to enhance our understanding of the biochemical and/or biological mechanisms of drug actions.
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