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.
|Robins, H I; Tutsch, K; Katschinski, D M et al. (1999) Phase I trial of intravenous thymidine and carboplatin in patients with advanced cancer. J Clin Oncol 17:2922-31|
|Berlin, J; Stewart, J A; Storer, B et al. (1998) Phase I clinical and pharmacokinetic trial of penclomedine using a novel, two-stage trial design for patients with advanced malignancy. J Clin Oncol 16:1142-9|
|Berlin, J; Tutsch, K D; Hutson, P et al. (1997) Phase I clinical and pharmacokinetic study of oral carboxyamidotriazole, a signal transduction inhibitor. J Clin Oncol 15:781-9|
|Bailey, H H; Ripple, G; Tutsch, K D et al. (1997) Phase I study of continuous-infusion L-S,R-buthionine sulfoximine with intravenous melphalan. J Natl Cancer Inst 89:1789-96|