DESCRIPTION: (Applicant's Description) One major goal of a phase I trial is identification of the optimal clinical dose, route and schedule to be used in subsequent phase II studies which will quantitate clinical efficacy against specific human cancers. Phase I clinical trials are the culmination of the costly and laborious preclinical screening process and are the foundation for studies of human antitumor activity. The University of Wisconsin has had continuous NCI funding for its phase I studies since 1979. From 1994 to 1996 our NCI grant accrual totaled 261 with 100 patients entered on trial during 1996. We currently have eleven open trials. This proposal details our extensive experience in conducting phase I trials and outlines our goals for continuation of such work as detailed in our specific aims: Aim 1: Determination of the Maximum Tolerable Dose and Dose Limiting Toxicities of Novel Anticancer Agents. Aim 2: Use of Laboratory and Clinical Correlates to Improve Understanding of Mechanisms of Drug Action. Aim 3: Integration of Pharmacokinetics/Pharmacodynamic Studies in Phase I Trials. Aim 4: Development of Novel Phase I Study Designs.