The primary focus of this project is always on the application of pharmacokinetic principles to questions of relevance to the treatment of cancer. The emphasis upon specific disease targets changes somewhat, as do the classes of drugs under investigation. The past year has continued trends towards emphasis of intracellular measurements in general, and pyrimidines in particular. Over the last year, specific areas of interest included: 1. A clinical trial has been conducted with Radiation Oncology Branch for the combined delivery of iododeoxyuridine and fluorodeoxyuridine. In addition to plasma pharmacokinetics, DNA from peripheral granulocytes has been studied for indications of biochemical modulation. This study will be completed when ongoing measurements of tumor DNA are completed. Most of our current efforts focus upon the hepatic arterial administration of iododeoxyridine as a cytotoxic agent as well as a radiosensitizer. 2. Phase I trials are an important milestone in the clinical pharmacology of anticancer drugs. The Blood Level Working Group is focusing specifically on the interface between preclinical and clinical studies. 3. Clinical pharmacokinetics studies have been completed for azidothymidine and are nearly finished for dideoxycytidine. It is anticipated that this is the final year for work on anti-AIDS drugs under this project.
