The interactions between bioinorganic metal compounds (platinum-based, gallium-based, cadmium-based, etc.) and cellular DNA, cellular proteins, etc., are assessed, with a focus on modulating the potential cytotoxic activity of these agents. We have just published our phase II study of gallium nitrate in metastatic prostate cancer. Gallium was of modest activity in this clinical setting; and molecular correlations were made between gallium measurements and clinical endpoints. Assay development was completed for the enhancement of sensitivity of an AAS method to detect cadmium in biological matrixes. Now, picogram quantities of elemental cadmium can be reproducibly assayed. Methods to measure elemental platinum after therapeutic levels of drug exposure continue to be utilized. Studies conducted in this area include: support of a Surgery Branch study to assess continuous hyperthermic peritoneal perfusion (CHPP); support of a large multi-institutional randomized trial for the initial treatment of advanced stage ovarian cancer by the Gynecologic Oncology Group (GOG); support of a leukemia study conducted by Case Western Reserve to assess the efficacy of a carboplatin-based chemotherapy regimen; support of intramural clinical trials in recurrent ovarian cancer; and, the conduct of laboratory studies on the molecular modulation of cisplatin-DNA adduct repair in human ovarian cancer cell lines.
