CLINICAL RADIATION AND DRUG PROTECTION WITH WR-2721

WR-2721是保护正常组织的磷酸化氨基硫醇化合物

WR-2721 is phosphorylated aminothiol compound which protects normal tissues selectively (as compared to tumor) in experimental animals. Human toxicology is nearing completion. WR-2721 may be useful in humans to 1) decrease the adverse effects of radiotherapy and alkylating agents on various normal tissues, 2) allow higher doses of radiotherapy and certain chemotherapeutic agents without increasing the toxicity of standard doses of each , 3) decrease the overall time of radiotherapy courses providing lesser patient costs and inconvenience. Although specific assays for WR-2721 are lacking, two promising quantitative methods, are being developed; a) immunoquantitation with monoclonal antibodies, and b) electrochemical detection with high performance liquid chromatography. These may provide information to maximize the difference in WR-2721 concentration in normal tissues vs. tumor, to optimize infusion times and intervals from pretreatment with WR-2721 and treatment with alkylating agents or radiotherapy. Dose modifying factors with WR-2721 pretreatment before cyclophosphamide, nitrogen mustard, cis-platinum and various fractionation schedules of radiotherapy will be determined in human subjects. Reduction in adverse effects by pretreatment with WR-2721 will be investigated in multiple anatomic sites. WR-2721 administration decreases serum calcium and paradoxically parathormone levels. The clinical usefulness of this effect will be explored. Since WR-2721 appears to increase venous blood oxygen content, the mechanisms of this observation and its influence on protection will be investigated.