INTRATUMORAL TOREMIFENE THERAPY AND TISSUE DISTRIBUTION IN THE BABOON

The purpose of the present study was to evaluate the tissue distributi on of toremifene (TOR) in baboons following intratissue injections and to examine the effectiveness of intratumoral TOR therapy of baboons w ith various spontaneous neoplasms. Five healthy baboons (Papio sp.) we re used to examine the distribution of TOR following intratissue injec tions. Twenty-three different tissue specimens were collected for HPLC analysis. In addition, four baboons with various spontaneous neoplasm s (myxoma, squamous cell carcinoma, lymphosarcoma and adenocarcinoma) were treated with intratumoral TOR and their responses were evaluated. Tissue TOR distribution was also examined in these animals. In the ti ssue distribution study, target tissue/serum TOR concentration ratios ranged from 138 to 8873 and the target tissue/other tissue ratios rang ed from 1.2 to 2428. The distribution of TOR was very favorable, with the highest concentrations outside the injection sites noted in adjace nt organs. A marked response was observed in the myxoma and partial re sponses were observed in the other three cases. Drug level analysis da ta from these four animals revealed tissue concentrations similar to t hose seen in the TOR tissue distribution study. Intratumoral administr ation of TOR can achieve effective local tumor and tissue concentratio ns, while systemic distribution via circulation to other organs is lim ited. [(C) 1998 Rapid Science Ltd.].