Intratumoral toremifene therapy and tissue distribution in the baboon.
The purpose of the present study was to evaluate the tissue distribution of toremifene (TOR) in baboons following intra-tissue injections and to examine the effectiveness of intratumoral TOR therapy of baboons with various spontaneous neoplasms. Five healthy baboons (Papio sp.) were used to examine the distribution of TOR following intra-tissue injections. Twenty-three different tissue specimens were collected for HPLC analysis. In addition, four baboons with various spontaneous neoplasms (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 tissue distribution study, target tissue/serum TOR concentration ratios ranged from 138 to 8873 and the target tissue/other tissue ratios ranged from 1.2 to 2428. The distribution of TOR was very favorable, with the highest concentrations outside the injection sites noted in adjacent organs. A marked response was observed in the myxoma and partial responses were observed in the other three cases. Drug level analysis data from these four animals revealed tissue concentrations similar to those seen in the TOR tissue distribution study. Intratumoral administration of TOR can achieve effective local tumor and tissue concentrations, while systemic distribution via circulation to other organs is limited.
Wurz
G T
GT
Department of Internal Medicine, Cancer Center, University of California, Davis, Sacramento 95817, USA.
Mäenpää
J U
JU
Hubbard
G B
GB
Cadman
T B
TB
Seymour
R C
RC
Soe
L
L
DeGregorio
M W
MW
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005260:Female; D015552:Injections, Intralesional; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D009232:Myxoma / Q000188:drug therapy / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D010215:Papio; D010307:Parotid Neoplasms / Q000188:drug therapy / Q000378:metabolism; D017312:Toremifene / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D018931:Antineoplastic Agents, Hormonal; D017312:Toremifene