Assessment of the preclinical activity of budotitane in three different transplantable tumor systems, its lack of mutagenicity, and first results of clinical phase I studies.
The antitumor activity of budotitane was investigated in three different tumor systems--the transplantable murine ascitic-colon-adenocarcinoma MAC 15A, the TD-osteosarcoma of the rat, and the intramuscularly transplanted murine sarcoma 180. Marked inhibition of tumor growth was observed in the intramuscularly transplanted sarcoma 180, and cure rates of 50-80% were achieved in the colon adenocarcinoma MAC 15A. In contrast to these findings, bulotitane was inactive in the transplantable TD-osteosarcoma of the rat. Preliminary mutagenicity studies with the Salmonella typhimurium/mammalian microsome assay of Ames did not show any evidence of mutagenicity for the compound. The first results of the phase I clinical trials showed mild hepatotoxicity at a dose level of 15 mg/kg, dose-limiting nephrotoxicity at 21 mg/kg, and a reversible impairment of the sense of taste, beginning at a dose of 9 mg/kg.
Keppler
B K
BK
Anorganisch-Chemisches Institut der Universität, Heidelberg, Fed. Rep. of Germany.
Heim
M E
ME
Flechtner
H
H
Wingen
F
F
Pool
B L
BL
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity; D004341:Drug Evaluation; D005260:Female; D051379:Mice; D009152:Mutagenicity Tests; D009153:Mutagens; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D009942:Organometallic Compounds / Q000627:therapeutic use* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains
D000970:Antineoplastic Agents; D009153:Mutagens; D009942:Organometallic Compounds; C043899:diethoxy-(1-phenyl-1,3-butanedionato)titanium (IV)