Antitumor activity of a new orally active organotin compound: a preliminary study in murine tumor models.
The toxicity and antitumor activity of the novel organotin compound triethyltin(IV)lupinylsulfide hydrochloride (IST-FS 29), administered by the oral route, have been evaluated against three transplantable murine tumor models: P388 lymphocytic leukemia, B16F10 melanoma and 3LL Lewis lung carcinoma. Mild and reversible signs of acute toxicity such as behavioral symptoms, weight loss and histological alterations were mainly reported at the highest single dose of 28 mg/kg. Conversely, lower concentrations of compound ranging from 7 to 21 mg/kg did not result in major toxic effects, even after repeated dosing. The antitumor activity studies showed that fractionation dosing, rather than single bolus administration, over 1 week, might prove more active and better tolerated by allowing the achievement of the highest therapeutic total dose of IST-FS 29 (42 mg/kg). Indeed, repeated administrations of IST-FS 29 resulted in marked significant improvement of antitumor activity against B16F10 (50% of tumor volume inhibition, p = 0.0003) and, to a greater extent, 3LL (90% of tumor volume inhibition, p = 0.0001) tumors. These results indicate that IST-FS 29 might be a suitable candidate as an orally administrable anticancer drug and support its further development in human tumor xenografts.
Barbieri
Federica
F
Laboratory of Pharmacology and Neuroscience, National Institute for Cancer Research, 16132 Genoa, Italy.
Viale
Maurizio
M
Sparatore
Fabio
F
Schettini
Gennaro
G
Favre
Anna
A
Bruzzo
Cristina
C
Novelli
Federica
F
Alama
Angela
A
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy; D005260:Female; D007941:Leukemia P388 / Q000188:drug therapy; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D009947:Organotin Compounds / Q000494:pharmacology* / Q000633:toxicity; D014267:Triethyltin Compounds / Q000494:pharmacology* / Q000633:toxicity; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C408503:IST-FS 29; D009947:Organotin Compounds; D014267:Triethyltin Compounds