Comparative anti-tumor efficacy of two orally administered platinum(IV) drugs in nude mice bearing human tumor xenografts.
The oral anti-tumor activity of a novel platinum(IV) complex, coded as LA-12, with a bulky adamantylamine ligand was evaluated and compared with another platinum(IV) complex satraplatin. The human carcinoma xenografts of colon HCT116, prostate PC3, and ovarian A2780 and A2780/cisR (resistant to cisplatin) were used to evaluate the in-vivo anti-tumor activity. The daily x 5 repeated dose regimen in equimolar doses of LA-12 and satraplatin, administered in 2 cycles, was selected for this evaluation. All doses of LA-12 and satraplatin were significantly effective in comparison with the control. The activities of LA-12 in all doses and all used tumor xenografts were higher than equimolar doses of satraplatin. The highest effect was reached with LA-12 at a dose of 60 mg/kg. The shapes of growth curves of ovarian carcinoma A2780 and its subline resistant to cisplatin after therapy with LA-12 were very similar. This shows that LA-12 is able to overcome resistance to cisplatin.
Sova
Petr
P
Research and Development, PLIVA-Lachema a.s., Brno, Czech Republic. sova@lachema.cz
Mistr
Adolf
A
Kroutil
Ales
A
Zak
Frantisek
F
Pouckova
Pavla
P
Zadinova
Marie
M
D000547:Amantadine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000009:adverse effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D019008:Drug Resistance, Neoplasm; D005260:Female; D008024:Ligands; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D008024:Ligands; D009944:Organoplatinum Compounds; C482801:bis(acetato)(1-adamantylamine)amminedichloroplatinum(IV); C081294:satraplatin; D000547:Amantadine; D002945:Cisplatin