Comparative anti-tumor efficacy of two orally administered platinum(IV) drugs in nude mice bearing human tumor xenografts

Anticancer Drugs. 2006 Feb;17(2):201-6. doi: 10.1097/00001813-200602000-00012.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amantadine / analogs & derivatives*
  • Amantadine / therapeutic use
  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cisplatin / adverse effects
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / prevention & control
  • Drug Resistance, Neoplasm
  • Female
  • Ligands
  • Male
  • Mice
  • Mice, Nude
  • Organoplatinum Compounds / therapeutic use*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / prevention & control
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / prevention & control
  • Transplantation, Heterologous

Substances

  • Antineoplastic Agents
  • Ligands
  • Organoplatinum Compounds
  • bis(acetato)(1-adamantylamine)amminedichloroplatinum(IV)
  • satraplatin
  • Amantadine
  • Cisplatin