Evaluation of a platinum-doxorubicin complex in experimental tumor systems

Invest New Drugs. 1990 Nov;8(4):341-5. doi: 10.1007/BF00198589.

Abstract

On the basis of previous observations indicating that the platinum (II)-doxorubicin complex (coordinated via the amino sugar) was active against resistant ascitic leukemias, the preclinical evaluation of this complex was extended to a variety of experimental tumors, including solid doxorubicin-resistant tumors (P388/DX, B16 melanoma with acquired resistance, and MXT mammary carcinoma with natural resistance). In the treatment of sensitive tumors (Gross leukemia and Lewis lung tumor) the complex provided efficacy comparable to that of doxorubicin. Among resistant models, only P388/DX, which is only weakly responsive to cisplatin itself, showed significant sensitivity to the platinum complex. Since all resistant tumors were transplanted in the same site (s.c.) of the same mouse strain, it is likely that the different tumor response reflects different underlying mechanisms of cell resistance rather than alterations in pharmacologic behavior of the anthracycline after covalent binding to platinum. The data reported in this preclinical study support the potential value of this approach to overcome selected manifestations of resistance to anthracyclines. In contrast to the highly toxic doxorubicin/cisplatin combination, doxorubicin complexation with platinum was not associated to an increase in toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Cisplatin / administration & dosage
  • Cisplatin / toxicity
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / therapeutic use
  • Doxorubicin / toxicity
  • Drug Resistance
  • Drug Screening Assays, Antitumor
  • Drugs, Investigational / therapeutic use*
  • Mice
  • Neoplasm Transplantation
  • Neoplasms, Experimental / drug therapy*
  • Organoplatinum Compounds / therapeutic use*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Drugs, Investigational
  • Organoplatinum Compounds
  • cis-(platinum-dichloro(doxorubicin)(tert-butylamine))
  • Doxorubicin
  • Cisplatin