Antitumour activity of miltefosine alone and after combination with platinum complexes on MXT mouse mammary carcinoma models

J Cancer Res Clin Oncol. 1993;119(3):142-9. doi: 10.1007/BF01229528.

Abstract

Miltefosine, an alkylphosphocholine structurally related to alkyllysophospholipids showed highly selective antitumour activity against the hormone-sensitive variant of the s.c. transplantable MXT mouse mammary adenocarcinoma, the ovary-dependent MXT (M3.2), whereas it was inactive against the hormone-insensitive MXT (M3.2) OVEX variant. A dose of 32 mg/kg miltefosine p.o. daily for 5 weeks was well tolerated. Histopathological evaluation gave no signs of gastroenteral toxicity. After therapy the microarchitecture of the MXT (M3.2) tumours changed from that of a moderately differentiated adenocarcinoma to that of an anaplastic mammary carcinoma. A dose of 16 mg/kg miltefosine p.o. daily, though in effective per se, enhanced the antitumour activity of suboptimal i.p. doses of cisplatin and the hormone-like platinum analogue meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl) ethylenediamine]dichloroplatinum(II). Furthermore, it was shown, that miltefosine exhibited no (anti)hormonal properties. However, the mechanism of action of miltefosine remains unclear.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma / drug therapy*
  • Carcinoma / pathology
  • Cisplatin / administration & dosage
  • Drug Resistance
  • Drug Screening Assays, Antitumor
  • Female
  • Mammary Neoplasms, Animal / drug therapy*
  • Mammary Neoplasms, Animal / pathology
  • Methotrexate
  • Mice
  • Mice, Inbred Strains
  • Organ Size
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / pathology
  • Phosphorylcholine / administration & dosage
  • Phosphorylcholine / analogs & derivatives
  • Tumor Cells, Cultured
  • Uterus / drug effects
  • Uterus / pathology

Substances

  • Phosphorylcholine
  • miltefosine
  • Cisplatin
  • Methotrexate