title: Antitumour activity of miltefosine alone and after combination with platinum complexes on MXT mouse mammary carcinoma models.
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.
authors.affiliation: Universität Regensburg, Institut für Pharmazie, Federal Republic of Germany.
authors.forename: T
authors.initials: T
authors.lastname: Spruss
authors.forename: G
authors.initials: G
authors.lastname: Bernhardt
authors.forename: H
authors.initials: H
authors.lastname: Schönenberger
authors.forename: J
authors.initials: J
authors.lastname: Engel
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D005260:Female; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy* / Q000473:pathology; D008727:Methotrexate; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014407:Tumor Cells, Cultured; D014599:Uterus / Q000187:drug effects / Q000473:pathology
chemical_list: D010767:Phosphorylcholine; C039128:miltefosine; D002945:Cisplatin; D008727:Methotrexate