Altretamine hydrochloride

Altretamine is an alkylating agent proposed as an antineoplastic.

Doxorubicin-hexamethylmelamine therapy of small cell carcinoma of the lung.[Pubmed:6271385]

Cancer. 1981 Nov 1;48(9):1944-6.

Eighteen patients with small cell carcinoma of the lung treated with doxorubicin hydrochloride and hexamethylmelamine are presented. Fifteen of these patients had extensive disease at presentation. Four patients in this group died after one or fewer courses of chemotherapy. The median duration of survival for the entire group of patients is 15 months. Six patients are alive from 18 to 56 months without evidence of disease. Drug toxicity was minimal and well tolerated, which permitted this regimen to be given in an outpatient setting.

Ovarian cancer. Effective treatment after alkylating-agent failure.[Pubmed:107337]

JAMA. 1979 May 4;241(18):1908-11.

Combination chemotherapy consisting of hexamethylmelamine and cisplatin, alone or with doxorubicin hydrochloride, was given to 27 patients with advanced ovarian cancer who had disease progression with therapy including alkylating agents. Eighteen (67%) had greater than 50% regression of measurable disease or disease that could be evaluated but not measured, for a projected median duration of seven months. The projected median survival for all patients is nine months from the time of entry into the study and 33 months from the time of diagnosis of ovarian cancer. The treatment could be readily administered on an outpatient basis with a regimen of hydration and diuresis that nearly completely prevented platinum-induced renal tubular damage. Myelosuppression was severe in 11 patients (40%), but there was no treatment-related deaths. Agents of such high activity should be considered as components of initial therapy for stage III and IV cancers.

Hexamethylmelamine and hexamethylmelamine hydrochloride.[Pubmed:6808457]

Pharm Weekbl Sci. 1982 Apr 23;4(2):25-31.

Methods of analysis of the anticancer drug hexamethylmelamine, its physicochemical properties, its therapeutic uses and its fate in vivo upon oral administration, are described. The data are taken in part from the literature, in part from our own studies. The low solubility of hexamethylmelamine in water has prevented the parenteral administration of the drug to humans. The preparation of the water-soluble monohydrochloride of hexamethylmelamine, which may be suitable for this purpose, is reported, as well as its physicochemical characteristics and methods of analysis.

Comparison of DNA damage by methylmelamines and formaldehyde.[Pubmed:6788992]

J Natl Cancer Inst. 1981 Jul;67(1):217-21.

The cytoxicity and DNA damaging activity of S9-activated hexamethylmelamine (HMM) and pentamethylmelamine (PMM) were compared with suspected active metabolites in mouse leukemia L1210 cells. The presence of semicarbazide hydrochloride did not alter the cytotoxicity of S9-activated HMM and PMM or that of their hydroxylated analogs monomethylolpentamethylmelamine (MPM) and trimethyloltrimethylmelamine (TTM), which have been suggested as active metabolites. Following treatment of L1210 cells with high concentrations of activated HMM and PMM, there were no DNA single-strand breaks or interstrand cross-links observed by DNA alkaline elution and only a low frequency of DNA-protein cross-links. Formaldehyde (FA) at nonlethal concentrations caused far greater DNA-protein cross-linking. In contrast, the polyfunctional TTM produced both DNA-protein cross-linking and DNA interstrand cross-linking. The cytotoxicities of HMM and PMM were found unlikely to be related to extracellular or intracellular release of FA.