Disease relevance of HEXAMETHYLMELAMINE

• Role of hexamethylmelamine in the treatment of ovarian cancer: where is the needle in the haystack [1]?
• 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 [2].
• Toxicity and antitumor activity of hexamethylmelamine and its N-demethylated metabolites in mice with transplantable tumors [3].
• Hexamethylmelamine is known to be effective in humans in the treatment of certain malignant tumors, especially bronchial carcinoma [4].
• Although altretamine displays some activity in small cell lung cancer, it is unlikely to have any clinical role in the management of non-ovarian cancer [5].

Psychiatry related information on HEXAMETHYLMELAMINE

• Patient compliance with prolonged oral altretamine treatment in relapsed ovarian cancer [6].

High impact information on HEXAMETHYLMELAMINE

• BACKGROUND: In the previous meta-analysis of dose intensity (dosage) of chemotherapy in advanced ovarian cancer, we analyzed data on cyclophosphamide, altretamine (hexamethylmelamine), doxorubicin, and cisplatin [7].
• Response evaluation by a strict CA125 definition gave a similar estimate of the efficacy of altretamine as EORTC criteria [8].
• Two Phase I clinical trials, with accompanying pharmacokinetic studies, have been conducted by using a parenteral formulation in which hexamethylmelamine was prepared by Intralipid 10% [9].
• Trimelamol is an analogue of hexamethylmelamine and pentamethylmelamine which does not require metabolic activation and is sufficiently soluble to allow parenteral administration [10].
• Pharmacokinetics of hexamethylmelamine in intralipid following hepatic regional administration in rabbits [11].

Chemical compound and disease context of HEXAMETHYLMELAMINE

• The relationship between outcome and dose intensity was analyzed for first-line chemotherapy of advanced ovarian cancer using a particular CHAP (cyclophosphamide, hexamethylmelamine, Adriamycin [Adria Laboratories, Columbus, OH], cisplatin) regimen as the standard [12].
• Four-drug combination chemotherapy (methotrexate, cyclophosphamide, hexamethylmelamine, and CCNU) for non-small cell bronchogenic carcinoma: a Cancer and Leukemia Group B study [13].
• Primary treatment of regional and disseminated pancreatic cancer with hexamethylmelamine, mitomycin C and 5-fluorouracil infusion [14].
• 27 patients with ovarian cancer FIGO stages IIc-IV were treated with carboplatin 7 x (glomerular filtration rate + 25) mg given intravenously on day 1 and hexamethylmelamine (HMM) 150 mg/m2 orally on days 2-15, every 28 days [15].
• A phase I study of paclitaxel and altretamine as second-line therapy to cisplatin regimens for ovarian cancer [16].

Biological context of HEXAMETHYLMELAMINE

• Low oral bioavailability of hexamethylmelamine in the rat due to simultaneous hepatic and intestinal metabolism [17].
• Cellular and subcellular studies of the biotransformation of hexamethylmelamine in rat isolated hepatocytes and intestinal epithelial cells [18].
• Sequence analysis of the mutations induced by hexamethylmelamine, a crosslinking agent extensively used in the treatment of ovarian cancer, in male germ cells of Drosophila was conducted using the v locus as reporter gene [19].
• Reproduction and teratology studies on hexamethylmelamine in the rat and rabbit [20].
• The antineoplastic drug hexamethylmelamine (HMM) was evaluated for effects on reproduction and postnatal development in the rat and on embryonal and fetal development in the rat and rabbit [20].

Anatomical context of HEXAMETHYLMELAMINE

• The antitumor agent hexamethylmelamine is subject to oxidative metabolic conversion in rat isolated liver and small intestinal cells (conversion 40 times higher in hepatocytes) [18].
• Hexamethylmelamine (HMM) is metabolized by rat hepatic microsomal preparations to reactive species which covalently bind to microsomal protein and to calf thymus DNA added to microsomal incubation mixtures [21].
• In a reexamination of the effects of hexamethylmelamine, two tumors were found to be very sensitive, namely, a mouse plasma cell tumor (PC6) and a human bronchial carcinoma (P246) growing in immune deprived mice [4].
• Hexamethylmelamine is a potent inducer of deletions in male germ cells of Drosophila melanogaster [19].
• Effect of a hepatic activation system on the antiproliferative activity of hexamethylmelamine against human tumor cell lines [22].

Associations of HEXAMETHYLMELAMINE with other chemical compounds

• Cross-resistance was found between CTX, L-phenylalanine mustard, chlorambucil, and hexamethylmelamine [23].
• Data from recently analysed and mature trials demonstrate that the addition of hexamethylmelamine to first-line combination chemotherapy results in significant improvements in survival compared to what is achieved with regimens of cisplatin and cyclophosphamide with or without doxorubicin [24].
• Eighteen patients were treated in an ongoing prospective trial with combination chemotherapy consisting of melphalan, cis-platinum, and hexamethylmelamine++ (HexaPAMP) [25].
• When 1-h incubations were carried out in the presence of a 9,000 g rat liver supernatant preparation and an NADPH-generating system, hexamethylmelamine markedly reduced colony formation [22].
• Chemotherapeutic agents, cyclophosphamide, vincristine, and hexamethylmelamine, were investigated in a murine neuroblastoma model that, in part, histologically and morphologically resembles the human tumor [26].

Gene context of HEXAMETHYLMELAMINE

• The CHAD and HAD regimens in advanced ovarian cancer: combination chemotherapy including cyclophosphamide, hexamethylmelamine, adriamycin, and cis-dichlorodiammineplatinum(II) [27].
• Hexamethylmelamine (altretamine) in small cell lung cancer (SCLC) [28].
• Between April 1981 and June 1985, 195 patients with ovarian cancer, International Federation of Gynecology and Obstetrics (FIGO) Stages IIB, IIC, III, and IV, entered a trial that consisted of surgery and chemotherapy with cisplatin (P) and melphalan (PAM) with or without hexamethylmelamine (HexaPAMP or PAMP regimens) every 4 weeks for 6 cycles [29].
• A newly developed hexamethylmelamine derivative, SAE9 with both antitumor and aromatase-inhibitory activity [30].
• Testing of medical electrical and hospital laboratory equipment: DHSS recognition of the BSI Test House, Hemel Hempstead [31].

Analytical, diagnostic and therapeutic context of HEXAMETHYLMELAMINE

• Objective response rates to orally administered altretamine as salvage therapy in patients with advanced ovarian cancer were 0 to 33%, with disease stabilisation in a further 8 to 78% of patients [5].
• The inter-hand intrapatient variability of the bioavailability of altretamine after oral administration represents an important drawback for effective clinical use of this drug [32].
• The potential role of hexamethylmelamine in combination chemotherapy in the diseases in which it has single agent activity is largely unexplored and should be investigated in clinical trials [33].
• In vivo antitumor activity of hexamethylmelamine against human breast, stomach and colon carcinoma xenografts [34].
• A panel of cytokines/chemokines was measured in duplicate using the Bioplex Protein Array system (BioRad Hemel Hempstead, UK) [35].

References