Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Altretamine”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources
PubMed2000

Comparative study on three chemotherapeutic regimens for the treatment of advanced epithelial ovarian cancer.

To investigate the best first-line chemotherapy regimen for the treatment of advanced epithelial ovarian cancer (AEOC), the efficacy of three chemotherapy regimens for treatment of the patients with AEOC in our hospital during Jan. 1992-Jan. 1999 was retrospectively analyzed. The therapeutic effects were compared with the supplement of Melphalan + Hexamethylme (PAM + HMM), cisplatin + adriamycin + cyclophosphamide or isofamide (PAC) or cisplatin + cyclophosphamide or isofamide (PC), Taxol + cisplatin (TP) combined chemotherapy after cytoreductive surgery. The results showed that the overall effective rate of TP was significantly higher than that of PAM + HMM (P < 0.05); The complete remission rate of TP was significantly higher than that of PAM + HMM and PAC or PC (all P < 0.05); The 2-year survival rate free of tumor of TP was obviously higher than that of PAM + HMM and PAC or PC (all P < 0.05). It was concluded that the therapeutic effect of TP regimen in the treatment of AEOC was better than PAM + HMM and PAC or PC and TP regimen could be recommended currently as the preferred first-line one for the treatment of AEOC.

Adult↗
PubMedDate not supplied

A new algorithm for computing the parameters of linear compartment models in pharmacokinetics.

A new algorithm (FADHA) for computing pharmacokinetic parameter estimates has been developed. This technique is based on the simplex method which is used to minimize a nonlinear cost function. An important property of this program is that the convergence is ensured contrary to the well-known linear or nonlinear least-squares regression analysis which lead to a lack of convergence or to a false one. Two investigations of the comparative performances of FADHA program and other algorithms were undertaken (hexamethylmelamine and Piracetam pharmacokinetics). Least square analysis of data yielded biased estimates whereas FADHA estimates were unbiased and more precise. This new technique, takes into account all the possible observation errors and uses the concept of a weighting function rather than weights as such.

Altretamine↗
PubMed1979

Hexamethylmelamine: an evaluation of its role in the treatment of ovarian cancer.

Hexamethylmelamine (HMM), NSC 13875, a synthetic agent structurally related to triethylenemelamine, has clinical antitumor activity and a role in the treatment of ovarian cancers of epithelial origin. Fifty-four patients, with International Federation of Gynecology and Obstetrics Stage III or IV carcinomas, previously untreated with chemotherapy or irradiation therapy, were treated with HMM (8 mg/kg/day) as a single agent at the M. D. Anderson Hospital and Tumor Institute in Houston, Texas, between January, 1973, and May, 1976. The response end points analyzed were complete plus partial response rate, duration of remission, and survival time. The complete and partial responses were verified whenever possible by "second-look" operation. Seventeen patients (31.8%) responded to HMM and three had no evidence of cancer, determined by multiple biopsies at second-look operation. Gastrointestinal, hematologic, and nervous system toxic effects were severe in 10 patients, requiring discontinuation of HMM. This study shows that HMM can induce a complete response and provide an extended disease-free interval without maintenance chemotherapy.

Adult↗
PubMed1983

Cisplatin regimens and improved prognosis of patients with poorly differentiated ovarian cancer.

Patients with advanced ovarian carcinoma, Stage III or IV (International Federation of Gynaecology and Obstetrics), were randomized to primary chemotherapy with doxorubicin (Adriamycin) and cisplatin plus or minus hexamethylmelamine, and cyclophosphamide (CHAP). The four-drug CHAP regimen produced a 57% complete clinical response rate and a 26% partial response rate for clinically evaluable patients. The median survival of CHAP patients is 25 months. The two-drug Adriamycin-cisplatin (AP) regimen produced a 43% complete response rate and a 35% partial response rate. The median survival is 18 months. The four-drug regimen produced a significantly longer median survival (28 versus 18 months) for patients with poorly differentiated tumors than for patients with well-differentiated tumors on either treatment. Examination of treatment failure or death by treatment, histology, and size of largest residual tumor and comparison to similar patients treated with AP in this and two preceding controlled trials also suggest that CHAP is superior to AP for patients with poorly differentiated tumors.

Altretamine↗
PubMed1983

Multiagent chemotherapy in relapsing ovarian cancer.

A multiagent regimen (vinblastine, bleomycin, hexamethylmelamine, and cis-platinum) partly designed on the basis of data from a human tumor stem cell assay was used to treat 36 patients with relapsing epithelial ovarian cancer. All patients included in this study had previously received alkylating agent therapy, and 78% (28/36) had also received Adriamycin. Thirty-five patients were clinically evaluable for response; eight achieved complete clinical remission, and nine achieved partial remission, for an overall response rate of 49%. The median duration of response was 10 months, and three of the complete responders are in remission at 10+, 17+, and 22+ months. Mild to moderate peripheral neuropathy was the major side effect, occurring in 11% (4/35) of patients. Myelotoxicity was well tolerated. We conclude that this four-drug regimen is effective in the treatment of relapsing ovarian cancer patients and should be considered for study as a front-line combination chemotherapy for previously untreated patients.

Altretamine↗
PubMed1991

Hexamethylmelamine chemotherapy for persistent or recurrent epithelial ovarian cancer.

The purpose of this study was to determine the activity and toxicity of hexamethylmelamine chemotherapy in patients with persistent or recurrent epithelial ovarian cancer. Forty-nine women received hexamethylmelamine 100 to 150 mg/day for 14 days, repeated at 4-week intervals. All patients had previously received at least one chemotherapy regimen, and 46 (94%) had received cisplatin. Among 25 patients with clinically measurable disease there were three complete and two partial responses, for an objective response rate of 20%. The mean progression-free interval for responders was 38.6 months versus 9.6 months for nonresponders or patients with nonmeasurable disease (p less than 0.001). Thirteen patients are alive, eight with no clinical evidence for disease. Only four patients discontinued therapy because of toxic reactions. Hexamethylmelamine appears to be a well-tolerated drug with activity against ovarian cancer previously treated with cisplatin.

Adult↗
PubMed1982

Studies of the mode of action of antitumour triazenes and triazines-III. Metabolism studies on hexamethylmelamine.

These is good evidence that the antitumour agent hexamethylmelamine (HMM) undergoes oxidative metabolic activation which might occur in the liver and/or extrahepatically. The hepatic microsomal N-methylmelamine metabolizing enzymes were investigated in mice and exhibited different affinities for different melamine derivatives. The apparent Km values are 0.09 mM for HMM, 0.23 mM for pentamethylmelamine, 0.91 mM for 2,2,4,6-tetramethylmelamine and 1.7 mM for trimethylmelamine. HMM inhibited its own metabolism in vitro at substrate concentrations greater than 0.05 mM. Its hepatic microsomal N-demethylation rate was reduced when the mice were pretreated with the hepatic glutathione depleting agent methyliodide. Injection of hexaethylmelamine, a derivative of HMM without antineoplastic properties against the M5076 sarcoma in mice, lead to plasma concentrations of drug and metabolite pentaethylmelamine which were only a fraction of the drug and metabolite levels achieved after a similar dose of HMM.

Altretamine↗
PubMed1984

Central side effects of pentamethylmelamine: biochemical and behavioural studies.

The central side effects of pentamethylmelamine (PMM), an antitumoral agent, were studied on brain neurotransmitters from the biochemical and behavioural points of view. PMM causes a dose-related reduction in the body temperature and motility of mice. 100 mg/kg of PMM lowers the levels of noradrenaline (NA) and raises 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) in the telencephalon. A similar dose increased striatal levels of dopamine (DA) metabolites, homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC), at earlier times (30 min), reducing their levels at 2 hr. These effects disappear at longer times (4 hr). No changes were observed in the levels of 3-methoxytyramine (3-MT), the extraneuronal metabolite of DA. The serotonin metabolite 5-hydroxyindolacetic acid (5HIAA) was almost not affected. PMM and its metabolites do not displace [3H]-spiroperidol from mouse striatal binding sites. These data show that some of the neurological effects induced by PMM are associated with changes in the metabolism and/or release of brain catecholamines but are not mediated by direct action on DA receptors.

Altretamine↗
PubMed1984

Studies of the mode of action of antitumour triazenes and triazines-V. The correlation of the in vitro cytotoxicity and in vivo antitumour activity of hexamethylmelamine analogues with their metabolism.

Experiments were conducted to ascertain whether the antitumour activity of hexamethylmelamine analogues correlated with their in vitro cytotoxicity and metabolism. Two analogues, namely pentamethylmelamine (PMM) and 2,2,4,4-tetramethylmelamine (TMM), and hexamethylmelamine (HMM) itself were shown to be active towards the murine ADJ/PC6A (PC6) plasmacytoma; another three, 2-chloro-4,6-bis(dimethylamino)-1,3,5-triazine (CBDT), 2,4-bis-(dimethylamino)-6-hydrazino-1, 3,5-triazine (HBDT) and 2,4,6-trimethylmelamine (TriMM) were inactive against the same tumour. The cytotoxicity of these compounds was examined against a PC6 tumour cell line in vitro. In the absence of liver microsomal activation only CBDT proved to be significantly cytotoxic at a concentration of 5 mM. In the presence of murine liver microsomes the three active antitumour agents were all cytotoxic at this concentration whereas HBDT and TriMM remained non-toxic. The degree of cytotoxicity correlated with the extent of metabolism for these analogues. The products of biotransformation of these compounds were stable precursors of formaldehyde (presumably N-hydroxymethyl intermediates) (FP) rather than formaldehyde itself. After injection of these 6 compounds to Balb/c mice the levels of FP generated in the plasma were markedly greater for the three active antitumour agents than for the inactive analogs. No free formaldehyde was detected in the plasma after administration of any of the compounds. These results suggest that for these compounds in vitro cytotoxicity correlates with in vitro biotransformation and their antitumour activity correlates with plasma levels of FP generated by metabolism in vivo.

Altretamine↗
PubMed1984

Biochemical studies on the ability of pentamethylmelamine to interact in vivo with DNA and proteins in a sensitive murine ovarian reticular cell sarcoma.

The metabolism of 14C-PMM and its irreversible interaction with DNA and proteins were studied in M5076/73A reticular cell sarcoma, a murine solid tumor previously shown to be sensitive to the drug. Metabolism and irreversible binding were determined 0.25, 1, 8 and 104 hours after a single i.p. injection of radiolabelled PMM, tumor and liver macromolecular binding were compared with two differently 14C-labelled PMM, i.e. ring- and methyl-PMM. Ring-PMM derived macromolecular binding appeared to have more relevance in vivo and had a similar time profile in both liver and tumor. Ring-PMM derived DNA binding was then related to metabolic steps between PMM and 2,2,4,6 TMM and 2,2,4,6 TMM itself and 2,4,6 TriMM.

Altretamine↗
PubMed1995

The role of the N-(hydroxymethyl)melamines as antitumour agents: mechanism of action studies.

The hexamethylmelamine analogue trimelamol (tris-hydroxymethyl[trimethyl]melamine) and its equicytotoxic stable analogues CB 7547, CB 7639 and CB 7669 have been used to clarify the mechanism of action for the N-(hydroxymethyl)melamines as antitumour agents. Two main mechanisms have been proposed and explored: (i) formation of a reactive iminium species forming covalent adducts with DNA; and (ii) local formaldehyde release leading to cytotoxic damage. 32P-postlabelling and thermal denaturation experiments showed these compounds to be interactive with cytosine and guanine. Trimelamol gave rise to DNA-interstrand crosslinks in naked plasmid DNA and in cultured cell lines, whereas the analogues failed to do so under a variety of experimental conditions. Along with our observations that cell lines with acquired resistance to the N-(hydroxymethyl)melamines showed no significant cross-resistance to classical bifunctional alkylating agents, DNA crosslinking may play only a minor role in their mechanism of action. In cultured cell lines treatment with formaldehyde, trimelamol and CB 7639 gave rise to high levels of DNA-protein crosslinks with a gradual disappearance over a 24 hr period. Along with our earlier observation that resistance to trimelamol coincides with cross-resistance to formaldehyde, we conclude that formaldehyde-release may be an important factor in their cytotoxicity. Further, the cytotoxicity of trimelamol or formaldehyde towards human ovarian cancer cells was not influenced by glutathione depletion. As the precise mechanism of action for the N-(hydroxymethyl)melamines is apparently not shared by many commonly used anticancer agents, this may confer their broad-spectrum activity versus heavily pretreated tumours.

Alkylating Agents↗
PubMed1977

Analogues of hexamethylmelamine. The anti-neoplastic activity of derivatives with enhanced water solubility.

The preparation of some water soluble analogues of the tumour growth inhibitory hexamethylmelamine is described. The ultra-violet absorption characteristics, solubility and n-octanol/water partition coefficients of these new derivatives and some related compounds have been determined. Rates of demethylation by a liver microsomal preparation and anti-tumour assays against the ADJ/PC6A mouse plasma cell tumour and a human lung tumour xenograft are reported. Two of the derivatives, pentamethylmelamine and N2, N4, N6-trimethyl-N2, N4, N6-trimethylolmelamine, which have shown activity against the xenograft are potential candidates for clinical trials using the intravenous route of administration.

Altretamine↗
PubMed1980

In vitro cytotoxicity of the methylmelamines.

Hexamethylmelamine (HMM) and a number of its derivatives are toxic to PC6 plasmacytoma cells in vitro. However, there is no correlation between in vitro cytotoxicity and activity against this tumour in vivo. N-Methylolmelamines are significantly more toxic than HMM itself. These compounds break down to release formaldehyde which is itself a highly cytotoxic agent. Pentamethylmonomethylolmelamine rapidly inhibits the growth of PC6 cells in culture, whereas HMM and pentamethylmelamine (PMM) require prolonged contact with the cells in order to exert a cytotoxic effect. HMM and its metabolites are also toxic to a number of other cell lines. The toxicity of the N-methylols to cultured L1210 leukaemia and Walker 256 ascites cells appears to be due entirely to formaldehyde release, whereas in PC6 cells the methylols appear to be acting more selectively.

Altretamine↗