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At least 307 records · Page 17Linked to original sources
PubMed1979

Phase II evaluation of hexamethylmelamine in advanced breast cancer: a Southwest Oncology Group study.

Ninety-eight patients with metastatic breast cancer, heavily pretreated with other agents, were entered in a phase II trial of hexamethylmelamine (HEX). Patients were randomized to receive HEX alone or combined with prophylactic pyridoxine. There was a 2% response rate in 89 partially or fully evaluable patients. Seven percent of these patients developed neurologic toxicity which occurred in the HEX-alone group only.

Aged↗
PubMed1979

Hexamethylmelamine in ovarian cancer resistant to cyclophosphamide and adriamycin.

Thirty-four patients resistant to cyclophosphamide and Adriamycin received hexamethylmelamine at one of two dose regimens: 6 mg/kg/day orally for 21 days every 4 weeks or 8 mg/kg/day orally for 21 days every 6 weeks. Only five patients responded. Tolerance to the drug was, however, satisfactory; nausea, pyrosis, and vomiting were the only frequent side effects. Myelosuppression occurred in only one case.

Adult↗
PubMed1979

Disposition and metabolism of pentamethylmelamine and hexamethylmelamine in rabbits and humans.

The disposition and metabolism of pentamethylmelamine (PMM) and hexamethylmelamine (HMM) were studied in the rabbit, and the disposition of PMM was studied in humans. Parent compound and metabolites were identified by thin-layer chromatography, gas chromatography, and gas chromatography/mass spectrometry analyses. Plasma elimination in both species following i.v. administration of each drug was best described by a two-compartment open model. Both compounds were extensively demethylated with less than 1% of the total dose administered recovered in the urine over 24 hr. The areas under the plasma time-concentration curves of PMM and HMM following p.o. administration to rabbits were 5 and 25% of the areas following i.v. administration. Gastrointestinal absorption was rapid and efficient with 75 to 89% of drug equivalents recoverable in the urine after p.o. administration of [ring-14C]PMM or [ring-14C]HMM to rabbits. Reduced bioavailability of PMM and HMM p.o. appears to be a consequence of rapid metabolism presumably in the liver.

Altretamine↗
PubMedDate not supplied

Phase II study of hexamethylmelamine alone and in combination with mitomycin C and vincristine in advanced breast carcinoma.

Fifty-three patients with metastatic breast carcinoma were randomized to treatment with hexamethylmelamine (HMM) as a single agent versus a three-drug reimen of HMM, vincristine, and mitomycin C (HOM). All patients had received prior treatment with 5-fluorouracil, Adriamycin, and cyclophosphamide with or without methotrexate. HMM alone was used in a dose of 300 mg/m2/day x 14 days every 21 days. In the HOM regimen, the HMM dose was 200 mg/m2/day x 21 days, the vincristine dose was 1.5 mg on Days 1, 8, and 15, and the mitomycin C dose was 12 mg/m2 once every 6 weeks. No objective responses were observed with HMM in 15 evaluable patients. The HOM regimen resulted in five partial responses among the 27 evaluable patients. Gastrointestinal toxicity was the limiting toxicity of HMM, and thrombocytopenia was the major toxicity of the HOM regimen.

Adult↗
PubMed1992

Replacement of cisplatin with carboplatin in combination chemotherapy against ovarian cancer: long-term treatment results of a study of the Gynaecological Cancer Cooperative Group of the EORTC and experience at The Netherlands Cancer Institute.

Carboplatin-based chemotherapy has been evaluated in three studies of ovarian cancer patients. In the first, combination cisplatin and carboplatin plus doxorubicin/hexamethylmelamine/cyclophosphamide were compared as first-line treatment of ovarian cancer in 341 women with stage IIB to IV disease. There were no observed differences in results between the two treatment groups. In the second study, conventional doses of intravenous carboplatin (350 mg/m2, given on day 1) plus oral cyclophosphamide (100 mg/m2 days 2 to 6) were given to late-relapsing patients (12 to 72 months) previously treated with cisplatin. Mature data showed a 55% overall response rate, acceptable toxicity, and an absence of additive neurotoxicity. Finally, 65 patients with refractory disease or in early relapse after cisplatin therapy (within 12 months) were treated with high-dose carboplatin (800 mg/m2). Toxicity was severe, but the 45% combined response rate was considered encouraging and worthy of further evaluation. It was concluded that carboplatin is an appropriate replacement for cisplatin in the treatment of ovarian cancer.

Adult↗
PubMed1978

[New substances in oncologic therapy].

After presentation of several important methodological problems in the development of new cytostatic agents, the newer substances adriamycin, the nitroso-urea derivatives, ICDT, diaminodichloro-cisplatinum, VP 16-213 and tamoxifen are briefly discussed with regard to their pharmacology and activity spectra. In this context adriamycin, diaminochloro-cisplatinum and VP 16-213 may be considered break-throughs in the field of therapeutic oncology. Finally, several newer drugs still in phase I studies are mentioned.

Alkylating Agents↗
PubMed1991

[Study of vinorelbine (V) combined with hexamethylmelamine (H) (combination V-H) in adenocarcinoma of the ovary: results a phase I-IIA trial, NHO-88, of ARTAC "ovarian" group].

The lack of decisive progress in ovarian cancer chemotherapy in recent years led the ARTAC "Ovary" group to initiate a study based on the hypothesis of collateral sensitivities. In this phase I-II trial, NHO-88, the V-H combination (associating vinorelbine (VNB) and hexamethylmelamine (HMM) was studied in patients with advanced ovarian adenocarcinomas, most of which had become resistant to previous chemotherapy. The aim of the study was to find an active combination without complete cross resistance with first-line platinum salt based combinations, such as CAP, FAP or CACb-300. A pilot feasibility study was first carried out to determine the maximum tolerated weekly dose (MTWD) of VNB (20 mg/m2/week), HMM being administered per os on days 1-14 of every 28-day cycle at a standard dose of 250 mg/m2/day. An open phase II-A study was further carried out according to a 2-step sequential analysis method for phase II clinical trials. We observed: 1), a good tolerance of the V-H combination apart from frequent neutropenia; 2), a response rate of 35% (95% confidence interval: 23-47%); 3), a median response duration of 4 months (range: 1-7 months); 4), in some cases, the absence of a complete cross-resistance between the V-H regimen and the previously administered platinum-based combinations. These results, which are currently being validated (phase II-B ongoing), constitute the first step in the search for active systems of sequential or alternate chemotherapeutic regimens for the treatment of advanced carcinomas.

Adenocarcinoma↗
PubMed1990

Phase I and clinical pharmacological evaluation of a parenteral hexamethylmelamine formulation.

Hexamethylmelamine has been evaluated in single agent and combination regimen studies for many years, but only following p.o. administration. Pharmacological studies in animals and humans have shown that systematic availability of parent drug following p.o. administration is relatively low and variable due to extensive first-pass metabolism rather than due to poor absorption. 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%. The parenteral formulation was well tolerated by all patients receiving hexamethylmelamine by 1-day and by daily for 5-days schedules. Nausea and vomiting were the dose-limiting toxicities. Maximally tolerated doses on the 1-day and daily for 5-days schedules were approximately 850 mg/m2 and 630 mg/m2/day, respectively. No responses were observed in either study. Following i.v. administration of 540 mg/m2 hexamethylmelamine, plasma elimination was best described by a three-compartment open model with terminal half-life, total body clearance, and steady-state volume of distribution values of 10.4 h, 0.75 liter/min/m2 and 460 liters/m2, respectively. Twenty-four h urinary recoveries of parent drug were less than 1% for all patients. Accumulation of hexamethylmelamine during the 5-day treatment at 945 mg/m2 suggested possible saturation of parent drug elimination at that dose. Phase II studies are currently under way with the parenteral formulation of hexamethylmelamine.

Altretamine↗
PubMedDate not supplied

In vitro cytotoxicity of hexamethylmelamine (HMM) and its derivatives.

The cytotoxicity of hexamethylmelamine (HMM) and its metabolites was investigated in three murine cell lines: one in vitro naturally sensitive to HMM (RC) and two in vivo naturally resistant (P388 and P388D1). The percentage of viable cells was determined both by the in situ reduction of a tetrazolium salt (MTT assay) and by the uptake of labelled thymidine into DNA (3HTdR assay). Short (1h) and long (48h) exposures of cells to drugs were considered. In all experimental conditions used, HMM was found to be inactive, whereas its hydroxylated metabolite hydroxymethylpentamethylmelamine (HMPMM) and one analog N, N 'dihydroxymethyltetramethylmelamine (DHTMM) were found to be cytotoxic. The results further indicated that HMM must be metabolized before it can exert its cytotoxic effect. The activity of HMPMM and DHTMM was found unlikely to be related to extracellular or intracellular release of formaldehyde.

Altretamine↗