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At least 91 records · Page 5Linked to original sources
PubMed1983

Cis-diamminedichloroplatinum (II): second line induction chemotherapy in advanced ovarian adenocarcinoma.

Twenty-one evaluable patients received second-line chemotherapy for recurrent ovarian adenocarcinoma with induction Cisplatin given weekly followed by monthly combination chemotherapy. Forty-two percent of the patients responded to induction weekly Cisplatin. Of the responders, 77% are alive as compared to only 8% of the nonresponders. Maintenance of the responses by monthly combination chemotherapy remains a significant problem. Moreover, 83% and 70% of patients who received weekly Cisplatin as first- and third-line induction chemotherapy, respectively, had objective responses. Of the total 43 patients who received weekly Cisplatin as first-, second-, or third-line chemotherapy, 60% responded, including complete clinical responses in 14% and partial responses in 46%.

Adenocarcinoma↗
PubMed1981

Adriamycin, vincristine, dibromodulcitol, and hexamethylmelamine in advanced previously treated breast cancer: an ECOG pilot study.

A combination of adriamycin, vincristine, dibromodulcitol, and hexamethylmelamine was piloted in patients with advanced breast cancer who had failed prior CMFP chemotherapy, as a part of ongoing trials by the Eastern Cooperative Oncology Group to improve second-line chemotherapy for this disease. The vincristine was given as an intensive 5 week induction regimen and hexamethylmelamine was administered on days 15-27 of a 28 day cycle, at the time of anticipated nadir peripheral blood counts. The study was terminated early after only 9 patients had been entered because of severe neurotoxicity related to the intensive schedule of vincristine as well as hematologic and gastrointestinal side effects. Three patients responded for 11, 18 and 21 weeks. The limited therapeutic benefit did not justify the toxicity produced, and suggested that intensive dosage schedules of vincristine, and use of low dose hexamethylmelamine during the time of anticipated hematologic nadir counts would not be of substantial benefit.

Aged↗
PubMed1983

Hexamethylmelamine in adenocarcinoma of the pancreas and liver.

Ten patients with advanced adenocarcinoma of the pancreas were treated with hexamethylmelamine 8 mg/kg/day in oral, divided doses. One of the five patients with measurable disease had a partial response which lasted 5 months. One of the five patients with no measurable disease treated for 52 months with hexamethylmelamine survived a total of 59 months. This experience suggests that hexamethylmelamine may be an active drug in the treatment of pancreatic cancer.

Adenocarcinoma↗
PubMed1984

Treatment of advanced ovarian carcinoma with hexamethylmelamine, doxorubicin, and cis-platinum (HAC): results in both untreated and previously treated patients.

Twenty-two patients with advanced (FIGO stages III and IV) adenocarcinoma of the ovary were treated with 28-day cycles of hexamethylmelamine, doxorubicin, and cis-dichlorodiamine-platinum (II) (HAC). After 45 months, there were 21 evaluable patients. The median survival was 16 months. Response was achieved in 82% (9/11) who had received no prior chemotherapy, and in 50% (5/10) previously treated. HAC therapy was readily administered on an outpatient basis, with comparatively low major toxicities, primarily hematologic, neurologic, and gastrointestinal. These results indicate that HAC therapy is an effective regimen for patients with advanced ovarian carcinoma, regardless of their prior treatment status.

Adenocarcinoma↗
PubMed1984

The chemotherapy of granulosa cell tumors of the ovary: experience of the Wisconsin Clinical Cancer Center.

We reviewed the clinical records of 32 patients with granulosa cell tumor of the ovary treated at the Wisconsin Clinical Cancer Center (WCCC) between 1970 and 1982. Eleven of these patients were treated with one or more chemotherapeutic regimens, yielding a total of 22 treatment trials. Objective response was observed in 7 of 17 evaluable treatment trials (41%). The response to chemotherapy could not be assessed in five treatment trials due to the concomitant administration of radiotherapy. We conclude that granulosa cell tumor of the ovary is responsive to chemotherapy. However, the optimal chemotherapeutic regimen for this rare neoplasm remains to be established on the basis of prospective clinical trials.

Adult↗
PubMed1993

Hexamethylmelamine/altretamine as second-line therapy for epithelial ovarian carcinoma.

The purpose of this report was to review second-line hexamethylmelamine (HMM) chemotherapy of epithelial ovarian cancer to determine if HMM was active in cisplatin-resistant disease. Forty-four women with measurable disease received 100-300 mg/day HMM for 14 days, courses repeated every 4 weeks. There were 6 complete and 3 partial responses for an objective response rate of 20%. Among responding patients disease-free survival was 55% and overall survival was 88% at 3 years. Five of the 6 patients with a complete response remained disease-free at 10-117 months. Only 7/35 (20%) nonresponding patients were alive with mean follow-up of 16 months, and all had persistent cancer. Five women manifesting disease progression during cisplatin or carboplatin were subsequently treated with HMM, and none responded. Seventeen patients developing progressive cancer while receiving HMM were subsequently treated with cisplatin or carboplatin and objective responses occurred in 5 (29%). HMM was an active drug against epithelial ovarian cancer previously treated with cisplatin, but further study is needed to determine its activity against cisplatin-resistant ovarian cancer.

Adult↗
PubMed1995

The subrenal capsule assay in selecting chemotherapy for ovarian cancer: a prospective randomized trial.

In order to find out whether the response rate and survival in epithelial ovarian cancer can be improved by aid of sensitivity testing with the subrenal capsule assay (SRCA), 196 patients with FIGO Stage II-IV epithelial ovarian cancer were randomized to be treated with either cyclophosphamide-doxorubicin-cisplatin (CAP) or SRCA-guided chemotherapy. The drug combinations tested with the SRCA were (1) cyclophosphamide-doxorubicin-carboplatin (CACAR), (2) CAP, (3) carboquone-methotrexate-tegafur (CQ-MTX-TEG), (4) cisplatin-etoposide-hexamethyl-melamine (P-VP-HXM), and (5) bleomycin-epirubicin-cisplatin (BEP). A total of 132 patients (CAP, 69; SRCA, 63) were eligible for efficacy analysis based on relaparotomy findings. The overall response rate was 59% in the CAP arm and 62% in the SRCA arm. In the SRCA arm, 16 patients were treated with CACAR, 24 with CAP, 10 with CQ-MTX-TEG, 11 with P-VP-HXM, and 2 with BEP. The response rate to CACAR was 63% and to SRCA-CAP was 75%. The number of complete responses was higher when CAP was given as guided by the assay than when given at random (14/24 vs 23/69; P = 0.03, Pearson chi 2). Survival curves as estimated by Kaplan-Meier method gave a median survival of 24 (SE = 4) months to the SRCA arm and 28 (SE = 5) for the CAP arm (P = 0.7; log-rank test). Because no survival benefit was achieved, the SRCA obviously needs further development before it can be routinely recommended in the choice of first-line chemotherapy for patients with ovarian cancer.

Aged↗
PubMed1995

Carboplatin (CBDCA)-hexamethylmelamine (HMM)-oral etoposide (VP-16) first-line treatment of ovarian cancer patients with bulky disease: a phase II study.

Hexamethylmelamine (HMM) and oral etoposide (VP-16) have shown to be active against platinum-resistant epithelial ovarian cancer. On this basis a three-drug regimen including carboplatin (CBDCA) plus HMM and oral VP-16 was tested in previously untreated ovarian cancer patients with tumor size > 2 cm. Since October 1991, 29 chemotherapy-naive ovarian cancer patients with tumor larger than 2 cm (20 stage III and 9 stage IV) have been treated for a total of 153 courses. CBDCA was administered i.v. on Day 1. The dose was individualized using the Calvert formula (the target dose was AUC = 5). VP-16 was administered orally at the dose of 50 mg/m2 Days 1-14, HMM at the dose of 150 mg/m2 po Days 14-28. Therapy was repeated every 28 days for a total of 6 courses. In order to avoid severe leukopenia and delays in the treatment administration, G-CSF 5 micrograms/kg/day sc Days 8-14 (or until postnadir recovery of neutrophil count > 10,000/mm3) and Days 22-28 was administered. All patients were evaluable for toxicity. No treatment-related deaths occurred. Myelotoxicity was the main side effect. It was grade 3-4 in a total of 13/29(45%) patients. One patient discontinued treatment after the first course due to HMM-related gastrointestinal toxicity. The actual delivered dose intensity was 89% of the planned dose. At the time of this analysis (April 1994) 26 patients are evaluable for response. Fifteen patients achieved a clinical complete remission and 9 a partial response for a 92% overall response rate. Fourteen patients accepted second-look laparotomy. We observed 11 pathological complete regressions (42%; 95% CI, 21-63). At a median follow-up of 16 months 3 deaths have occurred. Only 2 patients with NED at second-look laparotomy have relapsed. We stopped the accrual since the 95% confidence interval of the pCR-rate observed exceeded 20%. This new first-line regimen seems to be highly effective in patients with poor-prognosis advanced ovarian cancer, although the data are not yet sufficiently mature for a final analysis of time to progression and overall survival.

Administration, Oral↗
PubMed1997

Hexamethylmelamine as a single second-line agent in ovarian cancer: follow-up report and review of the literature.

From December 1982 to December 1986, 52 patients with recurrent ovarian cancer were treated with single-agent HMM. Chemotherapy was given for a period of 1 year unless progression of disease or toxicity was noted. Survival was determined from the time of diagnosis to the date of death or September 30, 1992. The regimen was well tolerated with only one case of severe gastrointestinal toxicity. Nine patients were found to be clinically free of disease following completion of HMM treatment; they had initially responded to cisplatin-based therapy (i.e., potentially cisplatin-sensitive) and subsequently recurred. Four were found to have gross disease at the time of reassessment laparotomy. Three of these 9 patients are alive 81-92 months since diagnosis, having maintained disease-free intervals of up to 6 years. The median survival for the 9 patients without evidence of disease at the end of therapy was 75 months versus 9 months for the nonresponders. No patient who had progressive disease on first-line cisplatin-based combination chemotherapy (i.e., primary cisplatin-resistant) responded to second-line single-agent oral hexamethylmelamine. With a follow-up close to 10 years, our data show that hexamethylmelamine, with reasonable toxicity, can provide an extended, disease-free interval to a selected group of patients.

Adult↗
PubMed2001

Phase II study of vinorelbine in the treatment of platinum-resistant ovarian carcinoma.

OBJECTIVE: The purpose of this phase II study was to evaluate on an intent-to-treat basis the activity and toxicity of single-agent vinorelbine (VRL) as second-line chemotherapy of patients with platinum-resistant ovarian cancer. Platinum-resistant disease was defined as disease refractory to or relapsing within 12 months after finishing platinum-containing chemotherapy. METHODS: VRL (30 mg/m(2)) was administered intravenously as a bolus injection days 1 and 8 every 21 days. Initially, four courses of VRL were given. Patients with responding or stable disease received four more courses of VRL to a maximum of eight courses. RESULTS: Twenty-eight of 33 eligible patients were considered evaluable for response. The overall response rate was 21% (7/33) (95% CI: 7--35). Median time to progression was 3.1 months and median survival was 10.1 months. Toxicity was generally mild. Leukopenia was the dose-limiting toxicity. CALGB grade III/IV infection was observed in 15/0% of patients. The most important nonhematologic toxicities were nausea and constipation. Grade III/IV nausea was observed in 6/0% and grade III/IV constipation in 3/3% of patients. Peripheral neurotoxicity was only a minor problem with no grade III/IV toxicity. No patients stopped treatment because of toxicity and no toxic death was reported. CONCLUSION: VRL was generally well tolerated, but the activity in platinum-resistant ovarian cancer was only modest, although fully comparable to other second-line treatments. Further studies are required to define the role of VRL in combination chemotherapy for ovarian cancer.

Adult↗
PubMed1989

Changes in serum copper and zinc during treatment with anticancer drugs interfering with pyridoxal phosphate.

Hexamethylmelamine, pentamethylmelamine and procarbazine are anticancer drugs known to interfere with pyridoxal phosphate. This paper presents results on copper and zinc serum levels during the treatment with each of these drugs used as single agents. Six NZW rabbits weighing 2.7-4.5 kg were used in these experiments. Hexamethylmelamine and procarbazine were administered by gastric gavage and pentamethylmelamine by intravenous route at the daily doses of 100 mg, 30 mg and 50 mg/kg of body weight respectively for up to four days. Blood samples were collected in metal free tubes at fasting state before and during the treatment. Student's paired t-test was used for statistical analysis. The pretreatment serum copper concentration significantly (p = 0.05) increased and conversely the serum zinc concentration significantly (p = 0.05) decreased during each drug treatment. Consequently the copper/zinc ration significantly increased from 0.32, 0.33 and 0.27 to 1.16, 0.63 and 1.13 for hexamethylmelamine, pentamethylmelamine and procarbazine respectively. These results indicate, that daily administration of three anticancer drugs interfering with pyridoxal phosphate causes changes in serum copper and zinc levels with inversed relationship between both changes.

Altretamine↗
PubMed1983

Human central nervous system pharmacology of pentamethylmelamine and its metabolites.

Pentamethylmelamine (PMM) 80 mg/m2 was administered I.V. to 8 patients during surgical resection of intracerebral tumors. PMM concentrations in tumors were generally much higher than concurrent plasma concentrations, ranging from undetectable (less than .01 micrograms/g) to as high as 4.47 micrograms/g and were much higher in malignant melanoma samples than in astrocytoma samples. PMM was barely detectable or undetectable in most samples of edematous brain tissue adjacent to intracerebral tumor and in temporalis muscle. The PMM metabolites tetramethylmelamine (TeMM), trimethylmelamine (TrMM), and dimethylmelamine (DMM) were each detectable in tumor samples from one or two patients. Monomethylmelamine (MMM) was present in tumor samples from all except one patient. MMM was noted in samples of edematous brain tissue adjacent to tumor from 4 of 8 patients. It was the only PMM metabolite found in brain. TrMM, DMM, and MMM but not PMM, and TeMM were found in tumor cyst fluid from a patient with an intracerebral malignant melanoma. Two patients receiving therapeutic doses of PMM had biopsies taken of subcutaneous malignant melanoma deposits. PMM was undetectable in samples from one patient but reached high concentrations in the other patient. In both patients, MMM was the major metabolite. There was no indication that PMM penetrated into extracerebral tumors more readily than into intracerebral tumors Cerebrospinal fluid (CSF) samples were obtained from one patient without neurological toxicity who received low doses of PMM and from 4 patients receiving high doses of PMM who had developed neurological toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Altretamine↗
PubMed1988

Pharmacokinetics and metabolism of hexamethylmelamine in mice bearing renal cell tumors.

The pharmacokinetics of hexamethylmelamine (HMM) and its main metabolites hydroxymethylpentamethylmelamine (HMPMM), pentamethylmelamine (PMM), and 2,2,4,6, tetramethylmelamine (2,2,4,6 TetrMM) were studied in renal cell (RC) tumor tissues and plasma of CDF1 mice that had received IP bolus injections of the maximally tolerated dose (200 mg/kg) of HMM. HMM, PMM, and 2,2,4,6 TetrMM concentrations determined in RC tissues were much higher than the plasma values, as indicated by the pharmacokinetic parameters (Cmax and AUC). On the other hand, very low levels of HMPMM, generally considered to be a potentially active antitumor compound, were detected in the target tissues, whereas this hydroxylated metabolite was stable and easily determined in plasma. High HMM concentrations in RC tissues could correlate with the high sensitivity of the tumor to this drug. However, the behavior of HMPMM remains unclear; related hypotheses are presented in this paper.

Altretamine↗
PubMed1986

Preclinical toxicology, pharmacokinetics and formulation of N2,N4,N6-trihydroxymethyl-N2,N4,N6-trimethylmelamine (trimelamol), a water-soluble cytotoxic s-triazine which does not require metabolic activation.

N2,N4,N6-Trihydroxymethyl-N2,N4,N6-trimethylmelamine (Trimelamol) is a water-soluble synthetic s-triazine which, unlike hexamethylmelamine (HMM) and pentamethylmelamine (PMM), does not require metabolic activation. The physico-chemical characteristics of Trimelamol were studied with the aim of overcoming the problems of chemical instability, low solubility and polymerisation which had hindered the development of the drug for clinical use. Trimelamol had similar activity to PMM against the murine PC6 plasmacytoma, but enhanced activity with respect to PMM against the Walker 256 carcinosarcoma in the rat, a species which metabolizes PMM less efficiently. Pharmacokinetic studies in mouse, rat and man did not show the major species differences characteristic of PMM. The drug exhibited similar toxicity to PMM against rodents, but had virtually no neurotoxicity. The potential advantages of Trimelamol over previously tested melamines are discussed.

Altretamine↗