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At least 19 recordsLinked to original sources
PubMed1992

Ten-year outcome of patients with advanced epithelial ovarian carcinoma treated with cisplatin-based multimodality therapy.

PURPOSE: At the end of the 1970s it was thought that advanced epithelial ovarian cancer (EOC) could be cured by multimodality treatment using surgery, cisplatin-based combination chemotherapy, and radiotherapy (RT). Such multimodality treatment was used as standard therapy at our institution. Our long-term results are reviewed. PATIENTS AND METHODS: One hundred ninety-five previously untreated patients with stage III or IV EOC were treated between April 1979 and December 1982. All patients were to have debulking surgery, when feasible, followed by the administration of doxorubicin and cisplatin at 50 mg/m2 every 3 weeks until a total dose of doxorubicin of 450 mg/m2 had been reached. RT was used in addition in patients with disease remaining after the chemotherapy. Maintenance chemotherapy with oral cyclophosphamide and hexamethylmelamine (altretamine) was administered to patients who did not have a documented histologic complete remission. RESULTS: The 10-year overall and failure-free survivals were 4% and 8%, respectively. The median overall survival was 2 years. The achievement of a histologic complete response (n = 32) did not equate to cure because 20 (63%) of the patients eventually relapsed. Multivariate analysis identified residual disease of greater or less than 2 cm as the only independent prognostic factor. CONCLUSIONS: Our multimodality treatment program was noncurative for the majority of the patients. Innovative therapies are needed before we can hope to cure such disease.

Adult↗
PubMed1992

Hypersensitivity reactions.

All cancer chemotherapeutic agents, except altretamine, the nitrosoureas, and dactinomycin, have produced at least an isolated instance of a HSR. Certain drugs, such as L-asparaginase and mitomycin (administered intravesically), cause HSRs of significant degree in approximately 10% of patients. All four types of HSRs are represented in the reactions produced by antitumor drugs, although Type I is the most common. Some of the Type I reactions are IgE-mediated, and others are probably mediated by nonspecific release of vasoactive substances from targets such as mast cells. It is possible to continue therapy with some drugs, despite a prior HSR, if the prophylactic measures outlined in Table 2 are taken. An example of this is provided by taxol in which the lengthening of the infusion time and the administration of preventive medication allowed some patients to continue taxol therapy. The mechanisms of the HSRs have been carefully assessed in only a minority of patients who sustained such toxicity. Such evaluation would increase our understanding of this form of drug toxicity and perhaps lead to means of effectively reducing the risk and severity.

Antibiotics, Antineoplastic↗
PubMed1979

Ovarian cancer. Effective treatment after alkylating-agent failure.

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.

Adenocarcinoma↗
PubMed1976

Hexamethylmelamine. An evaluation of its role in the therapy of cancer.

Hexamethylmelamine (HMM) has been undergoing clinical trials for about a decade under the sponsorship of the National Cancer Institute. It has been tested in Phase II and III cooperative group studies and has a wide spectrum of activity in solid tumors. Its activity is most marked in ovarian cancer, lymphomas, and carcinoma of the cervix; the drug is also active in bronchogenic carcinoma and carcinoma of the breast. Considerable clinical evidence suggests a lack of cross-resistance between HMM and alkylating agents. the currently popular dose is 300 mg/m2/day p.o. for indefinite periods if tolerated. The dose-limiting toxicity is neurologic, but gastrointestinal side effects and a moderate degree of myelosuppression are also observed. Combination chemotherapy using HMM is underway in ovarian and lung cancer. Futher exploration of its activity as a single agent in tumors such as those of the bladder, prostate, and uterus, and in combination chemotherapy in lymphomas, and mammary, cervical, and pulmonary tumors is warranted.

Altretamine↗
PubMed1977

Advances in the staging and treatment of ovarian cancer.

The age adjusted death rate for ovarian cancer has remained unchanged for the past 20 years. Recent data obtained by staging ovarian cancer patients with lymphangiography and peritoneoscopy demonstrated that many patients with apparently localized disease actually have occult dissemination within the abdomen. These new staging techniques plus the determination of the histologic grade of anaplasia may permit a more precise determination of a patient's prognosis and therefore better design of therapeutic stategy. Radiotherapeutic techniques are being adapted to attempt to treat some areas of occult disease. Numerous single chemotherapeutic agents are capable of producing objective tumor responses. Preliminary data suggest that combination chemotherapy can increase the objective response rate above that seen with single agents. Longer follow-up is necessary to determine whether combination chemotherapy can prolong survival.

Alkylating Agents↗
PubMed1977

Ovarian cancer: use of multiple modality programs involving surgery, radiation therapy and chemotherapy.

Appreciating the past reports of effectiveness for various therapeutic modalities in ovarian cancer, the Gynecologic Oncology Group activated eight protocols. Three involved epithelial lesions with randomized multimodality trials alone or in combination. The other protocols were devoted to registration of rare tumor case reports. Conclusions are still difficult to reach due to inconsistencies in pathologic diagnoses and deficiencies in radiation therapy, chemotherapy and surgery inherent in the initial phases of group development by diverse specialist in oncology. Adjuvant therapy for early cancer seems to have no advantage. Single drug, melphalan therapy may be as effective as multi-drug, irradiation or combined drug-irradiation therapy and less toxic. For the rare tumors, preliminary results suggest therapeutic advantage for at least one triple drug program in malignant teratoma. With the lessons of the past, it is anticipated that new studies briefly described herewith may be more effectively applied.

Altretamine↗
PubMed1978

Hexamethylmelamine in alkylating agent-resistant ovarian carcinoma.

Twenty-one patients with advanced ovarian cancer proven resistant to standard alkylating chemotherapy were evaluated in a prospective study of Hexamethylmelamine. All but three patients received 8 mg/kg daily with dose modifications appropriate to the degree of toxicity; the latter three patients were treated on an intermittent 14 day course of 8 mg/kg daily. Six patients (28%) experienced an objective response with a median duration of 2.5 months (range 1--5 months). The toxic effects requiring dose modification were gastrointestinal in 57%, hematologic in 62%, and neurologic in 28.5%. An average of 60.5% of the total projected dose was tolerated for a median of 44 days (range 7--113). Twelve patients (57%) experienced severe toxicity requiring discontinuation of therapy. It is apparent from this study that Hexamethylmelamine is an active agent in ovarian cancer and is not invariably cross-resistant to conventional alkylating agent therapy. These two characteristics make it an attractive agent for use in combination. Its toxicity in previously treated patients in the schedules used here, however, is substantial.

Adenocarcinoma↗
PubMedDate not supplied

Advances in the chemotherapy of gynecologic malignancies.

Chemotherapy is playing an ever increasing role in the treatment of patients with the common gynecologic malignancies, including ovarian, cervical cancer, and endometrial cancer. Chemotherapy has its most defined role in the treatment of patients with ovarian cancer where virtually all patients will receive cytotoxic chemotherapy. There are four major areas of research in chemotherapy in gynecologic malignancies. In retrospective studies it has been demonstrated that dose intensity is an important factor in maximizing response rates. Clinical studies are now prospectively evaluating the importance of dose intensity, particularly with the new platinum analogue carboplatin. In addition, it has been demonstrated in endometrial cancer and cervical cancer that patients with poor prognostic features such as high grade tumours and large volume disease have a low probability of cure by standard modalities such as surgery and radiation. In this group of patients combined modality approaches are being evaluated. In addition, regional therapy, either in the form of intra-arterial therapy for patients with cervical cancer or intraperitoneal therapy for patients with ovarian cancer, is being investigated. The primary factor limiting the effectiveness of chemotherapy in gynecologic malignancies is the development of drug resistance. It has recently been demonstrated that several drugs such as taxol, ifosfamide, and hexamethylmelamine have activity in patients who have had previous treatment with platinum-based compounds. In addition, the mechanism associated with the development of drug resistance in ovarian cancer have recently been identified. Clinical trials have been initiated with compounds such as buthionine sulfoximine in an attempt to specifically reverse resistance associated with alkylating agents and platinum compounds.

Alkaloids↗
PubMed1975

Complexation in formulation of parenteral solutions: solubilization of the cytotoxic agent hexamethylmelamine by complexation with gentisic acid species.

The apparent solubility of hexamethylmelamine in aqueous solutions suitable for intravenous use was increased by complexation with gentisic acid. Studies were carried out in the pH 0-8 range. Unprotonated hexamethylmelamine did not form complexes with the gentisate ion, while the hexamethylmelammonium ion appeared to form several different complexes with both the gentidate ion and gentisic acid. Two different solid complexes were isolated and characterized. The solubility increases observed at pH 3.5-5.0 are described by mathematical relationships involving the stability constants of some postulated complex species. From these results, sultable formulations for use as parenteral solutions are proposed. The increase in the apparent aqueous solubility of hexamethylmelamine in such formulations may range from five- to 90-fold, depending upon the pH and total gentisateion concentrations.

Altretamine↗
PubMed1976

Studies and characterization of a murine neuroblastoma model.

Clinical chemotherapy in the treatment of neuroblastoma is undergoing further evaluation. Chemotherapeutic agents, cyclophosphamide, vincristine, and hexamethylmelamine, were investigated in a murine neuroblastoma model that, in part, histologically and morphologically resembles the human tumor. The tumor was inoculated subcutaneously (SC), intramuscularly (IM), intraperitoneally (IP), intrarenally (IR). Growth of tumor was observed at all sites, as well as the appearance of metastases. Maximal survival of 32 +/- 1 days was seen (SC) and the minimum was 15 +/- 1 days (IR) (p less than 0.05). Corresponding survival rate for IM was 26 +/- 1 days and IP 21 +/- 1 days. For this reason SC was selected for drug testing. Cyclophosphamide 100 mg/kg/week showed the most favorable results, as determined by autopsy status with fewer tumors and a greater tumor weight decrease over time. This agent also showed a significantly longer survival in comparison to all other drugs (p less than 0.0001). The results with vincristine and hexamethylmelamine in the dose ranges employed differed little from the placebo, except for the finding of a slight decrease in body weight at autopsy.

Altretamine↗
PubMed1978

A comprehensive protocol for management of cancer of the bilharzial bladder.

A randomized clinical trial for the management of bilharzial bladder cancer is presented. A multidisciplinary approach is adopted. The objective of the study is to evaluate the role of adjuvant radiotherapy in improving the results of surgery in deeply infiltrating tumours, and to screen a number of chemotherapeutic agents for their effectiveness in bladder cancer. A large number of cases will be admitted into the study and the results will hopefully help to achieve better results in the management of this disease.

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↗
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↗