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At least 199 records · Page 11Linked to original sources
PubMed1982

Multimodality treatment of patients with advanced ovarian carcinoma.

A multimodality treatment program has been applied to ovarian carcinoma at the Johns Hopkins Hospital since August 1975. Forty-nine patients were subdivided into 23 patients with maximally resected Stage III micrometastatic, and 26 patients with significant retained disease, 20 with Stage III macrometastatic and 6 with Stage IV. After initial pilot studies, those patients with minimally retained disease entered a randomized prospective study. Antiovarian antiserum was used in one arm of the study; in both study arms colloidal P-32, delayed split whole abdominal irradiation, and maintenance melphalan were used. For the 23 patients with micrometastatic disease the cumulative survival and survival without evidence of disease at four years is 78 and 34% respectively. Twenty-six patients with macrometastatic disease were treated with or without intraperitoneal antiserum and multiagent chemotherapy; their cumulative one year survival is 50%. The lack of significant toxicity of intraperitoneal antiovarian antiserum and the results of multimodality therapy indicate the feasibility of this therapeutic approach to further improve ovarian cancer therapy.

Adenocarcinoma, Mucinous↗
PubMed1987

The treatment of advanced stage ovarian carcinoma with a combination of chemotherapy, radiotherapy, and radiosensitizer: report of a pilot study from the National Cancer Institute.

Twenty-eight patients with Stage III or IV ovarian carcinoma were treated with combined chemotherapy-radiotherapy employing a unique protocol. Four cycles of cyclophosphamide and hexamethylmelamine alternated with four cycles of concurrent cisplatin, whole abdominal radiotherapy, and intraperitoneal misonidazole. The entire treatment program lasted six months. Clinical complete responses were seen in 50% of the patients with an overall response rate of 61%. Pathologic complete response (PCR) confirmed at second look surgery occurred in 18% of the group (5 patients). Median survival of the entire group was 15.2 months with all PCR's alive NED. This outcome was no different than our previous experience with combination chemotherapy alone. Toxicities seen included leukopenia, thrombocytopenia, nausea, vomiting, and weight loss. However, these side effects were manageable. Two non-tumor deaths occurred. This study demonstrates the feasibility of combining drug and radiation therapy concurrently in the treatment of ovarian cancer; further research is needed to explore different sequencing and dose levels that could improve the outcome.

Adult↗
PubMed1995

The hypermutability conferred by the mus308 mutation of Drosophila is not specific for cross-linking agents.

The hypersensitivity of the mus308 mutant of D. melanogaster to cross-linking agents has been suggested to be the consequence of a possible defect of this mutant in DNA cross-link repair. Moreover, the mus308 mutation has been proposed as an animal model for the study of Fanconi's anemia. In order to obtain more information about the function controlled by this locus, we have measured the mutability of the mus308 mutant to several mutagens with different modes of action using the sex-linked recessive lethal test. We show that this mutation confers hypermutability not only to the cross-linking agents tested, hexamethylphosphoramide and hexamethylmelamine, but to the point mutagen N-ethyl-N-nitrosourea as well, whereas the response to methyl methanesulfonate was normal. The results suggest that the mus308 locus is not defective in a repair pathway specific for cross-links but is rather involved in a step of a more general post-replication repair process responsible for the removal of non-excised adducts.

Alkylating Agents↗
PubMed1995

A phase II study of carboplatin and hexamethylmelamine as induction chemotherapy in advanced epithelial ovarian carcinoma.

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. 3 patients were not evaluable for response. Clinical response was seen in 17 patients (71%), with six (25%) complete and 11 (46%) partial responses. The median progression-free survival was 15.6 months and the median cancer-related survival was 21.3 months. 4 patients (15%) experienced grade 3 mental depression; none had peripheral neuropathy above grade 1. The haematological toxicity was moderate, none had grade 4 leucopenia, but 4 (15%) had grade 4 thrombocytopenia. Carboplatin plus HMM had few side-effects and a high response rate with a survival comparable to other platinum-based combinations.

Adult↗
PubMed1985

Intraperitoneal chemotherapy for advanced ovarian cancer.

Treatment of patients with advanced ovarian cancer who have failure of first-line chemotherapy is rarely effective. Preliminary pharmacokinetic and phase II clinical studies established the feasibility of delivering relatively high concentrations of cisplatin intraperitoneally via a semipermanent catheter, while using intravenous sodium thiosulfate as a neutralizing agent to decrease the nephrotoxicity of cisplatin. Sixty patients with advanced ovarian cancer, all of whom had failure of first-line chemotherapy (including cisplatin in 56 of 60), were treated with high-dose intraperitoneal cisplatin in combination with doxorubicin and/or cytarabine. Of the 46 patients evaluable for response, 19 (42%) showed an objective response, most often (12/19) disappearance of malignant ascites. No serious drug-associated morbidity was observed aside from three cases of intestinal obstruction which may have been due in part to drug-induced adhesions. It is felt that prospective studies to compare the efficacy of intraperitoneal chemotherapy with other forms of "salvage" therapy, as well as its use as initial chemotherapy for advanced ovarian cancer, need to be done.

Altretamine↗
PubMed1988

Hexamethylmelamine as first-line chemotherapy in the treatment of advanced or recurrent carcinoma of the endometrium: a phase II trial of the Gynecologic Oncology Group.

Thirty-eight patients with advanced or recurrent carcinoma of the endometrium who had received no prior chemotherapy were placed on study by the Gynecologic Oncology Group. One was deemed histologically ineligible. Three patients had insufficient trials to evaluate response. Of the remaining 34 who received hexamethylmelamine 280 mg/m2 orally daily on Days 1 through 14 of each 4-week course, there were only three objective responses, two complete and one partial. Although toxicity was tolerable, hexamethylmelamine has minimal activity in advanced or recurrent endometrial carcinoma at the dose and schedule tested.

Adult↗
PubMed1984

Randomised trial comparing two combination chemotherapy regimens (Hexa-CAF vs CHAP-5) in advanced ovarian carcinoma.

186 patients with advanced epithelial ovarian carcinoma were treated with either a combination of hexamethylmelamine, cyclophosphamide, methotrexate, and 5-fluorouracil (Hexa-CAF) or cyclophosphamide and hexamethylmelamine alternating with doxorubicin and a 5-day course of cisplatin (CHAP-5). Treatment with CHAP-5 resulted in more complete remissions as determined by laparatomy or peritoneoscopy (p = 0.004), better overall response (p = 0.0001), and longer overall survival and progression-free survival (p less than 0.002). Therapy, histological grade, and Karnofsky index were reliable predictors of overall response, whereas therapy, FIGO-stage, and size of residual tumour before chemotherapy were independent predictors for complete remission and for prolonged survival. Peripheral neurotoxicity was a major problem in patients assigned to the CHAP-5-group and was likely to be due to the simultaneous administration of hexamethylmelamine and cisplatin. The CHAP-5 regimen is one of the most effective regimens for the initial treatment of ovarian cancer.

Altretamine↗
PubMed1984

Current status of systemic chemotherapy in the treatment of advanced ovarian cancer with emphasis on CHAP-5.

In patients with advanced ovarian cancer, initial treatment with combination chemotherapy, including cyclophosphamide and cis-platinum diamminedichloride (cis-platinum), produces response and progression-free survival results which are superior to those achieved with alkylating single-agent chemotherapy. Unfortunately most schedules have not resulted in a statistically significant improvement of overall survival. So far one of the most effective combination regimens is the four-drug regimen CHAP-5 that consists of cyclophosphamide, hexamethylmelamine, adriamycin, and cis-platinum. This regimen is the first schedule to result in significant improved survival times compared with a second combination schedule, i.e. Hexa-CAF, which is at least as good as alkylating therapy alone. The CHAP-5 regimen was rather toxic but it was manageable and easy to apply in daily practice. Further improvement of the treatment results in advanced ovarian carcinoma will be difficult because no effective new drugs are available. In future clinical research it must be tried to decrease the toxicity and morbidity of the current schedules without reducing efficacy and survival.

Altretamine↗
PubMed1985

Combined modality treatment for stage III ovarian carcinoma.

Thirty-eight Stage III ovarian carcinoma patients were treated with a combined modality protocol consisting of sequential initial surgery with a maximal tumor reduction, CHAD combination chemotherapy, second look reductive surgery and whole abdominal irradiation. Sixteen patients (42%) had minimal residual tumors (less than 2 cm) after initial surgery (Stage IIIA) and 22 (58%) had large residual tumors (greater than 2 cm) (Stage IIIB). The patients received 3-14 courses of CHAD combination chemotherapy, with a response rate (CR + PR) in the evaluable (Stage IIIB) patients of 91%. Twenty-eight patients had a second attempt of cytoreductive operation (10 Stage IIIA patients and 18 Stage IIIB patients). In 10 patients no residual tumor was found. In another 12 patients residual tumor (less than 2 cm) was found and completely resected, whereas in six patients a complete resection of large residual tumors (greater than 2 cm) was not possible. Twenty-one of the patients also completed a course of whole abdominal radiotherapy. Radiation was well-tolerated with the usual expected amounts of nausea, vomiting, diarrhea and transient leukopenia and thrombocytopenia. 11/21 (52%) of the patients relapsed within the first 18 months after completion of radiotherapy. The actuarial relapse-free survival at 36 months from completions of radiotherapy was 44%. The actuarial survival for the whole group from diagnosis was 43% at 3 years (70% for Stage IIIA and 41% for Stage IIIB). The data indicated that this combined modality protocol is both feasible and well-tolerated but its curative potential for patients with advanced ovarian carcinoma is as yet unknown.

Adenocarcinoma↗
PubMed1995

Oral therapy for small cell lung cancer.

After a remarkable improvement of the very poor prognosis of small cell lung cancer with very simple therapy such as iv and oral cyclophosphamide the role of oral therapy has become minimal. However, since more than a decade results of combination chemotherapy are at a plateau and it is necessary to reconsider the role of simple therapy in patients without the prospect of cure. Oral therapy might be worthwhile because it is probably less effecting the quality of life of the patient and makes it unnecessary to visit the hospital frequently. All drugs available for oral use with known activity against small cell lung cancer are reviewed. The best example of the success of oral therapy is etoposide, other candidates that need to be tested in a modern way are oral cyclophosphamide and hexamethylmelamine. New concepts of prolonged chemotherapy and dose-intensity are easier evaluated by using oral drugs. The discovery of the activity of prolonged oral etoposide is an excellent example how to test a new concept in a very simple way.

Administration, Oral↗