Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1140680 (ovarian cancer)
28,141 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A clinical trial of the oral form of VP 16-213 (NSC-141540), a semisynthetic podophyllotoxin, was undertaken. In 20 patients, treatment was started at 200 mg/day p.o. for 5 days; courses were repeated after a rest period of 16 days. Five patients were treated at the same dose, repeated with only 9-day rest periods. Subsequently, 65 patients were given 300-400 mg/day for 5 days, with rest periods of 9 days between courses. The side effects encountered included anorexia, nausea and vomiting, stomatitis, diarrhea, leukopenia, thrombocytopenia, alopecia, and pruritus. Substernal discomfort with or without palpitations was reported by 18 patients; no explanation for this symptom could be found. No complete remissions (CR) were observed. Parital remissions (PR) and improvement (IMP) were seen as follows: small cell carcinoma, lung (10 patients)--2 PR, 3 IMP; adenocarcinoma, lung (4 patients)--1 PR; alveolar cell carcinoma, lung (1 patient)--1 IMP; mesothelioma (4 patients)--1 IMP; ovarian cancer (12 patients)--3 PR, 3 IMP; breast cancer (20 patients)--4 IMP; colon cancer (8 patients)--2 IMP; bladder cancer (4 patients)--2 IMP; histiocytic lymphoma (7 patients)--2 PR, 3 IMP; chronic myeloid leukemia (1 patient)--1 IMP.
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PMID:A clinical trial of the oral form of 4'-demethyl-epipodophyllotoxin-beta-D ethylidene glucoside (NSC 141540) VP 16-213. 16 75

cis-Dichlorodiammineplatinum(II) (cis-platinum) was used in the treatment of 25 patients with advanced ovarian adenocarcinoma refractory to alkylating agents. Seven of 24 evaluable patients (29%) responded to cis-platinum (one complete response and six partial responses). Life-table analysis of survival indicates that patients responding to therapy survive longer than those who fail to respond (9 months versus 3.2 months) (P = 0.014). In previously treated patients given 70 mg/m2 iv with forced diuresis, there was substantial nausea and vomiting (100%), hematologic toxicity (67%), and renal toxicity (34%). A review of the single-agent activity of cis-platinum in other ovarian cancer studies indicates an overall response rate of 25% (40 of 161 patients). At least nine combination chemotherapy studies utilizing cis-platinum are in progress, and preliminary information from several of these is encouraging and suggests that cis-platinum-containing combinations may have a major role in the treatment of ovarian adenocarcinoma.
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PMID:cis-Dichlorodiammineplatinum(II) for the treatment of advanced ovarian cancer. 38 24

Thirty women with histologically proven advanced ovarian or breast cancer were treated with cytembena. Of nine patients with ovarian cancer and 21 with breast cancer none had worthwhile objective remissions. Cytembena was given at a dose of 250 mg/m2/day for a course of 5 days repeated at weekly intervals. Improvement, particularly relief of pain from skeletal metastases, was observed in 16 of the patients; an additional seven patients had stable disease while treated with cytembena. Cytembena has no hemopoietic toxicity, but nausea and vomiting and an "autonomic storm" phenomenon are dose-limiting factors. Further studies incorporating this drug in combination regimens seem warranted.
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PMID:Phase II trial of cytembena in patients with advanced ovarian and breast cancer. 103 86

Topoisomerase I represents a unique new target that can be exploited for development of new antineoplastic agents. There are now two new topoisomerase I inhibitors that are in early clinical trials that have generated a tremendous amount of interest. Topotecan (SKF 104864-A) is a topoisomerase I inhibitor that has been explored in phase I trials using a variety of dosages and schedules. The dose-limiting toxicity of the agent is neutropenia. Other toxicities include alopecia, very mild nausea and vomiting, anemia, and occasional fever. Responses have already been noted in patients with advanced, refractory ovarian cancer and non--small-cell lung cancer. The drug is currently undergoing intense phase II testing. Irinotecan (CPT-11) is also a topoisomerase I inhibitor, which has already undergone extensive phase I and early phase II clinical testing in both Japan and the United States. Dose-limiting toxicities of the agent have included neutropenia and diarrhea. Responses have been noted in patients with refractory colorectal cancer, non--small-cell lung cancer, lymphoma, ovarian cancer, head and neck cancer, pancreatic cancer, and breast cancer. There is no doubt both of these agents will be important additions to our chemotherapy armamentarium.
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PMID:Clinical trials with the topoisomerase I inhibitors. 133 79

A pharmacological, behavioural and nursing intervention strategy was evaluated for prevention of cisplatin (50 mg m-2) induced emesis in ovarian cancer patients. 46 patients received metoclopramide 2.5 mg kg-1 i.v., b.i.d., dexamethasone 20 mg i.v., lorazepam and biperiden as well as training in relaxation, nutritional advice and continuity in nursing care. Controls (n = 34) received standard treatment (metoclopramide 10-20 mg i.v. or dixyracin 20 mg i.v.). The intensity and duration of nausea and vomiting were significantly lower and measures of quality of life higher for patients on the experimental ward during the three cycles that were studied. No significant changes in emesis were observed between the cycles. There was no correlation between emesis and any of the parameters of quality of life measured. The reliability and validity of nausea ratings are discussed and we suggest that an underreporting of nausea and vomiting might be common.
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PMID:Control of cisplatin induced emesis--a multidisciplinary intervention strategy. 134 20

A total of 61 patients with recurrent or persistent clinically measurable platin-resistant epithelial ovarian carcinoma were treated with 260 mg/m2 oral hexamethylmelamine daily for 14 days, repeated at 4-week intervals. Platin resistance was defined as progression or stable disease during cis- or carboplatin treatment (used alone or in combination with other drugs), or relapse within 6 months after the end of that therapy. Fifty patients were evaluable for response and 57 for toxicity. The objective response rate was 14% (3 complete and 4 partial responses). The response rate was higher in patients with relapse within 6 months than in patients with progression or stable disease on platin-based therapy. This observation underscores the importance of defining response and time to progression after first-line chemotherapy. The median duration of response was 8 months and the median survival in responding patients was 9+ months versus 5 months for patients with progression on hexamethylmelamine. Nausea and vomiting requiring antiemetic treatment occurred in 8 (14%) patients and reversible peripheral neuropathy in 3 patients. Two patients developed agitation, insomnia, and depression during hexamethylmelamine therapy. In conclusion, the 14% objective response rate and the occurrence of complete responses with oral hexamethylmelamine treatment in a group of ovarian cancer patients with true platin resistance are noteworthy.
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PMID:Hexamethylmelamine as second-line therapy in platin-resistant ovarian cancer. 147 37

A Phase II trial of an intravenous preparation of Hexamethylmelamine was performed in ovarian cancer. Patients who had received prior Platinum based chemotherapy and had measurable disease were eligible. Among 15 evaluable patients, there were no objective responses. Two patients did show clinical and laboratory evidence of improvement. Toxicity was predominantly nausea and vomiting with minimal other toxicity. This intravenous form of Hexamethylmelamine has not shown meaningful activity in ovarian cancer patients who have failed prior platinum treatment.
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PMID:Phase II trial of intravenous hexamethylmelamine in patients with advanced ovarian cancer. 148 3

Fourteen patients with advanced ovarian cancer received a 72 hour infusion of a new DNA intercalator, crisnatol mesylate, administered intravenously. There was no evidence of antitumor efficacy. A syndrome of nausea and vomiting associated with vertigo, dizziness and ataxia was observed in nearly all patients. Two of the patients developed severe CNS toxicity manifested in one by a grand-mal seizure and in the other by peripheral neuropathy. Further explorations into the potential efficacy of crisnatol mesylate administered intraperitoneally are underway.
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PMID:A phase II study of crisnatol mesylate in patients with ovarian carcinoma. 150 Feb 64

Carboplatin is a cisplatin analog that causes less nephrotoxicity, neurotoxicity and nausea and vomiting than its parent compound. In prospective clinical trials, carboplatin has been shown to be as active, but less toxic, than cisplatin in previously untreated patients with advanced ovarian cancer. However, carboplatin has not led to improved survival, compared with cisplatin. Studies are in progress to reduce the dose-limiting myelo-suppression of carboplatin in order to increase the dose intensity. In addition, new carboplatin combinations are also to be evaluated in clinical trials. The molecular basis for resistance to platinum compounds is also undergoing study and future clinical trials will evaluate modulations of resistance.
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PMID:Role of carboplatin in ovarian cancer. Current results and thoughts for the future. 150 94

The propensity of ovarian cancer to recur--even after initial chemotherapeutic responses--is a problem that has been given a great deal of attention during the past year in the literature dealing with the treatment of ovarian cancer. Most of the articles address techniques to improve the percent of initial and secondary treatment responses. Several studies have described cytoreductive techniques to decrease the remaining tumor size for improved chemotherapeutic response. Cross-resistance between platinum analogues has been reconfirmed. However, improved secondary responses were seen when repeat treatment with platinum agents were preceded by a longer interval from initial platinum agent therapy. Radiation therapy has been shown to offer little solution to recurrent disease except possibly in a select group of patients with microscopic disease at second-look laparotomy. Reports on the use of carboplatin continue to demonstrate good initial responses, with decreased toxicity compared with cisplatin. Granisetron has been shown to significantly decrease the nausea and vomiting caused by emetogenic chemotherapy like cisplatin.
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PMID:Therapeutic advances in ovarian cancer. 154 23


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