Gene/Protein Disease Symptom Drug Enzyme Compound
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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

We have conducted a phase I clinical trial of maytansine, a plant alkaloid with potent tubulin-binding activity. For evaluation of toxicity, the schedule of drug administration consisted of a single iv infusion given every 3 weeks. Dose-limiting toxicity was observed at 2 mg/m2, and was manifested as profound weakness, diarrhea, nausea, and vomiting. Symptoms persisted for 3--14 days after drug administration. No consistent myelosuppression occurred at any dose level. Responses were observed in two patients (one each with non-Hodgkin's lymphoma and ovarian cancer) who were treated on the every-3-week schedule, as well as in two patients with acute lymphocytic leukemia treated with single weekly doses. Three of the four responding patients had received extensive prior treatment with vincristine, and two were clearly resistant to vincristine.
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PMID:Initial clinical trials of maytansine, an antitumor plant alkaloid. 34 11

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 phase II study of 5'-DFUR was conducted in uterine cervical cancer and ovarian cancer by the cooperative study group consisting of 26 institutions. Forty-four cases with uterine cervical cancer and 40 cases with ovarian cancer were enrolled. A daily dose of 800-1,200 mg was administered orally for more than 8 weeks. In 34 evaluable cases with uterine cervical cancer, the overall efficacy rate was 20.6%: CR was shown in 2 cases, PR in 5 cases, MR in 2 cases, NC in 17 cases and PD in 8 cases. Histologically, the response rate was 27.3% in large cell non-keratinizing type, 20.0% in small cell non-keratinizing type and 15.4% in keratinizing type of squamous cell carcinoma. The overall response rate was 20.7% in squamous cell carcinoma, while 25.0% in adenocarcinoma. In 31 evaluable cases with ovarian cancer, the overall efficacy rate was 16.1%: PR was shown in 5 cases, MR in 3 cases, NC in 11 cases and PD in 12 cases. Histologically, the response rate was 16.7% in serous cystadenocarcinoma, 25.0% in endometrioid adenocarcinoma and 33.3% in undifferentiated carcinoma. No responses were observed in cases with mucinous cystadenocarcinoma, clear cell adenocarcinoma, mature cystic teratoma with malignant transformation and mesodermal mixed tumor. Some adverse effects were observed in 43.2% (32 out of 74 cases evaluated for adverse effects), but those of grade 4 were not observed. Most of them were gastro-intestinal disturbances such as diarrhea and anorexia. Diarrhea of grade 3 was observed in 12.2% and anorexia of grade 3 in 5.4%. Severe myelosuppression or hepatic toxicity was not observed. These results suggested that 5'-DFUR is a useful anticancer drug against uterine cervical cancer and ovarian cancer.
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PMID:[Phase II study of 5'-DFUR in uterine cervical cancer and ovarian cancer]. 166 Jul

105 patients with advanced ovarian cancer previously treated with cisplatin or carboplatin were entered into a study of iproplatin as second-line therapy. Patients were either clinically resistant to cisplatin or carboplatin, or had relapsed after complete response to these agents. Patients were treated intravenously at an initial dosage of 270 mg/m2 with dosage adjustments to 340, 200 or 135 based on observed toxicity. Of 101 eligible patients, 7 responses (3 complete, 4 partial; 12%) were observed in 60 patients resistant to cisplatin. 2 partial responses (11%) occurred in 18 patients resistant to carboplatin. 2 complete and 3 partial responses were observed in 19 patients (26%) previously treated with but not resistant to cisplatin. Response durations were 2-20 months. Toxicities of iproplatin included thrombocytopenia in 93% of patients, leukopenia in 76% of patients, anaemia in 68% of patients, and diarrhoea in 40% of patients. Thus iproplatin shares cross-resistance with cisplatin and carboplatin in the treatment of ovarian cancer and is not recommended as an effective second-line agent for platinum-resistant ovarian cancer.
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PMID:Second-line treatment of advanced measurable ovarian cancer with iproplatin: a Southwest Oncology Group study. 182 75

A late phase II study of CPT-11, a new derivative of camptothecin, in uterine cervical cancer and ovarian cancer was carried out by a cooperative study group at 26 institutions. Out of 144 patients enrolled, total cases were 110, involving 55 uterine cervical cancers and 55 ovarian cancers. In uterine cervical cancer, 5 cases of complete response (CR) and 8 cases of partial response (PR) were observed, with a response rate of 23.6% and a CR rate of 9.1%. In ovarian cancer, 13 cases of PR were observed, response rate was 23.6%. Both in uterine cervical cancer and ovarian cancer, the 95% confidence interval of response rate was 12.4-34.8%. In cases having undergone previous chemotherapy including platinum, derivatives, the response rate in ovarian cancer was 23.1% (12/52). In cases of uterine cervical cancer having previous radiotherapy, the response rate was 26.8% (11/41). In ovarian cancer of various histological types, a response was observed for not only serous cystadenocarcinoma but also mucinous cystadenocarcinoma, etc. A response was observed in distant metastatic lesions such as lung metastasis as well as primary lesion in uterine cervical cancer and ovarian cancer. Major adverse reactions were leukopenia, nausea and vomiting, diarrhea and anorexia, and these incidences (grade 2 or more) were 87.3, 60.3, 44.0 and 67.2%, respectively. Since some patients experienced severe adverse reactions, caution should be taken in treatment with CPT-11. Besides these reactions, alopecia was observed (33.1%), but severe adverse reactions such as nephropathy were not found. No significant difference in the efficacy and adverse reactions were observed between administration methods; A, 100 mg/m2 once weekly and B, 150 mg/m2 once every 2 weeks. Both were thought to be clinically useful. These results suggest that CPT-11 is clinically effective against uterine cervical cancer and ovarian cancer.
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PMID:[A late phase II study of CPT-11 on uterine cervical cancer and ovarian cancer. Research Groups of CPT-11 in Gynecologic Cancers]. 187 24

An early Phase II study of CTP-11, a new derivative of Camptothecin, in gynecologic cancers was carried out by a cooperative study group of 9 institutions. Forty-six patients were enrolled, and there were 14 cases of ovarian cancers, 7 of cervical cancer, 6 of uterine body cancers and 1 of endometrial stromal sarcoma which satisfied study criteria. The response rate in ovarian cancers was 21.4%, and in cervical cancers 42.9%, among an overall rate of 21.4%. Three out of 6 patients with objective response had undergone previous chemotherapies including cisplatin, suggesting that CPT-11 was effective for patients with no response or refractory to these therapies. Leukopenia was a major adverse reaction with an incidence of 60.0% (grade 2 or more). Gastrointestinal symptoms such as nausea vomiting, anorexia and diarrhea were frequently observed (grade 2 or more; 13.3-43.3%). These were generally tolerable except in a few cases. Besides these reactions, alopecia was also observed (33.3%), but severe adverse reactions such as nephropathy were not. These results suggested that CPT-11 was effective against ovarian cancer and cervical cancer. The recommended dose regimen for a late phase II study is considered to be 100 mg/m2 once weekly and 150 mg/m2 once every 2 weeks.
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PMID:[An early phase II study of CPT-11 in gynecologic cancers. Research Group of CPT-11 in Gynecologic Cancers]. 201

Ten patients with ovarian cancer refractory to conventional therapy were treated with intraperitoneal (i.p.) recombinant interleukin-2 (rIL-2) and lymphokine-activated killer cells (LAK). The 28-day protocol consisted of 6 priming i.p. rIL-2 infusions on days 0, 4, 6, 8, 10, and 12. Leukapheresis was performed for mononuclear cell collection on days 15, 16, 17, and 18 and lymphokine-activated killer cells were given i.p. with the rIL-2 on days 19 and 21. Three additional i.p. rIL-2 infusions were given on days 23, 25, and 27. Three dose levels of rIL-2 were tested: 5 X 10(5), 2 X 10(6), and 8 X 10(6) units/m2 body surface area. The dose-limiting toxicity was abdominal pain secondary to ascites accumulation with significant weight gain. Other toxic effects included decreased performance status, fever, nausea and vomiting, diarrhea, and anemia. Peripheral lymphocytosis and eosinophilia were seen at all dose levels. The maximum tolerated dose is 8 X 10(6) units/m2/dose. Peripheral and peritoneal IL-2 levels were measured with a bioassay using an IL-2-dependent cell line. At the highest dose level, serum IL-2 was greater than 10 units/ml for 18 h. After the first infusion, a 2-log dilution of the i.p. IL-2 was measured in the serum. In the postleukapheresis i.p. IL-2-dosing period less IL-2 was detected in the serum than in the earlier i.p. IL-2-priming period. The induction and persistence of LAK activity were studied. Peritoneal LAK activity was detected as early as 4 days after the first i.p. infusion, by day 11 in all evaluable patients, and persisted for the 6-day interval between priming IL-2 and LAK/IL-2 infusion. Peritoneal lytic activity persisted until day 28 in 5 tested patients. These peritoneal cells retained lytic activity 48 h in culture medium without rIL-2 present. Peritoneal LAK activity correlated with the percentage of mononuclear cells and the percentage of CD56-positive mononuclear cells in the peritoneum. The yield of peripheral lymphocytes after the six i.p. priming doses of rIL-2 correlated with the dose level of rIL-2 infused. Peripheral blood LAK activity showed a minimal, however progressive, increase during the treatment protocol. LAK activity could be enhanced if rIL-2 was present during the 4-h assay. These studies indicate that i.p. rIL-2 infusion induced durable regional LAK activity and primes peripheral blood cells for LAK activity if exposed briefly to additional IL-2.
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PMID:Phase I trial of intraperitoneal recombinant interleukin-2/lymphokine-activated killer cells in patients with ovarian cancer. 220 79

Autologous lymphokine-activated killer (LAK) cells and recombinant human interleukin-2 (rIL-2) were administered intraperitoneally (IP) to 24 patients with malignancies limited to the peritoneal space. Ten patients had ovarian cancer, 12 had colorectal cancer, and one patient each had endometrial carcinoma and primary small-bowel adenocarcinoma. All ovarian cancer patients, three of twelve colorectal cancer patients, and one patient with endometrial carcinoma had received prior therapy. Patients received IL-2 100,000 U/kg every 8 hours intravenously (IV) for 3 days, and 2 days later underwent daily leukapheresis for 5 days. LAK cells were generated in vitro by incubating the peripheral blood mononuclear cells in IL-2 for 7 days and were then administered IP daily for 5 days through a Tenckhoff catheter (Davol, Inc, Cranston, RI) together with IL-2 25,000 U/kg IP every 8 hours. All but one patient completed at least one cycle of therapy. Toxic side effects included minor to moderate hypotension, fever, chills, rash, nausea, vomiting, abdominal pain and distension, diarrhea, oliguria, fluid retention, thrombocytopenia, and minor elevations of liver function tests; all of these rapidly improved after discontinuation of IL-2. One patient had a grand mal seizure, and one suffered a colonic perforation; these were felt to be treatment-related. IP fibrosis developed in 14 patients and limited repeated cyclic administration of this therapy in five patients. Two of 10 (20%) ovarian cancer patients and five of 12 (42%) colorectal cancer patients had laparoscopy- or laparotomy-documented partial responses. We conclude that LAK cells and rIL-2 can be administered IP to cancer patients, resulting in moderate to severe short-term toxicity and modest therapeutic efficacy. Further investigation of this form of adoptive immunotherapy modified to address the problem of IP fibrosis and with lower IP IL-2 doses is justified by these initial results.
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PMID:Intraperitoneal lymphokine-activated killer-cell and interleukin-2 therapy for malignancies limited to the peritoneal cavity. 221 99

Sixteen patients with advanced epithelial ovarian cancer who were treated with cytoreductive surgery followed by multiagent chemotherapy were found to have residual tumor masses less than 2 cm in greatest diameter at reexploration and were treated with whole-abdominal radiation (19-31 Gy). Thirteen patients also received pelvic boosts to a total pelvic dose of 41-53.7 Gy. Radiotherapy was completed in all but 2 patients after treatment delays in 7 patients. Early treatment complications included myelosuppression in 11 patients, diarrhea in 3, and a self-limited small bowel obstruction in one. Delayed complications were severe and included 9 patients with radiation enterocolitis, 8 of whom required intestinal resection or diversion. One additional patient with radiation cystitis required instillation of formalin to control bleeding. Two patients are without evidence of disease 28 and 30 months following radiotherapy, while the remaining 14 patients have recurred after a median progression-free interval of 9 months (range 1-30 months). All patients who recurred failed within the treatment field and died of cancer after a median interval of 19 months following radiotherapy and 9 months after documentation of progression. These data suggest that few patients with persistent ovarian cancer following surgery and chemotherapy will be salvaged with radiotherapy.
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PMID:Whole-abdominal radiotherapy for patients with minimal residual epithelial ovarian cancer. 231 42


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