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)

Twenty evaluable patients with minimal residual ovarian cancer at second look laparotomy were treated with human recombinant interferon alpha-2b (IFN) intraperitoneally. The dose administered was 50 x 10(6) units once weekly for 8 weeks. Seventeen patients were evaluated by a relaparotomy: five had a pathological complete remission, four a partial response, six patients disease stabilization and two patients had progression. Three patients, two stable and one with clinical progression, had no laparotomy. Nine of the 11 patients with residual tumor smaller than 5 mm had a response, while no response was found in six patients with residuals over 5 mm. The median duration of CR is 11+ months (6-13+ months) after evaluation. For toxicity, 156 treatment cycles could be studied. Fever was seen in 80% of all cycles within 24 h following administration of IFN, in 58 cycles (37%) over 38 degrees C and in 65 cycles (43%) over 39 degrees C. Abdominal pain was slight in 32% and moderate in 3% of all cycles. The peripheral blood leukocyte counts dropped after 52% of all cycles, in 27% below 4.0, in 22% below 3.0, and in one patient below 2.0 x 10(9)/l. IFN dosage was not reduced for leukopenia, but in one patient reduction was necessary for thrombopenia, resulting from insufficient marrow reserve after a previous autologous bone marrow transfusion. Pharmacokinetic studies showed i.p. IFN levels 50-100 times the blood levels. Blood levels were still elevated 2 days after i.p. infusion, but normalized within 1 week on repeated administration. At the second instillation, lower peak serum levels were reached. In conclusion, high doses of i.p. IFN appear to be active in patients with minimal residual disease, with ongoing response in CR patients. Apart from general malaise on the day of treatment, toxicity was acceptable. IFN may be active in patients with minimal residual ovarian cancer through local as well as systemic effects.
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PMID:Intraperitoneal human recombinant interferon alpha-2b in minimal residual ovarian cancer. 214 93

The biotechnological production of human recombinant tumour necrosis factor (rHuTNF) makes this drug available for clinical application. This endogenous compound exhibits tumouricidal activity and regulatory functions within the immune system. 20 out of 23 (87%) patients with refractory recurrent malignant ascites from ovarian cancer were successfully treated in a phase-I and II-study. The production of ascites was either completely suppressed or reduced to a minimum for at least 4 weeks after maximally three intraperitoneal (i.p.) applications. Two of the three non-responders were mucinous carcinomas. In the phase-I study the evaluation of a maximal tolerable dose was not possible due to the rapid therapeutic success at low doses of TNF. The effective dosage was 0.08-0.14 mg TNF/m2 given i.p. Side effects which occurred 2 to 24 hours after the application of TNF were flue-like symptoms combined with general malaise. The side effects were not dose related. All concomitant signs and symptoms could be minimized by prophylactic or therapeutic application of indometacine, paracetamol or pethidine. This applied especially for the typical early phase cytokine side effects e.g. chills and febrile temperatures. The side effects were not dose related. The i.p. treatment with rHuTNF appears to be a novel practicable and effective method for palliation in patients with recurrent ascites even in multiple pretreated patients.
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PMID:[Therapy of ascites with tumor necrosis factor in ovarian cancer]. 217 16

Fourteen patients with relapsing ovarian cancer were treated with a regimen of intravenous interferon gamma (IFN gamma). During an initial induction phase, patients received 2 mg/m2 IFN gamma intravenously over 2 h daily for 5 days, repeated every 2 weeks for six courses. Patients who responded were continued on a maintenance phase, receiving 3 mg/m2 intravenously over 2 h, twice weekly every 2 weeks for 2 to 6 months. All patients had received prior cisplatin containing chemotherapy regimens. Of the 14 patients entered, 7 completed the six courses of the induction treatment. Four patients were clinical responders and continued on maintenance therapy. The most commonly reported toxicities included malaise, fever, and deteriorating performance status. There appears to be some clinically apparent antitumor activity demonstrated by this dosing schedule of interferon gamma in ovarian cancers.
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PMID:A phase II study of the efficacy of recombinant interferon gamma in relapsing ovarian adenocarcinoma. 313 45

The thymidylate synthase (TS) inhibitor CB 3717 was administered intravenously to 24 adult patients as a single bolus repeated every 3-4 weeks. The doses were escalated from 50 to 400 mg/m2. At the highest level, hydration and urinary alkalinization were routinely performed. A greater than 20% decrease of the creatinine clearance value occurred in 35% of the cycles performed at 400 mg/m2, a dose which could be recommended for phase II studies. Hepatic toxicity, represented by an increase of the glutamic pyruvic transaminase (GPT) plasma levels, occurred in 70% of the patients after the first cycle. GPT peak levels were neither related to the dose nor to the peak drug plasma concentrations or AUC values in the dose range from 225 to 400 mg/m2. Malaise, reported after 46% of the cycles, was the most disturbing side-effect and its occurrence was statistically correlated with the degree of elevation of GPT. A suggestion of antitumor activity was reported for dosages of 300 and 400 mg/m2 in three patients with ovarian cancer refractory to cisplatin. Further clinical evaluations of TS inhibitors rely on the development of more water soluble and less hepato- and nephrotoxic agents.
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PMID:Phase I study of the antifolate N10-propargyl-5,8-dideazafolic acid, CB 3717. 338 77

CB 3717, N10-propargyl-5,8-dideazafolic acid, is a tight-binding inhibitor of thymidylate synthase (TS) whose cytotoxicity is mediated solely through the inhibition of this enzyme. Recent preclinical studies have focused on the intracellular formation of CB 3717 polyglutamates. Following a 12-hour exposure of L1210 cells to 50 microM [3H]CB 3717, 30% of the extractable radioactivity could be accounted for as CB 3717 tetra- and pentaglutamate, as determined by high-pressure liquid chromatography (HPLC) analyses. As inhibitors of isolated L1210 TS, CB 3717 di-, tri-, tetra- and pentaglutamate are 26-, 87-, 119- and 114-fold more potent than CB 3717, respectively, and their formation may, therefore, be an important determinant of CB 3717 cytotoxicity. In early clinical studies with CB 3717, activity has been seen in breast cancer, ovarian cancer, hepatoma, and mesothelioma. Toxicities included hepatotoxicity, malaise, and dose-limiting nephrotoxicity. This latter effect is thought to be due to drug precipitation within the renal tubule as a result of the poor solubility of CB 3717 under acidic conditions. In an attempt to overcome this problem, a clinical trial of CB 3717 administered with alkaline diuresis is under way. Preliminary results at 400 and 500 mg/m2 suggest that a reduction in nephrotoxicity may have been achieved with only 1 instance of renal toxicity in 10 patients. Hepatotoxicity and malaise are again the most frequent side effects. Evidence of antitumor activity has been seen in 3 patients. Pharmacokinetic investigations have shown that alkaline diuresis does not alter CB 3717 plasma levels or urinary excretion and that satisfactory urinary alkalinization can be readily achieved.
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PMID:Recent preclinical and clinical studies with the thymidylate synthase inhibitor N10-propargyl-5,8-dideazafolic acid (CB 3717). 343 91

A clinical study on human lymphoblastoid interferon (HLBI) in various advanced malignant diseases was performed. HLBI was administered to a total of 25 patients with various advanced malignant diseases in order ot investigate antitumor effect and toxicity. The diseases evaluated were as follows: 8 multiple myeloma (MM), 2 chronic lymphocytic leukemia (CLL), 2 adult T cell leukemia (ATL), 1 acute lymphocytic leukemia (ALL), 8 breast cancer, 3 gastric cancer and 1 ovarian cancer. Twenty-three patients received either 3 million or 6 million units of HLBI by daily intramuscular injection or every other day. One patient with ATL received 18 million units of HLBI by i. v. daily and 1 patient with ALL received 30.32 million units of HLBI i. v. daily. Tumor regression (PR) was observed in 2 patients with MM, each one patient with ATL and ALL, respectively. Major toxicities were pyrexia, myelosuppression, general malaise and G.I. toxicity. Several patients showed abnormality of hepatic or renal function. Two patients who received HLBI for more than a year developed cardiac toxicity.
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PMID:[Clinical trial of human lymphoblastoid interferon on advanced malignancy]. 635 2

The hematopoietic growth factor, recombinant human interleukin-3 (rhu IL-3), stimulates production of both leukocytes and platelets, and thus potentially has greater utility than growth factors that solely stimulate leukocytes production when employed with dose-intensive chemotherapeutic regimens. To determine the optimal schedule for administration of rhu IL-3 in combination with cyclophosphamide and carboplatin, an aggressive regimen for the treatment of advanced ovarian cancer, a phase I trial was initiated by the New York Gynecologic Oncology Group. Following surgical debulking, all patients received cyclophosphamide and carboplatin for 6 cycles. rhu IL-3 was administered at 50, 250, or 500 microgram subcutaneously for 5 days either immediately prior to or after administration of chemotherapy. Cohorts of six patients were treated at each dose level (three pre- and three postchemotherapy). Eighteen patients received 91 cycles of treatment. The major toxicities attributable to rhu IL-3 included fevers, chills, malaise, nausea, and headache, but were not dose-limiting at the doses of rhu IL-3 employed. The major finding of this study was that rhu IL-3 administered after chemotherapy offered greater platelet protection than rhu IL-3 administered prior to chemotherapy as assessed by median platelet nadir and duration of platelet counts < 50,000/mm3. A second major finding was a dose-response relationship for rhu IL-3: the two higher doses employed, 250 and 500 micrograms, offered more effective platelet protection than the lower dose employed, 50 micrograms. rhu IL-3 had no significant effects on leukocyte nadirs or duration of nadirs at any schedule or dose employed. rhu IL-3 may reduced the thrombocytopenia associated with aggressive treatment with cyclophosphamide and carboplatin, although this remains to be confirmed in a randomized, placebo-controlled trial. The effects of rhu IL-3 are dose- and schedule-dependent.
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PMID:A phase I trial of cyclosphosphamide and carboplatinum combined with interleukin-3 in women with advanced-stage ovarian cancer. 770 73

This phase II study was designed to assess the therapeutic potential of intensive course treatment with three anticancer agents: 50 mg of cisplatin on day 1, 40 mg/m2 of epirubicin on day 2, and 250 mg of 5-fluorouracil on days 2 through 5. Drug courses were repeated every 2 weeks and most patients received between 4 and 6 courses. Thirty-five patients with measurable advanced solid cancers entered the study. They consisted of 16 gastric, 5 colorectal, 4 gallbladder, 3 pancreatic, 3 lung, 2 esophageal, 1 uterine, and 1 ovarian cancers. Of the 35 patients, 29 were evaluated for therapeutic effect of the regimen, and the overall response rate was 31.0% (5 CR + 4 PR/29). A 33.3% rate of tumor regression, consisting of 2 complete responses (CR) and 3 partial responses (PR) out of 15 patients (2 CR + 3 PR/15), was seen for gastric cancers. For the other types of tumors the responses were achieved in 2 lung cancers (1 CR + 1 PR/3). 1 uterine cancer (1 CR/1), and 1 ovarian cancer (1 CR/1). The esophageal, colorectal, pancreatic, and gallbladder cancers were unresponsive to this regimen. Toxicities of the drug treatment were clinically tolerable and consisted of general malaise, nausea, vomiting, stomatitis, alopecia, and leucopenia. However, two patients died of uncontrollable metabolic acidosis after 1 and 2 courses, respectively. This intensive course treatment appears to promote the regression of gastric, lung, and gynecologic cancers.
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PMID:A phase II study of 5-fluorouracil, cisplatin, and 4'-epirubicin in the treatment of advanced solid cancers. 845 15

A large study of tumors of low malignant potential confirmed the favorable survival in this group of patients compared to invasive epithelial ovarian tumors. Only 8% of patients died with recurrent disease after surgery. Patients with stage IA borderline tumors with mucinous histology tended to recur later and carried a poorer prognosis than patients with serous histology and similar stage. The group at highest risk for relapse were age greater than 70, stage II or III tumors, and histology other than serous. Long-term survival in this group was less than 75%. This high-risk group of patients should be targeted for innovative adjuvant treatment strategies. This year several well-designed studies with large sample sizes showed DNA ploidy to be an important new independent prognostic factor in stage I ovarian carcinoma. In patients with well-differentiated early stage ovarian cancer, DNA flow cytometric analysis may indicate subgroups with less favorable prognostic characteristics. This method of analysis may be beneficial in determining the need for additional treatments after surgery for early stage ovarian carcinoma. Recommendations for the definitive management of early stage ovarian cancer awaits completion of current GOG and European randomized prospective studies. Paclitaxel given in combination with platinum-containing agents is an intense area of research for treatment of advanced stage disease. Early data from a prospective randomized trial of patients with advanced ovarian cancer showed a higher response rate and longer disease-free survival in patients treated with paclitaxel and cisplatin compared to a standard regimen of cyclophosphamide and cisplatin. The impact of this treatment on long-term survival awaits maturation of data. Preliminary results evaluating G-CSF in combination with paclitaxel and cisplatin for dose escalation was reported. Paclitaxel, 250 mg/m2, and cisplatin, 75 mg/m2, were the maximally tolerated doses, with peripheral neuropathy or myalgias the dose limiting toxicities. Further studies are now underway to test the effect of dose-response with escalation therapies and to determine the optimal dose and schedule for the management of patients with advanced ovarian cancer. IL-3 significantly ameliorated neutropenia but did not prevent cumulative platelet toxicity in a regimen utilizing high-dose carboplatin. This mild improvement in myelosuppression was obtained at the cost of significant toxicity. Nausea, vomiting, malaise, bone pain, headache, fever, chills and facial flushing were frequent. Intraperitoneal chemotherapy was tested as a means of consolidation treatment for patients after having a negative second-look laparotomy. These treatments were shown to be feasible; however, prospective randomized trials will be necessary to determine a benefit over operative therapy alone. Several studies addressed to problem of residual disease after primary surgery and adjuvant chemotherapy. A large phase II study conducted by the GOG confirmed the activity of salvage cisplatin-based intraperitoneal chemotherapy in patients with small-volume residual ovarian cancer with favorable pretreatment characteristics. Whether intraperitoneal platinum-based therapy represents an advantage over systemic platinum therapy is being addressed in a prospective SWOG study. The use of six additional cycles of CAP for treatment of residual disease after primary treatment of surgery and adjuvant chemotherapy did not significantly improve complete pathological response and survival. Prolonged duration of chemotherapy above six cycles is not likely to impact treatment for residual disease. A regimen of high dose carboplatin was compared to whole abdominal radiotherapy for treatment of residual disease after initial chemotherapy. There was no difference in survival or disease-free survival between treatments.(ABSTRACT TRUNCATED)
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PMID:Gynecological malignancies. 863 1

An early phase II cooperative study of Gemcitabine Hydrochloride (abbreviated to "gemcitabine" herewith) was conducted in patients with a variety of solid tumors (i.e., lung cancer, gastric cancer, pancreatic cancer, colon/rectum cancer, cervical cancer, ovarian cancer and breast cancer) at 56 institutions. The aim of the first step (Step I) was to investigate the feasibility of gemcitabine in a variety of different solid tumors, including lung cancer regarding efficacy and safety. The aim of the second step (Step II) was as a result of step I (Responses were observed) to continue to investigate the efficacy and safety of gemcitabine in chemonaive patients with non-small cell lung cancer. As a Step I study, gemcitabine was administered once weekly at a dose of 800 mg/m2 for a consecutive 3-week period followed by a week of rest, in multiple courses. Among the 29 eligible patients with lung cancer, partial response (PR) was achieved in 3 patients (25.0%, 95% confidence interval: 5.5-57.2%) out of 12 chemonaive patients. Adverse reactions (grade 3 or higher) seen in 29 patients with lung cancer were neutropenia (27.6%), leukopenia (13.8%), decreased hemoglobin (13.8%), thrombocytopenia (10.3%), malaise (6.9%), anorexia (3.4%), nausea/vomiting (3.4%), diarrhea (3.4%), dyspnea (3.4%) and interstitial pneumonia (3.4%). In other types of solid tumors, PR was achieved in 2 (8.7%) out of 23 eligible patients with cervical cancer and in 1 (5.3%) of 19 eligible patients with ovarian cancer, while the use of analgesics became unnecessary in 1 patient with pancreatic cancer. Incidence as well as severity of main adverse reactions in these patients were comparable to those seen in patients with lung cancer. A Step II study, in which gemcitabine was administered once weekly at a dose of 1,000 mg/m2 to chemonaive patients with non-small cell lung cancer, was conducted, referring to the results of Step I and clinical studies conducted overseas. The results of the Step II study demonstrated PR in 5 (14.3%, 95% confidence interval: 4.8 - 30.3%) out of 35 eligible patients with non-small cell lung cancer and that the main adverse reactions were comparable to those seen in the Step I study, posing no tolerability problems in particular.
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PMID:[An early phase II study of gemcitabine hydrochloride (LY 188011). Gemcitabine Cooperative Study Group for Early Phase II]. 893 92


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