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)

Treatment with a combination of adriamycin (ADM) and cis-dichlorodiammineplatinum(II) (DDP) has been evaluated in 24 patients with advanced ovarian cancer. Twenty patients had received prior chemotherapy and/or radiation therapy. Objective remissions were seen in ten patients. The usual toxic manifestations of ADM and DDP were observed. It is concluded that the combination is effective therapy for ovarian cancer. Further investigation of this combination versus single agents is warranted.
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PMID:cis-Dichlorodiammineplatinum(II) and adriamycin treatment of advanced ovarian cancer. 75 11

The use of high doses of cisplatin (DDP) in the treatment of different solid tumors is often prevented by the onset of a disabling sensory neuropathy. In an attempt to minimize DDP-induced neurotoxicity different schedules of DDP administration have been tested. Moreover, during the past few years some putative neuroprotective drugs have been reported as reducing DDP neurotoxicity. In this prospective, randomized study we evaluated in a series of 33 patients affected by relapsing ovarian cancer the effect on the sensory pathway of a non-conventional schedule of DDP administration as monochemiotherapy or in combination with one of the neuroprotective drugs (i.e. glutathione). The results of the neurophysiologic examinations performed before and immediately after chemotherapy suggest that these schedules besides being safe and effective in the treatment of the ovarian cancer, have an extremely low peripheral neurotoxicity.
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PMID:Evaluation by somatosensory evoked potentials of the neurotoxicity of cisplatin alone or in combination with glutathione. 133 8

Aphidicolin, a reversible inhibitor of DNA polymerase alpha and delta, has recently been reported to reverse the resistance to cisplatin (DDP) of an ovarian cancer cell line. We investigated the pharmacokinetics of aphidicolin in mice and examined its activity either alone or in combination with DDP in the DDP-sensitive M5076 (M5) murine reticular cell sarcoma as well as in a DDP-resistant subline (M5/DDP). The drug was cleared from plasma very rapidly (clearance, 41.6 ml min-1 kg-1), showing a half-life of 15 min. Aphidicolin concentrations in the tumor were approximately 50% of those found in plasma at steady state. Using several dose schedules and continuous infusions we failed to detect significant antitumor activity for aphidicolin glycinate. Potentiation of the activity of DDP by aphidicolin glycinate was moderate in mice bearing M5 tumor as well as in those bearing M5/DDP tumor. These data do not support the possible clinical use of aphidicolin in combination with DDP. However, further studies should be carried out in different tumor models before this possibility is conclusively ruled out.
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PMID:Activity of aphidicolin glycinate alone or in combination with cisplatin in a murine ovarian tumor resistant to cisplatin. 139 2

The efficiency of cis Platin (DDP) alone and in combination with Adriamycine (ADM) and Cyclophosphamid (CTX) were evaluated in a prospective randomized trial containing 173 pat. suffering from advanced ovarian cancer (FIGO III/IV). Therapeutic schedule and results: (table; see text) The most side effects concerned vomiting (WHO Grad 2) in 90%, nausea (WHO Grad 2) in 95% and alopecia in 50% out of all pat.
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PMID:[Effectiveness of cisplatin alone and in combination within the scope of primary therapy of ovarian cancer. Results of a prospective multicenter study]. 169 49

A total of 248 analyzable patients with Stages III-IV ovarian epithelial cancer (114 with and 134 without prior chemotherapy) were randomized to one of four cisplatin (DDP)-hexamethylmelamine (HMM) regimens. In each, HMM, 200 mg/m2 was given orally daily on days 8-21 of each 21-day cycle. DDP was given i.v. on Day 1 at a dose of 37.5 mg/m2 (regimens A and B) or 75 mg/m2 (regimens C and D). In addition, since pyridoxine administration has been reported to reduce the neurotoxicity of HMM, that agent was given at a dose of 300 mg/m2 orally on Days 1-21 in regimens B and D. Randomization was stratified for performance status (0-1, 2-3) and largest tumor diameter at entry (greater than 2- less than or equal to 10 cm, greater than 10 cm) for previously untreated patients, and for performance status and time from initial diagnosis to entry on study (less than or equal to 1 year, greater than 1 year) for previously treated patients. The overall response rate (PR + CR) was 54%, with 25% of patients achieving a complete response. The 61% response rate with the higher dose DDP regimens was significantly greater than the 47% response rate with the lower dose regimens (p = 0.031). Multivariate analysis identified higher DDP dose, age less than 60 years, no prior chemotherapy, small tumor bulk and favorable tumor grade as significant prognosticators for response. The overall median response duration was 8.3 months (range 1-70 months). Prior chemotherapy, pyridoxine administration, recent diagnosis, and large tumor size were identified by multivariate analysis as factors adversely affecting response duration. Patients treated with the higher dose DDP regimens had more severe nausea, vomiting, and neurotoxicity. This study demonstrates that the combination of DDP + HMM is an effective regimen for advanced ovarian carcinoma that yields response rates comparable to other more complex regimens, and that there is a dose-response relationship for DDP in ovarian cancer. Although pyridoxine administration significantly reduced neurotoxicity, its adverse effect on response duration suggests that the agent should not be administered with DDP or HMM. The mechanism by which pyridoxine may unfavorably affect response duration deserves further investigation.
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PMID:Hexamethylmelamine and low or moderate dose cisplatin with or without pyridoxine for treatment of advanced ovarian carcinoma: a study of the Eastern Cooperative Oncology Group. 173 9

A nation-wide clinical trial on a new antineoplastic drug, carboplatin(CP) supplied by Qilu Pharmaceutical Company, was carried out during the period of January to September 1989. Two hundred and forty-three patients with various malignant tumors were treated by CP as a single agent, 167-436 mg/m2 by intravenous infusion, repeated every 4 weeks, and 2-4 cycles as a course. The response rate was 75% (6/8) in testicular cancer, 56% (9/16) in ovarian cancer, 63% (15/24) in head and neck cancer, 37% (15/41) in small cell lung cancer and 60% (25/42) in non-Hodgkin's lymphomas. Randomized study of combination chemotherapy containing CP or cisplatin (DDP) was also conducted. The results showed that in small cell lung cancer, 73% (30/41) of the the patients responded to CE (CP + VP - 16) and 67% (24/36) responded to PE (DDP + VP - 16) and in ovarian cancer, the response rate was 60% (6/10) to CAC (CP + adriamycin + cyclophosphamide) and 36% (4/11) to PAC (DDP + adriamycin + cyclophosphamide) regimen. In addition, gastrointestinal reaction and renal toxicity were less severe in regimens containing CP than in regimens containing DDP. However, CP had more marked myelosuppressive effect.
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PMID:[Clinical results of carboplatin in the treatment of malignant tumors. Clinical Cooperative Group of Carboplatin]. 217 94

Cisplatin (DDP) is the most effective drug for the treatment of human ovarian cancer, but the mechanisms that determine sensitivity to the cytotoxic action of DDP are not well understood. Treatment of two human ovarian carcinoma cell lines with epidermal growth factor (EGF) simultaneously increased sensitivity to DDP and caused a persistent change in morphology in the absence of any mitogenic effect. Sensitization to DDP was shown to be dependent on both EGF concentration and EGF receptor number in C127 mouse fibroblasts expressing the human EGF receptor after transfection with a pBPV plasmid construct containing the human EGF receptor gene under control of the transferrin receptor 3'-inducible regulator. Sensitization of human ovarian carcinoma cells to DDP was not blocked by inhibition of protein synthesis. EGF did not enhance sensitivity to DDP or alter morphology in DDP-resistant human ovarian carcinoma cells despite the presence of functional EGF receptors on these cells. These results showed that elements of the signal transduction pathway activated by EGF determined cellular sensitivity to DDP, and that a DDP-resistant phenotype is associated with a defect in this signal transduction pathway.
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PMID:Epidermal growth factor regulates the in vitro sensitivity of human ovarian carcinoma cells to cisplatin. 224 36

A human ovarian cancer cell line resistant to cis-diamminedichloroplatinum(II) (DDP) (2780CP) was compared with its DDP-sensitive parental cell line (A2780) to determine whether differences in the removal rate of DNA-bound platinum were related to resistance. Both cell lines were treated in vitro with various doses of DDP for 2 h and subsequently incubated in arginine-deficient Eagle's minimum essential medium with 2.5% dialyzed fetal bovine serum in the presence or absence of aphidicolin. After 0, 12, and 24 h, DNA was isolated from the cells and DNA-bound platinum was determined by flameless atomic absorption spectrophotometry. Binding of platinum to DNA of either cell line was a linear function of concentration ranging from 20 to 80 microM DDP. Platinum binding was almost equal at each dose in both cell lines. 2780CP cells that were 3-fold resistant to DDP lost 30.5 to 40.1% of their total DNA-bound platinum, compared with a 1.3 to 16.1% loss for A2780 cells, 12 to 24 h after a 2-h exposure to 40 microM DDP, respectively. Aphidicolin (3.0 micrograms/ml) increased the cytotoxicity in 2780CP cells by about 2-fold and caused a significant delay in the time required for platinum removal in the resistant cells (14.6 and 18.9% at 12 and 24 h). These studies indicate that the mechanism of DDP resistance in the 2780CP cell line is related to an increased ability to remove platinum-DNA adducts, and not to a difference in initial DDP binding to DNA.
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PMID:Increased removal of DNA-bound platinum in a human ovarian cancer cell line resistant to cis-diamminedichloroplatinum(II). 230 38

cis-Platinum (DDP) and cyclophosphamide are commonly used for the treatment of ovarian cancer; however, survival remains poor. The degree of cytotoxicity of the standard antineoplastic agents DDP, 4-hydroperoxy-cyclophosphamide (4-OH-CTX), mitomycin C (MITOM C), vincristine (VCR), etoposide (VP-16), 5-fluorouracil (5-FU), cytosine arabinoside (ARA-C), and interferon (IF) in four representative ovarian cancer cell lines was studied using the ATP assay, which measures total cell kill. Cell lines CAOV-3, OVCAR-3, SKOV-3, and BG-1, which were derived from both pretreated and untreated patients, were exposed to six different concentrations for 90 min. On Day 7, intracellular ATP determinations were done. Sensitivity was defined as greater than or equal to 50% cell kill at 0.5 x peak plasma concentration as compared to controls. For 4-OH-CTX and ARA-C, 3 and 0.5 micrograms/ml were chosen as 0.5 x reference values. For each drug in each cell line, a highly reproducible dose-response relationship was observed. CAOV-3 cells were sensitive to all drugs except DDP, ARA-C, and IF, and OVCAR-3 cells to all except DDP and IF. SKOV-3 cells were resistant to all agents except VCR, and BG-1 cells to all except MITOM C and 5-FU. The apparent heterogeneic response to antineoplastic agents observed in the above cell lines underscores the importance of assessing individual patients' sensitivity profiles before treatment.
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PMID:Comparative chemosensitivity profiles in four human ovarian carcinoma cell lines measuring ATP bioluminescence. 238 29

Cisplatinum (DDP) is a cell cycle-independent drug used to prolong the survival time in ovarian cancer patients operated palliatively. After six therapeutic cycles of 100 mg of cisplatinum (Platidiam, Lachema, Brno) per square meter of body surface each changes in the sensation of hearing like tinnitus without any limitation of the faculty of hearing felt individually have been reported in four out of twelve ovary cancer patients. A high frequency loss of more than 4,000 Hz could be detected by threshold audiometry in three out of these twelve patients.
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PMID:[Ototoxic side effects in patients with ovarian cancer treated with cisplatin]. 337 11


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