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)

The death rate from epithelial ovarian cancer has only slightly decreased in the past decade. In contrast, there have been dramatic improvements in the treatment of germ cell tumors of the ovary and the majority of patients even with advanced disease is now cured because of the development of effective platinum-based combination chemotherapy. Unfortunately, most patients with ovarian cancer have the epithelial histologic type, and only one third of these patients can be cured with standard approaches. It has recently been shown that a subset of patients with early stage ovarian cancer has a greater than 90% cure rate without chemotherapy. Consequently, a major focus of current research is to develop effective screening modalities in order to diagnose epithelial tumors when they are still confined to the ovaries and pelvis. Currently, three fourths of patients are diagnosed at the time the disease has spread throughout the peritoneal cavity, and the standard approach has been cytoreductive surgery followed by combination chemotherapy. The two-drug combination of carboplatin plus cyclophosphamide has now become the treatment of choice, although it is equally effective as and less toxic than a regimen of cisplatin plus cyclophosphamide. In addition, Taxol has been identified as an extremely active agent against this disease, and new Taxol-containing combinations are under clinical investigation. Clinical trials are also in progress with hexamethylmelamine and ifosfamide combinations as well as with more dose-intense regimens based on considerable retrospective evidence that survival is correlated with the dose intensity of platinum compounds. New agents such as WR2721, IL-3, and IL-1 alpha are undergoing clinical evaluation to determine whether the toxicities of platinum compounds can be decreased and lead to further exploitation of the dose response relationship. After induction chemotherapy, approximately 50% of patients will be in a clinical complete remission. Unfortunately, 30% to 50% of these patients will have recurrent disease; clinical trials are currently in progress to determine whether any form of therapy following the initial induction regimen can prevent or delay recurrences. Based on laboratory investigations in relevant models of human ovarian cancer, clinical trials are also in progress with novel new agents that may be capable of reversing drug resistance to platinum compounds and alkylating agents. For patients with germ cell tumors of the ovary, platinum-based combination chemotherapy has produced the same dramatic effects as in testicular cancer. Clinical trials are now focused on retaining therapeutic efficacy but decreasing the toxicity of treatment in these tumors that frequently affect women in their reproductive ages.
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PMID:Ovarian cancer, Part II: Treatment. 161 96

Ifosfamide is an oxazaphosphorine alkylating agent with a broad spectrum of antineoplastic activity. It is a prodrug metabolised in the liver by cytochrome P450 mixed-function oxidase enzymes to isofosforamide mustard, the active alkylating compound. Mesna, a uroprotective thiol agent, is routinely administered concomitantly with ifosfamide, and has almost eliminated ifosfamide-induced haemorrhagic cystitis and has reduced nephron toxicity. Therapeutic studies, mostly noncomparative in nature, have demonstrated the efficacy of ifosfamide/mesna alone, or more commonly as a component of combination regimens, in a variety of cancers. In patients with relapsed or refractory disseminated nonseminomatous testicular cancer, a salvage regimen of ifosfamide/mesna, cisplatin and either etoposide or vinblastine produced complete response in approximately one-quarter of patients. As a component of both induction and salvage chemotherapeutic regimens, ifosfamide/mesna has produced favourable response rates in small cell lung cancer, paediatric solid tumours, non-Hodgkin's and Hodgkin's lymphoma, and ovarian cancer. Induction therapy with ifosfamide/mesna-containing chemotherapeutic regimens has been encouraging in non-small cell lung cancer, adult soft-tissue sarcomas, and as neoadjuvant therapy in advanced cervical cancer. As salvage therapy, ifosfamide/mesna-containing combinations have a palliative role in advanced breast cancer and advanced cervical cancer. Ifosfamide/mesna can elicit responses in patients refractory to numerous other antineoplastic drugs, including cyclophosphamide. With administration of concomitant mesna to protect against ifosfamide-induced urotoxicity, the principal dose-limiting toxicity of ifosfamide is myelosuppression; leucopenia is generally more severe than thrombocytopenia. Reversible CNS adverse effects ranging from mild somnolence and confusion to severe encephalopathy and coma can occur in approximately 10 to 20% of patients after intravenous infusion, and the incidence of neurotoxicity may be increased to 50% after oral administration because of differences in the preferential route of metabolism between the 2 routes of administration. Other adverse effects of ifosfamide include nephrotoxicity, alopecia, and nausea/vomiting. In general, intravenously administered mesna is associated with a low incidence of adverse effects; however, gastrointestinal disturbances are common following oral administration. Thus, ifosfamide/mesna is an important and worthwhile addition to the currently available range of chemotherapeutic agents. It has a broad spectrum of antineoplastic activity and causes less marked myelosuppression than many other cytotoxic agents. At present, the role of ifosfamide/mesna in refractory germ cell testicular cancer is clearly defined; however, its overall place in the treatment of other forms of cancer awaits delineation in future well-controlled comparative studies.
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PMID:Ifosfamide/mesna. A review of its antineoplastic activity, pharmacokinetic properties and therapeutic efficacy in cancer. 172 Mar 82

Previous studies have shown that platinum-DNA adduct level in leukocyte DNA (measured by antibody methodology) is directly related to disease response in ovarian cancer and testicular cancer. To determine if this principle could be more broadly applied, platinum-DNA damage was studied in a blinded fashion in leukocyte DNA of 21 cancer patients who received carboplatin (day 1) and cisplatin (day 3) in a phase 1 clinical trial. Fifteen different tumor types were included in this cohort. Using atomic absorption spectrometry with Zeeman background correction, DNA-bound platinum was measured during cycles 1 (C1) and 2 (C2) of therapy for most patients. For each of two cycles of therapy, most patients developed measurable levels of adduct after carboplatin, and in most patients adduct levels increased further after cisplatin, often in a supra-additive fashion. Total mg dose levels varied by less than 2-fold, whereas individual patients differed by as much as 10(3) in their adduct measurements after C1 and after C2, and by 29-fold after the very first carboplatin dose. All patients had refractory disease at the initiation of therapy, and 19 patients were evaluable for disease response. Adduct determinations were made 24 h after the first dose of platinum therapy in 17 of these individuals. Mean adduct levels after the first dose of carboplatin were higher in six responders (50 fmol/micrograms DNA +/- 26) than in 11 non-responders (14 fmol/micrograms DNA +/- 10); Wilcoxon two sample test two-sided P = 0.0071. The six responders were patients with pleural mesothelioma (2), breast cancer, buccal mucosa cancer, esophageal cancer and ovarian cancer. Adduct levels were consistently higher in the group of responders on each day that adduct was measured, with a summary two-sided P value of 0.00011. We conclude that analysis of platinum-DNA adduct formation may help determine whether pharmacogenetics are important in cancer drug resistance; and may help to determine the relationship between DNA damage in the peripheral blood compartment and internal organ response to in vivo exposures to DNA-damaging agents.
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PMID:Platinum-DNA damage in leukocyte DNA of patients receiving carboplatin and cisplatin chemotherapy, measured by atomic absorption spectrometry. 207 Apr 90

Fifty patients with histologically confirmed advanced malignancies were treated with ifosfamide and mesna plus other cytostatics. The other cytostatic drugs added to the treatment regimen were cisplatin (36 pts), etoposide (31 pts) and doxorubicin (20 pts). Among previously untreated patients objective response was documented in 12 of 19 pts with ovarian cancer, 9 of 14 with small cell cancer of the lung and in all 3 pts with Ewing's sarcoma. Among patients with disease refractory to prior cytostatic treatment, objective response was documented in 8 of 9 with testicular cancer, 1 of 3 with high grade lymphoma and 0 of 2 with osteosarcoma. Side-effects due to the combination of ifosfamide plus mesna and other cytostatics were acceptable. No life-threatening or lethal toxicities occurred. Most commonly encountered toxicities were leukopenia (64%), nausea and vomiting (84%), alopecia (63%), CNS toxicity (30%) and renal toxicity (12%).
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PMID:Ifosfamide and mesna in combination with other cytostatic drugs in the treatment of patients with advanced cancer. 216 21

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

The current status of clinical investigations of combination chemotherapies was reviewed. A randomized trial comparing low-vs high-dose cisplatin conducted in cases of testicular cancer indicated that a high-dose regime (120 mg/m2 D1) was superior to a low-dose regime (15 mg/m2 D1-5) while similar studies conducted in head & neck cancer and cervical cancer showed no significant differences. PVB or BEP in testicular cancer and CAP in ovarian cancer appear to have on established clinical role, but other combinations containing CDDP for use on various tumors are in the stage of phase II trial. Alternating non-cross combination is an attractive direction in clinical investigation but no such regimes tested in the past has shown any significant superiority over the results obtained from standard combinations.
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PMID:[Current status of combination chemotherapy]. 241 88

Placental-like alkaline phosphatase (PLAP) was measured by its catalytic activity (CA), using an amplified enzyme-linked immunoassay, and by its immunologic activity (IA), using an enzyme-linked immunosorbent assay. In both assays the same monoclonal anti-PLAP antibody was used as the primary reagent. This antibody reacts with the main epitope on PLAP that is common to PLAP of ovarian and testicular origin, as well as of PLAP that is induced by smoking. Determinations of CA and IA of PLAP were carried out in serum samples from 101 patients with epithelial ovarian cancer (49 patients with progressive or recurrent disease, 52 patients with no evidence of disease), 20 patients with testicular cancer (8 non-seminoma testis, 12 seminoma testis) and 61 healthy controls. Smoking status was taken into consideration. The main findings from this study are: 1. In prolonged follow-up of patients who were treated for ovarian cancer, progressive or recurrent disease was never accompanied by rising values of CA or IA of PLAP. Therefore in this study, PLAP was not a good monitor for this disease. 2. In all instances where expression of PLAP was reflected by raised serum levels of these antigens, the measurement of the catalytic activity proved to be a more sensitive parameter than that of the immunologic activity. The value of PLAP measurements in the follow-up of patients with testicular cancer remains to be elucidated.
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PMID:Catalytic and immunologic activities of placental-like alkaline phosphatase in clinical studies. The value of PLAP in follow-up of ovarian cancer. 244 78

Bone marrow autotransplantation involves the administration of very high doses of chemotherapy or radiation therapy, or both, followed by infusion of autologous hematopoietic stem cells. This treatment was used in the past as a salvage therapy for patients with end-stage cancers. Occasional cures in patients with chemotherapy-responsive malignancies encouraged oncologists to utilize this treatment earlier when a better result might be achieved. This has led to a substantial number of long-term disease-free survivors in non-Hodgkin's lymphoma, Hodgkin's disease, acute leukemia, and neuroblastoma. Studies are currently ongoing in the treatment of breast cancer, multiple myeloma, testicular cancer, and ovarian cancer. Important areas for future investigation include the identification of optimal criteria for patient selection and timing of the therapy, the need for infusion of hematopoietic stem cells as cloned hematopoietic growth factors become available, the identification of the most effective high-dose regimens, and the need for "purging" tumor cells from the marrow before re-infusion. Successfully addressing these issues will increasingly require large comparative trials.
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PMID:Bone marrow autotransplantation. 264 72

In this study we report serum sialyltransferase and nucleoside diphosphatase activities of patients with malignant tumors of various primary sites and extent, prior to and during chemotherapy. Enzyme levels were compared to clinical and laboratory parameters. The sialyltransferase and uridine diphosphatase (UDPase) activities in samples of 43 patients with advanced ovarian cancer was four to ten fold above the normal mean value (sialyltransferase 85.1 +/- 58 pmol/hr/ml and UDPase 26.6 +/- 7.2 nmol/hr/ml). After effective chemotherapy with adriamycin and cisplatin, the enzyme activity decreased markedly. In cases of complete remission, enzyme activity decreased to the normal range. In three cases after initial response for several months a rise of both enzymes was observed before any other biochemical finding of the forthcoming relapse. Similar patterns were observed in testicular cancer (6 cases). Clinical correlation is also obvious in other tumors except malignant lymphomas. Our findings show that the activities of these enzymes correlated with the clinical course, and therefore they can be the basis for clinical application for tumor monitoring, especially during chemotherapy.
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PMID:Sialyltransferase and nucleoside diphosphatase as markers for tumor monitoring. 299 17

Using a solid-phase monoclonal antibody enzyme immuno-assay, we evaluated in a multicenter study (18 laboratories) the utility of evaluating catalytic activity of human placental alkaline phosphatase (hPLAP, EC 3.1.3.1) in serum as a potential tumor marker. We determined hPLAP in serum samples from 130 patients with ovarian cancer, 79 patients with testicular cancer (53 seminoma testis, 26 nonseminoma testis), 537 patients with various other malignant diseases (95 lung, 39 gastrointestinal, 195 breast, 208 others), 291 patients with benign diseases, and 213 healthy controls. To assess the influence of smoking on hPLAP activity in serum, we evaluated 79 serum samples from patients with noncancerous diseases for whom smoking habits had been recorded. Our main findings are: (a) hPLAP activity is frequently increased (greater than 100 mU/L) in pre-operative serum samples from ovarian cancer patients (49%) and from testicular cancer patients (59% overall; 72% seminoma, 35% nonseminoma); (b) heavy smoking may increase hPLAP activity; (c) excluding heavy smokers, a 96% specificity for cancerous lesions was observed; (d) in patients with ovarian malignancies, CA 125 and hPLAP may behave as independent markers; and (e) in patients with seminoma, hPLAP is clearly more frequently increased than is beta-choriogonadotropin.
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PMID:Multicenter evaluation of human placental alkaline phosphatase as a possible tumor-associated antigen in serum. 316 10


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