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)

The preliminary results of Cycloplatin in non small cell lung cancer were presented. Cycloplatin is a new derivative of Cisplatin but less nephrotoxic. Its. referring preparation is Carboplatin 14% remissions were found in the cases of inoperable non small cell lung cancer and 12% remissions in advanced ovarian cancer. 84% of patients suffered from vomiting what was the most common reported side-effect.
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PMID:[Studies of the clinical use of cycloplatin--a new derivative of cisplatin]. 133 30

In a European joint project carried out in 6 laboratories a disease-oriented program was set up consisting of a panel of 7 tumor types, each represented by 4 to 8 different human tumor lines, for secondary screening of promising anticancer drugs. Human tumor lines were selected on the basis of differences in histology, growth rate, and sensitivity to conventional cytostatic agents. Xenografts were grown s.c. in nude mice, and treatment was started when tumors reached a mean diameter of 6 mm in groups of mice where at least 6 tumors were evaluable. Drugs were given at the maximum tolerated dose. For evaluation of drug efficacy, median tumor growth curves were drawn, and specific growth delay and treated/control x 100% were calculated. Doxorubicin (8 mg/kg i.v. days 1 and 8) was effective (treated/control < 50%, and specific growth delay > 1.0) in 0 of 2 breast cancers, 1 of 3 colorectal cancers, 2 of 5 head and neck cancers, 3 of 6 non-small cell lung cancers, 4 of 6 small cell lung cancers, 0 of 3 melanomas, and 3 of 6 ovarian cancer lines. Amsacrine (8 mg/kg i.v. days 1 and 8) was not effective, while datelliptium (35 mg/kg i.p. days 1 and 8) was active against 2 of 6 small cell lung cancer lines. Brequinar sodium (50 mg/kg i.p. days 1-5) showed efficacy in 4 of 5 head and neck cancers, 5 of 8 non-small cell lung cancers, and 4 of 5 small cell lung cancer lines. The project has been shown to be a feasible approach. Clinical activity for doxorubicin and inactivity for amsacrine against solid tumor types was confirmed in the human tumor xenograft panel. Additional anticancer drugs will be studied in the European joint project to further define the reliability of this novel, promising screening approach.
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PMID:Phase II preclinical drug screening in human tumor xenografts: a first European multicenter collaborative study. 139 20

Carboplatin is well suited to dose escalation because its major dose-limiting toxicity is myelosuppression when given in 1,200 mg/m2 doses without marrow support. Repeated 800 mg/m2 doses can be given in an investigational setting. With autologous bone marrow rescue the maximum tolerated single-agent dose is approximately 1.8 to 2 g/m2, with dose-limiting toxicities being hepatitis, renal dysfunction, and ototoxicity. Combinations of carboplatin with other agents plus bone marrow rescue are now being investigated in germ cell tumors, ovarian cancer, breast cancer, and small cell lung cancer. High-dose carboplatin plus etoposide combinations are being evaluated with colony-plus stimulating factors in an effort to ameliorate myelosuppression. Future high-dose carboplatin studies could be designed with more predictable toxicity, using an assessment of carboplatin renal clearance. Carboplatin is an important new drug warranting further investigation at escalated doses.
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PMID:Current experience with high-dose carboplatin therapy. 141 26

Teniposide and etoposide are third-generation semi-synthetic derivatives of epipodophyllotoxin. Following the initial clinical introduction of teniposide in the 1970s, investigations focused almost exclusively on its analogue, etoposide, because of its formulation, which was felt to have advantages in addition to oral administration. Despite consistently inadequate dosing and scheduling, early phase I and II trial results with teniposide were promising, and current trends encourage a second look. The substantial antitumor activity of teniposide is comparable with that of etoposide, and clinical interest was rekindled when it was shown to have considerable activity against small cell lung cancer (SCLC). In view of the inadequacy of early trials and the premature cessation of clinical study, it is recommended that teniposide be reevaluated for its activity against malignant lymphomas, Hodgkin's disease, leukemias, and SCLC, against all of which its early results were encouraging. In addition, consideration should be given to its activity against brain tumors, neuroblastomas and other childhood solid tumors, and ovarian cancer; its potential value against gastric, hepatocellular, breast, and bladder cancers also should be investigated. Other areas that warrant further study include elucidation of the exact mechanism of action of teniposide, its role in both single- and multiple-agent chemotherapeutic regimens, and resolution of its optimal dose and schedule. Finally, it is suggested that with new routes of administration and improved formulations, teniposide may be expected to play a significant role in the treatment of malignant lymphomas, SCLC, and pediatric lymphocytic leukemia and neuroblastoma.
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PMID:Teniposide in adult solid tumors: a historical perspective. 141 38

Chemotherapy cures a minority of adult tumours (e.g. Hodgkin's and non-Hodgkin's lymphoma, acute leukaemia, teratoma) and the majority of childhood tumours. Prolongation of survival by chemotherapy has been shown for small cell lung cancer, ovarian cancer and breast carcinoma (when used as an adjuvant). However, in the majority of solid tumours there is a less than 20% response to chemotherapy and even curable tumours may relapse and become resistant. Resistance may be de novo, acquired as a stable change within the cell, or be rapidly inducible within the cell after drug administration. Several mechanisms have been described including multidrug resistance, glutathione transferases and DNA repair. Understanding these mechanisms may help to improve the therapeutic ratio and develop new approaches.
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PMID:Drug resistance. 165 Jun 21

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

The meninges are a unique site of recurrence for certain malignancies because of the limited penetration of systemically administered cytotoxic drugs across the blood-brain barrier. While this phenomenon was first recognized in children with acute lymphoblastic leukemia, a similar pattern is also occurring in breast cancer, ovarian cancer, and small cell lung cancer. Recognition of the limitations of standard systemic antileukemic therapy for the treatment of meningeal disease led to the development of new therapeutic strategies targeted directly at the CNS. These include intralumbar therapy using methotrexate or cytarabine, intraventricular chemotherapy, and high-dose systemic drug administration. New agents showing promise are intrathecal diaziquone, 6-mercaptopurine, and mafosfamide.
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PMID:Pharmacologic approaches to the treatment of meningeal malignancy. 183 94

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 diagnostic value of the presence of anti-neuronal antibodies in serum was examined in 21 patients suspected of paraneoplastic disorders of the nervous system (NS) (group 1) and was compared to three control groups; group 2: 25 patients with a neurological disease, without cancer and no sign of paraneoplastic disorder; group 3: 27 patients with neurological disease and cancer and no signs of a paraneoplastic disorder; group 4: 94 patients with cancer and without neurological disease. In group 1, anti-neuronal nuclear antibodies were detected in eight patients (38%), in titres from 1:1000 to 1:32,000. A small cell lung cancer was present in six patients, ovarian cancer in one patient and in one patient no tumour could be detected. The neurological symptoms preceded a diagnosis of cancer in five out of eight patients. Anti-neuronal antibodies were found in the serum of two out of 94 patients (2%) from control group 3 but not in serum from any of the other control groups. These data indicate a moderate sensitivity of 38%, but a high specificity of 98.6% (95% confidence interval 95.5-99.8%) for the presence of anti-neuronal nuclear antibodies if a paraneoplastic NS disorder is suspected.
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PMID:Diagnostic value of anti-neuronal antibodies for paraneoplastic disorders of the nervous system. 217 80

Seventy-seven patients were treated with oral mitozolomide to assess the activity of this drug in melanoma, lung and ovarian cancer. Partial responses were seen in five of 18 evaluable patients with small cell lung cancer (SCLC) and three of 20 with melanoma. No activity was apparent in non small cell lung or epithelial ovarian cancer. The major toxicity was myelosuppression which necessitated reduction in the initial dosage from 115 to 90 mg/m2. However, even at this dose level, unpredictable WHO grade 4 toxicity occurred in non-pretreated patients. Thrombocytopenia was more common than leucopenia and eight patients required platelet transfusion for spontaneous or tumour-related haemorrhage. Myelotoxicity was considered responsible for two deaths and was a significant contributory factor in a further three. Non-haematological toxicity was minor. Thus, despite demonstrable activity in SCLC and melanoma, unpredictable myelosuppression is likely to preclude further assessment in combination chemotherapy regimes in these tumours.
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PMID:Phase II studies of mitozolomide in melanoma, lung and ovarian cancer. 254 29


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