Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A survey of 118 patients seen in the last twenty years in Newcastle upon Tyne forms the basis of this report. All of these 118 patients fulfilled clearly defined clinical, electrophysiological and pathological criteria for the diagnosis of polymyositis: muscle pain, weakness and characteristic EMG and/or muscle biopsy 55%; and characteristic muscle biopsy 17%; muscle weakness and characteristic EMG 7%; muscle weakness and pain, and raised serum CK activity in an established collagen-vascular disease 5%. A smaller group of 25 patients were selected in whom the clinical characteristics, EMG, muscle biopsy and serum enzyme levels were all completely diagnostic of polymyositis. The patients were followed for two months to twenty-six years, with a mean follow-up duration of six years. Analysis was made of the features at presentation and during the course of the illness, and of prognostic factors bearing upon the disability, response to treatment and mortality. Cases were classified according to the system of Rose and Walton (1966). Groups I, II, and III each constituted approximately one-third of the total cases, while only 8% of all cases were associated with carcinoma. The female to male ratio was 1.4:1. Though cases were seen in all age groups, the largest number was in the sixth decade. The sedimentation rate was raised in 55% of cases. Electromyography was characteristic of polymyositis in 45% of cases, and in only 11% was it normal. The serum creatine kinase activity was raised in 64% of cases. There was no correlation between the extent of these abnormalities and the degree of weakness or disability. 65% of muscle biopsies had changes with inflammatory infiltration virtually diagnostic of polymyositis. 17% of cases had a normal muscle biopsy. Most of the patients (89%) were treated with high-dose prednisone therapy, commencing with 30-100 mg/day, gradually reducing to a maintenance dose of 5-15 mg/day over two or three months. All clinical groups showed considerable improvement in average disability with time on "high dose" corticosteroid therapy, the maximum improvement occurring within the first three years. The degree of improvement in disability was considerably less in those inadequately treated, though the mortality rate was similar in the two groups. 66% of all survivors had essentially no functional disability at follow-up three or more years later, and in the majority of these cases the disease appeared to have burned itself out. 33% of cases had significant disability after three years, and in half of these the disease appeared to be still active.
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PMID:Polymyositis: its presentation, morbidity and mortality. 121 71

A dose optimization study was carried out with the aim of identifying the maximally tolerated dose of recombinant alpha interferon-2a (raIFN-2a) in combination with 5-fluorouracil (5FU). 5FU was given at the dose of 750 mg/m2 over a 4-hour infusion on day 1- - greater than 5 followed by 750 mg/m2 weekly i.v. bolus. Recombinant aIFN-2a was started at 3 x 10(6) IU subcutaneously three times/week. 12 patients with advanced colorectal carcinoma were included in the study. 10 patients had previously received chemotherapy for advanced disease. Severe fatigue, most likely attributable to rIFN, was the dose-limiting toxicity. The dosage of raIFN-2a could not be further escalated above 12 x 10(6) IU. At this dose level all patients required dose reduction due to fatigue, fever, myalgia and severe reduction of performance status.
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PMID:5-Fluorouracil and recombinant alpha interferon-2a in the treatment of advanced colorectal carcinoma: a dose optimization study. 209 Jul 72

A drug schedule has been devised based on a strategy of G2 blockade followed by prolonged infusion of tubulin-binding agents. The regimen consists of doxorubicin 32 mg/m2 i.v. and cyclophosphamide 320 mg/m2 i.v. on day 1 followed by vinblastine (0.3 to 1.2 mg/m2/day), cisplatin (3 to 12 mg/m2/day), and vincristine (0.04 to 0.16 mg/m2/day) by continuous intravenous infusion on days 5 to 12. Courses are repeated every 28 days. Eighteen patients with advanced solid tumors received 37 courses of chemotherapy in a pilot study to determine safe drug concentrations for the three-drug infusion for 7 days. Dose limiting toxicity was myelosuppression. Patients who received prior mitomycin-C experienced more profound thrombocytopenia than those who did not. Nonhematologic toxicities included mild nausea, vomiting, and transient elevations of serum alkaline phosphatase and serum creatinine. One patient with squamous cell carcinoma of the esophagus who erroneously received vincristine 0.8 mg/m2 instead of 0.08 mg/m2 for 4 1/2 days developed transient myalgia, ileus, and a transient peripheral neuropathy; the patient achieved a sustained complete remission for 15 months and died of unrelated causes. Minor responses and stable disease were seen in two patients with renal cell carcinoma (1 and 2.5 months), three patients with colorectal carcinoma (1.5, 2, and 4 months), and one patient with squamous cell carcinoma of the tongue (2 months). The ViVACCy drug regimen can be given without undue toxicity and may be active in solid tumors.
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PMID:ViVACCy--a drug schedule based on G2 blockade and prolonged infusion of multiple tubulin-binding agents. A pilot study. 219 39

Fenofibrate is a fibric acid derivative with enhanced potency and specificity of action on lipids. Preclinical toxicology reveals minimal toxic effects; dose-related changes occurred seldom, with only hepatic effects in rodents (mainly enzyme changes), some renal effects in dogs, and no reactions in monkeys. Teratogenicity tests were negative, and mutagenicity was not associated with fenofibrate. Carcinogenicity was evident in rodents with liver carcinoma at doses of 12 or 40 times the human dose, but cancer has not been associated with fenofibrate in over 10 years of clinical research and use. European experience with fenofibrate involved 7,145 patients in short- and long-term clinical trials, plus 10 years of marketing experience with a patient exposure of 6 million patient-years. Adverse effects were relatively low in frequency (6%) in the European clinical trials and manifested as gastrointestinal effects, muscle pain, skin problems, and sweating or dizziness. Short- and long-term fenofibrate studies revealed basically the same scope and frequency of adverse effects. Experience in US clinical trials mirrored the European experience; three types of adverse effects occurred more commonly in fenofibrate patients versus placebo: skin reactions, neurologic effects, and musculoskeletal reactions. Laboratory tests were mildly abnormal for liver function, leukocytes, and hemoglobin; these reactions were significant enough to be considered adverse drug experiences only occasionally. Hepatobiliary tests for lithogenicity showed an increase in cholesterol saturation, but gallstones seldom have been associated with fenofibrate. Postmarketing, open experiences in Europe over 10 years have been consistent with the study results. The rate of reactions has been low (about 115/year or a 0.3% incidence rate). The reactions noted in these spontaneous reports were hepatic, renal, gallstones, cutaneous, hematologic, sexual asthenia, and weight loss. In general, fenofibrate can be considered a safe and well-tolerated lipid-lowering drug that has been scrutinized extensively for safety in clinical research and during an already long marketing period in Europe.
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PMID:Safety of fenofibrate--US and worldwide experience. 267 10

The case is reported of a 19-year-old patient with gastric carcinoma, in which clinical presentation (intermittent fever, myalgia, proximal muscle weakness and diffuse nodular-trabeculated infiltration of both lungs) was very unusual. The patient developed further complications (microangiopathic hemolytic anemia with disseminated intravascular coagulation) and died of subdural hematoma. Bone-marrow biopsy showed metastatic mucin-producing adenocarcinoma, but the gastric primary site of the tumor could only be demonstrated at autopsy.
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PMID:[Occult gastric adenocarcinoma with pulmonary carcinomatous lymphangitis and microangiopathic hemolytic anemia in a young adult]. 298 15

In the course of a phase I study monoclonal antibody BW 494 was injected i.v. at a dose of 180-340 mg to 18 patients with advanced ductal pancreatic carcinoma. The murine IgG1-antibody is directed against a pancreatic carcinoma-associated glycoprotein. The antibody inhibits the functions of human pancreatic carcinoma cells. Diffuse muscle pain, which disappeared spontaneously, was noted by two patients 14 days after injection. Other side-effects were anaphylactoid reactions in two patients 12 and 19 days, respectively, on repeat antibody infusions. This event led to changes in the administration schema so that the total amount was given within ten days, after which there were no further allergic side-effects. Terminal antibody half-life was 47.8 h (initial half-life 0.2 h). Human anti-mouse antibodies in all eight patients tested for them developed within two to three weeks of the end of treatment. There were no tumour remissions. Progression of the tumour after treatment occurred in 12 patients (67%). In five patients the course was stable for at least three months after treatment, i.e. unchanged clinical status, unchanged tumour extent (CT), and stable tumour markers (CEA, CA 19-9) in serum. One female patient with a T3N1M0 carcinoma has so far lived for 16 months in full employment. The results justify the use of the monoclonal antibody in future controlled trials.
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PMID:[Immunotherapy of advanced pancreatic carcinoma with the monoclonal antibody BW 494]. 334 38

Methyl-GAG was given to 71 patients with advanced malignancies as a weekly brief infusion (30-120 minutes) or as a biweekly 24- or 120-hour infusion. Mucositis (stomatitis, pharyngitis, esophagitis, and, rarely, inflammation of other mucous membranes) was dose-limiting in all three schedules. Generalized fatigue, malaise, myalgia, dysesthesias, nausea, and vomiting were more frequent in the brief-infusion schedule. Myelosuppression was mild and not dose-related. Fever, ventricular arrhythmias, skin rash, tender swelling of the palms, neuropathy, and paralytic ileus were rare. Toxicity was increased in patients with renal insufficiency or "third-space" fluid but was not increased by hepatic dysfunction. Cumulative and overlapping toxicity was evident only in the weekly schedule. Higher doses of methyl-GAG were tolerated when the duration of infusion was increased. The recommended doses for phase II trials are 700 mg/m2 weekly as a 1-2 hour infusion, 850 mg/m2/24 hours biweekly, and 1500 mg/m2/120 hours biweekly. Therapeutic effects were seen in all schedules and included objective responses in colon carcinoma (one of 13 patients), renal cell carcinoma (one of nine), and Hodgkin's lymphoma (one of two) and objective improvements in esophageal carcinoma (one of three), endometrial carcinoma (two of two), and leiomyosarcoma (one of three).
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PMID:Methyl-GAG in patients with malignant neoplasms: a phase I re-evaluation. 705 68

Paclitaxel is a plant product isolated from the bark of the Western yew (Taxus brevifolia) that promotes the formation and stabilization of microtubules. This leads to growth arrest in the G2/M phase of the cell cycle. Paclitaxel has demonstrated significant antineoplastic activity in different tumor types, most notably in ovarian and breast carcinoma. In two Phase II trials (Eastern Cooperative Oncology Group [ECOG]/M.D. Anderson) in patients with previously untreated Stage IIIB-IV non-small cell lung cancer (NSCLC), response rates of 21% and 24% were reported. We are performing a Phase II trial investigating the efficacy of paclitaxel in patients with inoperable Stage IIIB-IV NSCLC. Forty-three patients were treated, 31 males and 12 females, with a median age of 59 years (range, 29-75), ECOG performance status 0-2, Stage IIIB 30%, Stage IV 70%. Patients were treated every 3 weeks with 225 mg/m2 as a 3-h infusion with standard premedication. Preliminary efficacy results from 37 patients include partial remissions in eight (21.6%) patients, no change in 22 (59.5%) and disease progression in seven (19%) patients. Eight patients are still receiving therapy. The hematologic toxicities (n = 43) were mild, and no World Health Organization (WHO) Grade 4 neutropenia was observed. Nonhematologic toxicities were Grade 1/2 polyneuropathy in 97.6%, Grade 1-3 myalgia/arthralgia in 76%, and Grade 1-3 nausea/vomiting in 18.6% of the patients. In conclusion, paclitaxel is an active single agent in this patient population. Mild hematologic toxicities were observed in the 3-h infusion setting (compared with 24-h infusion) and therapy was well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase II study with paclitaxel for the treatment of advanced inoperable non-small cell lung cancer. 755 41

To define the toxicity profile of recombinant human interleukin-6 (rhIL-6) and to study its effect on hematopoiesis, biochemical parameters and other cytokines, rhIL-6 was administered in a phase I-II study to 20 patients with breast carcinoma or nonsmall cell lung cancer. RhIL-6 doses were 0.5, 1.0, 2.5, 5.0, 10, and 20 micrograms/kg/d, with at least three patients per dose level. RhIL-6 was administered 24 hours by continuous intravenous infusion followed by subcutaneous (SC) administration for 6 days, partly on an outpatient basis. RhIL-6-related side effects were fever, headache, myalgia, and local erythema. Starting at 2.5 micrograms/kg/d, these side effects were compounded by nausea, reversible increase in liver enzymes, and anemia. Flu-like symptoms were controllable up to and including 10 micrograms rhIL-6/kg/d with acetaminophen. RhIL-6 increased platelet counts with a decrease in mean platelet volume and increased leukocytes caused by neutrophil, monocyte, and lymphocyte increase, with an increase in T cells and natural killer cells at 1.0 and 2.5 micrograms rhIL-6/kg/d. The reversible anemia was characterized by a decrease in serum iron, and an increase in ferritin and erythropoietin without reticulocytosis. RhIL-6 reduced total cholesterol levels and a dose-related increase of C-reactive protein and serum amyloid A plasma levels was observed. Serum IL-6 levels were increased, especially at 10 and 20 micrograms/kg/d, whereas no change in IL-1 beta and tumor necrosis factor alpha levels was observed. RhIL-6 can be administered with controllable side effects in this setting, up to and including a SC dose of 10 micrograms/kg/d on an outpatient basis, and has a promising stimulating effect on leukopoiesis and thrombopoiesis.
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PMID:Effects of recombinant human interleukin-6 in cancer patients: a phase I-II study. 806 39

Between 1983 and 1992, 11 children and 38 adults were seen at Taichung Veterans General Hospital with a definite diagnosis of dermatomyositis. Their clinical pictures, laboratory findings, courses and outcomes were compared. The mean age at diagnosis was 12 years and 50 years, respectively. Children had a higher female-to-male ratio (2.7:1 vs. 1.2:1) and a more acute onset, while adults had a higher incidence of malignancy and other connective tissue disease associations. Clinically, shawl sign was more common in the adults, whereas myalgia was more frequently seen in the children (0.05 < p < 0.1). Hemograms, serological parameters and immunological investigations showed no significant differences between the two groups. Elevated erythrocyte sedimentation rate and circulating immune complexes were found in over half of both groups of patients; however, their values bore no relationship to either disease activity or future outcome. Although no significant differences were demonstrated between the two groups of patients with regard to either clinical manifestations or laboratory findings, the disease entity seemed not to be the same because evidence of vasculopathy in muscle pathology was more prominent in the children, with endothelial swelling and necrosis the most common findings. Steroids had been used as the first choice of therapy in both groups of patients, followed by cytotoxic drugs and immunosuppressants. Children had a more favorable outcome compared to a 24% mortality rate in the adult group. Experience here recommends a complete cancer work-up in adults, especially for nasopharyngeal carcinoma among the Chinese. Various autoantibodies screenings may also be helpful for early detection of other associated connective tissue diseases.
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PMID:Juvenile and adult dermatomyositis among the Chinese: a comparative study. 829 23


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