Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two cases of granulocytopenia and leukopenia developing after high-dosage oxacillin therapy given intravenously are described. One patient developed leukopenia and granulocytopenia after 17 days of therapy. The conditions were reversible when oxacillin therapy was discontinued. In the other case, the adverse reaction developed within 48 hours after therapy began and the patient died from heart failure. Leukopenia and granulocytopenia as adverse effects of oxacillin therapy should be kept in mind, especially when high dosages are used.
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PMID:Leukopenia and granulocytopenia after oxacillin therapy. 86 Jan 44

Weekly low dose mitoxantrone (3 mg/m2) plus doxorubicin (8 mg/m2) was administered as second-line chemotherapy to 33 patients with advanced breast cancer. Four out of 28 evaluable patients (14%) obtained a partial response with a median duration of 34 weeks (range 18-67+ weeks), while 8 patients (29%) showed stable disease with a median duration of 28 weeks (range 11+-60 weeks). Gastrointestinal toxicity and alopecia were mild. Grade II and III leukopenia occurred in 63% of the courses without serious infectious disease. Four patients experienced an asymptomatic drop of 16-20% in the left ventricular ejection fraction (LVEF) after relatively low cumulative doses of each drug, and one patient with a history of pericarditis carcinomatosa and mediastinal irradiation developed a heart failure. In conclusion, this second-line combination treatment had moderate activity in breast cancer and caused only few subjective side effects, especially with respect to gastrointestinal symptoms.
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PMID:Weekly low-dose mitoxantrone plus doxorubicin as second-line chemotherapy for advanced breast cancer. 162 16

Fifty evaluable patients with advanced lung cancer (28 small cell and 22 non-small cell carcinomas), mainly pretreated by chemotherapy, received 4'-epi-doxorubicin 90 mg/m2 every 3 weeks. Two partial responses were obtained in small cell lung cancer patients, which lasted 153 and 168 days. Leukopenia, emesis and alopecia were the most frequent side effects. Two patients who previously received anthracyclines died suddenly of cardiac failure, another patient had severe congestive heart failure, and four others had minor cardiac dysfunctions. 4'-epi-doxorubicin has a modest activity in advanced lung cancer, mainly pretreated by chemotherapy and is not devoid of significant cardiotoxicity in this patient population.
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PMID:4'-EPI-doxorubicin in advanced lung cancer. A phase II trial. 196 77

All major types of human interferons (IFNs) have been purified and clinically administered as antitumor agents. We summarize here experience to date with toxicity of IFNs in cancer patients. The acute syndrome consists of fever, chills, myalgias, arthralgias, and headache, with some variation according to type of IFN, route of administration, schedule, and dose. Fatigue, perhaps reflecting CNS toxicity, is the most prevalent nonacute symptom. At high doses, IFNs are neurotoxic; the abnormalities seen by EEG resemble those in diffuse encephalitis. Hematologic toxicity consists mainly of leukopenia, but anemia and thrombocytopenia occur in some patients. Nausea, vomiting, and diarrhea are the main gastrointestinal symptoms. Elevation of serum transaminases seems to reflect liver toxicity. Renal function is well preserved, except for rare instances of acute renal failure. Cardiac toxicity remains questionable, although heart failure and arrhythmias have been associated with the administration of IFNs. Most, if not all, of these effects are reversible or can be ameliorated. With IFN alpha, the type most widely used in clinical studies, doses of 1 million to 9 million units (MU) are generally well tolerated, but doses greater than or equal to 18 MU yield moderate to severe toxicity. Doses greater than or equal to 36 MU can induce severe toxicity and significantly alter the performance status of the patient.
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PMID:Clinical toxicity of interferons in cancer patients: a review. 241 69

A case of IBL-like T cell lymphoma with serum monoclonal gammopathy was reported. A 58-year-old woman, who had suffered from heart failure, was admitted because of asthma attack, fever and lymphadenopathy. Leucopenia with a small amount of atypical lymphocytes was detected. Serum analysis showed monoclonal elevation of IgM-kappa (M-protein) and hyperviscosity. Urinary Bence-Jones protein was detected. Lymph node biopsy revealed the disappearance of normal structure and proliferation of T cells with pale cells which characterized IBL-like T cell lymphoma. Immunocytochemistry revealed the pale cells to bear T cell markers (MT-1, CD 5, CD 8 or CD 4) and IgM-positive cell distribution. Tonsilar biopsy showed the infiltration of atypical lymphoids and pale cells. Bone marrow biopsy showed moderate lymphoplasmacytoid proliferation with lymph follicles. Clinical data and serum analysis suggested macroglobulinemia. Additional lymph node biopsy was performed and revealed IBL-like T cell lymphoma. IBL-like T cell lymphoma is characterized by polyclonal hypergammaglobulinemia. The present case probably occurred initially as IBL-like T cell lymphoma and lymphoplasmacytoid cell proliferation might have followed due to an excess of CD 4+ cells.
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PMID:IBL-like T cell lymphoma expressing monoclonal gammopathy (macroglobulinemia) in the serum. 252 Apr 62

Thirty-three adult patients with solid tumors were treated with menogaril, a new anthracycline antibiotic. The drug was given as a two-hour infusion every 4 to 5 weeks at doses ranging from 17 to 250 mg/m2. The maximum tolerated dose was 250 mg/m2. Reversible and dose-related leukopenia was the dose-limiting toxicity. Thrombocytopenia was less frequent. Hematologic toxicity was maximal 2 weeks after treatment, and recovery usually occurred within 4 weeks. There was no dissociation between WBC and neutrophil counts, and myelosuppression did not appear to be cumulative up to 200 mg/m2. Myelosuppression was more severe for patients with heavy pretreatment and/or bone marrow involvement. Local toxicity consisting of phlebitis and/or erythema was the most common nonhematologic toxicity, especially at 250 mg/m2 (eight out of nine patients). Usually, erythema appeared within 24 hours after treatment at or near the infusion site and resolved within a few days. Occasionally, a more persistent (several weeks) orange discoloration suggesting cutaneous deposits of menogaril was observed. Nausea and vomiting were uncommon and never severe. Alopecia and mucositis were rare. Minor arrhythmias were seen in several patients during treatment, but their relationship with menogaril therapy was unclear, and in no patient did heart failure develop. Plasma concentrations were best described by a tricompartmental model with a mean terminal half-life of 29.5 hours and a mean total-body clearance of 20.2 L/h/m2. Doses of 160 and 200 mg/m2 are recommended for phase II trials in poor- and good-risk patients, respectively.
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PMID:Phase I study of intravenous menogaril administered intermittently. 293 3

Eighteen adult patients with solid tumors were treated with oral menogaril, a new anthracycline antibiotic active against human breast cancer after intravenous administration. The drug was given orally on 3 consecutive days every 4 weeks at doses ranging from 50 to 175 mg/m2/day. Reversible and dose-related leukopenia was the dose-limiting toxicity. Thrombocytopenia was less frequent. Hematologic toxicity was maximal usually 2 weeks after treatment and recovery usually occurred within 4 weeks. At doses from 50 to 150 mg/m2/day, non-hematologic side-effects of oral menogaril were infrequent and mild and consisted of nausea and vomiting (one patient), alopecia (two patients), mucositis (two patients) and liver function test abnormalities (three patients). The single patient treated at a daily dose of 175 mg/m2/day developed grade IV leucothrombocytopenia, with fever and gastrointestinal bleeding. This was followed by heart failure and the patient died from multisystem organ failure. Peak plasma concentrations of menogaril ranged from 0.043 to 0.409 microM and were linearly correlated with the dose. Similarly, the area under the plasma concentration versus time curve varied from 0.33 to 9.59 microM X h and was linearly correlated with the dose. The mean harmonic half-life was 11.3 +/- 6.4 h. A comparison of the data from the present trial and our previous study with intravenous menogaril indicates a bioavailability of 32 +/- 12%. There was an excellent relationship between the white blood cell decrease (as a percentage of the pretreatment value) and several pharmacokinetic parameters; the best correlation was obtained with the plasma concentration of menogaril at 4 h after treatment. A dose of 150 mg/m2/day for 3 consecutive days is recommended for phase II trials with oral menogaril but the bioavailability of the drug should be monitored carefully and, more specifically, the concept of a pharmacokinetic adjustment of the dose of menogaril should be evaluated prospectively.
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PMID:Phase I clinical and pharmacokinetic trial of oral menogaril administered on three consecutive days. 297 Mar 91

(2'' R)-4'-O-Tetrahydropyranyl Adriamycin (THP) is a new antitumor agent discovered among series of similar anthracycline compound synthesized by Umezawa et al. Phase I study revealed dose limiting factor of leukopenia with upper GI toxicity. Alopecia, cardiac failure and transient hepatic failure were extremely mild. Definite responses were demonstrated in acute leukemia, lymphoma, ovarian carcinoma, head and neck carcinoma, breast carcinoma and GU carcinoma. Pharmacokinetic studies revealed rapid cell uptake and outputs in bile (20%) and urine (8%) in 24 hours. Transfer to third spaces were poor but definite. In vivo a part of THP was converted to ADM in the liver, but not in other tissues including tumors. THP would be an extremely interesting compound, because of comparable spectrum of responses to various tumors with extremely low toxicity compared with other anthracycline compounds.
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PMID:Clinical studies of (2''R)-4'-O-tetrahydropyranyl adriamycin (THP). 331 Nov 90

Thirty-seven evaluable patients with progressive disseminated breast carcinoma were treated with a combination of mitoxantrone 14 mg/m2 i.v. every 3 weeks plus prednisone 20 mg/m2 p.o. daily with a reducing dose over several weeks. Thirteen of 37 patients (35%) achieved an objective response with two complete regressions. The median duration of response was 7 months and the median duration of survival 14 months. The cardiac function of all patients was monitored by serial left ventricular ejection fraction, at rest and after stress, and 3-monthly thereafter. Ten patients showed a deterioration in the ejection fraction after a minimum cumulative dose of 86 mg/m2 (six cycles), but only four developed clinical cardiac failure which was easily reversible after stopping mitoxantrone. Leucopenia was the dose-limiting toxicity. Nausea and/or vomiting were generally mild and transient. Alopecia was minimal. These results confirmed that this combination is effective and well tolerated in the treatment of disseminated breast carcinoma, and cardiotoxicity can be avoided with adequate monitoring of the left ventricular ejection fraction after six cycles of therapy (86 mg/m2).
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PMID:Primary chemotherapy with mitoxantrone and prednisone in advanced breast carcinoma. A phase II study. 338 49

In this study, 30 evaluable patients with advanced carcinoma of the breast were treated with cyclophosphamide 600 mg/m2 i.v. followed one day later with mitoxantrone (Novantrone; dihydroxyanthracenedione) 16 mg/m2 i.v. Drug treatment was repeated every 3-4 weeks, for a maximum of 12 cycles. The overall response rate was 43%; five of 30 patients (16%) attained a complete remission, and eight of 30 (27%) had a partial remission. Median response duration was 12+ months. The greater number of responses was seen in skin and soft tissues. Hematologic toxicity was limiting with 75% of patients experiencing substantial-severe leukopenia. Clinically evident heart failure developed in one patient; in three other patients there was minor-moderate alteration of cardiac function during mitoxantrone-cyclophosphamide therapy. Based on these data, it is believed that this regimen may provide significant long-lasting palliation in patients with advanced breast cancer.
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PMID:First-line combination chemotherapy with mitoxantrone and cyclophosphamide in advanced breast cancer. 401 20


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