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)

A multicentre pilot study has been conducted to determine an intensive regimen of cyclophosphamide, epirubicin, and fluorouracil which was tolerable and acceptable to patients with node positive breast cancer. Consecutive patients with operable axillary node positive breast cancer (T1-3, N1-2, M0), 266 patients, or locally advanced breast cancer (T4), 22 patients, were treated with cyclophosphamide post-operatively for 14 days and epirubicin and fluorouracil, both intravenously on days 1 and 8. Each cycle was repeated monthly for 6 months. Dosages were increased according to predetermined guidelines. Outcome measures were admission to hospital for febrile neutropenia and change in cardiac function as assessed by radionuclide angiography. The first 46 patients were treated at the doses of cyclophosphamide = 75 mg/m2, epirubicin = 50 mg/m2, fluorouracil = 375 mg/m2 (level 1), then 42 patients at cyclophosphamide = 75 mg/m2, epirubicin = 50 mg/m2 and fluorouracil = 500 mg/m2 (level 2), 69 patients at cyclophosphamide = 75 mg/m2, epirubicin = 60 mg/m2, and fluorouracil = 500 mg/m2 (level 3), and 42 patients at cyclophosphamide = 75 mg/m2, epirubicin = 70 mg/m2, and fluorouracil = 500 mg/m2 with concurrent antibiotics (level 4). The rates of febrile neutropenia were 8.7% (level 1), 7.1% (level 2), 18.8% (level 3), and 31% (level 4), respectively, P = 0.002. Accrual to level 4 was discontinued according to study guidelines and a further 89 patients were recruited at level 3 dosages with antibiotic prophylaxis (level 3a), resulting in a 5.6% rate of febrile neutropenia. The difference in febrile neutropenia rates between levels 3 and 3a was statistically significant. There were no toxic deaths and 2 cases of heart failure. In conclusion, through a careful dose-finding study in patients with operable or locally advanced breast cancer, an intensive epirubicin-containing adjuvant regimen has been established which is presently being compared with standard CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy in a randomised trial. In addition, this study suggests that antibiotic prophylaxis reduces the risk of febrile neutropenia in breast cancer patients receiving intensive chemotherapy.
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PMID:A pilot study of intensive cyclophosphamide, epirubicin and fluorouracil in patients with axillary node positive or locally advanced breast cancer. 144 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.
Breast Cancer Res Treat 1992
PMID:Weekly low-dose mitoxantrone plus doxorubicin as second-line chemotherapy for advanced breast cancer. 162 16

The authors investigated the effects of radiation therapy on the immune system by studying lymphocyte subsets and other parameters in 32 patients undergoing radiation therapy for solid cancer. With monoclonal antibody techniques, we studied both T- and B-lymphocytes; cell suspensions were analyzed by means of a Facs Spectrum III Ortho (Ortho-Diagnostic) unit. The first control was performed right after the beginning of radiotherapy, when the dose to the patients was 50 Gy or higher. The second control was performed at 40 Gy because all patients received this dose. 30% of the patients exhibited lymphopenia from the beginning of the study; at 40 Gy the number of T-lymphocytes was low and helper/suppressor ratio was altered. A variable response of B-cells was observed, although all patients exhibited restoration of normal values at 6 months. Four patients only suffered from side-effects: a patient with tongue cancer presented oral mycosis, and a woman--treated for breast cancer--presented vaginal mycosis. Two cases of cystitis were also observed, after 18 Gy, in patients with uterine carcinoma undergoing pelvic irradiation. Disease progression was observed in 2 patients with head and neck cancer, while 3 patients died from lung cancer progression. Another one, with head and neck cancer, died because of heart failure.
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PMID:[Influence of radiotherapy on lymphocyte subpopulations]. 202 47

The mitomycins are antitumor antibiotics that are under investigation now for more than 30 years. Mitomycin C (MMC) is the best investigated subtype. It serves as a prototype for drugs with bioreductive alkylation, which is a unique feature of this class. MMC is mainly active under anaerobic circumstances. The pharmacokinetics are linear in a two-compartment model. The main toxicities of MMC are thrombocytopenia and leucocytopenia. Rare but severe side effects are a hemolytic uremic syndrome, pneumonitis and cardiac failure. MMC has a wide clinical antitumor spectrum with efficacy in various tumor types such as gastric cancer, pancreatic cancer, breast cancer, non-small cell lung cancer, cervical cancer, prostate cancer and bladder cancer. Still, the above mentioned side effects prevent a more widespread use. The most important features of the drug will be reviewed.
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PMID:Mitomycin C: mechanism of action, usefulness and limitations. 213 Oct 38

Prior to the introduction of tamoxifen, diethylstilbestrol (DES) was widely used as the first-line endocrine therapy in postmenopausal women with advanced breast cancer. Since randomized trials reported that tamoxifen has a similar response rate but fewer side effects than DES, its use has declined markedly. We administered DES in a dose of 10-20 mg daily to 11 postmenopausal women with advanced breast cancer, all of whom had received previous endocrine and some cytotoxic therapy also. Four women showed tumour responses to DES (1 complete and 3 partial), 5 had stable disease, and 2 progressive disease. Amongst the patients who responded, 2 had previously been unresponsive to other endocrine treatments. Of the women with stable disease, 3 had prolonged relief of symptoms. No withdrawal responses were noted. The major side effects were nausea (severe in 2 patients, mild in 1) and cardiac failure (2 patients). We conclude that DES remains a useful, active agent in the management of advanced breast cancer in postmenopausal women, even in patients with tumours unresponsive to other endocrine therapy.
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PMID:Diethylstilbestrol revisited in advanced breast cancer management. 235 92

Fifty patients with advanced breast cancer (21 undergoing first and second stage palliative treatment: group 1, and 29 undergoing stage three or more: group 2), were included in a phase II trial with administration of a combination relay chemotherapy consisting of cisplatin (100 mg/m2/day) and fluorouracil (1,000 mg/m2/day), in continuous perfusion during 4 days, in cycles of five days repeated every three weeks (mean duration: 12 weeks). Toxicity was frequent and severe (a total of 17 treatments discontinued, and five deaths, 3 in group 1, 2 in group 2). The main manifestations of intolerance were threefold: haematological and leucopenia, in almost half of the patients, including 2 severe with 1 case of infectious complication and 4 thrombopenias requiring discontinuation of the treatment, including 2 with a severe haemorrhagic syndrome; cardiovascular, with three deaths due to heart failure; renal, most of the time laboratory tests disorders with 1 clinical syndrome. An objective response of more than fifty p. cent was obtained in five patients in group 1 (29.4%) and 3 patients in group 2 (11.1%); it lasted an average of 6.5 months and varied according to the locations: nodes (43%), liver (40%), pleuro-pulmonary (22%). Responses were obtained (13%) for lesions which resisted to previous chemotherapy. Five patients (14%) presented a functional improvement. The survival (mean = 4.8 months) was correlated, in group 1, to initial life conditions (p = 0.01) and was longer in group 1 for menopausal patients who had well tolerated the treatment (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Relay chemotherapy using continuous perfusion of cisplatin and fluoro-uracil in advanced cancer of the breast. Analysis of a series of 50 cases]. 236 99

To detect Adriamycin cardiomyopathy, radionuclide myocardial imagings with Tl-201, Tc-99m pyrophosphate, I-123 metaiodobenzylguanidine and Ga-67 were performed in a 49 year-old-woman receiving Adriamycin (a total dose of 230 mg/m2) for the treatment of breast cancer. This patient demonstrated symptoms of congestive heart failure 2 months after the last intravenous administration. At the period of performing the radionuclide studies, echocardiographic LV ejection fraction (EF) was 22%. Despite severe deterioration of cardiac function, Tl-201 SPECT demonstrated no defect and Tc-99m pyrophosphate (PYP) SPECT demonstrated no positive finding. I-123 metaiodobenzylguanidine (MIBG) scintigraphy demonstrated no regional defect. However, I-123 MIBG washout rate during 4 hours was markedly enhanced, probably reflecting abnormalities of norepinephrine kinetics due to the progression of heart failure. Compared to these pharmaceuticals, Ga-67 was diffusely accumulated in the heart. Then, 5 months after the first study, when LV EF improved to 30% and congestive symptoms disappeared probably owing to beta-blockade therapy, myocardial accumulation of Ga-67 markedly reduced. It has been reported that Ga-67 accumulates in malignant tumor cells and leukocytes. Since, in Adriamycin cardiomyopathy, myocardial accumulation of leukocytes with myocardial fibrotic changes have been histologically demonstrated, the results of Ga-67 scintigraphy may reflect the accumulation of leukocytes. Thus, this case indicates that Ga-67 scintigraphy is advantageous for detecting Adriamycin cardiomyopathy and may be more useful than Tl-201 and Tc-99m PYP scintigraphies.
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PMID:[Gallium-67 myocardial imaging for the detection of adriamycin cardiomyopathy]. 239 31

Epirubicin is a new anthracycline with a potentially more favorable toxicity profile than the parent compound, doxorubicin. Accordingly, the feasibility and toxicity of 6 courses of adjuvant chemotherapy with cyclophosphamide (C), epirubicin (E), and 5-fluorouracil (F) were assessed in 10 patients with Stage 2 (node positive) breast cancer. Doses of C and F were 600 mg/m2 and E was 75 mg/m2. Moderate granulocytopenia (median count = 610/mm3) occurred on day 14 of the first 21 day treatment course and was the main toxicity encountered with treatment, although there were no episodes of granulocytopenic fever. Grade 3 or 4 vomiting occurred in 40% and significant alopecia in 30% of patients. Four patients experienced transient asymptomatic decreases in calculated radionuclide cardiac ejection fraction of greater than or equal to 10% but no signs or symptoms of cardiac failure were observed. If epirubicin proves to be less cardiotoxic than doxorubicin, this combination would merit further evaluation as potential adjuvant therapy for early breast cancer.
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PMID:Phase I trial of adjuvant chemotherapy with cyclophosphamide, epirubicin and 5-fluorouracil (CEF) for stage II breast cancer. 284 91

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

Multiconcomitant therapy using adriamycin, cyclophosphamide, tegafur and tamoxifen was employed as chemo-endocrine therapy against progressive breast cancer, and the effects, toxicity and prognosis associated with this regimen were studied. This therapy was performed in 24 cases of both inoperable progressive breast cancer and postoperatively recurrent breast cancer. Efficacy was noted in 14 cases, including 4 cases of complete remission, giving an efficacy rate of 58%. Ten patients among the total of 24 are presently alive. The median survival time for all cases was 19.5 months, versus 34.0 months for effective cases and 12.5 months for ineffective cases. The main side effects noted were hematological toxicity, gastrointestinal symptoms and alopecia, but none of these symptoms were serious. Symptoms of heart failure occurred in one patient due to cardiotoxicity of adriamycin, but were not fatal. It can be concluded that ACFT therapy for the treatment of progressive breast cancer results in a good efficacy rate and longer survival time.
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PMID:[ACFT therapy using adriamycin, cyclophosphamide, tegafur and tamoxifen against progressive breast cancer]. 313 Aug 5


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