Gene/Protein Disease Symptom Drug Enzyme Compound
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 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fifteen patients with ventricular premature complexes (VPCs) were included in this open study designed to assess the relative efficacy of bid (two times daily) and tid (three times daily) dosing regimens for cibenzoline as compared with qid (four times daily) administration. Patients started therapy with qid administration; this was followed in sequence by tid and bid administration at the maximum effective total daily dose determined during the qid administration. Of the nine patients evaluated for efficacy for suppression of VPCs, eight demonstrated a 75% or greater suppression of VPCs with cibenzoline administered qid (total daily dose of 130-325 mg). This effectiveness was maintained in four patients with a bid regimen and in three with a tid regimen. All four patients who had ventricular tachycardia (VT) had a decrease in the number of VT episodes while receiving cibenzoline (only one of these patients had satisfactory suppression of VPCs at the same dosage regimen). Twelve patients continued to receive extended therapy with cibenzoline for up to two years, as this was considered to be the optimum antiarrhythmic treatment for these patients. Two patients had to be removed from the study and two had the dosage lowered because of adverse reactions (dry mouth, blurred vision, dizziness, congestive heart failure) although in one instance, the congestive heart failure was subsequently considered to be unrelated to cibenzoline. One patient was able to complete the short-term phase of the trial, but was not given extended treatment because of persistent dry mouth. Two patients had treatment discontinued during the extended therapy phase because of adverse reactions (fever, nausea, vomiting, asthenia).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of dosing interval and optimum dose of cibenzoline. 368 May 96

New agents with increased activity and/or reduced toxicity are needed for the treatment of advanced breast cancer. The anthracene derivatives mitoxantrone and bisantrene had significant activity and acceptable toxicity in phase II trials. In an ongoing phase III trial we have now randomized 150 patients with advanced breast cancer to either doxorubicin (60 mg/m2), mitoxantrone (14 mg/m2) or bisantrene (260 mg/m2) i.v. q 3 weeks with re-randomization for cross-over at the time of progression to determine the relative efficacy and toxicity of these three agents. To be eligible, patients must have had only one previous chemotherapy regimen. ER positive patients must have failed endocrine therapy. Patients with CHF or severe cardiac disease were ineligible. In this preliminary evaluation, 117 patients are evaluable for response and 110 for toxicity. Median age for all patients is 58 years (range 26-78). The majority (86%) are postmenopausal. Fifty-nine percent percent of the patients have visceral dominant disease. Estrogen receptor is positive in 37%, negative in 39% and unknown in 24% of patients. Median performance status (SWOG) is 1, range 0-2. Objective responses have been observed on each arm (doxorubicin 9/35, mitoxantrone 6/38, bisantrene 6/44). Thirty-two patients are evaluable for cross-over response (doxorubicin 2/13, mitoxantrone 1/11, bisantrene 0/8). The predominant toxicity is leukopenia with a nadir WBC count less than 2000 in 45% of all courses administered. Leukopenia is similar with the three drugs. Significant nausea, vomiting and alopecia are common with doxorubicin and uncommon with the other agents. Congestive heart failure has been observed in one patient (doxorubicin). Definitive conclusions regarding the efficacy and toxicity of these agents await the completion of this trial.
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PMID:A randomized trial of doxorubicin, mitoxantrone and bisantrene in advanced breast cancer (a South West Oncology Group Study). 389 77

Mitoxantrone (Novantrone; dihydroxyanthracenedione) is an anthraquinone previously shown to be active in human breast cancer. It appears to have less toxicity than doxorubicin. Results of this phase II-III randomized cross-over trial to determine the relative efficacy and toxicity of mitoxantrone in comparison to doxorubicin, are presented. Patients with measurable, recurrent breast cancer with limited prior chemotherapy with or without radiotherapy for metastatic disease, and who had not been exposed to prior doxorubicin, were randomized to receive either mitoxantrone or doxorubicin every three weeks with cross-over on progression. Response rates, duration of remission, time to treatment failure, and drug toxicity, including cardiac toxicity evaluated with serial radionuclide angiocardiography, were evaluated. Differences in the response rates for the two groups were not statistically significant. Neither time to treatment failure nor duration of response are significantly different (p greater than 0.05). With respect to toxicity, mitoxantrone treated patients consistently exhibited a lower incidence and less severe drug toxicity as compared to their doxorubicin-treated counterparts. Cardiac toxicity was carefully monitored and thus four patients on doxorubicin have had drug related congestive heart failure, as compared to none on mitoxantrone. In summary, mitoxantrone appears to be as active as doxorubicin in patients with stage IV breast cancer previously treated with chemotherapy; however, mitoxantrone causes significantly less nausea, vomiting, stomatitis and alopecia at doses which induce equal or greater myelosuppression than doxorubicin, and appears to be less cardiotoxic.
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PMID:A randomized trial comparing mitoxantrone with doxorubicin in patients with stage IV breast cancer. 389 78

Aclarubicin, discovered by Umezawa in 1975, is a new cytostatic anthracycline antibiotic. It is one of the anthracyclines with the lowest cardiotoxicity, it is not mutagenic and it stimulates differentiation of tumour cells. The therapeutic index of aclarubicin (efficacy related to toxicity) is higher than that of doxorubicin and daunorubicin, using a proper dose schedule. Single dose therapy of aclarubicin shows only marginal efficacy, whereas multiple divided dose therapy exhibits efficacy comparable to that of doxorubicin and daunorubicin. Thus for clinical trials two dose schedules were designed: 25 mg/m2/day, days 1-7 for acute leukaemia; and 30 mg/m2/day, days 1-4 for solid tumours. Aclarubicin was shown to be highly active in acute leukaemia with 58% complete remissions in first relapse of AML. Good results were also seen in acute leukaemia in combination with cytosine arabinoside and thioguanine. In clinical trials with breast cancer and thyroid cancer the efficacy was in the same range as would be expected for doxorubicin, but side-effects were markedly reduced. Anorexia, mild nausea and infrequent vomiting were observed. Myelosuppression was common but dose reduction was not necessary. There was no alopecia and no congestive heart failure.
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PMID:Aclarubicin: experimental and clinical experience. 391 80

The effects of combination chemotherapy including mitoxantrone (MXN) "M-VEMFH" for advanced breast cancer were studied. The M-VEMFH regimen consisted of MXN 7 mg/m2, VCR 0.7 mg/m2, EX 333 mg/m2, MTX 13.3 mg/m2 i.v. on day 1, 5-FU 333 mg/m2 i.v. from day 1 to day 5 and pred. (H) 60 mg/m2 p.o. with tapering off in 2 weeks. In 7 cases heavily pretreated with combination chemotherapy including ADR, CR 2, PR 2, NC 2 and PD 1 were observed (response rate 57.1%). In 5 cases without prior ADR, PR 1, NC 2 and PD 2 were obtained. One case given 586 mg/m2 of prior ADR died of congestive heart failure after administration of 47 mg/m2 of NXN. One case died of sepsis. The other side effects were stomatitis, vulvitis, abnormal gustation, nausea, vomiting and alopecia. M-VEMFH is effective combination chemotherapy for advanced breast cancer resistant to ADR, but care must be exerted due to the accompanying cardiotoxicity and leukopenia.
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PMID:[Effects of combination chemotherapy M-VEMFH including mitoxantrone in advanced breast cancer]. 405 16

Cardiac glycosides still belong to the most frequently prescribed drugs, although the usefulness of digitalization in patients with sinus rhythm has been repeatedly challenged. In elderly patients, especially, the objective hemodynamic improvement remains minimal and treatment can often be interrupted without subsequent deterioration. On the other hand, signs of digitalis toxicity, such as nausea, vomiting, AV-block, ventricular extrasystoles or CNS-symptoms, occur in 15-30% of patients. Adverse effects are mainly due to toxic accumulation of digoxin in cases with age related reduction of kidney function. In view of its non-renal elimination digitoxin would seem to have a certain advantage in geriatric patients, however, its long t 1/2 (6-7 days) makes dose adjustments more difficult, as peak effects will only be attained after 4-5 weeks. For these reasons digitalis treatment in elderly patients should not be given without clinically manifest congestive heart failure and/or atrial fibrillation. Even in such cases a periodic reassessment of the therapeutic indication is recommended. Suspected "latent" cardiac failure or cerebrovascular insufficiency are no reasons for utilizing such potentially toxic drugs.
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PMID:[Digitalis therapy in the aged]. 618 78

The palliative treatment of esophageal carcinoma has included intubation, bypass, dilation, irradiation, and esophagogastrectomy. The last has been criticized by some on the basis of high operative morbidity and mortality. To assess the success of this method at our institution, we reviewed the 60 consecutive resections performed for carcinoma of the esophagus from January, 1972, through June, 1983. Forty-six patients had squamous cell tumors and 14, adenocarcinomas. There were 47 men and 13 women, and the mean age was 59.9 years (range, 38.5 to 78.9 years). The most frequent preoperative findings included dysphagia (55), weight loss (34), chest pain (22), and vomiting (49). Fifty (83%) out of the 60 resections were performed by the resident staff under the supervision of an attending surgeon. Four patients died within 30 days of operation, an operative mortality of 6.7%. Immediate causes of death included respiratory failure, myocardial infarction, hemorrhage, and renal failure. One of the patients who died and 3 of the survivors had an anastomotic leak. There were 27 additional complications in 24 patients: respiratory problems (8), arrhythmias (5), pleural effusion (4), gastric outlet obstruction (2), wound infection (2), and 1 each of pulmonary embolus, acute brain syndrome, congestive heart failure, myocardial infarction, chylothorax, and empyema. The one-, two-, three-, and five-year actuarial survival rates were 46%, 27%, 10%, and 5%, respectively. Mean survival for the 46 patients dead at the time of this study was 13.5 months. Outpatient follow-up data were available on 53 (95%) of the operative survivors and showed an absence of dysphagia in 87.5% during most of the follow-up period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Esophagogastrectomy as palliative treatment for esophageal carcinoma: results obtained in the setting of a thoracic surgery residency program. 621 66

A Phase II clinical evaluation of 4'-epi-doxorubicin has been carried out in 100 patients with various types of solid tumors. Hematopoietic toxicity was dose-limiting but reversible and of mild to moderate degree. Other acute toxic manifestations such as vomiting and alopecia were qualitatively similar to those usually reported for doxorubicin, but lower in frequency and less severe. A number of responding patients received cumulative doses of 4'-epi-doxorubicin in excess of 500 mg/m2. One patient manifested reversible clinical congestive heart failure at cumulative dose of 1,080 mg/m2. Therapeutic activity has been observed in breast carcinoma, in rectal carcinoma and in melanoma. In chemoresistant tumors as rectal cancer and melanoma 4'-epi-doxorubicin deserves further study.
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PMID:Clinical evaluation of 4'-epi-doxorubicin in advanced solid tumors. 659 May 32

Thirty-two patients with advanced ovarian cancer were treated with a combination of 4'-epi-doxorubicin, a new analog of doxorubicin, and cisplatin at a dose of 60 and 50 mg/m2, respectively, every 28 days. Twelve patients had previously received chemotherapy and/or radiotherapy. Of 29 evaluable patients, six (21%) achieved complete remission for a median duration of 19+ months, and 13 (45%) achieved partial remission for a median duration of 8 months. All complete remissions were confirmed by a "second-look" procedure. Main side effects included vomiting in all patients, moderate myelosuppression (67%), and alopecia (65%). No case of congestive heart failure was observed. 4'-Epi-doxorubicin plus cisplatin is an effective and relatively well-tolerated regimen in the treatment of advanced ovarian cancer.
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PMID:4'-epi-doxorubicin in combination with cisplatin in advanced ovarian cancer. 659 96

We report here our first experience with the use of a total artificial heart in a human being. The heart was developed at the University of Utah, and the patient was a 61-year-old man with chronic congestive heart failure due to primary cardiomyopathy, who also had chronic obstructive pulmonary disease. Except for dysfunction of the prosthetic mitral valve, which required replacement of the left-heart prosthesis on the 13th postoperative day, the artificial heart functioned well for the entire postoperative course of 112 days. The mean blood pressure was 84 +/- 8 mm Hg, and cardiac output was generally maintained at 6.7 +/- 0.8 liters per minute for the right heart and 7.5 +/- 0.8 for the left, resulting in postoperative diuresis and relief of congestive failure. The postoperative course was complicated by recurrent pulmonary insufficiency, several episodes of acute renal failure, episodes of fever of unidentified cause (necessitating multiple courses of antibiotics), hemorrhagic complications of anticoagulation, and one generalized seizure of uncertain cause. On the 92nd postoperative day, the patient had diarrhea and vomiting, leading to aspiration pneumonia and sepsis. Death occurred on the 112th day, preceded by progressive renal failure and refractory hypotension, despite maintenance of cardiac output. Autopsy revealed extensive pseudomembranous colitis, acute tubular necrosis, peritoneal and pleural effusion, centrilobular emphysema, and chronic bronchitis with fibrosis and bronchiectasis. The artificial heart system was intact and uninvolved by thrombosis or infectious processes. This experience should encourage further clinical trials with the artificial heart, but we emphasize that the procedure is still highly experimental. Further experience, development, and discussion will be required before more general application of the device can be recommended.
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PMID:Clinical use of the total artificial heart. 1476 80


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