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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

We questioned 113 patients with subsequently diagnosed sustained ventricular tachycardia (VT) regarding the symptoms that prompted their seeking hospital treatment, eliciting the following: 15% of patients had lost consciousness, 15% had near syncope, 35% had mild lightheadedness and 35% had no cerebral symptoms. Patients with preexisting congestive heart failure or a VT rate of 200 beats per minute or greater more often lost consciousness. Other symptoms included palpitations in 57% of patients, chest pain in 27%, dyspnea in 25%, weakness in 6%, nausea or diaphoresis in 3% each and flushing in 2%. In approximately 50% of patients who had mild lightheadedness or no cerebral symptoms, their condition was incorrectly diagnosed as supraventricular tachycardia based on the absence of severe symptoms during the tachycardia. In some patients, VT may be associated with mild or atypical symptoms. The differentiation of supraventricular from ventricular tachycardia should be based on electrocardiographic criteria and should not be influenced by the nature or severity of a patient's symptoms. The severity of cerebral symptoms is at least partially related to the VT rate and a patient's underlying heart disease.
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PMID:Clinical symptoms in patients with sustained ventricular tachycardia. 399 9

Amrinone, a new inotropic agent, was used to treat 24 patients with chronic congestive heart failure who were classified as clinically stable and who were in New York Heart Association's classes II and III. Patients were treated for up to 30 months (mean, 12.5 months). Exercise tolerance improved in 20 patients, but only eight experienced significant improvement in symptoms of fatigue, dyspnea, and orthopnea and only nine tolerated the drug without apparent side effects. Eight were unable to continue amrinone therapy because of limiting side effects. The most significant adverse effects were cardiac arrhythmias, thrombocytopenia, abnormal results of liver function tests, diarrhea, fever, and nausea. Amrinone has a narrow therapeutic-toxic ratio, but a significant proportion (42%) of patients tolerate and benefit from amrinone therapy.
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PMID:Clinical effects and side effects of amrinone. A study of 24 patients with chronic congestive heart failure. 399 60

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

The central and peripheral vascular haemodynamic effects of glucagon were studied in 29 patients. With a single dose method of 2 or 5 mg. glucagon intravenously the inotropic action of the drug produced immediate increased myocardial contractility with significant increase in cardiac output and enhanced cardiac performance, and lowering of pulmonary arterial pressure and pulmonary vascular resistance. No primary peripheral vascular effect was evident, and the increased systemic pressure and lowered systemic resistance appear to be secondary to the central action of the drug. With the dosage used there were no undesirable side-effects apart from a feeling of slight nausea. Though the haemodynamic effects are abrupt, reaching their maximum values in the first 10 minutes after injection, they tend to be dissipated within half an hour, presumably due to the very rapid destruction of the drug. Repeated booster doses rather than continuous infusion may be the method of choice to maintain an increased cardiac output. The positive chronotropic action of the drug may cause transient palpitations. Glucagon increased the cardiac output in the acute phase of myocardial infarction by 42 per cent. The haemodynamic effects in chronic rheumatic heart disease are more varied, and it may increase left atrial pressure in mitral stenosis, which is undesirable. Hyperglycaemia results from liver glycogenolysis but blood sugar levels rarely exceeded 200 mg./100 ml. These results warrant further study of the value of glucagon as a positive inotropic agent in low output heart failure, especially in acute myocardial infarction with cardiogenic shock, or after cardiac surgery, or in unrelieved chronic congestive heart failure.
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PMID:Haemodynamic effects of glucagon. 542 74

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

Nitrates are potent relaxers of vascular smooth muscle and act by dilating veins, arteries, and arterioles (especially at high doses). Their clinical effects have been considered to be dominantly related to peripheral actions: systemic venodilatation and a decrease in systemic vascular resistance, reducing the preload and afterload of the heart. Considerable experimental work confirms potent salutary effects on the coronary circulation. These drugs are readily absorbed across mucosal surfaces; they are available in multiple formulations, including sublingual, buccal, oral, and topical delivery systems. Nitrate administration should begin with low doses and increased to doses that are often higher than previously recommended until a specific clinical end point or limiting side effects occur. Organic nitrate esters are effective in the treatment of stable angina pectoris, unstable angina, coronary vasospastic syndromes, and in vasodilator therapy in severe congestive heart failure. The pathophysiology of these syndromes is reviewed with respect to the clinical actions of nitrates on the central and peripheral circulations. The side effects of nitrates include headache, dizziness, and nausea. Nitrate tolerance, a controversial subject, does not appear to be an important clinical problem. Using the guidelines presented in this review, nitrate therapy provides effective, inexpensive, well-tolerated therapy for many patients with cardiovascular disease.
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PMID:Nitroglycerin and long-acting nitrates in clinical practice. 640 16

A phase I study of 4'deoxydoxorubicin (esorubicin) was performed on an every-21-day bolus intravenous (IV) schedule in 36 patients with advanced cancer. Thirty-four patients were evaluable for toxicity analysis. Toxicity included mild nausea, occasional local skin reactions, and mild to moderate alopecia. Myelo-suppression was dose limiting. Clinically evident congestive heart failure was not observed. However, two patients developed premature ventricular contractions. Overall, esorubicin was better tolerated than doxorubicin at equally potent doses. Although response analysis was not the primary objective of this phase I study, minor responses were observed in melanoma, breast cancer, lymphoma, and gastric cancer. On the basis of this study, a starting dose of 30 mg/m2 IV every 21 days is recommended for good-risk patients with escalation to 32.5 mg/m2 depending on bone marrow tolerance. For patients with poor bone marrow reserve, a starting dose of 25 mg/m2 every 21 days is recommended. Phase II trials with esorubicin in this dosage schedule are clearly warranted in a wide variety of metastatic neoplasms including a substantial population of patients who have not received prior chemotherapy.
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PMID:Phase I trial of esorubicin (4'deoxydoxorubicin). 647 Jul 53


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