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)

Intra-arterial hepatic chemotherapy (IAHC) with adriamycin (ADM) has not increased its therapeutic index. For our preclinical studies, we selected pirarubicin (THP), an ADM derivative with faster cellular uptake. In rabbits with VX2 tumor in the liver we compared plasmatic and cellular pharmacokinetics of ADM and THP after i.v. and IAH therapy. For ADM, there were no differences in plasma and heart concentrations, with only a slight increase in tumoral levels after IAH compared to i.v. administration; on the other hand, with IAH THP, there was important reduction in systemic exposure with a major increase in tumoral drug distribution. In the phase I study, involving nine patients with implanted catheters, the starting dose of THP was 30 mg/m2 with a 10 mg/m2 intrapatient escalation every 3 weeks in the absence of toxicity. Pharmacokinetics were compared for i.v. and IAH administration in seven patients. The limiting toxicity was neutropenia and the maximal tolerated dose (MTD) ranged from 50 to 110 mg/m2. Moderate nausea-vomiting (grade 1-2) and alopecia (grade 1) occurred at the MTD. No arterial occlusion, gastroduodenal ulcer, hepatitis, or sclerosing cholangitis were seen. In the phase II study, in colorectal cancer patients (CRC) with metastasis confined to the liver, patients were enrolled until June 1990. THP (40 min infusion every 3 weeks) was initiated at 60 mg/m2 with 10 mg/m2 increment until grade 2 hematotoxicity. The median MTD was 85 mg/m2 (range of 60-120 mg/m2), and the median number of cycles was 7 (range of 2-11) with cumulated doses from 180 to 1,030 mg/m2. Grade 2-4 neutropenia was reached in 15 patients. Other toxicities included two arterial occlusions, one episode of gastritis, but no hepatic toxicity and no heart failure. Antitumor effect (in 18 patients) included 1 CR, 5 PR, 3 MR, 6 NC, and 3 PD. The median survival was 18+ months and 1-year survival was 73% +/- 12%. Seven patients had extrahepatic progression at this time. In conclusion, besides 5-FU or Fudr, THP is active in IAHC (probably in relation with high local extraction) on CRC liver metastases usually unresponsive to ADM. It can be given in an outpatient setting with minimal toxicity.
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PMID:Intra-arterial hepatic chemotherapy with pirarubicin. Preclinical and clinical studies. 229 52

A rare case of primary papillary adenocarcinoma of the renal pelvis is reported. A 75-year-old man was introduced to our institute because of chance hematuria. He had no history of urolithiasis or urinary tract infection. Excretory urography showed a space taking lesion at the lower position of left renal pelvis with low function. Because of advanced stage with paraaortic lymphnode invasion, simple nephrectomy followed by irradiation and systemic chemotherapy with 5-FU was done. He died of pneumonia and acute heart failure after subtotal gastrectomy for peptic ulcer four months after the nephrectomy. Excised specimen revealed papillary adenocarcinoma of the renal pelvis without mucin production. This case was the 51st case reported in the literature. A short review of the disease is also reported.
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PMID:[Primary papillary adenocarcinoma of renal pelvis: a case report and review of the literature]. 356 86

Five cases of recurrent cervical carcinoma with restricted recurrent site in the pelvis were treated with intra-arterial infusion of oncostatics via the internal iliac artery. The tip of the catheter was put in the internal iliac artery, just proximal to the superior glutea artery, through the a. glutea inferior or superior with ligation of both the a. glutea superior and inferior so as to get a high concentration of drugs at the lesion. Several chemotherapeutic agents, such as Cisplatin, adriamycin, pepleomycin, mitomycin C and 5-FU, were infused through the other end of the catheter, which was fixed at the subclavian fossa of the anterior chest. The clinical efficacies according to Karnofsky's criteria were 0-C in one case, 1-A in 1 case and 1-B in 3 cases. The overall response rate above 1-B was 60%. Two cases were dead, one due to inflammation in the pelvic dead space and D.I.C. and other due to myocarditis and heart failure. The other three were alive and treated with weekly intra-arterial infusion at our outpatient clinic. No troubles, such as spontaneous removal of the catheter, inflammation around the catheter or bleeding, have been encountered. The toxicities in the case of intra-arterial infusion were less prominent than in the case of intravenous administration of the same dosage of the oncostatics.
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PMID:[Intra-arterial infusion of oncostatics in recurrent cervical carcinoma]. 619 90

Vesnarinone (3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)- quinolinone), a quinolinone derivative, is an orally active inotropic agent used in Japan for the treatment of chronic heart failure. Recently, it has been reported that vesnarinone induces differentiation and apoptosis in certain types of leukaemia and solid tumour cells, and exhibits antitumour effect on several tumours xenografted in nude mice. In the present study, we examined the antitumour effect of vesnarinone in combination with radiation and conventional anticancer agents in nude mice xenografted with human gastric carcinoma, a poorly-differentiated adenocarcinoma, MKN-45 cell line which has a wild-type p53 gene. Vesnarinone treatment combined with radiation resulted in a higher antitumour activity compared with a single treatment with either vesnarinone or radiation alone. Further, vesnarinone treatment together with radiation and conventional anticancer agents including 5-FU and picibanil (an immunopotentiator) produced the highest antitumour effect compared with any other treatment. Additionally, the combination treatment induced marked differentiation and apoptosis of the tumour cells and an increase in the expression of p53 gene in the treated tumour cells. The results suggest that vesnarinone, in combination with radiation and the conventional antitumour agents, may be of clinical interest for treatment of certain types of gastric tumours.
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PMID:Enhancement of anticancer effects of radiation and conventional anticancer agents by a quinolinone derivative, vesnarinone: studies on human gastric cancer tissue xenografts in nude mice. 956 10

Cardiotoxicity is an uncommon side-effect of 5-FU-based chemotherapy. Coronary artery vasospasms have been postulated to be involved in the pathogenesis of this rare but serious problem. We found high plasma levels of ET-1, a potent natural vasoconstrictor, in two patients who experienced two of the commonest clinical manifestations of 5-FU-induced cardiac toxicity--i.e., angina pectoris and chronic heart failure. We, therefore, propose ET-1 as the ultimate mediator of this toxicity, even though the mechanism of ET-1 increase in peripheral venous blood is still unknown. Finally, another important question still remains unresolved: is the release of ET-1 from normal coronary endothelial cells the prime cause or simply the consequence of 5-FU-related cardiotoxicity?
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PMID:Endothelin-1 and 5-fluorouracil-induced cardiotoxicity. 968 87

Cardiovascular emergencies in oncology patients include all of the usual cardiac problems, as well as complications of cancer and its therapy. Pericardial effusions and tamponade, cardiac masses, and extrinsic compression of the heart and great vessels by tumor masses, or fluid collections may all occur. Certain tumors may secrete mediators that are directly toxic to the heart; for example, catecholamines are secreted by pheochromocytomas and serotonin is secreted by carcinoid tumors. Tumors can also cause arrhythmias due to the mediators they secret or to direct mechanical irritation of the heart or pericardium. Cancer therapy is also associated with cardiac emergencies. Perioperative myocardial ischemia or infarction, as well as arrhythmias, may complicate surgery. Pericardial effusions and tamponade can follow surgery, radiation, or chemotherapy. Chemotherapy with anthracyclines, mitoxantrone, and trastuzumab may prompt acute and chronic heart failure. 5-Fluorouracil causes coronary spasm in some patients, leading to angina, myocardial infarction, arrhythmias, and/or sudden death. Cyclophosphamide, particularly in high doses, may produce acute myopericarditis. Radiation may cause acute pericardial disease and late sequelae such as myocardial infarction, acute valvular insufficiency, or effusive constrictive pericarditis. Endocarditis also occurs in cancer patients in association with vascular access devices and immune compromise. This review will discuss each of these complications of cancer and its therapy.
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PMID:Cardiovascular emergencies in the cancer patient. 1086 14

There have been few effective chemotherapeutic regimens for scirrhous type gastric cancer. A 62-year-old male patient was admitted to our hospital because of anorexia and abdominal discomfort. Gastroendoscopy showed a type 4 advanced gastric cancer in the upper gastric body. Histologic study of biopsy specimens from the tumor revealed poorly differentiated adenocarcinoma. Examination by computed tomography and ultrasonography revealed swollen paraaortic lymph nodes and peritonitis carcinomatosa. The patient was diagnosed as having a nonresectable scirrhous type gastric cancer with peritonitis carcinomatosa and paraaortic lymph node metastasis. This patient was treated weekly with an intraarterial 5-FU (500 mg) and MTX (100 mg) including AT-II by a subcutaneously implanted port system placed into the thoracic aorta. Furthermore, he was administered tegafur/uracil (400 mg/day) 5 days weekly as a pharmacokinetic modulating chemotherapy (PMC). After eight courses of treatment of PMC, paraaortic lymph node swelling and ascites decreased. This chemotherapy produced a partial response in the peritonitis carcinomatosa and paraaortic lymph nodes. This chemotherapy was repeated preoperatively. We reconsidered this case to show indications for operation. The patient died suddenly of acute heart failure before the operation. This therapy was considered an effective treatment for nonresectable gastric cancer.
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PMID:[A case of nonresectable scirrhous type gastric cancer treated by hypertensive subselective chemotherapy with pharmacokinetic modulating chemotherapy]. 1152 32

5-fluorouracil (5FU) is a largely employed antimetabolite, responsible for several well-known toxicities like hand-foot syndrome, diarrhoea, mucositis or leucopenia. Cardiotoxicity of 5-FU is known but uncommon and usually not life-threatening. The incidence has varied from 1.5 and 18%. The physiopathology is controversial, although more recent data suggest a myocardial toxicity. Clinical presentation include chest-pain, cardiac arrythmia, myocardial infarction or global cardiac failure. Electrocardiographic features are usually aspecific, with ischemic signs. The main treatment is to stop the 5-FU infusion and to introduce symptomatic cardiologic treatment. Although the prognosis is good, the mortality ranges between 2.2 and 13% in case of symptomatic cardiotoxicity. Secondary prophylaxis remains controversial.
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PMID:[Cardiotoxicity of 5-fluorouracil]. 1589 22

Over the last 20 years, the increase in the cure rate of childhood cancer and leukemia of almost 80% has facilitated the observation of middle and long-term sequelae, particularly of cardiovascular origin; such after-effects are the consequence of cytotoxic damage to the cells of the cardiovascular system, in particular by anthracyclines and radiotherapy, and all the more so by their combined use. Such destructive lesions to myocytes greatly hinder the capacity of the cardiac muscle to hypertrophy to meet the needs of bodily growth, pregnancy and certain intense sports activities. Endothelial cells also accelerate an early arteriosclerotic process, a potential cause of sudden death in the case of ostial stenosis. All such phenomena build up over time, together with the usual adult cardio-vascular risk factors. Finally, no cardiac tissue, pericardial, valvular endocardium or autonomic nervous tissue escapes these cytotoxic effects, giving rise to pericarditis, calcification, valvular leaks and arrythmias and conduction abnormalities. The resulting excessive cardiac mortality is one of the major concerns of paediatric oncologists, along with secondary tumours and leukaemia. This article analyses physiopathological consequences that are often asymptomatic or clinical, together with diagnostic, screening and follow-up methods for these patients, encouraging lifestyle modifications where appropriate or, when possible, treatment before the appearance of cardiac failure, myocardial infarction or sudden death. Other cytotoxic drugs such as high-dose cyclophosphamide, amsacrin, 5-FU and tubulin acting agents are also mentioned as a result of their cardiac toxicity, but this is not usually dose-cumulative.
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PMID:[Cardiac toxicity of cancer treatment regimes in children and adolescents: physiopathology, clinical data and the paediatric oncologist's point of view]. 1589 26

Newer cancer therapies have improved the survival of patients with cancer and, in some cases, turned cancer into a chronic disease. Patients are now surviving long enough for the adverse cardiovascular effects of some cancer therapies to become apparent. The anthracyclines are perhaps the most notorious offenders. Acute reactions include chest discomfort and shortness of breath consistent with a myopericarditis. Toxicity can also develop months after the last chemotherapy dose and typically presents as new onset heart failure with left ventricular systolic dysfunction. Late reactions are seen years after presentation as new-onset cardiomyopathy, often in patients who were treated for childhood neoplasms. 5-Fluorouracil, its prodrug capecitabine, and trastuzumab, a tumor-specific antibody, have also been associated with cardiotoxicity. Until adequate predictive models, prevention modalities, and treatments can be identified, the clinician's focus should be on aggressive monitoring for early signs of cardiac dysfunction in order to prevent severe systolic dysfunction and its concomitant morbidity and mortality.
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PMID:Chemotherapy and cardiotoxicity. 1866 Jul 28


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