Magnesium supplements with cisplatin chemotherapy.
Explore the source record for details and available documents.
Antineoplastic Agents↗
Biomedical subjects
T R Evans
Publications and source records attributed to T R Evans.
A phase II study of continuous-infusion 5-fluorouracil with cisplatin and epirubicin in inoperable pancreatic cancer.
Carcinomas of the exocrine pancreas respond poorly to most chemotherapy regimens. Recently continuous infusional 5-fluorouracil (200 mg m-(2)day-1) with 3 weekly cisplatin (60 mg m-2) and epirubicin (50 mg m-2) (the ECF regimen) has proven to be an active regimen in gastric and breast cancer and consequently worthy of further study in pancreatic cancer. Thirty-five patients were treated with the ECF regimen as above, of whom 29 were evaluable for response and 32 were evaluable for toxicity. The mean age was 59 years (range 37-75). Sixteen patients had locally advanced disease at presentation and 19 had metastases. Objective tumour responses were documented in five (17.3%) patients who achieved a partial response; in 18 (62%) patients there were no change and six (20.7%) patients progressed on therapy. Patients with either stable disease or partial response had a significantly improved overall survival (median = 253 days) compared with patients who progressed (median = 170 days; P = 0.01). Grade 3/4 (WHO) toxicity (all cycles) included alopecia in 18 (56%) patients, nausea/vomiting in eight (25%) stomatitis in three (9%) and diarrhoea in seven (22%) patients, with rhinorrhoea and excessive lacrimation in one patient each. Neutropenic sepsis occurred in 13 cycles in ten patients, and there was one toxic death due to sepsis. There were eight other episodes of non-neutropenic sepsis requiring hospital admission. Fourteen patients (40%) experienced complications with their Hickman lines, including thrombotic episodes (six patients) or their line falling out (five patients). ECF can prolong survival in patients with locally advanced or metastatic pancreatic cancer who demonstrate a response or stabilisation of their disease. However, this is associated with considerable toxicity.
Adenocarcinoma↗
A randomised study to determine whether routine intravenous magnesium supplements are necessary in patients receiving cisplatin chemotherapy with continuous infusion 5-fluorouracil.
Cisplatin is an effective antineoplastic agent, but can cause renal tubular damage leading to urinary magnesium wasting and hypomagnesaemia. Cisplatin and 5-fluorouracil, when used in combination, have synergistic antitumour activity in upper gastrointestinal malignancies, but it is unclear whether they have additive effects on renal magnesium loss. To determine the optimal regimen for magnesium supplementation in these patients, we have conducted a randomised trial of routine intravenous magnesium supplements compared with magnesium given on an 'as required' basis. 32 patients were randomised to receive magnesium intravenously in prehydration and posthydration fluids with cisplatin chemotherapy, or to receive magnesium only when the serum level was low. 5-fluorouracil was given as a continuous infusion. Serum magnesium was measured on admission for each cycle of chemotherapy and an interim measurement performed between each cycle. 28 patients were evaluable. All patients randomised to receive magnesium on an 'as required' basis had at least one episode of hypomagnesaemia. On subsequent admissions for chemotherapy (cycles 2 and 3), the mean serum magnesium level was significantly lower in these patients compared with patients who received magnesium routinely (P < 0.05). After omission of magnesium from the first cycle of cisplatin, magnesium supplements were necessary in 50% of subsequent cycles, usually by the second or third cycle. Moreover, there were several instances of symptomatic hypomagnesaemia requiring further intravenous supplements in mid-cycle. Patients treated with a combination of cisplatin and 5-fluorouracil should be given intravenous magnesium supplements with each cycle of cisplatin chemotherapy. Nevertheless, episodes of hypomagnesaemia still occur, and additional intravenous supplements may be required, highlighting the importance of measuring this electrolyte.
Adult↗
Oesophageal varices: a potentially fatal complication of liver metastases.
Haemorrhage from oesophageal varices is a common and potentially life-threatening complication of portal hypertension, which is usually due to cirrhosis of the liver. Although liver metastases and hepatic dysfunction frequently occur in malignant disease, reports of oesophageal varices arising as a consequence of metastatic liver disease are sporadic, suggesting that this complication is unusual. Indeed, one review of the literature identified only 23 cases, although a few others have subsequently been reported. The management of such patients bleeding from oesophageal varices is clearly very different from bleeding due to other causes such as peptic ulceration. We report three cases and review the literature. All of our cases presented to us within a period of one year, suggesting that this complication of metastatic liver disease is more common than originally considered to be the case.
Aged↗
Primary non-Hodgkin's lymphoma of the thyroid with bone marrow infiltration at presentation.
Primary non-Hodgkin's lymphoma of the thyroid is predominantly a disorder of elderly females. Most patients present with limited disease and receive local irradiation. Presentation with advanced disease is uncommon and, consequently, bone marrow examination is not always done. We report a patient with primary thyroid lymphoma who had bone marrow infiltration at presentation and discuss the importance of this investigation in management.
Aged↗
Eosinophilic folliculitis occurring after bone marrow autograft in a patient with non-Hodgkin's lymphoma.
Eosinophilic pustular folliculitis is a rare disorder previously reported predominantly in Japanese people who are otherwise healthy. Recently, the disorder has been noted in patients with acquired immune deficiency syndrome, as has eosinophilic folliculitis, a similar but distinct entity. The authors report a patient with eosinophilic folliculitis who was immunocompromised after high dose chemotherapy and bone marrow autograft for treatment of non-Hodgkin's lymphoma.
Adult↗
Mechanisms in removal of tumor by antibody.
We report two preliminary trials of antibody treatment of B-cell lymphoma. Advanced lymphoma was treated with chimeric FabFc2, in which mouse Fab' gamma is linked to two human Fc gamma 1 fragments so as to recruit natural effectors to tumor targets. Terminal lymphoma was treated with bispecific antibody (BsAb) which recruits the ribosome-inactivating protein saporin. These different mechanisms led to interesting differences in patterns of tumor clearance. Eight patients were treated with chimeric antibody of two specificities, each at 12 mg/kg: anti-CD37, plus either anti-CD38 or anti-CD19 according to tumor phenotype. On completion of the 3-wk treatment, residual plasma antibody had a half-life exceeding 10 d. Tumor cells in blood disappeared rapidly. However significant reductions in solid masses occurred in only three patients, becoming apparent 3-4 wk after beginning treatment and then continuing slowly. Five patients were treated with preformed immune complexes of saporin and F(ab' gamma)2 BsAb. Although doses of saporin reached 10 mg weekly, contact with the tumor can only have been fleeting: plasma antibody was undetectable (< 0.5 micrograms/mL) 48 h after infusion, whereas the saporin disappeared even faster and was undetectable (< 4 ng/mL) at 24 h. Tumor cells disappeared from the blood more slowly than occurred with chimeric antibody. In contrast shrinkage of extravascular tumor was more rapid, and occurred in all patients, but proved less durable.
Antibody Specificity↗
Student nurses can defibrillate within 90 seconds. An evaluation of a training programme for third year student nurses in the use of an automatic external defibrillator.
Automatic external defibrillators (AEDs) provide a means of reducing the response time in cardiac arrests but policies based on their use must take into account the costs of retraining. These depend on the level of retention of skills over time. This paper describes the retention of skills by student nurses following a training programme on the use of AEDs in cardiac resuscitation. Sixty-three student nurses were studied at intervals of 1 week, 1, 3 and 6 months following training. There was a slight deterioration in skills at 1 week and 1 month but the scores returned to the baseline level at 3 months and remained there. We conclude that there is now a case for a major study of the use of nurse-operated AEDs in the hospital setting.
Clinical Competence↗
Training St John Ambulance volunteers to use an automated external defibrillator.
The key to improving survival from pre-hospital cardiac arrest lies in reducing the time interval between onset of cardiac arrest and defibrillation. Placing automated external defibrillators at strategic points in the community could potentially reduce this time interval, but would necessitate widespread training in defibrillation for lay people in addition to health care workers. There are unanswered questions regarding the ability of lay people to acquire and retain this skill when the training programme is, by necessity, very brief, (otherwise it would not be possible to train large enough numbers of people) and the skill is used infrequently. In this study, nurse and lay volunteer first-aiders were taught to use an automated external defibrillator, either by a 2-h, or a 4-h course, and their skills were assessed at training, and at 3 and 6 months afterwards. Using stringent assessment criteria, 54% of volunteers passed the assessment at every session. Little difference in acquisition or retention of skills between the nurse and lay volunteers, and the 2- and 4-h course groups was found. It is concluded that brief training in defibrillation for volunteer first-aiders is feasible.
Ambulances↗
Lack of inhibition of placental estrone sulfatase and aromatase enzymes by vitamin D3 and its analogs.
The aromatase and estrone sulfatase enzymes are important sources of biologically active estrogens in postmenopausal women with breast cancer. Promising initial results in the treatment of endocrine-responsive breast cancer have been exhibited by 1 alpha 25-dihydroxyvitamin D3 and the synthetic vitamin D analogues MC903 and EB1089. However, these compounds together with vitamin D3 and vitamin D3 sulfate did not inhibit the human placental aromatase enzyme when assayed up to 20 microns. Only vitamin D3 sulfate and 1 alpha 25-dihydroxyvitamin D inhibited the estrone sulfatase activity in human placental microsomes, albeit at high concentration (32 and 37% inhibition, respectively with 50 microns each inhibitor). It is unlikely that inhibition of aromatase or estrone sulfatase enzymes contribute to the inhibitory effect of this group of compounds on breast cancer cells in vivo.
Aromatase Inhibitors↗
Clinical applications of new aromatase inhibitors.
Explore the source record for details and available documents.
Animals↗
Intratumoral oestrone sulphatase activity as a prognostic marker in human breast carcinoma.
Oestrone sulphatase is an important source of local synthesis of biologically active oestrogens in human breast cancer. The oestrone sulphatase enzyme in the particulate fraction of human breast carcinoma was characterised. The Km was 8.91 microM, and the Vmax was 0.022 nmol min-1 mg-1. Oestrone sulphatase activity was detected in 93 of 104 human breast carcinoma samples (89%), and mean activity was 0.041 nmol min-1 mg-1 (range 0-0.399 nmol min-1 mg-1). There was no significant correlation between intratumoral oestrone sulphatase activity and oestrogen receptor status, or with any other prognostic factors. Intratumoral enzyme levels were not associated with time to recurrence or with overall survival time. It thus appears that, although a useful source of intratumoral oestrogens, oestrone sulphatase activity is not of prognostic significance in breast carcinoma.
Adult↗
Protracted oral etoposide in epithelial ovarian cancer: a phase II study in patients with relapsed or platinum-resistant disease.
This phase II study evaluates the efficacy and toxicity of a prolonged schedule of oral etoposide in patients with measurable advanced ovarian cancer resistant to, or relapsed following, platinum-based chemotherapy. Forty-seven patients participated, 20 of whom had received more than one prior treatment. Seventy-seven per cent had evidence of disease progression during or within 6 months of the previous chemotherapy. Initially, oral etoposide, 50 mg b.d. (regardless of patient size), was given for 14 days on a 21-day cycle. However, after encountering toxicity, the schedule was modified to 7 days' treatment escalating to 10 then 14 days if well tolerated. Among 41 assessable patients there were two complete and eight partial objective responses (24% response rate; 95% confidence interval 12-41%). Nine further patients (22%) had stable disease, four with a sustained fall of > 50% in CA-125. Median duration of response or stable disease was 35 weeks (range 21-49). Overall median survival was 41 weeks from study entry (range 2 to 96+ weeks). Toxicity for most patients was mild, but sporadic severe myelotoxicity occurred, with two treatment-related deaths. Risk factors for severe toxicity were: performance status 3; hepatic impairment; renal impairment. We conclude that oral etoposide has activity in platinum-resistant ovarian cancer and that it is a useful palliative therapy. It has significant toxicity which may be avoided by appropriate patient selection and an escalating-duration schedule.
Administration, Oral↗
A randomised prospective trial of surgical against medical tetracycline pleurodesis in the management of malignant pleural effusions secondary to breast cancer.
Malignant pleural effusion is a frequent complication of metastatic breast cancer leading to a significant degree of morbidity. Drainage of the effusion by thoracocentesis and pleurodesis with tetracycline as the sclerosing agent is an established means of symptomatic relief in these patients. To determine whether the efficacy of tetracycline pleurodesis is improved by surgical rather than medical drainage and instillation of sclerosant, 34 patients were prospectively randomised to a trial comparing the two treatment modalities, of whom 29 were evaluable for response. The total failure rate of primary pleurodesis was 13.4%, the rate of recurrence of effusion within the first month was 24%, and only 1 patient (3.4%) required repeat aspiration in that time period. There was no significant difference in the rate of recurrence or reaspiration of effusion between the two treatment groups. Although the overall survival time from treatment of effusion is significantly longer in the surgical treatment group than in the medical treatment group (P = 0.03), this is likely to be due to factors other than the method of treating the effusion. We conclude that surgical tetracycline pleurodesis has no advantage over medical tetracycline pleurodesis.
Adult↗
Prognostic significance of aromatase and estrone sulfatase enzymes in human breast cancer.
The aromatase and estrone sulfatase enzymes are important sources of local synthesis of biologically active estrogens in human breast cancer. Significant intratumoral aromatase activity was detected in 91/145 (63%) of tumors and estrone sulfatase was detected in 93/104 (89%) of tumors. There was no relationship between aromatase activity and tumor size, site, nodal status, menopausal status or estrogen receptor status. There was a significant correlation between the aromatase activity and histological grade, with an excess of aromatase-positive in the high grade tumors (P = 0.03). There was a marginally inverse correlation between the aromatase activity and time to relapse (P < 0.1), a significant correlation between aromatase activity and survival after relapse (P < 0.05) but not with overall survival (P > 0.1). Intratumoral estrone sulfatase activity was not significantly correlated to any putative prognostic factors, nor with time to relapse nor overall survival time.
Aromatase↗
Detection of breast cancer-associated estrone sulfatase in breast cancer biopsies and cell lines using polymerase chain reaction.
Steroid sulfatase (STS) is a single enzyme with a range of substrate specificities, including estrone sulfate. Using a 2.4 kb cDNA clone, expression of human STS was undetectable by Northern hybridization, but STS RNA was detected in human placenta, human breast cancer samples, and in breast carcinoma cell lines following reverse transcriptase-PCR amplification, using specific primers to yield a product of 472 bp. In preliminary studies, stimulation of MCF-7 cell lines with estradiol (10(-8) M) resulted in an increased level of amplifiable STS RNA, and this upregulation of STS RNA could be abolished by tamoxifen. The estrone sulfatase activity in mammary tumors derived from N-nitrosomethylurea (NMU) treated rats was significantly decreased in animals treated with tamoxifen compared to control animals, regardless of the response of the tumors to the antiestrogen (P < 0.05). Although tamoxifen does not inhibit the estrone sulfatase enzyme in vitro, it may modulate the expression of STS RNA and the enzyme activity in vivo.
Animals↗
The biological evaluation of novel antioestrogens for the treatment of breast cancer.
Explore the source record for details and available documents.
Breast Neoplasms↗
Response of metastatic anal carcinoma to single agent carboplatin.
The management of locoregional squamous cell carcinoma of the anus with a combined modality approach comprising chemotherapy and radiotherapy is well established. However, the optimum regimen for the management of metastatic disease has yet to be determined. Cisplatin has been shown to have some efficacy in this disease. We report a case of partial response of metastatic disease to single agent carboplatin, and discuss its role in this situation.
Anus Neoplasms↗