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At least 19 recordsLinked to original sources
PubMed1989

Consensus development conference statement: blood cholesterol and coronary heart disease. Academy of Finland, Medical Research Council.

Medical Research Council, Academy of Finland convened a Consensus Development Conference on Blood Cholesterol and Coronary Heart Disease on April 24-26, 1989. After hearing a series of expert presentations a consensus panel of cardiologists, lipoprotein experts, experts in preventive medicine, health administrators, nutritionists, social scientists, representatives of food industry and agriculture, and lay representatives considered the available evidence and agreed on answers to the following questions: 1) Why are blood cholesterol levels so high in Finland? 2) How could blood cholesterol levels be reduced in the population and in different population groups? 3) How should individuals with an exceptionally high blood cholesterol levels be identified? 4) When and how should cholesterol levels be reduced among individuals? 5) Are there any adverse effects from lowering blood cholesterol levels or in associated measures? 6) What are the problems that require further investigation? This paper contains the consensus statement of the panel.

Adult↗
PubMed1997

Immediate versus deferred treatment for advanced prostatic cancer: initial results of the Medical Research Council Trial. The Medical Research Council Prostate Cancer Working Party Investigators Group.

OBJECTIVE: To compare the effect on the course of advanced prostate cancer of hormone treatment commenced on diagnosis with that deferred until clinically significant progression occurs. PATIENTS AND METHODS: Nine hundred and thirty-eight patients with locally advanced or asymptomatic metastatic prostate cancer were randomized either to immediate treatment (orchidectomy or luteinizing hormone-releasing hormone analogue) or to the same treatment deferred until an indication occurred. Follow-up and management were otherwise according to the participating clinician's normal practice. Information was collected annually on survival, local and distant progression, and major complications (pathological fracture, spinal cord compression, ureteric obstruction and extra-skeletal metastases). RESULTS: Follow-up data were returned on 934 patients; 51 deferred patients died from causes other than prostate cancer before treatment was started (but only five of these presented at age < 70 years) and 29 died from prostate cancer before treatment could be started. Treatment was commenced for local progression almost as frequently as for metastatic disease. Progression from M0 to M1 disease (P < 0.001, two-tailed) and development of metastatic pain occurred more rapidly in deferred patients; 141 deferred patients needed transurethral resection for local progression compared with 65 treated immediately (P < 0.001, two-tailed). Pathological fracture, spinal cord compression, ureteric obstruction and development of extra-skeletal metastases were twice as common in deferred patients. Of the patients who died, 67% did so from prostate cancer; 361 patients died in the deferred arm compared with 328 in the immediate arm (P = 0.02, two-tailed), where 257 and 203 were deaths from prostate cancer, respectively (P = 0.001 two-tailed). This difference was seen largely in MO patients, with 119 and 81 deaths from prostate cancer, respectively (P < 0.001 two-tailed). CONCLUSIONS: The results consistently favour immediate treatment, although some of the data, especially on MO patients, are immature. The implications for management of advanced prostate cancer are discussed.

Adult↗
PubMed1994

The effect of intravesical thiotepa on tumour recurrence after endoscopic treatment of newly diagnosed superficial bladder cancer. A further report with long-term follow-up of a Medical Research Council randomized trial. Medical Research Council Working Party on Urological Cancer, Subgroup on Superficial Bladder Cancer.

OBJECTIVE: To determine the role, if any, of one and five installations of intravesical thiotepa in the treatment of newly diagnosed superficial bladder cancer. PATIENTS AND METHODS: A multicentre randomized clinical trial was carried out involving 417 patients with newly diagnosed superficial bladder cancer. After transurethral resection the patients were randomized into one of three treatment arms: no thiotepa; one instillation of thiotepa at the time of resection; one instillation at time of resection and then at 3-monthly intervals for one year (giving a total of five instillations). In all treatment arms the dosage was 30 mg thiotepa in 50 ml saline. The main outcome measures were time to first superficial recurrence, recurrence rate (defined as the number of possible cystoscopies per annum) and failure-free interval rate (where failure was defined as the development of invasive disease, metastatic disease or death from bladder cancer). RESULTS: After a median follow-up of 8 years and 9 months analysis showed no evidence of a difference between the three groups with respect to time to first recurrence, recurrence rates or the failure-free interval rate. CONCLUSIONS: This analysis confirms that the thiotepa regimens tested cannot be recommended for use outside clinical trials for patients with newly diagnosed superficial bladder cancer.

Administration, Intravesical↗
PubMed1999

Optimal planning target volume for stage I testicular seminoma: A Medical Research Council randomized trial. Medical Research Council Testicular Tumor Working Group.

PURPOSE: To compare relapse rates and toxicity associated with para-aortic (PA) strip or PA and ipsilateral iliac lymph node irradiation (dogleg [DL] field) (30 Gy/15 fractions/3 weeks) for stage I testicular seminoma. PATIENTS AND METHODS: Between July 1989 and May 1993, 478 men with testicular seminoma stage I (T1 to T3; no ipsilateral inguinoscrotal operation before orchiectomy) were randomized (PA, 236 patients; DL, 242 patients). RESULTS: Median follow-up time is 4.5 years. Eighteen relapses, nine in each treatment group, have occurred 4 to 35 months after radiotherapy; among these, four were pelvic relapses, all occurring after PA radiotherapy. However, the 95% confidence interval (CI) for the difference in pelvic relapse rates excludes differences of more than 4%. The 3-year relapse-free survival was 96% (95% CI, 94% to 99%) after PA radiotherapy and 96.6% (95% CI, 94% to 99%) after DL (difference, 0.6%; 95% confidence limits, -3.4%, +4.6%). One patient (PA field) has died from seminoma. Survival at 3 years was 99.3% for PA and 100% for DL radiotherapy. Acute toxicity (nausea, vomiting, leukopenia) was less frequent and less pronounced in patients in the PA arm. Within the first 18 months of follow-up, the sperm counts were significantly higher after PA than after DL irradiation. CONCLUSION: In patients with testicular seminoma stage I (T1 to T3) and with undisturbed lymphatic drainage, adjuvant radiotherapy confined to the PA lymph nodes is associated with reduced hematologic, gastrointestinal, and gonadal toxicity, but with a higher risk of pelvic recurrence, compared with DL radiotherapy. The recurrence rate is low with either treatment. PA radiotherapy is recommended as standard treatment in these patients.

Adolescent↗
PubMed1995

Intensification of treatment and survival in all children with lymphoblastic leukaemia: results of UK Medical Research Council trial UKALL X. Medical Research Council Working Party on Childhood Leukaemia.

The UK Medical Research Council trial MRC UKALL X was designed to investigate the benefit of one or two courses of additional intensification therapy in children with acute lymphoblastic leukaemia receiving standard treatment. From 1985 to 1990 1612 children, comprising more than 90% of eligible cases in the UK, were treated with intensive induction therapy, central nervous system directed therapy with cranial irradiation and intrathecal methotrexate, and continuing treatment for 2 years. 1171 children were randomised to receive additional intensification therapy at 5 weeks, 20 weeks, both, or neither. At follow-up of at least 3 years disease-free survival for all children at 5 years was 62% (95% confidence interval [Cl] 60.0-64.4), a significant improvement over the 56% (53.0-59.6) found in the preceding MRC UKALL trial. The 5-year disease-free survival was 71% (65.5-76.1) for children randomised to two blocks of intensification therapy, this being significantly better than the 62% (56.6-68.0), 61% (55.7-67.1), and 57% (50.9-62.7) rates for the groups randomised to one intensification block at 5 weeks, one at 20 weeks, and no intensification, respectively. The benefits of intensification therapy were seen irrespective of clinical factors known to influence outcome such as age, sex, and initial leucocyte count. We conclude that the addition of two courses of intensification therapy has produced a 14% improvement in disease-free survival and an 11% improvement in overall survival for the randomised patients. This additional treatment is of benefit to all children with acute lymphoblastic leukaemia, even those traditionally deemed at lower risk of relapse.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Improving survival without reducing quality of life in small-cell lung cancer patients by increasing the dose-intensity of chemotherapy with granulocyte colony-stimulating factor support: results of a British Medical Research Council Multicenter Randomized Trial. Medical Research Council Lung Cancer Working Party.

PURPOSE: The treatment of small-cell lung cancer patients with good performance status aims to improve survival. Dose-intensification could be a way to achieve improved survival but can be limited by neutropenia and thrombocytopenia. Preliminary, nonrandomized feasibility studies showed that doxorubicin, cyclophosphamide, and etoposide (ACE) could be given every 2 (instead of the usual 3) weeks with granulocyte colony-stimulating factor (G-CSF) (lenograstim; Chugai-Rh¿one-Poulenc, Tokyo, Japan) support. The present multicenter randomized trial was designed to examine whether such dose-intensification improves survival while maintaining acceptable toxicity levels. PATIENTS AND METHODS: All patients were randomized to receive six cycles of ACE either every 3 weeks (control [C] group) or every 2 weeks with G-CSF (G group). The standard dose-intensity of ACE was increased by 50% in group G. RESULTS: Four hundred and three patients (G group: n = 201; C group: n = 202) were randomized. The received dose-intensity was 34% higher in the G group than in the C group. Complete response rates were 40% for the G group and 28% for the C group (P =.02), and overall rates were 78% for the G group and 79% for the C group. Survival was longer in the G group (hazard ratio = 0.80; 95% confidence interval, 0.65 to 0.99; P =.04), survival rates for the G and C groups being 47% and 39% at 12 months and 13% and 8% at 24 months, respectively. Metastasis-free survival, nonhematologic toxicity, and quality of life were similar in the two groups. In the G group, there was less neutropenia but more thrombocytopenia and more frequent blood and platelet transfusions. CONCLUSION: Increasing the dose-intensity of ACE with G-CSF support improved survival while maintaining acceptable toxicity.

Adult↗
PubMed1997

Intensification of treatment for adults with acute lymphoblastic leukaemia: results of U.K. Medical Research Council randomized trial UKALL XA. Medical Research Council Working Party on Leukaemia in Adults.

The MRC UKALL XA trial for patients aged 15 years and over with acute lymphoblastic leukaemia was designed to evaluate short blocks of intensive 'AML-style' treatment. Between 1985 and 1992, 618 eligible patients were entered into the trial. 450 patients were randomized to receive early intensification at 5 weeks, late intensification at 20 weeks, both, or neither. Unlike the concurrent children's trial, UKALL X, which was of similar design, UKALL XA does not demonstrate a clear benefit for intensification, although there was a significant reduction in the relapse risk due to the early block. The estimated increase in disease-free survival at 5 years was 2% with 95% confidence interval from 1% reduction to 5% increase. There may be a real difference between the effect of these treatments in adults and in children, but this result may be somewhat weakened by poorer compliance, with a greater proportion of adults not receiving the treatment arm to which they were randomized.

Adolescent↗
PubMed2005

Early mortality after diagnosis of multiple myeloma: analysis of patients entered onto the United kingdom Medical Research Council trials between 1980 and 2002--Medical Research Council Adult Leukaemia Working Party.

PURPOSE: Early mortality in multiple myeloma (MM) is usually attributed to combined effects of active disease and comorbid factors. We have studied early deaths in a series of large multicenter trials to assess direct causes of death, their predictability, and whether current management strategies have reduced their frequency. PATIENTS AND METHODS: A total of 3,107 newly diagnosed patients entered onto United Kingdom Medical Research Council MM trials from 1980 to 2002 were studied. Trial files, final clinical summaries, and postmortem reports were analyzed. RESULTS: Death within 60 days of trial entry occurred in 299 patients (10%). Logistic regression modeling identified beta 2-microglobulin, performance status, and age as the most important predictors of early death, but only with 61% sensitivity and 73% specificity. Forty-five percent of deaths were attributable to infection, which was often associated with bone pain (particularly thoracic pain) and delay in presenting to medical care. Neutropenia was present at diagnosis in only 11 of the 135 deaths from infection. Renal failure was present in 28% of early deaths and was linked to light-chain MM, hypercalcemia, dehydration, and nonsteroidal anti-inflammatory drugs. There was no time related reduction in the percentage or nature of early deaths in 1,550 patients older than 65 years receiving similar therapy between 1982 and 2002. CONCLUSION: A tenth of patients die within 60 days of diagnosis of MM. Infection and renal failure are the main direct causes of early mortality, which cannot be accurately predicted by presenting prognostic features. All patients should be considered at high risk of death during induction therapy.

Age Factors↗
PubMed1987

Comparison of the antihypertensive efficacy and adverse reactions to two doses of bendrofluazide and hydrochlorothiazide and the effect of potassium supplementation on the hypotensive action of bendrofluazide: substudies of the Medical Research Council's trials of treatment of mild hypertension: Medical Research Council Working Party.

As substudies of the Medical Research Council's trials of treatment of mild hypertension and of hypertension in the elderly, two studies were carried out comparing the effects of different doses of two diuretics on blood pressure, concentrations of some biochemical variables, and the incidence of subjective adverse reactions. In one study, in which 484 patients with mild hypertension participated, daily doses of bendrofluazide 5 mg and 10 mg, with and without oral potassium supplements, were compared. In the second, involving 701 elderly patients with hypertension, daily doses of hydrochlorothiazide 25 mg together with amiloride 2.5 mg were compared with hydrochlorothiazide 50 mg together with amiloride 5 mg. The mean (+/- SD) durations of treatment were 35 +/- 17 months in the first study and 10 +/- 7 months in the second. Neither study showed any significant difference in blood pressure response to the two doses of diuretic, whereas biochemical changes and the reported incidence of subjective adverse reactions were dose-related. In the first study, potassium supplementation with potassium chloride 16.8 or 33.6 mmol did not have a significant effect on the fall in serum potassium level, which was only slightly reduced, and did not have any significant effect on the antihypertensive effect of either dose of bendrofluazide.

Adult↗
PubMed1998

Improved survival with early intensification: combined results from the Medical Research Council childhood ALL randomised trials, UKALL X and UKALL XI. Medical Research Council Working Party on Childhood Leukaemia.

The Medical Research Council (MRC) United Kingdom trial for childhood acute lymphoblastic leukaemia (UKALL X) randomised patients aged 0-14 years inclusive with an initial white blood count of less than 100 x 10(9)/l to receive an early intensification block, a late intensification block, both, or neither. The next trial, UKALL XI, for children aged 1-14 years, randomised between different central nervous system (CNS) directed therapies. At the beginning of the trial, all patients were also randomised between late intensification alone and both early plus late blocks. The effects of both the early and the late block in UKALL X alone have been reported previously. This paper examines the effect of the addition of the early intensification block to treatment which included late intensification, combining the data from UKALL X and the first part of UKALL XI. Early intensification was associated with fewer bone marrow relapses and a reduction in the odds of death of 0.63 (95% confidence interval: 0.46-0.87). Survival was significantly improved with an increase at 5 years of 8%, from 79 to 87%. Following this demonstration that early intensification improves survival, the effect of a third intensification block is under investigation.

Adolescent↗
PubMed1988

Coronary heart disease in the Medical Research Council trial of treatment of mild hypertension. Medical Research Council Working Party on Mild Hypertension.

Seventeen thousand three hundred and fifty four mildly hypertensive people with diastolic blood pressures between 90 and 109 mm Hg at screening were randomised to active treatment, with bendrofluazide or propranolol, or to placebo tablets. They were followed for a maximum of five and a half years, giving a total of 85,572 patient-years of observation. There were 456 myocardial infarctions or sudden coronary deaths. Drug treatment did not affect the overall rate of coronary events. Rates per thousand person-years were 8.3 and 9.0 in men and 1.8 and 1.7 in women in the active treatment and placebo groups respectively. Event rates were much higher in smokers than in non-smokers on placebo treatment (12.6 and 7.5 in men and 3.5 and 1.0 in women in smokers and non-smokers respectively). An analysis of subgroup results showed a lower event rate in non-smoking men on propranolol than in non-smokers on placebo (5.0 and 7.5 per thousand person-years respectively). Bendrofluazide had no apparent effect on the event rate. The interaction between the type of treatment (propranolol, bendrofluazide, or placebo) and smoking in determining the coronary event rate was not statistically significant, however. The incidence of electrocardiographic changes of silent infarction--that is major Q/QS abnormalities--differed little with sex, smoking habit, or treatment with either active drug.

Adult↗
PubMed1991

Results of Medical Research Council Childhood Leukaemia Trial UKALL VIII (report to the Medical Research Council on behalf of the Working Party on Leukaemia in Childhood).

During the 1970s, despite apparently similar treatment, the prognosis for children with lymphoblastic leukaemia (ALL) improved more in some countries, notably the United States and West Germany, than in others. To find out why, the first phase of the United Kingdom (UK) Medical Research Council (MRC) childhood ALL trial, UKALL VIII, was designed to see whether similar results to the United States Children's Cancer Study Group (CCSG) could be obtained in the U.K. using an identical protocol (CCG 162). Protocol 162 was one of a series of regimens devised by the American Children's Cancer Study Group in the 1970s and was used specifically for their average risk patients (all children with ALL with an initial white cell count up to 50 x 10(9)/l except those aged 3-6 years with white cell counts under 10 x 10(9)/l). One arm (1A) of their study was adopted by the MRC for all children in the U.K. aged 0-14 years with confirmed ALL. Eight hundred and twenty-nine consecutive patients were entered between 1980 and 1984. The first 199 patients formed a single arm study as per the original protocol 162 (arm 1A), but the subsequent 630 children were randomized to receive or not two doses of daunorubicin on the first 2 d of induction. This randomization was an attempt to answer the important question as to whether event-free survival was influenced by the use of four rather than three induction agents. A second randomization between 2 and 3 years continuing therapy was also introduced at this stage as it had been by the CCSG in their protocol. With a minimum follow up period of more than 5 years, disease-free survival for the whole group is 55%, a considerable improvement on all previous UKALL trials. Results for patients directly comparable with those in CCSG 162 ('average risk' patients) and their American counterparts were similar. Daunorubicin was associated with more early deaths but improved disease-free survival for those achieving remission. More children relapsed who stopped treatment after 2 years than those who continued for 3, but this was balanced by increased treatment mortality in the third year. The fact that for UKALL VIII the results were similar to those of the CCSG suggests that previous MRC protocols were not sufficiently sustained and intensive, particularly during the maintenance phase of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1998

Analysis of the immunophenotype of children treated on the Medical Research Council United Kingdom Acute Lymphoblastic Leukaemia Trial XI (MRC UKALLXI). Medical Research Council Childhood Leukaemia Working Party.

Despite many years of meticulous immunophenotyping of childhood acute lymphoblastic leukaemia (ALL) cases the prognostic significance of some subtypes remains unclear. The Medical Research Council UKALLXI trial (1990-1996) in which uniform treatment has been given to 2090 children with ALL below the age of 18 years and above the age of 1 year, has afforded the opportunity to review these issues. Children with ALL of mature B cell type were not entered into this trial. Immunophenotype analysis was performed in each individual trial centre, but results were centrally reviewed in all cases, and were both available and considered adequate in 1934 (93%) of the first 2090 patients entered. The main diagnostic categories were early pre-B or null reported in 60 cases (3.1%), common ALL in 1242 (64.2%), pre-B in 252 (13.0%), 'common' or pre-B in 172 (8.9%) and T cell in 207 (10.7%) cases. Children with T cell disease were significantly more likely to be over the age of 10 years, with central nervous system disease at diagnosis and to be CD34 negative. They also had a higher incidence of high white cell count and were more likely to be of the French-American-British (FAB) L2 morphological subtype. Patients with 'null' cell disease tended to be less than 2 years or greater than 10 years of age, and CD13 and CD33 positive. CD10 was associated with lower white cell count (WBC) at diagnosis, younger age and FAB L1 morphological subtype. The presence of cytoplasmic immunoglobulin in pre-B cells was not associated with any specific clinical or laboratory features. CD34 positivity was less common in T cell patients and was associated with low WBC. Disease-free survival (DFS) and 95% confidence intervals (CI) at 5 years from diagnosis was 52% (95% CI: 44-59%) for T cell disease, 58% (95% CI: 43-73%) for early pre-B (or null cell) disease and 65% (95% CI: 62-68%) for common or pre-B disease; there being no significant difference between common and pre-B disease with regard to disease outcome. Patients with T cell disease had a worse prognosis than any other immunophenotype group (P < 0.00005). However this worse outcome was no longer significant after allowing for the other principal prognostic factors of age, gender and white cell count at diagnosis except for the very small number with WBC <20 x 10(9)/l and T cell disease. Those with CD10-positive leukaemia did better than those who were CD10 negative (P < 0.00005), with DFS at 5 years 64% (95% CI: 62-67%) for positive vs 56% (95% CI: 49-62%) for CD10 negative. CD10 positivity did not have independent significance when white count, gender and age were taken into account. CD13, CD33, and cytoplasmic mu positivity carried no prognostic significance.

Adolescent↗
PubMed1981

Medical Research Council study on chemotherapy in advanced ovarian cancer. Medical Research Council's Working Party on ovarian cancer.

A total of 264 eligible patients with advanced ovarian cancer were randomised to single or triple agent cytotoxic therapy; 261 were available for analysis. The treatments were continuous oral cyclophosphamide (arm S), and a combination of oral cyclophosphamide, hexamethylmelamine and methotrexate on a pulsed basis (arm T). Mortality attributed to cancer was slightly lower on arm T (p = 0.06), but this was offset by the greater toxicity of this regimen, and overall survival and activity index were similar on the two arms. There was thus little evidence of greater clinical benefit on the triple agent regimen. Tumour mass removed at operation, extent of remaining tumour and age all showed significant correlation with prognosis. Survival was longer in patients whose disease responded to either therapeutic regimen.

Aged↗
PubMed1994

Does clinical experience with a treatment regimen affect survival of lung cancer patients? An analysis based on consecutive randomized trials of the Medical Research Council in small cell and non-small cell tumours. Medical Research Council Lung Cancer Working Party.

This paper investigates the influence on patient survival of an individual clinician's experience with a particular treatment regimen and the collective experience of the centre through which the patient is recruited to a particular clinical trial. Data were available from two series of randomized trials, one series in small cell and the other in non-small cell lung cancer, which were conducted by the Medical Research Council Lung Cancer Working Party. Successive small cell trials used the same chemotherapy regimen and successive non-small cell trials the same radiotherapy regimen. We found no evidence that either the degree of experience of individual clinicians with the regimen or the participation in terms of number of patients recruited to centres influenced patient survival. There is a strong suggestion, in non-small cell lung cancer that, as clinicians' experience with the regimen extended, they became increasingly likely to admit patients in poor condition to the trials. We stress how important it is to take account of patient prognostic characteristics in such an analysis, as we found that unadjusted comparisons suggested negative influences of increasing experience with the regimen. The implications for routine audit are self evident, in particular that it is not a substitute for the randomized controlled trial.

Aged↗