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M K Parmar

Publications and source records attributed to M K Parmar.

At least 19 recordsLinked to original sources
PubMed2000

Analysis of messy longitudinal data from a randomized clinical trial. MRC Lung Cancer Working Party.

The randomized clinical trial, LU19, conducted by the Medical Research Council Lung Cancer Working Party, was designed to compare ACE (doxorubicin, cyclophosphamide and etoposide) chemotherapy plus G-CSF (granulocyte colony-stimulating factor) at 2-week intervals versus ACE chemotherapy alone at standard 3-week intervals in patients with small-cell lung cancer. This trial investigated whether more intensive administration of ACE would improve overall survival and affect the quality of life of patients. The report on overall survival and other outcome measures will be published in the Journal of Clinical Oncology. In this paper we focus on methods of analysing aspects of data reflecting quality of life. Twelve symptoms of lung cancer and its treatment - cough, haemoptysis, pain, nausea, vomiting, hoarse voice, sore mouth, rash, lethargy, lack of appetite, alopecia, and dysphagia - were scheduled to be assessed on seven occasions for the ACE arm and on eight occasions for the ACE+G-CSF arm by clinicians during the first 18 weeks of the treatment period. However, in practice the number of assessment forms completed per patient ranged from 1 to 9, and assessment time-points were very different from those planned. These 'messy' longitudinal data are explored by both a summary measure approach, in which experience of a symptom is summarized by a single value, and an extensive model-based statistical approach, which explicitly takes into account correlation within repeated measures. These analyses provide a clear picture of symptom comparisons between the two treatments. The application of various methods offers not only an approach to assessing the robustness of the results but also a basis for investigating reasons for inconsistency of results across methods. We conclude that except lethargy, which is worse in the ACE+G-CSF arm, all symptoms are similar across the two arms during the treatment period.

Amsacrine↗
PubMed2000

A randomized trial of hypofractionated schedules of palliative radiotherapy in the management of bladder carcinoma: results of medical research council trial BA09.

PURPOSE: To compare the efficacy and toxicity of two hypofractionated radiotherapy schedules for the improvement of local symptoms from muscle-invasive bladder cancer. METHODS AND MATERIALS: A multicenter randomized trial was conducted comparing the efficacy and toxicity of two radiotherapy schedules (35 Gy in 10 fractions and 21 Gy in 3 fractions) for symptomatic improvement in patients considered unsuitable for curative treatment through disease stage or comorbidity. The primary outcome measures were overall symptomatic improvement of bladder-related symptoms at 3 months and changes in bladder- and bowel-related symptoms from pretreatment to end-of-treatment and 3-month assessments. Overall symptomatic improvement was defined prospectively as the improvement in one bladder-related symptom of at least one grade at 3 months, with no deterioration in any other bladder-related symptom. RESULTS: Five hundred patients were recruited, but data on symptomatic improvement at 3 months was only available on 272 patients. Of these, 68% achieved symptomatic improvement (71% for 35 Gy, 64% for 21 Gy), with no evidence of a difference in efficacy or toxicity between the two arms. There was no evidence of a difference in survival between the two schedules (hazard ratio [HR] = 0.99, 95% CI 0.82-1.21, p = 0. 933). CONCLUSION: This is the largest prospective trial to date in the palliative treatment of bladder cancer, and provides baseline data against which other results may be compared. The use of 21 Gy in 3 fractions appears as effective as 35 Gy in 10 fractions, although modest differences in survival, symptomatic improvement rates, and toxicity can not be reliably excluded.

Aged↗
PubMed2000

Preoperative radiotherapy for esophageal carcinoma. Oeosphageal Cancer Collaborative Group.

BACKGROUND: The existing randomized evidence has failed to conclusively demonstrate the benefit or otherwise of preoperative radiotherapy in treating patients with potentially resectable esophageal carcinoma. OBJECTIVES: This meta-analysis aimed to assess whether there is benefit from adding radiotherapy prior to surgery and whether or not any pre-defined patient subgroups benefit more or less from preoperative radiotherapy SEARCH STRATEGY: Medline and CancerLit searches were supplemented by information from trial registers and by hand searching relevant meeting proceedings and by discussion with relevant trialists, organisations and industry. SELECTION CRITERIA: Trials were eligible for inclusion in this meta-analysis provided they randomized patients with potentially resectable carcinoma of the esophagus (of any histological type) to receive radiotherapy or no radiotherapy prior to surgery. Trials must have used a randomization method which precluded prior knowledge of treatment assignment and completed accrual by December 1993, to ensure sufficient follow-up by the time of the first analysis (September 1995). DATA COLLECTION AND ANALYSIS: A quantitative meta-analysis using updated data from individual patients from all properly randomized trials (published or unpublished) comprising 1147 patients (971 deaths) from five randomized trials. This approach was used to assess whether preoperative radiotherapy improves overall survival and whether it is differentially effective in patients defined by age, sex and tumour location. MAIN RESULTS: With a median follow-up of 9 years, in a group patients with mostly squamous carcinomas, the hazard ratio (HR) of 0.89 (95% CI 0.78-1.01) suggests an overall reduction in the risk of death of 11% and an absolute survival benefit of 3% at 2 years and 4% at 5 years. This result is not conventionally statistically significant (p=0.062). No clear differences in the size of the effect by sex, age or tumor location were apparent. REVIEWER'S CONCLUSIONS: Based on existing trials, there was no clear evidence that preoperative radiotherapy improves the survival of patients with potentially resectable esophageal cancer. These results indicate that if such preoperative radiotherapy regimens do improve survival, then the effect is likely to be modest with an absolute improvement in survival of around 3 to 4%. Trials or a meta-analysis of around 2000 patients (90% power, 5% significance level) would be needed to reliably detect such an improvement (from 15 to 20%).

Esophageal Neoplasms↗
PubMed1999

Can the published data tell us about the effectiveness of neoadjuvant chemotherapy for locally advanced cancer of the uterine cervix?

The effect of neoadjuvant chemotherapy on survival of patients with locally advanced cervical cancer was investigated by conducting a systematic review and meta-analysis of the published data. Of the 21 randomised trials that we identified, only 15 were published. Furthermore, 2-year survival data could be extracted from only seven trial reports and 3-year survival from only nine trial reports. Meta-analyses of the published data at 2 and 3 years are neither clearly in favour of neoadjuvant chemotherapy nor control (2 years: odds ratio (OR) = 1.09, 95% confidence interval (CI) = 0.83-1.45, P = 0.37; 3 years: OR = 0.96, 95% confidence interval (CI) = 0.73-1.25, P = 0.45). Being restricted to only some of the data from a relatively small fraction of the randomised trials, these analyses potentially suffer from a number of biases and are therefore inconclusive. The only reliable way to judge the value of neoadjuvant chemotherapy in this disease is to perform a meta-analysis of centrally collected, updated, individual data on all patients from all known randomised trials. Such an analysis is currently being carried out by an international collaborative group.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Randomised trials in ovarian cancer: trial design considerations.

Randomised clinical trials are considered the definitive source of evidence for guiding decisions in clinical practice. The concept of a clinical trial is based on sound scientific, ethical, and practical principles. The strength of evidence that an individual trial provides is assessed on the manner in which these principles are incorporated into the design and execution of the trial. Since the way these principles are incorporated into a trial is judgmental, the strength of evidence from an individual trial is a matter of degree. The purpose of this paper is to present some of the scientific, ethical and practical considerations surrounding the selection of endpoints and determination of sample size for trials in ovarian cancer.

Female↗
PubMed1999

Advanced epithelial ovarian cancer: 1998 consensus statements.

BACKGROUND: During an international workshop held in September 1998, a group of specialists in the field of ovarian cancer reached consensus on a number of issues with implications for standard practice and for research of advanced epithelial ovarian cancer. METHODS: Five groups of experts considered several issues which included: biologic factors, prognostic factors, surgery, initial chemotherapy, second-line treatment, the use of CA 125, investigational drugs, intra-peritoneal treatment and high-dose chemotherapy. The group attempted to arrive at answers to questions such as: Are there prognostic factors, which help to identify patients who will not do well with current therapy? What is the current best therapy for advanced ovarian carcinoma? What directions should research take in advanced ovarian cancer? These issues were discussed in a plenary meeting. RESULTS: One of the major conclusions drawn by the consensus committee was that in previously untreated advanced ovarian cancer, cisplatin plus paclitaxel has been shown to be superior to previous standard therapy with cisplatin plus cyclophosphamide (level I evidence). However, for many patients, carboplatin plus paclitaxel is a reasonable alternative because of toxicity and convenience considerations. Most participants felt that the benefits in terms of toxicity for the paclitaxel-carboplatin are such that its widespread adoption at this stage is justified. Until mature survival data are available a minority of investigators would recommend continued use of cisplatin plus paclitaxel, specifically for those patients with advanced disease with the best prognostic characteristics. For future clinical research in this area, new end points for randomised clinical trials, together with a new Trials Network, are proposed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Intergroup collaboration in ovarian cancer: a giant step forward.

The rather slow evolution of so-called "optimal chemotherapy" for ovarian cancer is the result of suboptimal randomised clinical trials, not having the statistical power to identify truly superior regimens, and of the lack of systematic comparisons of new agents with relevant control arms. There is little doubt that we need international collaboration to move the field forward in a timely and coherent manner. European and transatlantic collaboration represents the beginning of the process and point to the success that can await us if the drive to work together remains strong. A similar organisation as for breast cancer (Breast International Group, BIG) needs to be established for ovarian cancer.

Clinical Trials as Topic↗
PubMed1999

Physical and psychological symptoms of quality of life in the CHART randomized trial in head and neck cancer: short-term and long-term patient reported symptoms. CHART Steering Committee. Continuous hyperfractionated accelerated radiotherapy.

The randomized multicentre trial of continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy in patients with advanced head and neck cancer showed no good evidence of a difference in any of the major clinical outcomes of survival, freedom from metastases, loco-regional control and disease-free survival. Therefore an assessment of the effect of treatment on physical and psychological symptoms is vital to balance the costs and benefits of the two treatments. A total of 615 patients were asked to complete a Rotterdam Symptom Checklist and the Hospital Anxiety and Depression Scale, which cover a variety of physical and psychological symptoms, at a total of ten time points. The data consisted of short-term data (the initial 3 months) and long-term data (1 and 2 years). The short-term data was split into an exploratory data set and a confirmatory data set, and analysed using subject-specific and group-based methods. Differences were only claimed if hypotheses generated in the exploratory data set were confirmed in the confirmatory data set. The long-term data was not split into two data sets and was analysed using a group-based approach. There was evidence of significantly worse symptoms of pain at day 21 in those treated with CHART and significantly worse symptoms of cough and hoarseness at 6 weeks in those treated conventionally. There was also evidence to suggest a higher degree of decreased sexual interest at 1 year and sore muscles at 2 years in those treated with conventional radiotherapy. There is no clear indication that one regimen is superior to the other in terms of 'quality of life', generally the initially more severe reaction in the CHART group being offset by the longer duration of symptoms in the conventionally treated group.

Anxiety↗
PubMed1999

Bayesian analysis.

Explore the source record for details and available documents.

Bayes Theorem↗
PubMed1999

Intravesical chemotherapy with epirubicin: a dose response study.

PURPOSE: We determined the difference in response to high and standard doses of intravesical epirubicin for treatment of superficial bladder cancer. MATERIALS AND METHODS: A total of 122 patients were entered into a randomized trial to compare the response of a marker tumor at 3 months, time to first recurrence and recurrence rates for 2 years after intravesical chemotherapy for superficial (pTa/pT1) bladder cancer. Patients were randomized to receive treatment for 1 hour with 1 (standard dose) or 2 mg./ml. (high dose) epirubicin (50 or 100 mg./50 ml. solution). RESULTS: There was no difference in the marker tumor response rate in 24 of 52 patients treated with the standard dose compared with 21 of 50 treated with the higher dose of epirubicin (p = 0.67). Similarly, the higher dose was not superior in regard to time to first recurrence, with a hazard ratio of 1.46 (p = 0.14, 95% confidence intervals 0.88 to 2.42). Considering the upper end of the confidence interval, we can reliably exclude an absolute difference of greater than 4% at 1 year for time to first recurrence in favor of higher dose chemotherapy. CONCLUSIONS: Epirubicin at double the standard dose for intravesical chemotherapy of superficial bladder cancer is not superior in regard to marker tumor response, time to first recurrence or recurrence rate.

Administration, Intravesical↗
PubMed1998

Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints.

Meta-analyses aim to provide a full and comprehensive summary of related studies which have addressed a similar question. When the studies involve time to event (survival-type) data the most appropriate statistics to use are the log hazard ratio and its variance. However, these are not always explicitly presented for each study. In this paper a number of methods of extracting estimates of these statistics in a variety of situations are presented. Use of these methods should improve the efficiency and reliability of meta-analyses of the published literature with survival-type endpoints.

Humans↗
PubMed1998

Preoperative radiotherapy in esophageal carcinoma: a meta-analysis using individual patient data (Oesophageal Cancer Collaborative Group).

PURPOSE: The existing randomized evidence has failed to conclusively demonstrate the benefit or otherwise of preoperative radiotherapy in treating patients with potentially resectable esophageal carcinoma. This meta-analysis aimed to assess whether there is benefit from adding radiotherapy prior to surgery. METHODS AND MATERIALS: This quantitative meta-analysis included updated individual patient data from all properly randomized trials (published or unpublished) comprising 1147 patients (971 deaths) from five randomized trials. RESULTS: With a median follow-up of 9 years, the hazard ratio (HR) of 0.89 (95% CI 0.78-1.01) suggests an overall reduction in the risk of death of 11% and an absolute survival benefit of 3% at 2 years and 4% at 5 years. This result is not conventionally statistically significant (p = 0.062). No clear differences in the size of the effect by sex, age, or tumor location were apparent. CONCLUSION: Based on existing trials, there was no clear evidence that preoperative radiotherapy improves the survival of patients with potentially resectable esophageal cancer. These results indicate that if such preoperative radiotherapy regimens do improve survival, then the effect is likely to be modest with an absolute improvement in survival of around 3 to 4%. Trials or a meta-analysis of around 2000 patients would be needed to reliably detect such an improvement (15-->20%).

Carcinoma↗
PubMed1998

Survey of the Administration of quality of life (QL) questionnaires in three multicentre randomised trials in cancer. The Medical Research Council Lung Cancer Working Party the CHART Steering Committee.

We surveyed centres collaborating in two trials in lung cancer (LU12, LU13) and one in lung and head and neck cancer (CHART) to find out how QL questionnaires were being administered, with the aim of standardising procedures and improving compliance. Dedicated local trials staff were funded for CHART but not for the other trials. In all three trials, patients completed a Rotterdam Symptom Checklist (RSCL) and a Hospital Anxiety and Depression Scale (HADS) at specified times. 17 of 22 LU12 centres, 9 of 11 LU13 and all 10 CHART centres returned survey forms. In LU12 and LU13, the category of staff responsible for questionnaires varied widely; in CHART, only research staff were involved. This led to more consistency in CHART centres in the administration and collection of questionnaires, and more frequent checking of forms. However, even the CHART administration, although better than in the other two trials, could not be regarded as standardised. All centres were equally affected by logistical problems. These embraced organisational deficits (e.g. unavailability of staff, lack of questionnaires) and patient-related factors (e.g. patient deemed to be too ill, had difficulty reading or left before completing the form). Patient refusals were an uncommon reason for non-compliance and patients were considered to be generally in favour of QL assessment. As a result of these findings, a number of measures have been put in place to increase standardisation of procedures and improve compliance. These include publishing guidelines for protocol writing, providing centres with guidelines for QL administration and information leaflets for patients, together with introducing staff training.

Carcinoma, Non-Small-Cell Lung↗