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Biomedical subjects

R Sylvester

Publications and source records attributed to R Sylvester.

At least 19 recordsLinked to original sources
PubMed2006

Ethnic variations in the management of patients with acute stroke.

BACKGROUND: There is increasing interest in the management of stroke in ethnic minorities but few studies have considered this issue. This study investigated if differences in acute stroke management exist between a white European and Bangladeshi populations living in London, England. METHODS: All stroke surviving patients discharged over a five year period in a major London teaching hospital based in an ethnically diverse area of inner city London were recruited. Cerebrovascular risk factors, their management, and investigation for acute stroke syndromes were recorded and comparison between white and Bangladeshi cohorts was made. Categorical data were analysed using Fisher's exact test. RESULTS: Measurement of cholesterol concentrations are undertaken less often in those from a Bangladeshi background (25%) compared with white Europeans (76%) (p<0.0001). Statin therapy tends to be given less often to Bangladeshis. However, neuroimaging (p<0.05) and echocardiography (p<0.0001) is performed more often in Bangladeshis compared with white Europeans. CONCLUSION: There are variations in the management of acute stroke because of ethnicity and these variations could have substantial consequences on secondary rates of cerebrovascular and cardiovascular disease. Whether the reasons for this disparity are attributable to inequity or iniquity of care need to be further investigated perhaps along with the development of ethnicity specific protocols. Overall the management of stroke and its risk factors in either racial group remains lamentable.

Acute Disease↗
PubMed2004

Randomized Phase II trial assessing estramustine and vinblastine combination chemotherapy vs estramustine alone in patients with progressive hormone-escaped metastatic prostate cancer.

Based on the results of combined data from three North American Phase II studies, a randomised Phase II study in the same patient population was performed, using combination chemotherapy with estramustine phosphate (EMP) and vinblastine (VBL) in hormone refractory prostate cancer patients. In all, 92 patients were randomised into a Phase II study of oral EMP (10 mg kg day continuously) or oral EMP in combination with intravenous VBL (4 mg m(2) week for 6 weeks, followed by 2 weeks rest). The end points were toxicity and PSA response in both groups, with the option to continue the trial as a Phase III study with time to progression and survival as end points, if sufficient responses were observed. Toxicity was unexpectedly high in both treatment arms and led to treatment withdrawal or refusal in 49% of all patients, predominantly already during the first treatment cycle. The mean treatment duration was 10 and 14 weeks, median time to PSA progression was 27.2 and 30.8 weeks, median survival time was 44 and 50.9 weeks, and PSA response rate was only 24.6 and 28.9% in the EMP/VBL and EMP arms, respectively. There was no correlation between PSA response and survival. While the PSA response in the patients tested was less than half that recorded in the North American studies, the toxicity of EMP monotherapy or in combination with VBL was much higher than expected. Further research on more effective and less toxic treatment strategies for hormone refractory prostate cancer is mandatory.

Administration, Oral↗
PubMed2004

An open multicentre comparative study of the efficacy, safety and tolerance of fluconazole and itraconazole in the treatment of cancer patients with oropharyngeal candidiasis.

Oropharyngeal candidiasis is a frequent infection in cancer patients who receive cytotoxic drugs. In this study, the efficacy, safety and tolerance of fluconazole and itraconazole were compared in non-neutropenic cancer patients with oropharyngeal candidiasis. Of 279 patients who were randomised between the two treatment groups, 252 patients were considered to be eligible (126 in each group). The clinical cure rate was 74% for fluconazole and 62% for itraconazole (P=0.04, 95% Confidence Interval (CI): 0.5-23.3%). The mycological cure rate was 80% for fluconazole and 68% for itraconazole (P=0.03, 95% CI: 1.2-22.6%). The safety and tolerance profile of both drugs were comparable. This study has shown that in patients with cancer and oropharyngeal candidiasis, fluconazole has a significantly better clinical and mycological cure rate compared with itraconazole.

Adolescent↗
PubMed2004

EAU guidelines on diagnosis and treatment of upper urinary tract transitional cell carcinoma.

OBJECTIVES: On behalf of the European Association of Urology (EAU) guidelines for diagnosis, therapy and follow-up of upper urinary tract transitional cell carcinoma (UUTT) patients were established. Criteria for recommendations are based of level 2 only, as large randomised clinical trials have not been performed in this type of disease. METHOD: A systematic literature research using Medline Services was conducted. References were weighted by a panel of experts. RESULTS: TNM classification 2002 is recommended. Recommendations are developed for diagnosis, radical and conservative treatment and for local chemo-immunotherapy. Prognostic factors are defined. Recommendations for follow-up after different types of treatment are given.

Carcinoma, Transitional Cell↗
PubMed2004

One immediate postoperative instillation of chemotherapy in low risk Ta, T1 bladder cancer patients. Is it always safe?

OBJECTIVE: The optimal treatment for solitary low grade, low stage papillary bladder tumours consists of transurethral resection (TUR) followed by one immediate postoperative instillation with a chemotherapeutic drug. However, when during TUR a bladder perforation or a near-perforation occurs, instillation of a chemotherapeutic drug may lead to leakage outside the bladder, possibly causing severe morbidity. So far, few case reports dealing with complications using mitomycin C have been published, but severe complications of leakage after an early adjuvant instillation with epirubicin have not been reported. METHODS: We describe 3 patients in whom we observed serious complications of one immediate postoperative instillation of epirubicin. RESULTS: Two of the patients recovered after conservative therapy, one patient died due to multi organ failure after explorative laparotomy. CONCLUSION: In order to prevent such complications, an immediate postoperative instillation has to be avoided when there is overt or even suspicion of bladder wall perforation.

Administration, Intravesical↗
PubMed2002

Statistical methodology of phase III cancer clinical trials: advances and future perspectives.

The methodology for conducting cancer clinical trials has undergone enormous changes over the past 25-30 years since the EORTC Data Center was created. The purpose of this paper is to highlight and to provide a historical perspective for the main methodological concepts, both practical and theoretical, which form the basis for the design and analysis of phase III cancer clinical trials within the EORTC Data Center. Some statistical aspects of other associated topics such as quality of life, health economics, meta-analysis and treatment outcome will also be briefly discussed. Finally, some future perspectives and topics for further statistical methodological research will be presented in order to spur statisticians to meet the challenge of efficiently designing and analysing the clinical trials of tomorrow.

Clinical Trials, Phase III as Topic↗
PubMed2002

Treatment outcome studies. pitfalls in current methods and practice.

The objective of a treatment outcome study is to investigate the heterogeneity in outcome between patients according to factors other than treatment, such as country, institution or physician. Results of treatment outcome studies have already been extensively presented in the medical literature. However, no clear methodology has emerged to perform treatment outcome studies and various methods have been used. This paper reviews the different types of questions addressed in treatment outcome studies, the different methodologies and the different endpoints used. Statistical techniques are mainly descriptive including tables, estimates of survival curves, but regression models have also been used. Most of the studies use registry data, while only a few use discharge data or data available from clinical trials.

Clinical Trials as Topic↗
PubMed2001

Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial.

BACKGROUND: Surgery is the main treatment for localised renal cell carcinoma, but use of radical nephrectomy for metastatic disease is highly controversial. We aimed to establish whether radical nephrectomy done before interferon-alfa-based immunotherapy improved time to progression and overall survival (primary endpoints) compared with interferon alfa alone. METHODS: We included 85 patients from June, 1995, to July, 1998: two (one per group) were ineligible. 42 of the 83 participants were randomly assigned combined treatment (study group) and 43 immunotherapy alone (controls). All patients had metastatic renal-cell carcinoma that had been histologically confirmed and was progressive at entry. In study patients, surgery was done within 4 weeks of randomisation, and immunotherapy (5x10(6) IU/m(2) subcutaneously three times per week) started 2-4 weeks later. In controls, immunotherapy was started within 1 working day of randomisation. Follow-up visits were monthly. All analyses were by intention to treat. FINDINGS: 40 (53%) of 75 patients received at least 16 weeks of interferon-alfa treatment, which was also the median duration of treatment. Time to progression (5 vs 3 months, hazard ratio 0.60, 95% CI 0.36-0.97) and median duration of survival were significantly better in study patients than in controls (17 vs 7 months, 0.54, 0.31-0.94). Five patients responded completely to combined treatment, and one to interferon alfa alone. Dose modification was necessary in 32% of patients, most commonly because of non-haematological side-effects. INTERPRETATION: Radical nephrectomy before interferon-based immunotherapy might substantially delay time to progression and improve survival of patients with metastatic renal cell carcinoma who present with good performance status.

Adult↗
PubMed2001

Need for alternative trial designs and evaluation strategies for therapeutic studies of invasive mycoses.

Studies of invasive fungal infections have been and remain difficult to implement. Randomized clinical trials of fungal infections are especially slow and expensive to perform because it is difficult to identify eligible patients in a timely fashion, to prove the presence of the fungal infection in an unequivocal fashion, and to evaluate outcome in a convincing fashion. Because of these challenges, licensing decisions for antifungal agents have to date depended heavily on historical control comparisons and secondary advantages of the new agent. Although the availability of newer and potentially more effective agents makes these approaches less desirable, the fundamental difficulties of trials of invasive fungal infections have not changed. Therefore, there is a need for alternative trial designs and evaluation strategies for therapeutic studies of invasive mycoses, and this article summarizes the possible strategies in this area.

Antifungal Agents↗
PubMed2001

Combined tamoxifen and luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer: a meta-analysis of four randomized trials.

PURPOSE: The logic behind the application of luteinizing hormone-releasing hormone (LHRH) agonists in combination with tamoxifen in premenopausal women is that LHRH agonists on the one hand suppress the tamoxifen-induced stimulation of the pituitary-ovarian function and, on the other hand, seem as effective as surgical castration. This meta-analysis combines all randomized evidence to compare the combined treatment with LHRH agonist alone with respect to overall survival, progression-free survival, and objective response in premenopausal women with advanced breast cancer. PATIENTS AND METHODS: Four clinical trials randomizing a total of 506 premenopausal women with advanced breast cancer to LHRH agonist alone or to the combined treatment of LHRH agonist plus tamoxifen were identified. Meta-analytic techniques were used to analyze individual patient data from these trials. RESULTS: With a median follow-up of 6.8 years, there was a significant survival benefit (stratified log-rank test, P = .02; hazards ratio [HR] = 0.78) and progression-free survival benefit (stratified log-rank test, P = .0003; HR = 0.70) in favor of the combined treatment. The overall response rate was significantly higher on combined endocrine treatment (stratified Mantel Haenszel test, P = .03; odds ratio = 0.67). CONCLUSION: The combination of LHRH agonist plus tamoxifen is superior to LHRH agonist alone in premenopausal women with advanced breast cancer. Therefore, if a premenopausal woman with advanced breast cancer is thought to be suitable for endocrine treatment, it is proposed that the combination of a LHRH agonist plus tamoxifen be considered as the new standard treatment.

Antineoplastic Agents, Hormonal↗
PubMed2001

Individual patient-versus literature-based meta-analysis of survival data: time to event and event rate at a particular time can make a difference, an example based on head and neck cancer.

The objective of this study is to compare the results of an individual patient-based and a literature-based meta-analysis in chemotherapy in head and neck cancer and to identify the sources of difference. For all head and neck cancer randomized controlled clinical trials comparing chemotherapy and loco-regional treatment with loco-regional treatment alone, both the literature data and the individual patient data are retrieved and meta-analyses performed and compared. Only survival data are used as outcome, although both time to death and mortality at specific time points are considered in different analyses. There are substantial differences between the individual patient-based and the literature-based meta-analyses. The most important reason for the differing results is that the individual patient-based meta-analysis is based on a time to event analysis, whereas the literature-based meta-analysis is based on mortality at a specific time point. Mortality can change substantially with follow-up time. The absolute survival differences in the case study, for instance, increase from 2.6% at 2 years to 5.6% at 5 years.

Antineoplastic Agents↗
PubMed2001

The ablative effect of quarter dose bacillus Calmette-Guerin on a papillary marker lesion of the bladder.

PURPOSE: Low dose bacillus Calmette-Guerin (BCG) for stage TaT1 transitional cell carcinoma of the bladder has been given in various studies with the aim of decreasing side effects while maintaining the same efficacy as full dose bacillus Calmette-Guerin. However, its application in clinical practice remains controversial. We examined the ablative activity and incidence of side effects of intravesical quarter dose BCG given for a papillary marker lesion of the bladder. MATERIALS AND METHODS: Included in our study were 44 patients with primary or recurrent, multiple but no more than 10 lesions of stage pTaT1, grades 1 to 2 transitional cell carcinoma of the bladder. Intravesical treatment begun 14 days after the complete transurethral resection of all visible tumors except 1 marker lesion no larger than 1 cm. consisted of instillations of 30 mg. Connaught strain BCG diluted in 50 ml. saline once weekly for 6 consecutive weeks. Two weeks after the last instillation any residual tumor was completely resected. In cases of complete disappearance of the marker lesion deep biopsy of the tumor area was done. Urine cytology was also performed. RESULTS: There was a complete response in 27 of the 44 patients (61%), no response in 12 (27%) and progression to carcinoma in situ in 1 (2%), while the response was not evaluable in 4. Local side effects included dysuria in 54% of cases and macroscopic hematuria in 39%. Neither BCG induced infection nor BCG sepsis was observed. CONCLUSIONS: Quarter dose BCG has a clear ablative effect on superficial bladder cancer with a 61% response rate. Phase III trials are now required to compare its efficacy and toxicity to those of full dose BCG.

Adjuvants, Immunologic↗
PubMed2001

Intravesical instillation of epirubicin, bacillus Calmette-Guerin and bacillus Calmette-Guerin plus isoniazid for intermediate and high risk Ta, T1 papillary carcinoma of the bladder: a European Organization for Research and Treatment of Cancer genito-urinary group randomized phase III trial.

PURPOSE: After transurethral resection, we compared the efficacy and side effects of weekly intravesical instillations of epirubicin, bacillus Calmette-Guerin (BCG), and BCG plus isoniazid during a 6-week interval followed by 3 weekly maintenance instillations at months 3, 6, 12, 18, 24, 30 and 36 in patients with intermediate and high risk Ta, T1 bladder cancer. MATERIALS AND METHODS: A total of 957 patients were randomized at 44 institutions in a phase III multicenter trial. RESULTS: The time to first recurrence was significantly longer in patients treated with BCG and BCG plus isoniazid compared to epirubicin (p = 0.0001) but there was no difference between the 2 BCG regimens (p = 0.27). Progression to muscle invasive cancer was rare (5%) and did not differ significantly among the 3 arms (p = 0.12). Drug induced cystitis was observed in 31% of the patients treated with epirubicin, 42% BCG and 45% BCG plus isoniazid. Systemic side effects, such as fever and malaise, were not observed in patients treated with epirubicin, but were noted in 31% BCG and 36% BCG plus isoniazid. CONCLUSIONS: Intravesical BCG with or without isoniazid provokes more side effects than epirubicin. Prophylactic isoniazid does not reduce the side effects of BCG, while BCG with or without isoniazid prolongs the time to first recurrence compared to epirubicin. Further followup is required before long-term conclusions can be made for progression-to-muscle invasive disease and survival.

Administration, Intravesical↗
PubMed2001

Intravesical BCG in patients with carcinoma in situ of the urinary bladder: long-term results of EORTC GU Group phase II protocol 30861.

OBJECTIVES: This phase II study was designed to assess the response rate, side effects and long-term efficacy of BCG in the treatment of carcinoma in situ (Cis) of the urinary bladder. METHODS: 103 eligible patients with Cis were treated with 6 consecutive weekly intravesical instillations of 120 mg BCG-Connaught. In case of no response, a second 6-week course was given. RESULTS: A complete response (CR) was observed in 77 of the 103 eligible patients (75%) and 93 evaluable patients (83%). In 6 of 10 patients the CR was induced by a second cycle of 6 weekly instillations. After a median follow-up of 7.6 years, 39 of the 77 CR patients (50%) are still alive and have retained their bladder, 31 (40%) without tumor recurrence. Another 7 patients underwent cystectomy and are still alive while 16 (20%) have died due to bladder cancer. Ten patients stopped treatment due to toxicity. In 2 patients, cystectomy was done because of severe cystitis and reduced bladder capacity. Drug cystitis, bacterial cystitis and fever occurred in 45, 15 and 15% of the patients, respectively. Severe drug cystitis was noted in 3 out of 10 patients receiving more than 6 instillations, necessitating cystectomy in 1 case. CONCLUSION: Intravesical short-term BCG is an effective treatment modality in Cis, yielding a high CR rate. This therapy may however be suboptimal in some patients as the 5-year disease-free rate in complete responders drops to 60%. Still, this is an acceptable result for patients in whom cystectomy would otherwise be performed in virtually all cases.

Adjuvants, Immunologic↗
PubMed2001

Frequency of positive biopsies after visual disappearance of superficial bladder cancer marker lesions.

INTRODUCTION AND OBJECTIVES: In phase II trials in superficial bladder cancer, marker lesions have been used to test the ablative activity of intravesical chemo- or immunotherapy. These studies provide important knowledge about drug activity and toxicity without exposing hundreds of patients in phase III trials to drugs which ultimately may not be successful in preventing tumour recurrence or progression. After treatment a deep biopsy was necessary at the site of the marker lesion even in the absence of any visual tumour. The question is if this biopsy, in the absence of any visual tumour, should be done. MATERIAL AND METHODS: The ablative effect of MMC, epirubicin, and quarter dose BCG instillations was evaluated in three different studies on a papillary marker lesion. Patients with multiple, primary or recurrent superficial bladder tumours were included. All visible Ta-T1 lesions were resected except for one marker lesion not exceeding 1 cm. TIS was excluded. In the last study, patients with T1 G3 tumours or multiple tumours >10 were also excluded. If the marker lesion disappeared completely, a deep biopsy was performed at the scar in order to prove histological disappearance of the tumour. RESULTS: 185 patients were evaluated. No visual tumours were seen in 110 patients and a TUR was performed in 101 of them. It revealed only 3 Ta lesions. In the 9 others no biopsy was performed but follow-up cystoscopy revealed no lesions. CONCLUSIONS: In the absence of any visual tumors, TUR and deep biopsy at the site of the scar of the marker lesion only rarely revealed (3 out of 110) the histological presence of a tumour. Therefore, this biopsy can be omitted in new marker lesion protocols in patient with Ta-T1, G1 G2 papillary superficial bladder tumours at intermediate risk for recurrence and low risk for progression.

Administration, Intravesical↗
PubMed2000

Radiotherapy in breast-conserving treatment for ductal carcinoma in situ: first results of the EORTC randomised phase III trial 10853. EORTC Breast Cancer Cooperative Group and EORTC Radiotherapy Group.

BACKGROUND: Ductal carcinoma in situ (DCIS) of the breast is a disorder that has become more common since it may manifest as microcalcifications that can be detected by screening mammography. Since selected women with invasive cancer can be treated safely with breast conservation therapy it is paradoxical that total mastectomy has remained the standard treatment for DCIS. We did a randomised phase III clinical trial to investigate the role of radiotherapy after complete local excision of DCIS. METHODS: Between 1986 and 1996, women with clinically or mammographically detected DCIS measuring less than or equal to 5 cm were treated by complete local excision of the lesion and then randomly assigned to either no further treatment (n=503) or to radiotherapy (n=507; 50 Gy in 5 weeks to the whole breast). The median duration of follow-up was 4.25 years (maximum 12.0 years). All analyses were by intention to treat. FINDINGS: 500 patients were followed up in the no further treatment group and 502 in the radiotherapy group. In the no further treatment group 83 women had local recurrence (44 recurrences of DCIS, and 40 invasive breast cancer). In the radiotherapy group 53 women had local recurrences (29 recurrences of DCIS, and 24 invasive breast cancer). The 4-year local relapse-free was 84% in the group treated with local excision alone compared with 91% in the women treated by local excision plus radiotherapy (log rank p=0.005; hazard ratio 0.62). Similar reductions in the risk of invasive (40%, p=0.04) and non-invasive (35%, p=0.06) local recurrence were seen. CONCLUSIONS: Radiotherapy after local excision for DCIS, as compared with local excision alone, reduced the overall number of both invasive and non-invasive recurrences in the ipsilateral breast at a median follow-up of 4.25 years.

Adult↗