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Biomedical subjects

R Sylvester

Publications and source records attributed to R Sylvester.

At least 73 records · Page 4Linked to original sources
PubMed1995

EORTC (30885) randomised phase III study with recombinant interferon alpha and recombinant interferon alpha and gamma in patients with advanced renal cell carcinoma. The EORTC Genitourinary Group.

In the treatment of renal cell carcinoma both complete (CRs) and partial remissions (PRs) have been obtained using recombinant (r) interferon alpha (IFN-alpha), with response rates ranging from 0 to 31% (mean 16%). rIFN-gamma is a potent immunostimulating agent, but the clinical experience of its use is limited and results are conflicting. In a phase II study with the combination of rIFN-alpha 2c (Boehringer Ingelheim) and rIFN-gamma (Genentech, supplied by Boehringer Ingelheim) in 31 eligible patients, a response rate of 25% was recorded. Based on this observation a randomised phase III study was initiated to investigate the possible advantage of the addition rIFN-gamma to rIFN-alpha 2c treatment. Treatment consisted of rIFN-alpha 2c 30 micrograms m-2 = 10 x 10(6) IU m-2 s.c. twice weekly in arm A and the same dose of rIFN-alpha combined with rIFN-gamma 100 micrograms m-2 = 2 x 10(6) IU m-2 in arm B. Eligibility criteria included documented progression of disease; patients with bone lesions only and overt central nervous system metastases were excluded. Between November 1988 and September 1990, 102 patients were entered into the study. An interim analysis showed a response in 7/53 (13%) patients (two CRs and five PRs) in the rIFN-alpha 2c monotherapy arm and in 2/45 (4%) (one CR and one PR) patients in the combination arm. This difference was not statistically significant (P = 0.17). The probability of missing an eventual 10% advantage for the combination is 0.001. The numbers are insufficient to rule out a negative effect of the addition of rIFN-gamma. The dose intensity of IFN-alpha 2c for the two treatment arms was the same. The addition of rIFN-gamma does not improve the response rate of rIFN-alpha 2c monotherapy. A possible detrimental effect cannot be excluded.

Adult↗
PubMed1995

Identifying patients with a high risk of relapse in quiescent Crohn's disease. The GETAID Group. The Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives.

No reliable identification of quiescent Crohn's disease (CD) patients with a high risk of relapse is available. The aim of this study was to develop a prognostic index to identify those patients. Untreated adult patients with quiescent disease (not induced by surgery) included in three phase III clinical trials were analysed retrospectively with respect to time to relapse. Nineteen factors related to biology, disease history, and topography were investigated. A relapse was defined as either a CD Activity Index (CDAI) > or = 200, a CDAI > or = 150 but over the baseline value by more than 100, or acute complications requiring surgery. The inclusion criteria were fulfilled by 178 patients. The median follow up was 23 months. The Cox model retained the following bad prognostic factors: age < or = 25 years, interval since first symptoms > 5 years, interval since previous relapse < or = 6 months, and colonic involvement (p < 0.001). Bootstrapping confirmed the variable selection. Patients were classified into three groups with an increasing risk of relapse (p < 0.001). The worst risk group was composed of patients presenting at least three of the four bad prognostic factors. These results make possible the design of clinical trials in quiescent CD patients with a high risk of relapse.

Adolescent↗
PubMed1995

Tryptophan metabolites, pyridoxine (vitamin B6) and their influence on the recurrence rate of superficial bladder cancer. Results of a prospective, randomised phase III study performed by the EORTC GU Group. EORTC Genito-Urinary Tract Cancer Cooperative Group.

This double-blind randomised phase III trial was designed to assess the effect of pyridoxine administration on the recurrence of Ta and T1 transitional cell tumours of the bladder. The trial accrued 291 patients and showed no significant difference between the pyridoxine and placebo treatment groups with respect to the time to first recurrence or the recurrence rate. Adjustment for the main prognostic factors, namely the recurrence rate prior to entry, the number of tumours at entry, the G grade and the levels of the tryptophan metabolites kynurenine plus acetyl kynurenine at entry do not change the overall conclusions.

Administration, Oral↗
PubMed1995

[Introduction to the statistical aspects of planning clinical oncologic phase III studies].

A phase III clinical trial is a comparative study in which one assesses the relative efficacy of a treatment or treatments. It generally has one of the following objectives: 1. To determine the effectiveness of a new treatment relative to the natural history of the disease, for example when comparing a new treatment to not treatment or to placebo in an adjuvant setting. 2. To determine if a new treatment is more effective than the best current standard therapy (at the risk of increasing the toxicity). 3. To determine if a new treatment is as effective as the best current standard therapy but is associated with less severe toxicity or a better quality of life (equivalence trial). Clinical trials must be properly designed in order to answer such questions with a high degree of certainty. The purpose of this paper is to present several concepts which must be taken into account during the process of designing a clinical trial.

Aged↗
PubMed1995

Intravesical adjuvant chemotherapy for superficial transitional cell bladder carcinoma: results of 2 European Organization for Research and Treatment of Cancer randomized trials with mitomycin C and doxorubicin comparing early versus delayed instillations and short-term versus long-term treatment. European Organization for Research and Treatment of Cancer Genitourinary Group.

The European Organization for Research and Treatment of Cancer genitourinary group has completed 2 parallel prospective randomized studies, one with 30 mg. mitomycin C and the other with 50 mg. doxorubicin as adjuvant intravesical treatment after transurethral resection of superficial transitional cell bladder carcinoma. These studies were designed to compare early (the day of resection) versus delayed (between 7 and 15 days after resection) instillations and short-term (6 months) versus long-term (12 months) treatment. The results indicate that in regard to recurrence rate patients having a delayed and short-term treatment do worse than those having early instillations (for 6 or 12 months) or those having prolonged treatment (either immediate or delayed). With an average followup of 4 years survival, progression beyond T1 disease, development of distant metastases and appearance of a second primary were not influenced by the therapeutic regimen. A multivariate analysis of prognostic factors is presented, which indicates that after adjustment for these factors, patients in the delay, no maintenance arm have a significantly higher recurrence rate than the other patients.

Administration, Intravesical↗
PubMed1995

The final analysis of the EORTC Genito-Urinary Tract Cancer Co-Operative Group phase III clinical trial (protocol 30805) comparing orchidectomy, orchidectomy plus cyproterone acetate and low dose stilboestrol in the management of metastatic carcinoma of the prostate.

This report is the final analysis of an EORTC Genito-Urinary Group Phase III trial (Protocol 30805) comparing orchidectomy, orchidectomy plus cyproterone acetate 50 mg 3 times a day and stilboestrol 1 mg daily in the management of metastatic carcinoma of the prostate. Three hundred and twenty-eight eligible patients admitted into the study have been followed up for a median period of 4 years. There was no difference in time to metastatic progression and overall survival between the treatment arms. The cardiovascular toxicity of stilboestrol 1 mg daily has resulted in more cardiovascular deaths as compared with the orchidectomy treatment arm. The outcome for individual patients has been determined by on-study prognostic factors, especially the performance status, rather than the treatment given.

Adenocarcinoma↗
PubMed1994

Design and analysis of prostate cancer trials.

This paper presents an overview of various statistical concepts related to the design and analysis of prostate cancer trials: the need for randomization, stratification for prognostic factors, sample size determination, trial objectives, the choice of a control group, patient entry criteria, the number of treatments to be compared, the choice of endpoints, analysis by the intent to treat principle, interim statistical analysis and early stopping rule, and subgroup analyses.

Clinical Trials as Topic↗
PubMed1993

Comparability of prostate trials.

The present overview of advanced prostate cancer required the identification of randomized clinical trials studying the question of maximal androgen blockade versus the classic castration therapy. The heterogeneity of the trials concerned the type of castration (surgical or chemical) and the type of antiandrogen (flutamide, Anandron, or cyproterone acetate) added to castration. This paper reviews the different types of heterogeneity that might exist among trials that are involved in the overview: study design, randomization procedure, treatment evaluation, statistical evaluation, and data maturity. In order to overcome these various types of heterogeneity and to compare like with like, the treatment comparison should be stratified a posteriori by question (i.e., type of castration or type of anti-androgen studied) and by study. In this way, one may draw valid conclusions. Of course, those trials with a larger number of patients and a longer follow-up will contribute more to the overview's results.

Androgen Antagonists↗
PubMed1993

Short-term versus long-term addition of cyproterone acetate to buserelin therapy in comparison with orchidectomy in the treatment of metastatic prostate cancer. European Organization for Research and Treatment of Cancer--Genitourinary Group.

In an open, multicenter, three-armed, randomized study, we compared the effects of short-term (2 weeks) and continuous addition of the antiandrogen cyproterone acetate to the luteinizing hormone-releasing hormone agonist buserelin to those of orchidectomy in patients with advanced prostate cancer. No significant differences among the three treatment arms with respect to response rate, subjective response, time-to-progression, overall survival, and cancer deaths were observed. It was concluded that the short-term or continuous addition of cyproterone acetate to buserelin administered intranasally did not improve treatment results compared to orchidectomy only.

Adult↗
PubMed1993

Orchidectomy versus goserelin plus flutamide in patients with metastatic prostate cancer (EORTC 30853). European Organization for Research and Treatment of Cancer--Genitourinary Group.

A total of 327 patients with metastatic prostate cancer were randomized to receive bilateral orchiectomy or treatment with Zoladex and flutamide. The trial aimed to evaluate subjective and objective time to progression, survival, and incidence and duration of response. Strict quality control and evaluation by independent ad hoc committees were organized. Progression was assessed for each of 13 parameters. The time to subjective and objective progression was in favor of the combination treatment, with statistical significances of P = 0.009 and P = 0.008, respectively. This delay in objective progression resulted in increased survival in favor of the combination treatment for death by cancer (P = 0.02) or overall survival (P = 0.05). Survival differences were more marked in the patients with better prognostic factors. The clinical significance of these differences for the individual patient requires detailed assessment.

Adult↗
PubMed1993

Goserelin acetate and flutamide versus bilateral orchiectomy: a phase III EORTC trial (30853). EORTC GU Group and EORTC Data Center.

Maximal androgen blockade (MAB), the eradication of the effects of adrenal androgens on prostate cancer cells after castration, has been used with differing success in the treatment of prostatic carcinoma. The aim of this randomized phase III study was to compare the efficacy and side effects of bilateral orchiectomy versus a combination of a luteinizing hormone-releasing hormone agonist (LHRH-A) depot formulation, goserelin acetate (3.6 mg s.c. once every four weeks), and flutamide (250 mg three times daily), in patients with metastatic cancer. Treatment usually continued until disease progression (or for a minimum of three months). Efficacy was assessed by response, time to disease progression, and duration of survival. Clinical evaluations, standard laboratory tests, and imaging examinations were carried out regularly. A total of 327 patients were entered in this study. There was a difference in response only for prostatic acid phosphatase (PAP) with a more frequent decrease of the serum values to normal in the serum in patients assigned to MAB treatment. The MAB treatment, however, proved significantly better for time to subjective progression, time to objective progression, time to first (subjective and objective) progression, and duration of survival. The most frequent side effects for both treatments included hot flushes and gynecomastia. In conclusion, significant time to progression and survival benefits are achieved by adding flutamide to an LHRH-A regimen, probably improving the quality of life of patients with metastatic cancer.

Aged↗
PubMed1993

Grading of soft tissue sarcomas: experience of the EORTC Soft Tissue and Bone Sarcoma Group.

A practical grading system for soft tissue sarcomas was developed, based on 282 eligible patients entered in an EORTC adjuvant clinical trial. The primary tumours in this trial had to be adequately treated. Histopathological parameters, which appeared significant in two preceding studies, were tested. These parameters were differentiation of the tumour, presence and amount of necrosis, the presence and amount of myxoid areas and the number of mitoses. In addition, the size of the tumour was also analysed. The quantitative data (mitotic count and size of the tumour) were not a priori grouped, but were divided into categories based on the results of the statistical analysis. Based on a multivariate analysis only mitotic count, the presence or absence of necrosis and the size of the tumour were significantly correlated with the duration of survival or the time to distant metastases. Of these parameters, the mitotic count was the most important.

Adolescent↗
PubMed1993

Mitomycin C versus estramustine in the treatment of hormone resistant metastatic prostate cancer: the final analysis of the European Organization for Research and Treatment of Cancer, genitourinary group prospective randomized phase III study (30865).

A total of 171 patients with progressive metastatic prostate cancer following hormonal therapy was randomized to receive either 560 to 700 mg. estramustine orally per day or 15 mg./m.2 mitomycin C by intravenous infusion every 6 weeks. The patients were recruited during a 2.5-year period, and 70% had undergone more than 1 previous therapy for prostate cancer, with some having received as many as 5 different previous treatments. The overall results were disappointing. The median time to progression was 5 months and 50% of the patients died within 10 months. There was no difference in efficacy between the 2 treatment arms. Toxicity was severe in both arms but appeared earlier in those patients receiving estramustine, leading to a tendency for earlier deterioration in performance status. In this group of heavily pretreated patients there appears to be no justification for the use of either of these agents at the present time.

Aged↗
PubMed1993

A prospective European Organization for Research and Treatment of Cancer Genitourinary Group randomized trial comparing transurethral resection followed by a single intravesical instillation of epirubicin or water in single stage Ta, T1 papillary carcinoma of the bladder.

A total of 431 eligible patients with solitary, primary or recurrent stages Ta and T1 transitional cell carcinoma of the bladder was included in a randomized multicenter trial to compare a single intravesical instillation of 80 mg. epirubicin with water given immediately after resection, with respect to the disease-free interval and recurrence rate. The interval to initial recurrence was significantly better in favor of the epirubicin group. After a mean followup of 2 years it became evident that the recurrence rate after a single epirubicin instillation was decreased by nearly half with the same trend being found in all subgroups examined. Toxicity was mainly restricted to bladder irritation in plus or minus 10% of the cases. Pathology review brought considerable changes in T category from stages T1 to Ta (53%). Changes in grade were less pronounced but nevertheless important.

Administration, Intravesical↗
PubMed1993

Prognostic factors in metastatic non-seminomatous germ cell tumours: an interim analysis of the EORTC GU-Group experience.

Univariate and multivariate analyses were performed in 632 patients treated with cisplatin combination chemotherapy for metastatic non-seminomatous testicular germ cell tumours. Multivariately, the most important poor prognosis factors for the prediction of survival were: HCG > or = 10,000 IU/l, lung metastases > or = 10, abdominal metastases with a horizontal diameter of > or = 5 cm and the presence of supraclavicular metastases. If patients had 2 or more of these factors the death rates increased from 30% for patients with 2 factors to 65% for patients with 3 or 4 factors. The patients studied here are not a random sample of the metastatic testicular cancer patients in general, as the population studied comprised a large proportion of low volume metastatic disease patients. Therefore, the final analysis will include patients from all the recently completed trials.

Analysis of Variance↗
PubMed1993

A plea for cold biopsy, fulguration and immediate bladder instillation with Epirubicin in small superficial bladder tumors. Data from the EORTC GU Group Study 30863.

The sensitivity of cystoscopy to distinguish infiltrating from superficial bladder tumors is very high. Only 28 (5.6%) of 501 single tumors, which were considered to be superficial by the urologist at visual inspection, were found to be infiltrating on pathological examination. If the size of the tumor and/or the cytological grade are considered, one can further reduce the number of infiltrating tumors missed, but it was impossible to identify them all. The recurrence rate of tumors at the resection site 4 weeks after TUR suggests the importance of trauma of the bladder mucosa in promoting recurrence. A single instillation of Epirubicin immediately after TUR prevents implantation of tumor cells and reduces the recurrence rate to nearly 50%. A combination of cold forceps biopsy and fulguration may be the most reasonable treatment for small bladder tumors.

Administration, Intravesical↗