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Biomedical subjects

M Buyse

Publications and source records attributed to M Buyse.

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

The CRP initial response to treatment as prognostic factor in patients with polymyalgia rheumatica.

To test the hypothesis that the initial response to corticosteroid treatment makes it possible to predict the further course of patients with polymyalgia rheumatica (PMR), 20 patients with PMR were prospectively given a therapeutic challenge with 15 mg of prednisolone (PDN) per day. The erythrocyte sedimentation rate (ESR), the fibrinogen and the C-reactive protein (CRP) were measured before and after 7 days of therapy. At the end of the challenge, the CRP had normalized in 11 patients (Group I), whereas it had remained elevated in 9 (Group II). The dose of PDN was thereafter tapered according to a strict and standard schedule integrating clinical and laboratory parameters, and was used as the index of disease control. The statistical analysis was made using a generalized linear model. Follow-up ranged from 8 to 60 months with a median of 38 months. With the PDN dose as the end point, Group I showed a significantly better course than Group II (p = 0.014). There were fewer adverse events due to corticosteroid treatment in Group I (3/11) compared to Group II (7/9). We conclude that the CRP initial response to the corticosteroid treatment is a prognostic factor in patients with PMR. Larger studies are needed to confirm these preliminary results.

Aged↗
PubMed1995

Effects of dipyridamole in combination with anticoagulant therapy on survival and thromboembolic events in patients with prosthetic heart valves. A meta-analysis of the randomized trials.

The addition of dipyridamole, an antiplatelet agent, to conventional anticoagulant regimens has been shown to reduce the frequency of embolization after valve replacement with a mechanical prosthesis. The purpose of this meta-analysis was to reevaluate the benefit of dipyridamole by analyzing the evidence from all randomized clinical trials. Summary data were extracted from the application to the Food and Drug Administration. Six randomized clinical trials had accrued 1141 patients, of whom 582 received anticoagulant therapy alone and 559 received additional dipyridamole at dosages ranging from 225 to 400 mg per day. The events analyzed were all thromboembolic events, both fatal and nonfatal; hemorrhagic events, both fatal and nonfatal; and the overall mortality. The combination of dipyridamole with anticoagulants reduced the risk of thromboembolic events (fatal or nonfatal) by 56% when compared with the use of anticoagulants alone (p = 0.0001). The risk reduction was seen in fatal and in nonfatal thromboembolic events (risk reduction for fatal events, 64%, p = 0.008; for nonfatal events, 50%, p = 0.005). The overall mortality rate was also significantly reduced by 40% in the group receiving dipyridamole (p = 0.013). There was no difference between treatment groups with respect to hemorrhagic events (risk reduction, -1%, p = 0.94). This meta-analysis supports the use of dipyridamole in this setting and warrants further trials with new antiplatelet agents.

Anticoagulants↗
PubMed1995

Clinical evaluation of virus safety and inhibitor incidence: statistical considerations.

The basic statistical issue in pharmacovigilance is to claim, with reasonable certainty, that the incidence of an event of interest in a population of subjects is less than a certain value. How many subjects and events must be observed before such a claim can be made? A first situation of practical importance is when a product has been on the market for some period of time, and the safety of this product regarding some outcome of interest is questioned (for instance, the viral safety of blood products). Having observed a few occurrences of the event of interest, how confident can we be that the product is responsible for an elevation of the incidence of this event compared with the baseline incidence in a reference population? This issue will increasingly need to be addressed prospectively: how many subjects need to be treated and how many events observed, to be reasonably certain that a product is safe? Multi-stage designs are appropriate to address this question, yet they do not seem popular in pharmacovigilance. Such approaches could complement the standard recommendations to assess the safety of blood products, which are adequate as a first screen against major safety problems, but wholly inadequate for the long-term surveillance of subjects at risk of rare events. It will be argued that, from a regulatory perspective, the implementation of prospective protocols for pharmacovigilance, using appropriate statistical tools, would permit a tight control of the safety of new products, while making these products available as early as possible to the patients who need them.

Antibody Formation↗
PubMed1995

Final results of a phase III clinical trial of adjuvant chemotherapy with the modified fluorouracil, doxorubicin, and mitomycin regimen in resectable gastric cancer.

PURPOSE: In a randomized clinical trial (European Organization for the Research and Treatment of Cancer [EORTC] no. 40813) on adjuvant chemotherapy in gastric cancer, results obtained after administration of the FAM2 regimen (fluorouracil [5-FU], doxorubicin, and mitomycin) were compared with results obtained after surgery alone to assess the effect of this regimen on overall survival, time to progression, and disease-free interval. PATIENTS AND METHODS: Three hundred fourteen patients who had undergone curative resection for stage II or stage III (International Union Against Cancer [UICC] 1978) gastric adenocarcinoma were randomized to receive chemotherapy (treatment arm) or no further treatment (control arm). The chemotherapy schedule was repeated every 43 days for seven cycles. The log-rank test and the Cox model were used for statistical analysis. RESULTS: Of 314 patients, 159 comprised the control group and 155 the FAM2 group. Nineteen FAM2 patients never received chemotherapy. The median number of cycles was five. Of the patients started on adjuvant treatment, severe hematologic and nonhematologic toxicity (grades 3 or 4, World Health Organization [WHO] scale) occurred, respectively, in 6% to 9% and in 1% to 29% of cases. The overall 5-year survival rate was 70% for stage II and 32% for stage III patients. No statistically significant difference was found between overall survival of the two treatment arms (P = .295). However, time to progression was significantly delayed in the FAM2 arm (P = .020) and disease-free survival showed borderline significance (P = .068). CONCLUSION: FAM2, in view of its high toxicity, cannot be advocated as standard adjuvant treatment for gastric cancer. Large-scale clinical trials using more active, less toxic regimens are required to demonstrate whether adjuvant chemotherapy provides any real benefit.

Adenocarcinoma↗
PubMed1995

Optimal combination therapy with Navoban (tropisetron) in patients with incomplete control of chemotherapy-induced nausea and vomiting. The Belgian Navoban Group.

Even with the availability of potent and selective serotonin antagonists, chemotherapy-induced nausea and vomiting remain a major problem for many patients. This study aims to evaluate the benefit of combination therapy based on Navoban (tropisetron) in patients who had incomplete control of nausea and/or vomiting induced by chemotherapy when using Navoban as a single antiemetic agent. In their first chemotherapy course, 1072 patients planned to receive at least two identical cycles of emetogenic chemotherapy were treated with 5 mg Navoban once daily. To evaluate three treatments additional to the recommended 5 mg once-daily Navoban regimen during Course 2 in those patients who had shown incomplete control of nausea and/or vomiting on any day of Course 1, a 2 x 2 x 2 factorial design was employed. Of these patients, 445 were centrally randomised to receive an additional dose of open-label dexamethasone (Day 1, 0.2 mg/kg i.v.; Days 2-6, 8 mg p.o.) and/or open-label alizapride (Day 1, 100 mg i.v. and 4 x 50 mg p.o.; Days 2-6, 4 x 5 mg p.o.) and/or double-blind Navoban--that is, doubling the dose to 10 mg once daily or placebo. Complete response rates during Course 1 (CRR, no nausea and no vomiting) were, for Day 1, 72% and for Days 1-6, 48%. More complete responders were observed when dexamethasone was added during Course 2, both on Day 1 (76% vs. 66%, p = 0.020) and on Days 1-6 (50% vs. 34%, p = 0.0004).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Treatment of patients with irresectable liver metastases from colorectal cancer by chemo-occlusion with degradable starch microspheres.

Chemo-occlusion of the liver increases the tumour concentration of drugs. Thirty-nine patients with colorectal liver metastases received a monthly bolus administration of mitomycin C (10 mg/m2 on day 1) plus a continuous infusion of 5-fluorouracil (500 mg/m2 daily from days 1 to 5). Drugs were given via both portal (one-third of the dose) and arterial (two-thirds) routes to control large and small metastases. Arterially administered mitomycin C was mixed with individualized doses of degradable starch microspheres. In 16 patients treatment was not started or was interrupted early because of arterial or portal catheter problems. In 23 patients who received two or more cycles of treatment the mean(s.d.) microsphere dose was 835(399) mg. Toxicity was mild, consisting mainly of pain. Five complete and five partial responses were seen, and six patients had stable disease. The median time to progression and length of survival were 6 and 16 months respectively. The relatively high rates of complete and overall response in hypovascular tumours (six of 12 lesions) may support the rationale of chemo-occlusion.

Adult↗
PubMed1994

Optimal combination therapy with tropisetron in 445 patients with incomplete control of chemotherapy-induced nausea and vomiting.

PURPOSE: This study evaluated tropisetron (Navoban; Sandoz Pharma, Basle, Switzerland)-based combination therapy in patients who had incomplete control of chemotherapy-induced nausea or vomiting when using tropisetron as a single antiemetic agent. PATIENTS AND METHODS: One thousand seventy-two patients, who were scheduled to receive at least two identical cycles of emetogenic chemotherapy, were treated with 5 mg tropisetron once daily in their first chemotherapy course. A 2 x 2 x 2 factorial design was used to evaluate three additional treatments to the recommended 5 mg once daily (intravenously [i.v.] on day 1; orally on days 2 through 6) tropisetron regimen during course 2 in those patients who had shown incomplete control of nausea and/or vomiting on any day of course 1. Four hundred forty-five patients were centrally randomized to receive, in addition, open-label dexamethasone (day 1, 0.2 mg/kg i.v.; days 2 through 6, 8 mg orally) and/or open-label alizapride (day 1, 100 mg i.v. and 4 x 50 mg orally; days 2 through 6, 4 x 50 mg orally) and/or double-blind tropisetron (ie, doubling the dose to 10 mg once daily) or corresponding placebo. RESULTS: Complete response rates (no nausea and no vomiting) were 72% for day 1 and 48% for days 1 through 6 of course 1. During course 2, more complete responders were observed when dexamethasone was added, both for day 1 (76% v 66%, P = .020) and for days 1 through 6 (50% v 34%, P = .0004). A moderate increase in the complete response rate was seen with the addition of conventional-dose alizapride (day 1, 75% v 68%, P = .14; days 1 through 6: 47% v 37%, P = .041). Doubling the dose of tropisetron did not change the complete response rate. CONCLUSION: The addition of dexamethasone significantly increases the complete response rate of both acute and delayed emesis in patients who have incomplete disease control with tropisetron alone.

Administration, Oral↗
PubMed1994

Secondary prevention of stroke: does dipyridamole add to aspirin?

BACKGROUND AND PURPOSE: The purpose of this paper is to evaluate, in the light of all available evidence, the place of aspirin alone and of aspirin combined with dipyridamole in the secondary prevention of cerebrovascular accidents. METHODS: We performed a meta-analysis of all identified double blind, controlled, studies in secondary prevention of cerebrovascular accidents for the following categories: studies comparing aspirin with placebo; studies comparing aspirin plus dipyridamole with placebo; studies comparing aspirin plus dipyridamole with aspirin alone. An indirect comparison was carried out to compare the results obtained with aspirin alone and those obtained with aspirin combined with dipyridamole. RESULTS: The meta-analysis of trials involving aspirin alone against placebo showed a risk reduction on strokes (17% reduction, p = 0.02), "important vascular events", i.e. a combination of vascular deaths, non-fatal strokes and non-fatal myocardial infarction (18% reduction, p = 0.003). Fatal vascular events (vascular deaths and fatal strokes) did not seem to be reduced at all. The overall mortality was reduced by 10%, but this reduction failed to reach statistical significance (p = 0.23). The meta-analysis of trials involving aspirin combined with dipyridamole showed more important risk reductions on every outcome whether fatal or not. Strokes were reduced by 42% (p < 0.001), fatal strokes by 43% (p = 0.02) and vascular deaths by 24% (p = 0.07, not significant). The overall mortality was reduced by 30% (p = 0.004). Direct comparisons of aspirin with aspirin plus dipyridamole did not indicate differences between the two treatment regimens. However the sample sizes involved in these comparisons were far too small to be informative. Indirect comparisons yielded statistically significant results in favour of the combination in terms of "important vascular events" (p = 0.007), all strokes (p = 0.007) and fatal strokes (p = 0.03). The results were also in favour of the combination but not statistically significant in terms of all deaths (p = 0.10) and vascular deaths (p = 0.08). CONCLUSIONS: Aspirin used alone reduces secondary occurrence of vascular events in cerebrovascular patients. There is no evidence, however, of a reduction of fatal events (vascular deaths and fatal strokes). In contrast, aspirin in combination with dipyridamole reduces non-fatal as well as fatal events. These results as well as the indirect comparisons of the risk reductions suggest that the combination of aspirin with dipyridamole may be superior to aspirin alone; this hypothesis is presently tested in a large randomized trial.

Aspirin↗
PubMed1993

Interim analyses, stopping rules and data monitoring in clinical trials in Europe.

A survey was carried out to identify the current policies of European cooperative groups with respect to interim analyses, stopping rules and data monitoring of ongoing clinical trials. The policies differ widely, from informal interim analyses distributed among all participating investigators, to planned interim analyses carried out by an independent statistician and scrutinized by a data monitoring committee. Different situations clearly call for different policies: for instance, trials of new drugs in AIDS need to be monitored more closely than trials of non-toxic adjuvant therapies for cancer. Likewise, trials with an immediately measurable end-point (such as the large-scale trials in myocardial infarction) need more intensive monitoring than those in which the outcome assessment requires prolonged follow-up. In all cases, however, it seems useful to articulate explicit data monitoring procedures in the trial protocol. In general, an independent data monitoring committee is essential to advise on the desirability to continue accrual into the trial, or to stop it early.

Acquired Immunodeficiency Syndrome↗
PubMed1993

What can we learn from a meta-analysis of trials testing the modulation of 5-FU by leucovorin? Advanced Colorectal Meta-analysis Project.

BACKGROUND AND DESIGN: We previously reported a meta-analysis of all randomized clinical trials comparing 5-FU to 5-FU plus intravenous d.l. leucovorin (LV) in patients with advanced colorectal cancer. RESULTS: The meta-analysis confirmed the advantage of 5-FU/LV over 5-FU alone in terms of response rate: overall, the response rate was 11% with 5-FU alone vs 23% with 5-FU/LV (p < 10(-7)). At the same time, it was showed that tumor regression can not be considered a surrogate end point for survival in patients with advanced colorectal cancer: no significant survival advantage was observed for patients allocated to 5-FU/LV. The present paper focuses on the interest of meta-analysis to study the role of the biomodulation of 5-FU by LV. This approach is compared with the analysis of individual clinical trials in terms of power, bias and credibility. It is argued that for the meta-analysis to be reliable, individual patient data from all available studies must be used, rather than summary data extracted from published papers. CONCLUSION: It is concluded that meta-analysis is very useful as a tool to explore and summarize available data on a given clinical problem, though its purpose is not to recommend any treatment modality. This meta-analysis has confirmed both the benefit of biomodulation of 5-FU by LV, and the limitations of the current modalities to impact significantly on overall patient survival. Further laboratory and clinical research is warranted on the biomodulation of 5-FU by LV.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Adjuvant treatment of stage I lung cancer with high-dose vitamin A.

PURPOSE: Vitamin A and retinoids are strong inhibitors of epithelial cancer promotion and progression in experimental carcinogenesis. This study examined whether they may prevent the occurrence of upper aerodigestive cancer in subjects heavily exposed to tobacco smoking, such as patients already cured of an early-stage lung cancer. PATIENTS AND METHODS: The adjuvant effect of high-dose vitamin A was tested on 307 patients with stage I non-small-cell lung cancer. After curative surgery, patients were randomly assigned to either a group prescribed retinol palmitate administration (orally 300,000 IU daily for 12 months) or a control group prescribed no treatment. RESULTS: After a median follow-up of 46 months, the number of patients with either recurrence or new primary tumors was 56 (37%) in the treated arm and 75 (48%) in the control arm. Eighteen patients in the treated group developed a second primary tumor, and 29 patients in the control group developed 33 second primary tumors. A statistically significant difference in favor of treatment was observed concerning time to new primary tumors in the field of prevention (P = .045, log-rank test). The treatment difference in terms of disease-free interval was close to statistical significance (P = .054, log-rank test) and just significant when adjusted for primary tumor classification (P = .038, Cox regression model). CONCLUSION: Daily oral administration of high-dose vitamin A is effective in reducing the number of new primary tumors related to tobacco consumption and may improve the disease-free interval in patients curatively resected for stage I lung cancer. The impact of such a treatment on survival needs to be further explored.

Adolescent↗