Abstract PL04-04: Vitamin E and selenium for prostate cancer prevention: The SELECT experience
Notice bibliographique
Résumé
Abstract The Selenium and Vitamin E Cancer Prevention Trial (SELECT) tested its namesake agents in the prevention of prostate cancer, a continuing major health threat, especially for African American men, in the United States, including Puerto Rico, and Canada. Designed as a large, simple trial conforming as closely as possible with community standards of care, SELECT was a phase III randomized, placebo-controlled trial of selenium (200 g/day from L-selenomethionine) and/or vitamin E (400 IU/day of all rac -tocopheryl acetate) in men at least 55 years of age (non-African American) or at least 50 years of age (African American) with a serum prostate-specific antigen (PSA) ≤ 4 ng/mL and a digital rectal examination (DRE) not suspicious for prostate cancer. The planned intervention duration was a minimum of 7 years, maximum of 12 years. The strongest evidence supporting the SELECT hypothesis came from secondary clinical results indicating that prostate cancer risk was reduced by vitamin E in the Alpha-Tocopherol, Beta-Carotene (ATBC) Study (designed to prevent lung cancer) and by selenium in the Nutritional Prevention of Cancer (NPC) trial (designed to prevent skin cancer); this evidence was supported by epidemiologic and preclinical data. 35,533 men were randomly assigned at a faster-than-expected accrual rate to the four, well-balanced study arms (selenium, vitamin E, selenium plus vitamin E, placebo) between 2001 and 2004. As a result of a planned interim analysis (at 7 years) and by recommendation of the Data and Safety Monitoring Committee, the interventions were discontinued because of convincing evidence of no benefit from either study agent (p < 0.0001) and no possibility of a benefit to the planned degree with additional follow-up. With a median overall follow-up of 5.46 years (range, 4.17 to 7.33 years), the primary analysis showed the following prostate cancer results (versus placebo, n=416): vitamin E hazard ratio (HR) = 1.13 (n=473; 99% confidence interval [CI], 0.95 - 1.35), selenium HR = 1.04 (n=432; 99% CI, 0.87 – 1.24), combination HR = 1.05 (n=437; 99% CI, 0.88 – 1.25). No significant differences were seen in any prespecified cancer endpoints including lung, colorectal, and overall cancer. A nonsignificant increased risk of prostate cancer occurred in the vitamin E arm (p=0.06; relative risk [RR]=1.13; 99% CI, 0.95 – 1.35), and the selenium arm showed a nonsignificant increased risk of Type 2 diabetes mellitus (p=0.16; RR=1.07; 99% CI, 0.94–1.22); neither of these increases appeared in the combination arm. Selenium, vitamin E, and their combination did not reduce the risk of prostate cancer in SELECT. One important lesson learned from the SELECT experience, building on lessons learned from the earlier ATBC and NPC experiences, is that we should step back and do more small, lead-up preclinical and early-phase clinical studies that increase our understanding of cancer biology and agent effects before moving ahead with large clinical trials of natural or other potential preventive agents. Epidemiologic and secondary clinical data are great pathfinders, but the heaviest supportive evidence for definitive trials may come mainly from more extensive preliminary research, including mechanistic studies that can validate the biologic plausibility of the clinical, risk reduction hypothesis. Another important lesson SELECT has provided for any large prevention trial is built-in opportunity for translational research. The SELECT design comprised sub-studies of molecular and standard epidemiology, diet and nutrition, and other important correlative endpoints that informed the collection of data and biospecimens in the trial and resulted in an invaluable repository for future research. Support for this work was received from Public Health Service Cooperative Agreement grant CA37429 (National Cancer Institute, National Institutes of Health, Department of Health and Human Services) and from the National Center for Complementary and Alternative Medicine (National Institutes of Health). Citation Information: Cancer Prev Res 2010;3(1 Suppl):PL04-04.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».