Abstract
After colectomy with ileorectal anastomosis (IRA) for treatment of familial adenomatous polyposis (FAP), the rectal mucosa remains, with the risk of malignant change. Locoregional (rectal) sulindac has been applied, with initial higher-dose therapy and subsequent low-dose maintenance therapy to minimise side-effects. The dose-finding study with sulindac suppositories started with a dose of 300 mg sulindac daily per patient over 6 weeks. Depending on proctoscopical evaluation of regression of polyposis, sulindac doses were reduced in predefined steps. Ten of 15 patients developed a complete remission following 42 weeks of treatment, while the rest had partial remission. Responses were recorded 6–24 weeks after beginning sulindac treatment. After 36 weeks, 13/15 patients received 25–50 mg sulindac daily. An increase in the number of partial remissions after 42 weeks of treatment at doses of 100 mg sulindac daily may indicate the first approach to a reduced dose between 100 mg to 25 mg sulindac daily, but may also point to the importance of long-term treatment rather than dose-intense therapy.
Résumé
Après colectomie et anastomose iléo-rectale (AIR) pour le traitement de la polypose adénomateuse familiale (PAF) il demeure un risque de malignisation de la muqueuse rectale. Une application locale (rectale) de Sulindac a été effectuée avec des doses initiales élevées et une poursuite du traitement avec des doses plus faibles afin de diminuer les effets nocifs. L'étude dose-relation avec des suppositoires de Sulindac a commencé avec une dose de 300 mg de Sulindac quotidiens par malade pendant 6 semaines. Selon l'évaluation de la régression des polypes en proctoscopie, les doses de Sulindac étaient réduites de façon prédéfinie. 10 des 15 malades ont développé une rémission complète après 42 semaines de traitement tandis que les autres avaient une rémission partielle. La réponse a été réévaluée 6 à 24 semaines après le début du traitement par Sulindac. Après 36 semaines, 13 des 15 patients avaient reçu 25 à 50 mg quotidiens. L'augmentation du nombre des rémissions partielles après 42 semaines de traitement à la dose de 100 mg de Sulindac quotidiens peut indiquer une première approximation pour des doses réduites entre 100 et 25 mg de Sulindac quotidiens mais peut aussi souligner l'importance du traitement à long terme plutot que de l'intensité des doses thérapeutiques.
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The study was supported by a grant of ribosepharm GmbH, W-5657 Haan 1, Germany
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Winde, G., Gumbinger, H.G., Osswald, H. et al. The NSAID sulindac reverses rectal adenomas in colectomized patients with familial adenomatous polyposis: clinical results of a dose-finding study on rectal sulindac administration. Int J Colorect Dis 8, 13–17 (1993). https://doi.org/10.1007/BF00341270
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DOI: https://doi.org/10.1007/BF00341270