Sirolimus for the treatment of polyposis of the rectal remnant and ileal pouch in four patients with familial adenomatous polyposis: a pilot study
Objective After prophylactic colectomy, adenomas continue to develop in the remaining intestine of patients with familial adenomatous polyposis (FAP). There is a lack of standard clinical recommendation for chemoprevention in patients with FAP. Because of promising in vivo studies, the aim of this p...
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BMJ Publishing Group
2020-12-01
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| Series: | BMJ Open Gastroenterology |
| Online Access: | https://bmjopengastro.bmj.com/content/7/1/e000497.full |
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| author | Evelien Dekker Lianne Koens Barbara A J Bastiaansen Victorine H Roos Bartolomeus J Meijer Frank G J Kallenberg Frederike J Bemelman Patrick M M Bossuyt Jarom Heijmans Gijs van den Brink |
| author_facet | Evelien Dekker Lianne Koens Barbara A J Bastiaansen Victorine H Roos Bartolomeus J Meijer Frank G J Kallenberg Frederike J Bemelman Patrick M M Bossuyt Jarom Heijmans Gijs van den Brink |
| author_sort | Evelien Dekker |
| collection | DOAJ |
| description | Objective After prophylactic colectomy, adenomas continue to develop in the remaining intestine of patients with familial adenomatous polyposis (FAP). There is a lack of standard clinical recommendation for chemoprevention in patients with FAP. Because of promising in vivo studies, the aim of this pilot study was to investigate the safety of sirolimus and its effect on progression of intestinal adenomas.Design Patients with FAP with InSiGHT Polyposis Staging System 3 of the retained rectum or pouch received sirolimus for 6 months, dosed at plasma concentration levels of 5–8 µg/L. Primary outcomes were safety and change in marked polyp size. Secondary outcomes were change in number of polyps and effect on proliferation and apoptosis assessed by immunohistochemistry.Results Each of the included four patients reported 4 to 18 adverse events (toxicity grades 1–3). One patient prematurely terminated the study because of adverse events. Marked polyp size decreased in 16 (80%)/20 and remained the same in 4 (20%)/20 patients. The number of polyps decreased in all patients (MD −25.75, p=0.13). Three out of four patients showed substantial induction of apoptosis or inhibition of proliferation.Conclusion Six months of sirolimus treatment in four patients with FAP showed promising effects especially on the number of polyps in the rectal remnant and ileal pouch, although at the cost of numerous adverse events.Trial registration number ClinicalTrials.gov ID NCT03095703. |
| format | Article |
| id | doaj-art-4ed12c2c41c74e5ab353a647b9f04bf6 |
| institution | Kabale University |
| issn | 2054-4774 |
| language | English |
| publishDate | 2020-12-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open Gastroenterology |
| spelling | doaj-art-4ed12c2c41c74e5ab353a647b9f04bf62024-12-14T15:50:08ZengBMJ Publishing GroupBMJ Open Gastroenterology2054-47742020-12-017110.1136/bmjgast-2020-000497Sirolimus for the treatment of polyposis of the rectal remnant and ileal pouch in four patients with familial adenomatous polyposis: a pilot studyEvelien Dekker0Lianne Koens1Barbara A J Bastiaansen2Victorine H Roos3Bartolomeus J Meijer4Frank G J Kallenberg5Frederike J Bemelman6Patrick M M Bossuyt7Jarom Heijmans8Gijs van den Brink91 Gastroenterology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsPathology, Amsterdam Universitair Medische Centra, Amsterdam, The NetherlandsDepartment of Gastroenterology and Hepatology, Amsterdam UMC - Location AMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, North Holland, The NetherlandsDepartment of Gastroenterology and Hepatology, Amsterdam UMC - Location AMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, North Holland, The NetherlandsDepartment of Gastroenterology and Hepatology, Amsterdam UMC - Location AMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, North Holland, The NetherlandsDepartment of Gastroenterology and Hepatology, Amsterdam UMC - Location AMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, North Holland, The NetherlandsDepartment of Internal Medicine, Division of Nephrology, Amsterdam UMC - Location AMC, University of Amsterdam, Amsterdam, North Holland, The NetherlandsDepartment of Clinical Epidemiology and Biostatistics, Academic Medical Centre, University of Amsterdam, Amsterdam, NetherlandsDepartment of Gastroenterology and Hepatology, Amsterdam UMC - Location AMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, North Holland, The NetherlandsDepartment of Gastroenterology and Hepatology, Amsterdam UMC - Location AMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, North Holland, The NetherlandsObjective After prophylactic colectomy, adenomas continue to develop in the remaining intestine of patients with familial adenomatous polyposis (FAP). There is a lack of standard clinical recommendation for chemoprevention in patients with FAP. Because of promising in vivo studies, the aim of this pilot study was to investigate the safety of sirolimus and its effect on progression of intestinal adenomas.Design Patients with FAP with InSiGHT Polyposis Staging System 3 of the retained rectum or pouch received sirolimus for 6 months, dosed at plasma concentration levels of 5–8 µg/L. Primary outcomes were safety and change in marked polyp size. Secondary outcomes were change in number of polyps and effect on proliferation and apoptosis assessed by immunohistochemistry.Results Each of the included four patients reported 4 to 18 adverse events (toxicity grades 1–3). One patient prematurely terminated the study because of adverse events. Marked polyp size decreased in 16 (80%)/20 and remained the same in 4 (20%)/20 patients. The number of polyps decreased in all patients (MD −25.75, p=0.13). Three out of four patients showed substantial induction of apoptosis or inhibition of proliferation.Conclusion Six months of sirolimus treatment in four patients with FAP showed promising effects especially on the number of polyps in the rectal remnant and ileal pouch, although at the cost of numerous adverse events.Trial registration number ClinicalTrials.gov ID NCT03095703.https://bmjopengastro.bmj.com/content/7/1/e000497.full |
| spellingShingle | Evelien Dekker Lianne Koens Barbara A J Bastiaansen Victorine H Roos Bartolomeus J Meijer Frank G J Kallenberg Frederike J Bemelman Patrick M M Bossuyt Jarom Heijmans Gijs van den Brink Sirolimus for the treatment of polyposis of the rectal remnant and ileal pouch in four patients with familial adenomatous polyposis: a pilot study BMJ Open Gastroenterology |
| title | Sirolimus for the treatment of polyposis of the rectal remnant and ileal pouch in four patients with familial adenomatous polyposis: a pilot study |
| title_full | Sirolimus for the treatment of polyposis of the rectal remnant and ileal pouch in four patients with familial adenomatous polyposis: a pilot study |
| title_fullStr | Sirolimus for the treatment of polyposis of the rectal remnant and ileal pouch in four patients with familial adenomatous polyposis: a pilot study |
| title_full_unstemmed | Sirolimus for the treatment of polyposis of the rectal remnant and ileal pouch in four patients with familial adenomatous polyposis: a pilot study |
| title_short | Sirolimus for the treatment of polyposis of the rectal remnant and ileal pouch in four patients with familial adenomatous polyposis: a pilot study |
| title_sort | sirolimus for the treatment of polyposis of the rectal remnant and ileal pouch in four patients with familial adenomatous polyposis a pilot study |
| url | https://bmjopengastro.bmj.com/content/7/1/e000497.full |
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