{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T03:58:44Z","timestamp":1784951924943,"version":"3.55.0"},"reference-count":14,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2018,1,25]],"date-time":"2018-01-25T00:00:00Z","timestamp":1516838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Lessons Learned<\/jats:title>\n                  <jats:p>Motivating patients to enroll in chemopreventive studies is challenging. Chemoprevention with toxic drugs is not feasible.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>LKB1 mutations are the underlying genetic abnormality causing Peutz-Jeghers syndrome (PJS) and are a potential target for everolimus. In this phase II study, the efficacy of everolimus on polyp and tumor growth in PJS patients was investigated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Adult patients with a proven LKB1 mutation and who were suitable for everolimus treatment were included in two different PJS cohorts: (a) patients with unresectable malignancies and (b) patients with high-risk polyps. Treatment in both groups was oral everolimus, 10 mg daily. Response rates were primary endpoints for both cohorts.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Between October 2011 and April 2016, only two patients were enrolled, one in each cohort. A 49-year-old patient with advanced pancreatic cancer in cohort 1 was progressive after 2 months. A 52-year-old male patient in cohort 2 experienced severe toxicity and refused treatment after 4 months, even though endoscopy suggested stabilization of polyps. Adverse events included dental inflammations, mucositis, and rash. In 2016, the trial was aborted for lack of accrual, despite extensive accrual efforts in an area where PJS is highly prevalent and care is highly centralized.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Due to accrual problems, no conclusions can be drawn about the value of everolimus in PJS treatment, questioning the feasibility of this agent for chemoprevention.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1634\/theoncologist.2017-0682","type":"journal-article","created":{"date-parts":[[2018,1,25]],"date-time":"2018-01-25T16:35:11Z","timestamp":1516898111000},"page":"399-e33","source":"Crossref","is-referenced-by-count":25,"title":["Chemoprevention in Patients with Peutz-Jeghers Syndrome: Lessons Learned"],"prefix":"10.1093","volume":"23","author":[{"given":"Justin","family":"de Brabander","sequence":"first","affiliation":[{"name":"University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferry A.L.M.","family":"Eskens","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne E.","family":"Korsse","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelien","family":"Dekker","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter","family":"Dewint","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Maria Middelares Hospital, Gent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique E.","family":"van Leerdam","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Netherlands Cancer Institute, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"van Eeden","sequence":"additional","affiliation":[{"name":"Department of Pathology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz-Josef","family":"Kl\u00fcmpen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, The 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