{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:51:34Z","timestamp":1790297494671,"version":"4.1.0"},"reference-count":10,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T00:00:00Z","timestamp":1638144000000},"content-version":"vor","delay-in-days":741,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 CA023100"],"award-info":[{"award-number":["P30 CA023100"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis. The BRAF inhibitor vemurafenib is approved by the U.S. Food and Drug Administration (FDA) for patients with ECD harboring a BRAF V600E mutation. Successful treatment has also been reported with MEK-targeted therapies, likely because of the fact that BRAF mutant\u2013negative patients harbor MEK pathway alterations. In our Rare Tumor Clinic, we noted that these patients have frequent drug-related toxicity, consistent with previous reports indicating the need to markedly lower doses of interferon-alpha when that agent is used in these patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients and Methods<\/jats:title>\n                  <jats:p>We performed a review of ten patients with ECD seen at the Rare Tumor Clinic at University of California San Diego receiving 16 regimens of targeted BRAF, MEK, or combined therapies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The median age of the ten patients with ECD was 53\u2009years (range, 29\u201377); seven were men. The median dose percentage (percent of FDA-approved dose) tolerated was 25% (range, 25%\u201350%). The most common clinically significant adverse effects resulting in dose adjustments of targeted therapies were rash, arthralgias, and uveitis. Renal toxicity and congestive heart failure were seen in one patient each. In spite of these issues, eight of ten patients (80%) achieved a partial remission on therapy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>Patients with ECD appear to require substantially reduced doses of BRAF and MEK inhibitors but are responsive to these lower doses.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1634\/theoncologist.2019-0606","type":"journal-article","created":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T20:39:12Z","timestamp":1574109552000},"page":"e386-e390","source":"Crossref","is-referenced-by-count":30,"title":["Real-World Toxicity Experience with BRAF\/MEK Inhibitors in Patients with Erdheim-Chester Disease"],"prefix":"10.1093","volume":"25","author":[{"given":"Ila M.","family":"Saunders","sequence":"first","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron M.","family":"Goodman","sequence":"additional","affiliation":[{"name":"Division of Blood and Marrow Transplantation, Department of Medicine, University of California San Diego, La Jolla, California, USA"},{"name":"Moores Cancer Center, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razelle","family":"Kurzrock","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, University of California San Diego, La Jolla, California, USA"},{"name":"Center for Personalized Cancer Therapy, University of California San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,11,19]]},"reference":[{"key":"2021122510121938800_R1","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1182\/blood-2014-03-561381","article-title":"Consensus guidelines for the diagnosis and clinical management of Erdheim-Chester disease","volume":"124","author":"Diamond","year":"2014","journal-title":"Blood"},{"key":"2021122510121938800_R2","doi-asserted-by":"crossref","first-page":"2992","DOI":"10.1182\/blood-2005-06-2238","article-title":"Successful treatment of Erdheim-Chester disease, a non-Langerhans-cell histiocytosis, with interferon-alpha","volume":"106","author":"Braiteh","year":"2005","journal-title":"Blood"},{"key":"2021122510121938800_R3","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.mayocp.2014.01.023","article-title":"Erdheim-Chester disease: Characteristics and management","volume":"89","author":"Munoz","year":"2014","journal-title":"Mayo Clin Proc"},{"key":"2021122510121938800_R4","doi-asserted-by":"crossref","first-page":"e633","DOI":"10.1200\/JCO.2010.29.9073","article-title":"Response of histiocytoses to imatinib mesylate: Fire to ashes","volume":"28","author":"Janku","year":"2010","journal-title":"J Clin Oncol"},{"key":"2021122510121938800_R5","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1001\/jamaoncol.2017.5029","article-title":"Vemurafenib for BRAF V600-mutant Erdheim-Chester disease and Langerhans cell histiocytosis: Analysis of data from the histology-independent, phase 2, open-label VE-BASKET study","volume":"4","author":"Diamond","year":"2018","journal-title":"JAMA Oncol"},{"key":"2021122510121938800_R6","first-page":"2777","article-title":"Erdheim-Chester disease: Comprehensive review of molecular profiling and therapeutic advances","volume":"37","author":"Haroun","year":"2017","journal-title":"Anticancer Res"},{"key":"2021122510121938800_R7","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1158\/1535-7163.MCT-18-1244","article-title":"Molecular profiling of tumor tissue and plasma cell-free DNA from patients with non-Langerhans cell histiocytosis","volume":"18","author":"Janku","year":"2019","journal-title":"Mol Cancer 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