{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T19:35:08Z","timestamp":1791142508749,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Evidence-Based Complementary and Alternative Medicine"],"published-print":{"date-parts":[[2013]]},"abstract":"<jats:p><jats:italic>Purpose.<\/jats:italic>European Mistletoe (<jats:italic>Viscum album<\/jats:italic>L.) extracts (mistletoe) are commonly used for cancer treatment in Europe. This phase I study of gemcitabine (GEM) and mistletoe in advanced solid cancers (ASC) evaluated: (1) safety, toxicity, and maximum tolerated dose (MTD), (2) absolute neutrophil count (ANC) recovery, (3) formation of mistletoe lectin antibodies (ML ab), (4) cytokine plasma concentrations, (5) clinical response, and (6) pharmacokinetics of GEM.<jats:italic>Methods.<\/jats:italic>Design: increasing mistletoe and fixed GEM dose in stage I and increasing doses of GEM with a fixed dose of mistletoe in stage II. Dose limiting toxicities (DLT) were grade (G) 3 nonhematologic and G4 hematologic events; MTD was reached with 2 DLTs in one dosage level. Response in stage IV ASC was assessed with descriptive statistics. Statistical analyses examined clinical response\/survival and ANC recovery.<jats:italic>Results.<\/jats:italic>DLTs were G4 neutropenia, G4 thrombocytopenia, G4 acute renal failure, and G3 cellulitis, attributed to mistletoe. GEM 1380\u2009mg\/m<jats:sup>2<\/jats:sup>and mistletoe 250\u2009mg combined were the MTD. Of 44 patients, 24 developed nonneutropenic fever and flu-like syndrome. GEM pharmacokinetics were unaffected by mistletoe. All patients developed ML3 IgG antibodies. ANC showed a trend to increase between baseline and cycle 2 in stage I dose escalation. 6% of patients showed partial response, 42% stable disease. Median survival was 200 days. Compliance with mistletoe injections was high.<jats:italic>Conclusion.<\/jats:italic>GEM plus mistletoe is well tolerated. No botanical\/drug interactions were observed. Clinical response is similar to GEM alone.<\/jats:p>","DOI":"10.1155\/2013\/964592","type":"journal-article","created":{"date-parts":[[2013,10,27]],"date-time":"2013-10-27T21:03:53Z","timestamp":1382907833000},"page":"1-11","source":"Crossref","is-referenced-by-count":29,"title":["NCCAM\/NCI Phase 1 Study of Mistletoe Extract and Gemcitabine in Patients with Advanced Solid Tumors"],"prefix":"10.1155","volume":"2013","author":[{"given":"Patrick J.","family":"Mansky","sequence":"first","affiliation":[{"name":"The Cancer Team at Bellin Health, 1580 Commanche Avenue, Green Bay, WI 54313, USA"},{"name":"National Center for Complementary and Alternative Medicine, NIH, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2772-9101","authenticated-orcid":true,"given":"Dawn B.","family":"Wallerstedt","sequence":"additional","affiliation":[{"name":"Samuelli Institute, Alexandria, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy S.","family":"Sannes","sequence":"additional","affiliation":[{"name":"Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9301-0942","authenticated-orcid":true,"given":"Jamie","family":"Stagl","sequence":"additional","affiliation":[{"name":"University of Miami, Miami, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Lee","family":"Johnson","sequence":"additional","affiliation":[{"name":"National Center for Complementary and Alternative Medicine, NIH, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc R.","family":"Blackman","sequence":"additional","affiliation":[{"name":"Research Service (151), Veterans Affairs Medical Center, and Department of Medicine, Georgetown University School of Medicine, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean L.","family":"Grem","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center, Omaha, NE, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra M.","family":"Swain","sequence":"additional","affiliation":[{"name":"Washington Cancer Institute, Washington Hospital Center, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian P.","family":"Monahan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hematology and Medical Oncology Division, Uniformed Services University of the Health Sciences, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"issue":"6","key":"1","first-page":"461","volume":"56","year":"2006","journal-title":"Arzneimittel-Forschung"},{"key":"2","year":"1985"},{"issue":"5-6","key":"3","first-page":"295","volume":"14","year":"1995","journal-title":"Natural Immunity"},{"issue":"1","key":"4","first-page":"33","volume":"47","year":"1994","journal-title":"European Journal of Clinical Pharmacology"},{"issue":"1","key":"5","first-page":"43","volume":"44","year":"1981","journal-title":"Laboratory Investigation"},{"issue":"5","key":"6","first-page":"407","volume":"7","year":"1993","journal-title":"In Vivo"},{"issue":"6-7","key":"7","doi-asserted-by":"crossref","first-page":"431","DOI":"10.3109\/08820139309063421","volume":"22","year":"1993","journal-title":"Immunological Investigations"},{"issue":"2","key":"8","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/0192-0561(87)90095-6","volume":"9","year":"1987","journal-title":"International Journal of Immunopharmacology"},{"issue":"2","key":"9","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1159\/000226342","volume":"43","year":"1986","journal-title":"Oncology"},{"issue":"1","key":"10","first-page":"S65","volume":"8","year":"1997","journal-title":"Anti-Cancer Drugs"},{"issue":"1","key":"11","first-page":"S39","volume":"8","year":"1997","journal-title":"Anti-Cancer Drugs"},{"issue":"2","key":"12","first-page":"103","volume":"90","year":"1996","journal-title":"Zeitschrift fur Arztliche Fortbildung"},{"issue":"1","key":"13","first-page":"23","volume":"43","year":"1986","journal-title":"Oncology"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1002\/1098-2825(20001212)14:6&lt;255::AID-JCLA1&gt;3.0.CO;2-J"},{"issue":"12","key":"15","first-page":"1185","volume":"48","year":"1998","journal-title":"Arzneimittel-Forschung"},{"issue":"6","key":"16","first-page":"441","volume":"56","year":"2006","journal-title":"Arzneimittelforschung"},{"key":"17","first-page":"223","volume-title":"Mistletoe lectins as immunostimulants (chemistry, pharmacology and clinic)","year":"1999"},{"issue":"33","key":"18","doi-asserted-by":"crossref","first-page":"23722","DOI":"10.1016\/S0021-9258(18)35897-6","volume":"267","year":"1992","journal-title":"The Journal of Biological Chemistry"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(96)04401-1"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1159\/000069428"},{"issue":"11","key":"21","first-page":"3322","volume":"50","year":"1990","journal-title":"Cancer Research"},{"issue":"4","key":"22","doi-asserted-by":"crossref","first-page":"697","DOI":"10.3109\/08923970009016433","volume":"22","year":"2000","journal-title":"Immunopharmacology and Immunotoxicology"},{"issue":"3","key":"23","first-page":"1785","volume":"19","year":"1999","journal-title":"Anticancer Research"},{"issue":"6","key":"24","first-page":"483","volume":"56","year":"2006","journal-title":"Arzneimittel-Forschung"},{"issue":"12","key":"25","first-page":"1174","volume":"46","year":"1996","journal-title":"Arzneimittel-Forschung"},{"issue":"6","key":"26","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1189\/jlb.68.6.845","volume":"68","year":"2000","journal-title":"Journal of Leukocyte Biology"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.1007\/BF01649034"},{"issue":"5","key":"28","first-page":"169","volume":"4","year":"1999","journal-title":"European Journal of Medical Research"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(98)00301-2"},{"issue":"6","key":"30","first-page":"37","volume":"5","year":"1999","journal-title":"Alternative Therapies in Health and Medicine"},{"key":"31","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-010-0830-5"},{"issue":"8","key":"41","first-page":"456","volume":"54","year":"2004","journal-title":"Arzneimittel-Forschung"},{"key":"42","doi-asserted-by":"publisher","DOI":"10.2174\/156652410791317057"},{"key":"43","doi-asserted-by":"publisher","DOI":"10.1016\/j.explore.2012.06.005"},{"key":"32","doi-asserted-by":"publisher","DOI":"10.1186\/1756-9966-28-79"},{"key":"33","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-9-451"},{"key":"34","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD003297.pub2"},{"issue":"3","key":"35","first-page":"103","volume":"12","year":"2007","journal-title":"European Journal of Medical Research"},{"issue":"3","key":"36","first-page":"57","volume":"7","year":"2001","journal-title":"Alternative Therapies in Health and Medicine"},{"issue":"3","key":"37","first-page":"2073","volume":"20","year":"2000","journal-title":"Anticancer Research"},{"key":"38","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(00)00360-9"},{"key":"44","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2012.11.007"},{"key":"39","doi-asserted-by":"publisher","DOI":"10.1177\/1534735403259061"},{"key":"45","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1958.10501452"},{"issue":"1-2","key":"46","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1093\/biomet\/41.1-2.133","volume":"41","year":"1954","journal-title":"Biometrika"}],"updated-by":[{"DOI":"10.1155\/2014\/606348","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2014,2,12]],"date-time":"2014-02-12T00:00:00Z","timestamp":1392163200000}}],"container-title":["Evidence-Based Complementary and Alternative Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/ecam\/2013\/964592.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/ecam\/2013\/964592.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/ecam\/2013\/964592.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T17:20:40Z","timestamp":1688577640000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.hindawi.com\/journals\/ecam\/2013\/964592\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013]]},"references-count":45,"alternative-id":["964592","964592"],"URL":"https:\/\/doi.org\/10.1155\/2013\/964592","relation":{"erratum":[{"id-type":"doi","id":"10.1155\/2014\/606348","asserted-by":"object"}]},"ISSN":["1741-427X","1741-4288"],"issn-type":[{"value":"1741-427X","type":"print"},{"value":"1741-4288","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013]]}}}