{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T23:10:01Z","timestamp":1791155401066,"version":"4.1.0"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2015,4,2]],"date-time":"2015-04-02T00:00:00Z","timestamp":1427932800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0121197","type":"journal-article","created":{"date-parts":[[2015,4,2]],"date-time":"2015-04-02T18:00:24Z","timestamp":1427997624000},"page":"e0121197","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["A Phase I Dose-Escalation Study of Lenalidomide in Combination with Gemcitabine in Patients with Advanced Pancreatic Cancer"],"prefix":"10.1371","volume":"10","clinical-trial-number":[{"clinical-trial-number":"nct01547260","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Gustav J.","family":"Ullenhag","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Rossmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Liljefors","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2015,4,2]]},"reference":[{"issue":"11","key":"ref1","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1002\/bjs.4794","article-title":"Current standards of surgery for pancreatic cancer","volume":"91","author":"N Alexakis","year":"2004","journal-title":"Br J Surg"},{"issue":"3","key":"ref2","first-page":"485","article-title":"Pancreatic cancer: diagnosis and management","volume":"73","author":"R Freelove","year":"2006","journal-title":"Am Fam Physician"},{"issue":"8","key":"ref3","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1002\/cncr.22193","article-title":"Annual report to the nation on the status of cancer, 1975\u20132003, featuring cancer among U.S. Hispanic\/Latino populations","volume":"107","author":"HL Howe","year":"2006","journal-title":"Cancer"},{"issue":"6","key":"ref4","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/S1091-255X(00)80105-5","article-title":"Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators","volume":"4","author":"TA Sohn","year":"2000","journal-title":"J Gastrointest Surg"},{"issue":"6","key":"ref5","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1200\/JCO.1997.15.6.2403","article-title":"Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial","volume":"15","author":"HA Burris 3rd","year":"1997","journal-title":"Journal of clinical oncology: official journal of the American Society of Clinical Oncology"},{"issue":"33","key":"ref6","doi-asserted-by":"crossref","first-page":"5487","DOI":"10.1200\/JCO.2009.23.3098","article-title":"Changing the paradigm in conducting randomized clinical studies in advanced pancreatic cancer: an opportunity for better clinical development","volume":"27","author":"J Tabernero","year":"2009","journal-title":"Journal of clinical oncology: official journal of the American Society of Clinical Oncology"},{"issue":"22","key":"ref7","doi-asserted-by":"crossref","first-page":"3617","DOI":"10.1200\/JCO.2010.28.1386","article-title":"Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the Cancer and Leukemia Group B (CALGB 80303)","volume":"28","author":"HL Kindler","year":"2010","journal-title":"Journal of clinical oncology: official journal of the American Society of Clinical Oncology"},{"issue":"3","key":"ref8","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/S1470-2045(11)70004-3","article-title":"Axitinib plus gemcitabine versus placebo plus gemcitabine in patients with advanced pancreatic adenocarcinoma: a double-blind randomised phase 3 study","volume":"12","author":"HL Kindler","year":"2011","journal-title":"Lancet Oncol"},{"issue":"19","key":"ref9","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1056\/NEJMoa1011923","article-title":"FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer","volume":"364","author":"T Conroy","year":"2011","journal-title":"The New England journal of medicine"},{"issue":"15","key":"ref10","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1200\/JCO.2006.07.9525","article-title":"Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group","volume":"25","author":"MJ Moore","year":"2007","journal-title":"Journal of clinical oncology: official journal of the American Society of Clinical Oncology"},{"issue":"18","key":"ref11","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1056\/NEJMoa1304369","article-title":"Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine","volume":"369","author":"DD Von Hoff","year":"2013","journal-title":"The New England journal of medicine"},{"key":"ref12","unstructured":"FDA US Food and Drug Administration (FDA) 2013. Available: www.fda.gov<\/ext-link>."},{"key":"ref13","unstructured":"European Medicine Agency (EMA) Science Medicine Health. SPC_Lenalidomide_PDF.REVLIMID\u2014revised Feb 2013 2013. Available: http:\/\/www.emea.europa.eu\/docs\/en_GB\/document_library\/EPAR_-_Product_Information\/human\/000717\/WC500056018.pdf<\/ext-link>."},{"issue":"1","key":"ref14","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1586\/ehm.12.62","article-title":"Immunomodulatory drugs in multiple myeloma","volume":"6","author":"S Andhavarapu","year":"2013","journal-title":"Expert Rev Hematol"},{"issue":"1\u20132","key":"ref15","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.mvr.2005.01.002","article-title":"Orally administered lenalidomide (CC-5013) is anti-angiogenic in vivo and inhibits endothelial cell migration and Akt phosphorylation in vitro","volume":"69","author":"K Dredge","year":"2005","journal-title":"Microvasc Res"},{"issue":"1","key":"ref16","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s00262-010-0919-9","article-title":"Lenalidomide enhances antibody-dependent cellular cytotoxicity of solid tumor cells in vitro: influence of host immune and tumor markers","volume":"60","author":"L Wu","year":"2011","journal-title":"Cancer immunology, immunotherapy: CII"},{"issue":"5","key":"ref17","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1182\/blood-2003-02-0361","article-title":"Immunomodulatory drug costimulates T cells via the B7-CD28 pathway","volume":"103","author":"R LeBlanc","year":"2004","journal-title":"Blood"},{"issue":"1","key":"ref18","doi-asserted-by":"crossref","first-page":"E14","DOI":"10.1208\/aapsj070103","article-title":"Properties of thalidomide and its analogues: implications for anticancer therapy","volume":"7","author":"SK Teo","year":"2005","journal-title":"AAPS J"},{"issue":"1","key":"ref19","doi-asserted-by":"crossref","first-page":"380","DOI":"10.4049\/jimmunol.163.1.380","article-title":"Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha","volume":"163","author":"LG Corral","year":"1999","journal-title":"Journal of immunology"},{"issue":"7","key":"ref20","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1080\/07357900500283101","article-title":"Immunomodulatory drugs","volume":"23","author":"E Crane","year":"2005","journal-title":"Cancer Invest"},{"issue":"3","key":"ref21","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1097\/COC.0b013e31815e451f","article-title":"Lenalidomide therapy for metastatic renal cell carcinoma","volume":"31","author":"RJ Amato","year":"2008","journal-title":"Am J Clin Oncol"},{"issue":"5","key":"ref22","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1038\/sj.bjc.6601579","article-title":"Phase I study to determine the safety, tolerability and immunostimulatory activity of thalidomide analogue CC-5013 in patients with metastatic malignant melanoma and other advanced cancers","volume":"90","author":"JB Bartlett","year":"2004","journal-title":"British journal of cancer"},{"issue":"5","key":"ref23","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1097\/01.JTO.0000268679.33238.67","article-title":"Phase I study of lenalidomide in solid tumors","volume":"2","author":"AA Miller","year":"2007","journal-title":"J Thorac Oncol"},{"issue":"14","key":"ref24","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1016\/j.ejca.2006.05.018","article-title":"Toxicity profile of the immunomodulatory thalidomide analogue, lenalidomide: phase I clinical trial of three dosing schedules in patients with solid malignancies","volume":"42","author":"RA Sharma","year":"2006","journal-title":"Eur J Cancer"},{"issue":"5","key":"ref25","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s10637-008-9200-x","article-title":"Phase I trial of docetaxel given every 3 weeks and daily lenalidomide in patients with advanced solid tumors","volume":"27","author":"SL Sanborn","year":"2009","journal-title":"Invest New Drugs"},{"issue":"2","key":"ref26","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.ejca.2010.09.002","article-title":"A phase I, dose-escalation study of pomalidomide (CC-4047) in combination with gemcitabine in metastatic pancreas cancer","volume":"47","author":"JR Infante","year":"2011","journal-title":"Eur J Cancer"},{"issue":"4","key":"ref27","doi-asserted-by":"crossref","first-page":"340","DOI":"10.4161\/cbt.23625","article-title":"Lenalidomide in combination with gemcitabine as first-line treatment for patients with metastatic carcinoma of the pancreas: a Sarah Cannon Research Institute phase II trial","volume":"14","author":"JR Infante","year":"2013","journal-title":"Cancer biology & therapy"},{"issue":"9","key":"ref28","first-page":"915","article-title":"Effect of gemcitabine on immune cells in subjects with adenocarcinoma of the pancreas. Cancer immunology, immunotherapy","volume":"54","author":"JM Plate","year":"2005","journal-title":"CII"},{"issue":"12","key":"ref29","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1093\/jjco\/hyp112","article-title":"Regular dose of gemcitabine induces an increase in CD14+ monocytes and CD11c+ dendritic cells in patients with advanced pancreatic cancer","volume":"39","author":"A Soeda","year":"2009","journal-title":"Japanese journal of clinical oncology"},{"issue":"10","key":"ref30","doi-asserted-by":"crossref","first-page":"4905","DOI":"10.4049\/jimmunol.170.10.4905","article-title":"Induction of tumor cell apoptosis in vivo increases tumor antigen cross-presentation, cross-priming rather than cross-tolerizing host tumor-specific CD8 T cells","volume":"170","author":"AK Nowak","year":"2003","journal-title":"Journal of immunology"},{"issue":"35","key":"ref31","doi-asserted-by":"crossref","first-page":"8950","DOI":"10.1200\/JCO.2005.12.147","article-title":"Chemo-immunotherapy of metastatic colorectal carcinoma with gemcitabine plus FOLFOX 4 followed by subcutaneous granulocyte macrophage colony-stimulating factor and interleukin-2 induces strong immunologic and antitumor activity in metastatic colon cancer patients","volume":"23","author":"P Correale","year":"2005","journal-title":"Journal of clinical oncology: official journal of the American Society of Clinical Oncology"},{"issue":"1","key":"ref32","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1002\/ijc.27990","article-title":"Low-dose gemcitabine depletes regulatory T cells and improves survival in the orthotopic Panc02 model of pancreatic cancer","volume":"133","author":"I Shevchenko","year":"2013","journal-title":"International journal of cancer Journal international du cancer"},{"issue":"1","key":"ref33","doi-asserted-by":"crossref","first-page":"70","DOI":"10.3892\/etm.2012.553","article-title":"Potential plasticity of T regulatory cells in pancreatic carcinoma in relation to disease progression and outcome","volume":"4","author":"B Vizio","year":"2012","journal-title":"Experimental and therapeutic medicine"},{"issue":"9","key":"ref34","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/s002620100229","article-title":"Treatment of human colon carcinoma cell lines with anti-neoplastic agents enhances their lytic sensitivity to antigen-specific CD8+ cytotoxic T lymphocytes","volume":"50","author":"ES Bergmann-Leitner","year":"2001","journal-title":"Cancer immunology, immunotherapy: CII"},{"issue":"9","key":"ref35","doi-asserted-by":"crossref","first-page":"3063","DOI":"10.1182\/blood-2002-03-0996","article-title":"Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma","volume":"100","author":"PG Richardson","year":"2002","journal-title":"Blood"},{"issue":"35","key":"ref36","doi-asserted-by":"crossref","first-page":"5965","DOI":"10.1200\/JCO.2009.22.3685","article-title":"Reporting of time-to-event end points and tracking of failures in randomized trials of radiotherapy with or without any concomitant anticancer agent for locally advanced head and neck cancer","volume":"27","author":"C Le Tourneau","year":"2009","journal-title":"Journal of clinical oncology: official journal of the American Society of Clinical Oncology"},{"issue":"16","key":"ref37","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.1002\/sim.903","article-title":"An evaluation of phase I clinical trial designs in the continuous dose-response setting","volume":"20","author":"BE Storer","year":"2001","journal-title":"Statistics in medicine"},{"issue":"9","key":"ref38","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1517\/17425255.2012.712685","article-title":"Evaluation of the pharmacokinetics, preclinical, and clinical efficacy of lenalidomide for the treatment of multiple myeloma","volume":"8","author":"S Bringhen","year":"2012","journal-title":"Expert Opin Drug Metab Toxicol"},{"issue":"14","key":"ref39","first-page":"4082","article-title":"Advanced pancreatic cancer: a multi-institutional trial with gemcitabine and thalidomide","volume":"22","author":"WJ Maples","year":"2004","journal-title":"Journal of Clinical Oncology ASCO Annual Meeting Proceedings (Post-meeting Edition)"},{"issue":"33","key":"ref40","doi-asserted-by":"crossref","first-page":"5513","DOI":"10.1200\/JCO.2009.24.2446","article-title":"Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer","volume":"27","author":"D Cunningham","year":"2009","journal-title":"Journal of clinical oncology: official journal of the American Society of Clinical Oncology"},{"issue":"11","key":"ref41","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/S1470-2045(04)01606-7","article-title":"Pancreatic cancer and thromboembolic disease","volume":"5","author":"AA Khorana","year":"2004","journal-title":"Lancet Oncol"},{"issue":"4","key":"ref42","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1586\/era.10.184","article-title":"The impact of thromboprophylaxis on cancer survival: focus on pancreatic cancer","volume":"11","author":"M Mandala","year":"2011","journal-title":"Expert Rev Anticancer Ther"},{"issue":"3","key":"ref43","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.ejca.2005.09.013","article-title":"High risk of venous thrombosis in patients with pancreatic cancer: a cohort study of 202 patients","volume":"42","author":"JW Blom","year":"2006","journal-title":"Eur J Cancer"},{"issue":"2","key":"ref44","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/sj.leu.2405062","article-title":"Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma","volume":"22","author":"A Palumbo","year":"2008","journal-title":"Leukemia"},{"issue":"15","key":"ref45","first-page":"e14640","article-title":"Lenalidomide in combination with gemcitabine in patients with untreated metastatic carcinoma of the pancreas: A Sarah Cannon Research Institute phase II trial. Abstract no 14640","volume":"29","author":"H Arkenau","year":"2011","journal-title":"Journal of Clinical Oncology ASCO Annual Meeting Proceedings (Post-meeting Edition)"},{"issue":"9","key":"ref46","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1016\/j.ejca.2011.10.017","article-title":"Gemcitabine versus gemcitabine plus dalteparin thromboprophylaxis in pancreatic cancer","volume":"48","author":"A Maraveyas","year":"2012","journal-title":"Eur J Cancer"},{"key":"ref47","unstructured":"Revlimid, highlights of prescribing information 2013. Available: http:\/\/www.revlimid.com\/docs\/Revlimid-Full-PI.pdf<\/ext-link>."},{"issue":"4","key":"ref48","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s11912-012-0238-8","article-title":"Incidence and management of gastrointestinal perforation from bevacizumab in advanced cancers","volume":"14","author":"T Abu-Hejleh","year":"2012","journal-title":"Curr Oncol Rep"},{"issue":"12","key":"ref49","doi-asserted-by":"crossref","first-page":"2764","DOI":"10.1182\/blood-2011-08-373514","article-title":"A review of second primary malignancy in patients with relapsed or refractory multiple myeloma treated with lenalidomide","volume":"119","author":"MA Dimopoulos","year":"2012","journal-title":"Blood"},{"issue":"19","key":"ref50","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1056\/NEJMoa1114083","article-title":"Lenalidomide after stem-cell transplantation for multiple myeloma","volume":"366","author":"PL McCarthy","year":"2012","journal-title":"The New England journal of medicine"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0121197","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T04:30:34Z","timestamp":1691555434000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0121197"}},"subtitle":[],"editor":[{"given":"Murray","family":"Korc","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,4,2]]},"references-count":50,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2015,4,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0121197","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,4,2]]}}}