{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T18:54:50Z","timestamp":1789584890368,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T00:00:00Z","timestamp":1397779200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2014,8,15]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Preclinical and clinical studies suggest synergistic activity between somatostatin analogues and mammalian target of rapamycin inhibitors. The activity and safety of everolimus was assessed in combination with octreotide long\u2010acting repeatable (LAR) in patients with neuroendocrine tumors (NETs) of gastroenteropancreatic and lung origin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>This was a phase 2, multicenter trial using a Simon's 2\u2010stage minimax design. Treatment\u2010naive patients with advanced well\u2010differentiated NETs of gastroenteropancreatic tract and lung origin received everolimus 10 mg daily, in combination with octreotide LAR 30 mg every 28 days. The primary endpoint was objective response rate (ORR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>A total of 50 patients (median age, 60.5 years) were enrolled. Primary tumor sites were: pancreas (14 patients), lung (11 patients), ileum (9 patients), jejunum and duodenum (2 patients), and unknown (14 patients). Thirteen patients (26%) had carcinoid syndrome. Treatment\u2010related adverse events (AEs) were mostly grade 1 or 2; the only grade 4 AE was mucositis in 1 patient, whereas grade 3 AEs included skin rash in 1 case (2%), stomatitis in 4 cases (8%), and diarrhea in 11 cases (22%). The ORR was 18%; 2% of patients had a complete response (CR), 16% a partial response (PR) and 74% achieved stable disease (SD). All CRs and all PRs as well as 92% of SDs had a duration \u22656 months. The clinical benefit (CR+PR+SD) was 92%. At a median follow\u2010up of 277 days, median time to progression and overall survival were not reached.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>\n                      The everolimus\u2010octreotide LAR combination was active and well tolerated in these previously treated patients with advanced NETs, suggesting a possible role as first\u2010line treatment in patients with NET.\n                      <jats:bold>\n                        <jats:italic>Cancer<\/jats:italic>\n                        2014;120:2457\u20132463.\n                      <\/jats:bold>\n                      \u00a9\n                      <jats:italic>2014 American Cancer Society<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.28726","type":"journal-article","created":{"date-parts":[[2014,4,19]],"date-time":"2014-04-19T06:41:03Z","timestamp":1397889663000},"page":"2457-2463","source":"Crossref","is-referenced-by-count":60,"title":["Everolimus in combination with octreotide long\u2010acting repeatable in a first\u2010line setting for patients with neuroendocrine tumors: An ITMO group study"],"prefix":"10.1002","volume":"120","author":[{"given":"Emilio","family":"Bajetta","sequence":"first","affiliation":[{"name":"Institute of Oncology Polyclinic Hospital Monza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Catena","sequence":"additional","affiliation":[{"name":"Institute of Oncology Polyclinic Hospital Monza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Fazio","sequence":"additional","affiliation":[{"name":"Gastrointestinal and Neuroendocrine Tumors Unit European Institute of Oncology Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Pusceddu","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit IRCCS Foundation National Cancer Institute Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Biondani","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit IRCCS Foundation National Cancer Institute Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giusi","family":"Blanco","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit Mediterranean Institute of Oncology Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Ricci","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit S. Chiara Hospital Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Aieta","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit Regional Oncology Hospital Rionero in Vulture Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Pucci","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit University Hospital Parma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Valente","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit Misericordia Hospital Grosseto Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Bianco","sequence":"additional","affiliation":[{"name":"Institute of Oncology Polyclinic Hospital Monza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara Maria","family":"Mauri","sequence":"additional","affiliation":[{"name":"Institute of Oncology Polyclinic Hospital Monza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Spada","sequence":"additional","affiliation":[{"name":"Gastrointestinal and Neuroendocrine Tumors Unit European Institute of Oncology Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,4,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2012.05.001"},{"key":"e_1_2_7_3_1","first-page":"417","volume-title":"World Health Organization Classification of Tumours","author":"WHO Classification of Tumours of the Digestive System","year":"2010"},{"key":"e_1_2_7_4_1","volume-title":"SEER Cancer Statistics Review, 1975\u20102010","author":"Howlader N","year":"2013"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.15.4377"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.24065"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1009290"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-011-9290-3"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.24.2669"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1003825"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.15.9020"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.22.8510"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19980715)83:2<372::AID-CNCR23>3.0.CO;2-P"},{"key":"e_1_2_7_14_1","first-page":"4193","article-title":"New perspectives in the treatment of neuroendocrine tumours","volume":"32","author":"Bajetta E","year":"2012","journal-title":"Anticancer Res"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-011-1835-8"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v16.i24.2963"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2007.08.012"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1210\/mend.13.1.0224"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.130.4.1816"},{"key":"e_1_2_7_20_1","first-page":"E17","volume-title":"Phase III Trial Results Favour Lanreotide Therapy in Patients with Gastroenteropancreatic Neuro\u2010Endocrine Tumours: new and compelling evidence for the antiproliferative effect of lanreotide. Presented at: 17th ECCO\u201338th ESMO\u201332nd ESTRO European Cancer Congress","author":"Caplin M. ESMO@ ECC 2013","year":"2013"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.5754\/hge11212"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.21.5988"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1677\/ERC-07-0202"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12122"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.16.7858"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hys123"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)61742-X"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-2925"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2012-0263"},{"key":"e_1_2_7_30_1","doi-asserted-by":"crossref","first-page":"4136","DOI":"10.1200\/jco.2013.31.15_suppl.4136","article-title":"Everolimus in combination with octreotide LAR as the first\u2010line treatment for advanced neuroendocrine tumors: a phase II trial of the I.T.M.O. (Italian Trials in Medical Oncology) group","volume":"31","author":"Bajetta E","year":"2013","journal-title":"J Clin Oncol"},{"key":"e_1_2_7_31_1","volume-title":"World Health Organization Classification of Tumours","author":"World Health Organization Classification of Tumours: Pathology & Genetics of Tumours of the Digestive System","year":"2000"},{"key":"e_1_2_7_32_1","volume-title":"World Health Organization Classification of Tumours. Pathology & Genetics: Tumours of the Lung, Pleura, Thymus, and Heart","author":"Travis WD","year":"2004"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPA.0b013e3181ebb2a5"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-3458"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djt135"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-3923"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcncr.28726","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.28726","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T22:58:21Z","timestamp":1760309901000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.28726"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,4,18]]},"references-count":35,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2014,8,15]]}},"alternative-id":["10.1002\/cncr.28726"],"URL":"https:\/\/doi.org\/10.1002\/cncr.28726","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718358360.793531217","asserted-by":"object"}]},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,4,18]]}}}