{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:14:31Z","timestamp":1790810071055,"version":"4.1.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T00:00:00Z","timestamp":1587686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Spanish Institute Carlos III","award":["ISCIII: PI13\/01751"],"award-info":[{"award-number":["ISCIII: PI13\/01751"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Standard treatment for glioblastoma is radiation with concomitant and adjuvant temozolomide for 6 cycles, although the optimal number of cycles of adjuvant temozolomide has long been a subject of debate. We performed a phase II randomized trial investigating whether extending adjuvant temozolomide for more than 6 cycles improved outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Glioblastoma patients treated at 20 Spanish hospitals who had not progressed after 6 cycles of adjuvant temozolomide were centrally randomized to stop (control arm) or continue (experimental arm) temozolomide up to a total of 12 cycles at the same doses they were receiving in cycle 6. Patients were stratified by MGMT methylation and measurable disease. The primary endpoint was differences in 6-month progression-free survival (PFS). Secondary endpoints were PFS, overall survival (OS), and safety (Clinicaltrials.gov NCT02209948).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>From August 2014 to November 2018, 166 patients were screened, 7 of whom were ineligible. Seventy-nine patients were included in the stop arm and 80 in the experimental arm. All patients were included in the analyses of outcomes and of safety. There were no differences in 6-month PFS (control 55.7%; experimental 61.3%), PFS, or OS between arms. MGMT methylation and absence of measurable disease were independent factors of better outcome. Patients in the experimental arm had more lymphopenia (P\u2005&amp;lt;\u20050.001), thrombocytopenia (P\u2005&amp;lt;\u20050.001), and nausea and vomiting (P\u2005=\u20050.001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Continuing temozolomide after 6 adjuvant cycles is associated with greater toxicity but confers no additional benefit in 6-month PFS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>1.\u2002Extending adjuvant temozolomide to 12 cycles did not improve 6-month PFS.<\/jats:p>\n                    <jats:p>2.\u2002Extending adjuvant temozolomide did not improve PFS or OS in any patient subset.<\/jats:p>\n                    <jats:p>3.\u2002Extending adjuvant temozolomide was linked to increased toxicities.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noaa107","type":"journal-article","created":{"date-parts":[[2020,4,20]],"date-time":"2020-04-20T15:12:07Z","timestamp":1587395527000},"page":"1851-1861","source":"Crossref","is-referenced-by-count":105,"title":["A phase II randomized, multicenter, open-label trial of continuing adjuvant temozolomide beyond 6 cycles in patients with glioblastoma (GEINO 14-01)"],"prefix":"10.1093","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0771-0390","authenticated-orcid":false,"given":"Carmen","family":"Balana","sequence":"first","affiliation":[{"name":"Medical Oncology Service, Institut Catal\u00e0 d\u2019Oncologia, Badalona, Spain"},{"name":"Applied Research Group in Oncology (B-ARGO) from the Institut Investigaci\u00f3 en Ci\u00e8ncies de la Salut Germans Trias i Pujol (IGTP), Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Angeles","family":"Vaz","sequence":"additional","affiliation":[{"name":"Medical Oncology Service, Hospital Ram\u00f3n y Cajal, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Manuel Sep\u00falveda","sequence":"additional","affiliation":[{"name":"Medical Oncology Service, Hospital Universitario 12 de Octubre, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Mesia","sequence":"additional","affiliation":[{"name":"Medical Oncology Service, Institut Catal\u00e0 d\u2019Oncologia, Hospitalet de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"del Barco","sequence":"additional","affiliation":[{"name":"Medical Oncology Service, Institut Catal\u00e0 d\u2019Oncologia Girona, Girona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estela","family":"Pineda","sequence":"additional","affiliation":[{"name":"Medical Oncology Service, Hospital Clinic de Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Mu\u00f1oz-Langa","sequence":"additional","affiliation":[{"name":"Medical Oncology Service, Hospital Universitario La Fe, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Estival","sequence":"additional","affiliation":[{"name":"Medical Oncology Service, Institut Catal\u00e0 d\u2019Oncologia, Badalona, Spain"},{"name":"Applied Research Group in Oncology (B-ARGO) from the Institut Investigaci\u00f3 en Ci\u00e8ncies de la Salut Germans Trias i Pujol (IGTP), Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram\u00f3n","family":"de las Pe\u00f1as","sequence":"additional","affiliation":[{"name":"Medical Oncology Service, Hospital Provincial de Castell\u00f3n, Castell\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Fuster","sequence":"additional","affiliation":[{"name":"Medical Oncology Service, Hospital Son Espases, Palma De Mallorca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"Giron\u00e9s","sequence":"additional","affiliation":[{"name":"Medical Oncology Service, Hospital Universitario La Fe, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis Miguel","family":"Navarro","sequence":"additional","affiliation":[{"name":"Medical Oncology Service, Hospital de Salamanca, Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Gil-Gil","sequence":"additional","affiliation":[{"name":"Medical Oncology Service, Institut Catal\u00e0 d\u2019Oncologia, Hospitalet de Llobregat, Spain"},{"name":"Bellvitge Biomedical Research Institute (IDIBELL) Hospitalet de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Alonso","sequence":"additional","affiliation":[{"name":"Medical Oncology Service, Hospital Virgen del Rocio, Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Herrero","sequence":"additional","affiliation":[{"name":"Medical Oncology Service, Hospital Miguel Servet, Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Peralta","sequence":"additional","affiliation":[{"name":"Medical Oncology Service, Hospital Sant Joan de Reus, Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Olier","sequence":"additional","affiliation":[{"name":"Medical Oncology Service, Fundaci\u00f3n Alcorc\u00f3n, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Perez-Segura","sequence":"additional","affiliation":[{"name":"Medical Oncology Service, Hospital Universitario Cl\u00ednico San Carlos, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Covela","sequence":"additional","affiliation":[{"name":"Medical Oncology Service, Hospital Lucus Agusti, Lugo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Martinez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Medical Oncology Service, Hospital del Mar, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Berrocal","sequence":"additional","affiliation":[{"name":"Medical Oncology Service, Hospital General Universitario de Valencia, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Gallego","sequence":"additional","affiliation":[{"name":"Medical Oncology Service, Hospital de Sant Pau, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Luque","sequence":"additional","affiliation":[{"name":"Medical Oncology Service, Hospital Universitario Virgen de las Nieves, Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franciso Javier","family":"Perez-Mart\u00edn","sequence":"additional","affiliation":[{"name":"Medical Oncology Service, Institut Catal\u00e0 d\u2019Oncologia, Hospitalet de Llobregat, Spain"},{"name":"Bellvitge Biomedical Research Institute (IDIBELL) Hospitalet de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Esteve","sequence":"additional","affiliation":[{"name":"Applied Research Group in Oncology (B-ARGO) from the Institut Investigaci\u00f3 en Ci\u00e8ncies de la Salut Germans Trias i Pujol (IGTP), Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Munne","sequence":"additional","affiliation":[{"name":"Pathology Service, Hospital Universitari Germans Trias i Pujol, Badalona, 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The impact of extended adjuvant temozolomide in newly diagnosed glioblastoma: a secondary analysis of EORTC and NRG Oncology\/RTOG","volume":"19","author":"Blumenthal","year":"2017","journal-title":"Neuro Oncol."},{"issue":"15","key":"2020121802292008900_CIT0004","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1212\/WNL.0000000000003809","article-title":"Limited role for extended maintenance temozolomide for newly diagnosed glioblastoma","volume":"88","author":"Gramatzki","year":"2017","journal-title":"Neurology."},{"issue":"10","key":"2020121802292008900_CIT0005","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1056\/NEJMoa043331","article-title":"MGMT gene silencing and benefit from temozolomide in glioblastoma","volume":"352","author":"Hegi","year":"2005","journal-title":"N Engl J Med."},{"issue":"1","key":"2020121802292008900_CIT0006","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s11060-012-0826-3","article-title":"Extended adjuvant temozolomide for treatment of newly diagnosed glioblastoma multiforme","volume":"108","author":"Rold\u00e1n Urgoiti","year":"2012","journal-title":"J Neurooncol."},{"issue":"3","key":"2020121802292008900_CIT0007","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s12094-013-1068-3","article-title":"Should we continue temozolomide beyond six cycles in the adjuvant treatment of glioblastoma without an evidence of clinical benefit? A cost analysis based on prescribing patterns in Spain","volume":"16","author":"Bala\u00f1\u00e1","year":"2014","journal-title":"Clin Transl Oncol."},{"issue":"10","key":"2020121802292008900_CIT0008","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1016\/S1470-2045(17)30517-X","article-title":"Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial","volume":"18","author":"Weller","year":"2017","journal-title":"Lancet Oncol."},{"issue":"23","key":"2020121802292008900_CIT0009","doi-asserted-by":"crossref","first-page":"2306","DOI":"10.1001\/jama.2017.18718","article-title":"effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial","volume":"318","author":"Stupp","year":"2017","journal-title":"JAMA."},{"issue":"32","key":"2020121802292008900_CIT0010","doi-asserted-by":"crossref","first-page":"4085","DOI":"10.1200\/JCO.2013.49.6968","article-title":"Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial","volume":"31","author":"Gilbert","year":"2013","journal-title":"J Clin Oncol."},{"issue":"11","key":"2020121802292008900_CIT0011","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1093\/neuonc\/not096","article-title":"The cost-effectiveness of temozolomide in the adjuvant treatment of newly diagnosed glioblastoma in the United States","volume":"15","author":"Messali","year":"2013","journal-title":"Neuro Oncol."},{"issue":"8","key":"2020121802292008900_CIT0012","doi-asserted-by":"crossref","first-page":"e430","DOI":"10.1016\/S1470-2045(17)30515-6","article-title":"Evidence-based management of adult patients with diffuse glioma. 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