{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:34:56Z","timestamp":1760315696628,"version":"build-2065373602"},"reference-count":14,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2005,8,30]],"date-time":"2005-08-30T00:00:00Z","timestamp":1125360000000},"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":[[2005,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>The current Phase I trial was conducted to determine the dose\u2010limiting toxicity (DLT), maximum tolerated dose, and recommended Phase II dose of oral fixed\u2010dose temozolomide when administered for 5 of every 7 days on a continuous basis.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Patients received a fixed dose of temozolomide daily for 5 of every 7 days continuously. Four weeks of treatment were considered 1 treatment cycle. Patients were accrued at 7 different dose levels ranging from 100 mg\/day to 360 mg\/day.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Forty\u2010six patients received 111 cycles of therapy. DLT consisted of myelosuppression, particularly thrombocytopenia. The primary nonhematologic toxicities were nausea and emesis, which were easily controlled with antiemetics.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Protracted administration of temozolomide at a fixed dose of 300 mg\/day for 5 of every 7 days continuously was well tolerated and allowed greater dose intensity compared with various other schedules. This regimen could potentially increase antitumor activity as protracted temozolomide schedules inhibit DNA repair by depletion of the repair protein O<jats:sup>6<\/jats:sup>\u2010methylguanine\u2010DNA methyltransferase. Cancer 2005. \u00a9 2005 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.21408","type":"journal-article","created":{"date-parts":[[2005,8,30]],"date-time":"2005-08-30T18:47:19Z","timestamp":1125427639000},"page":"1985-1991","source":"Crossref","is-referenced-by-count":3,"title":["A phase I trial of protracted oral fixed\u2010dose temozolomide"],"prefix":"10.1002","volume":"104","author":[{"given":"Suzanne F.","family":"Jones","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F. Anthony","family":"Greco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor G.","family":"Gian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando T.","family":"Miranda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric L.","family":"Raefsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John D.","family":"Hainsworth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noel T.","family":"Willcutt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aurelia F.","family":"Beschorner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glyndon","family":"Kennerly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"III","given":"Howard A.","family":"Burris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,8,30]]},"reference":[{"volume-title":"Temodar (temozolomide) capsules. Product package insert","year":"2005","key":"e_1_2_5_2_2"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001622-200311000-00002"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2004.10.004"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2000.18.1.158"},{"key":"e_1_2_5_6_2","first-page":"2309","article-title":"Temozolomide: the effect of once and twice\u2010a\u2010day dosing on tumor tissue levels of the DNA repair protein O6\u2010alkylguanine\u2010DNA\u2010alkyltransferase","volume":"7","author":"Spiro TP","year":"2001","journal-title":"Clin Cancer Res."},{"key":"e_1_2_5_7_2","first-page":"2585","article-title":"Temozolomide and treatment of malignant glioma","volume":"6","author":"Friedman HS","year":"2000","journal-title":"Clin Cancer Res."},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2002.06.110"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6600827"},{"key":"e_1_2_5_10_2","first-page":"4363","article-title":"Phase I trial of temozolomide using an extended continuous oral schedule","volume":"58","author":"Brock CS","year":"1998","journal-title":"Cancer Res."},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00944177"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112215"},{"key":"e_1_2_5_13_2","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1182\/blood.V88.5.1649.1649","article-title":"Human CD 34+ hematopoietic progenitors have low, cytokine\u2010unresponsive O6\u2010alkylguanine\u2010DNA alkyltransferase and are sensitive to O6\u2010benzylguanine plus BCNU","volume":"88","author":"Gerson SL","year":"1996","journal-title":"Blood."},{"key":"e_1_2_5_14_2","first-page":"705","article-title":"Evaluation of the efficacy of prolonged administration of temozolomide as a salvage therapy for advanced non\u2010small cell lung cancer","volume":"22","author":"Sharma P","year":"2003","journal-title":"Proc Am Soc Clin Oncol."},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.07.060"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcncr.21408","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.21408","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T12:29:38Z","timestamp":1760272178000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.21408"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,8,30]]},"references-count":14,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2005,11]]}},"alternative-id":["10.1002\/cncr.21408"],"URL":"https:\/\/doi.org\/10.1002\/cncr.21408","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"type":"print","value":"0008-543X"},{"type":"electronic","value":"1097-0142"}],"subject":[],"published":{"date-parts":[[2005,8,30]]}}}