{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T09:16:47Z","timestamp":1774084607131,"version":"3.50.1"},"reference-count":24,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2006,8,14]],"date-time":"2006-08-14T00:00:00Z","timestamp":1155513600000},"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":[[2006,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>A single\u2010institution Phase I clinical trial was conducted to determine the maximum tolerated dose (MTD) and define the safety profile of temozolomide and capecitabine when used in combination to treat brain metastases from breast cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Patients were eligible if they had bidimensionally measurable supratentorial or infratentorial brain metastasis from histologically confirmed breast carcinoma. Patients could have received up to 3 prior chemotherapy regimens. Temozolomide and capecitabine were administered concomitantly to 4 sequential cohorts at different dosing levels on Days 1\u20135 and Days 8\u201312, with cycles repeated every 21 days until disease progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Twenty\u2010four patients with multiple brain lesions were treated, including 14 patients with newly diagnosed brain metastases and 10 patients with recurrent brain metastases. Only 1 patient was chemotherapy\u2010naive. Fatigue and nausea were the most commonly observed toxicities observed at any dose levels. Significant antitumor activity was observed, with a total of 1 complete and 3 partial responses (18% objective response rate) in the brain. The median response duration was 8 weeks (range, 6\u201364 weeks) and the median time to progression in the brain was 12 weeks (range, 3\u201370 weeks). Neurocognitive function improved or remained stable in patients with a response or stable disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>The combination of temozolomide and capecitabine is an active, well\u2010tolerated regimen. The observed antitumor activity warrants further evaluation of this combination as an alternative to or in combination with whole\u2010brain radiation therapy for the treatment of multiple brain metastases. Cancer 2006. \u00a9 2006 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.22127","type":"journal-article","created":{"date-parts":[[2006,8,15]],"date-time":"2006-08-15T07:17:47Z","timestamp":1155626267000},"page":"1348-1354","source":"Crossref","is-referenced-by-count":132,"title":["Phase I study of capecitabine in combination with temozolomide in the treatment of patients with brain metastases from breast carcinoma"],"prefix":"10.1002","volume":"107","author":[{"given":"Edgardo","family":"Rivera","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Meyers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morris","family":"Groves","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vicente","family":"Valero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah","family":"Francis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Banu","family":"Arun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristine","family":"Broglio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guosheng","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel N.","family":"Hortobagyi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Buchholz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,9]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1052-5149(03)00016-9"},{"key":"e_1_2_6_3_2","first-page":"1531","article-title":"Brain metastases in breast cancer\u2014an in vitro study to evaluate new systemic chemotherapeutic options","volume":"25","author":"Honig A","year":"2005","journal-title":"Anticancer Res."},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.3816\/CBC.2005.n.013"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.01.175"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.56.10.1285"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.39.6.789"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1159\/000067443"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043330"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2002.04.140"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1012226718323"},{"key":"e_1_2_6_12_2","first-page":"88","article-title":"Temozolomide (TMZ) in metastatic breast cancer (BC) to central nervous system (CNS)","volume":"22","author":"Martinez\u2010Cedillo J","year":"2003","journal-title":"Proc Am Soc Clin Oncol."},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008354323167"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000421-200108000-00026"},{"key":"e_1_2_6_15_2","first-page":"833","article-title":"Complete response of brain metastases originating in breast cancer to capecitabine therapy","volume":"5","author":"Siegelmann\u2010Danieli N","year":"2003","journal-title":"Isr Med Assoc J."},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9681(60)90137-5"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1076\/clin.12.1.43.1726"},{"key":"e_1_2_6_18_2","volume-title":"Multilingual Aphasia Examination","author":"Benton AL","year":"1989"},{"key":"e_1_2_6_19_2","volume-title":"Wechsler Adult Intelligence Scale III","author":"Wechsler D","year":"1997"},{"key":"e_1_2_6_20_2","volume-title":"Neuropsychological Assessment","author":"Lezak MD","year":"1995"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1053\/apmr.2002.36959"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.05.128"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19920215)69:4<972::AID-CNCR2820690423>3.0.CO;2-P"},{"key":"e_1_2_6_24_2","first-page":"101","article-title":"Central nervous system (CNS) relapse following chemotherapy with docetaxel for metastatic breast cancer. 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