{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T05:39:26Z","timestamp":1769233166438,"version":"3.49.0"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T00:00:00Z","timestamp":1615507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Extrapulmonary neuroendocrine carcinoma (EPNEC) is a lethal disease with a poor prognosis. Platinum\u2010based chemotherapy is used as the standard first\u2010line treatment for unresectable EPNEC. Several retrospective studies have reported the results of the utilization of temozolomide (TMZ) as a drug for the second\u2010line treatment for EPNEC. Patients with unresectable EPNEC that were resistant to platinum\u2010based combination chemotherapy were recruited for a prospective phase II study of TMZ monotherapy. A 200\u00a0mg\/m<jats:sup>2<\/jats:sup> dose of TMZ was given from day 1 to day 5, every 4\u00a0weeks. Response rate (RR) was evaluated as the primary end\u2010point. The presence of O<jats:sub>6<\/jats:sub>\u2010methylguanine DNA methyltransferase (MGMT) in EPNEC patients was also evaluated as exploratory research. Thirteen patients were enrolled in this study. Primary lesions were pancreas (n\u00a0=\u00a03), stomach (n\u00a0=\u00a03), duodenum (n\u00a0=\u00a01), colon (n\u00a0=\u00a01), gallbladder (n\u00a0=\u00a01), liver (n\u00a0=\u00a01), uterus (n\u00a0=\u00a01), bladder (n\u00a0=\u00a01), and primary unknown (n\u00a0=\u00a01). Each case was defined as pathological poorly differentiated neuroendocrine carcinoma from surgically resected and\/or biopsied specimens. The median Ki\u201067 labeling index was 60% (range, 22%\u201090%). The RR was 15.4%, progression\u2010free survival was 1.8\u00a0months (95% confidence interval [CI], 1.0\u20102.7), overall survival (OS) was 7.8\u00a0months (95% CI, 6.0\u20109.5), and OS from first\u2010line treatment was 19.2\u00a0months (95% CI, 15.1\u201023.3). No grade 3 or 4 hematological toxicity had occurred and there was one case of grade 3 nausea. One case presented MGMT deficiency and this case showed partial response. Temozolomide monotherapy is a feasible, modestly effective, and safe treatment for patients with unresectable EPNEC following platinum\u2010based chemotherapy, especially those with MGMT deficiency.<\/jats:p>","DOI":"10.1111\/cas.14811","type":"journal-article","created":{"date-parts":[[2021,1,16]],"date-time":"2021-01-16T21:38:40Z","timestamp":1610833120000},"page":"1936-1942","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Phase II study of temozolomide monotherapy in patients with extrapulmonary neuroendocrine carcinoma"],"prefix":"10.1111","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9181-3722","authenticated-orcid":false,"given":"Noritoshi","family":"Kobayashi","sequence":"first","affiliation":[{"name":"Oncology Division Yokohama City University Hospital Yokohama 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