{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:41:42Z","timestamp":1791942102833,"version":"4.3.4"},"reference-count":39,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,5,5]],"date-time":"2014-05-05T00:00:00Z","timestamp":1399248000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Programme Hospitalier de Recherche Clinique grant COMETE 3","award":["AOM 06 179"],"award-info":[{"award-number":["AOM 06 179"]}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"crossref","award":["ANR 11 JSV1 007 01 MODEOMAPP"],"award-info":[{"award-number":["ANR 11 JSV1 007 01 MODEOMAPP"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:p>Cyclophosphamide\u2013dacarbazine\u2013vincristine regimen is recommended for the treatment of malignant pheochromocytoma and paraganglioma (MPP); however, dacarbazine is the only recognized active drug in neuroendocrine tumours. We investigated the therapeutic benefit of temozolomide (TMZ), an oral alternative to dacarbazine, in patients with MPP. This is a retrospective study of consecutive patients with documented progressive MPP. We examined the correlation between <jats:italic>Succinate dehydrogenase B<\/jats:italic> (<jats:italic>SDHB<\/jats:italic>) mutation and <jats:italic>O(6)\u2010methylguanine\u2010DNA methyltransferase<\/jats:italic> (<jats:italic>MGMT<\/jats:italic>) promoter methylation and MGMT expression in the French nation\u2010wide independent cohort of 190 pheochromocytomas or paragangliomas (PP). Progression\u2010free survival (PFS) according to RECIST 1.1 and PERCIST 1.0 criteria was the primary end point. Fifteen consecutive patients with MPP were enrolled; ten (67%) carried a mutation in <jats:italic>SDHB<\/jats:italic>. The mean dose intensity of TMZ was 172 mg\/m<jats:sup>2<\/jats:sup>\/d for 5 days every 28 days. Median PFS was 13.3 months after a median follow\u2010up of 35 months. There were five partial responses (33%), seven stable (47%) and three progressive diseases (20%). Grade 3 toxicities were lymphopenia in two patients and hypertension in one. Partial responses were observed only in patients with mutation in <jats:italic>SDHB<\/jats:italic>. MGMT immunohistochemistry was negative in tumour samples from four patients who responded to treatment. <jats:italic>SDHB<\/jats:italic> germline mutation was associated with hypermethylation of the <jats:italic>MGMT<\/jats:italic> promoter and low expression of <jats:italic>MGMT<\/jats:italic> in 190 samples of the French nation\u2010wide independent cohort. This study demonstrates that TMZ is an effective antitumour agent in patients with <jats:italic>SDHB<\/jats:italic>\u2010related MPP. The silencing of <jats:italic>MGMT<\/jats:italic> expression as a consequence of <jats:italic>MGMT<\/jats:italic> promoter hypermethylation in <jats:italic>SDHB<\/jats:italic>\u2010mutated tumours may explain this finding.<\/jats:p>","DOI":"10.1002\/ijc.28913","type":"journal-article","created":{"date-parts":[[2014,4,19]],"date-time":"2014-04-19T10:23:30Z","timestamp":1397903010000},"page":"2711-2720","source":"Crossref","is-referenced-by-count":198,"title":["<i>SDHB<\/i> mutations are associated with response to temozolomide in patients with metastatic pheochromocytoma or paraganglioma"],"prefix":"10.1002","volume":"135","author":[{"given":"Julien","family":"Hadoux","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine and Endocrine Tumors Gustave Roussy, University Paris\u2010Sud F\u201094800 Villejuif France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Favier","sequence":"additional","affiliation":[{"name":"INSERM, UMR970, 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Facult\u00e9 de M\u00e9decine F\u201075006 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Chougnet","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Endocrine Tumors Gustave Roussy, University Paris\u2010Sud F\u201094800 Villejuif France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Letouz\u00e9","sequence":"additional","affiliation":[{"name":"Programme Cartes d'Identit\u00e9 des Tumeurs, Ligue Nationale Contre Le Cancer F\u201075013 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Assistance Publique des H\u00f4pitaux de Paris, H\u00f4pital Bic\u00eatre F\u201094270 Le Kremlin\u2010Bic\u00eatre 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