{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T16:41:55Z","timestamp":1764002515127,"version":"3.40.5"},"reference-count":24,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18H02690"],"award-info":[{"award-number":["18H02690"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Patients with primary refractory and relapsed neuroblastoma have a poor prognosis since safe and effective chemotherapies for these patients are currently limited. The development of new chemotherapy regimens for these patients is imperative to improve survival outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrospectively analyzed 40 patients with refractory (<jats:italic>n<\/jats:italic>\u00a0=\u00a036) or relapsed (<jats:italic>n<\/jats:italic>\u00a0=\u00a04) neuroblastoma who received irinotecan, etoposide, and carboplatin (IREC) as a second\u2010line treatment. We evaluated their therapeutic response and the toxicity of IREC. We also assessed the impact of <jats:italic>UGT1A1<\/jats:italic> gene polymorphisms, which are involved in irinotecan metabolism, on outcomes and toxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 112 cycles of IREC were administered to 40 patients with a median of 2 cycles per patient (range, 1\u20139). Six (15%) patients (<jats:italic>UGT1A1<\/jats:italic> wild\u2010type [<jats:italic>n<\/jats:italic>\u00a0=\u00a02] and heterozygous [<jats:italic>n<\/jats:italic>\u00a0=\u00a04]) showed objective responses, including partial response (<jats:italic>n<\/jats:italic>\u00a0=\u00a01), tumor shrinkage (<jats:italic>n<\/jats:italic>\u00a0=\u00a04), and improved findings on their MIBG scan (<jats:italic>n<\/jats:italic>\u00a0=\u00a01). Grade 4 neutropenia, grade 4 leukopenia, and grades 3\u20134 gastrointestinal toxicity were observed in 110 (98%), 88 (79%), and 3 (3%) cycles, respectively. There was no IREC\u2010related mortality. Patients with <jats:italic>UGT1A1<\/jats:italic> polymorphisms showed a higher frequency of grade 4 leukopenia, but these patients did not have increased treatment\u2010related mortality or non\u2010hematologic toxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>IREC showed an objective response rate of 15% including 1 case with partial response. IREC was well tolerated regardless of <jats:italic>UGT1A1<\/jats:italic> genotype. This study suggests that IREC is a promising second\u2010line chemotherapy for refractory or relapsed neuroblastoma.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.4529","type":"journal-article","created":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T07:45:45Z","timestamp":1646207145000},"page":"1956-1964","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Combination chemotherapy consisting of irinotecan, etoposide, and carboplatin for refractory or relapsed neuroblastoma"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2970-1543","authenticated-orcid":false,"given":"Masayuki","family":"Imaya","sequence":"first","affiliation":[{"name":"Department of Pediatrics Nagoya University Graduate School of Medicine  Nagoya 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Pediatrics Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taro","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shunsuke","family":"Miwata","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kotaro","family":"Narita","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Ichikawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Nagoya University Graduate School of Medicine  Nagoya 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