{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T13:11:28Z","timestamp":1791465088499,"version":"4.3.4"},"reference-count":41,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"23","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2021,8,10]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> Induction therapy is a critical component of the therapy of high-risk neuroblastoma. We aimed to assess if the Memorial Sloan Kettering Cancer Center (MSKCC) N5 induction regimen (MSKCC-N5) would improve metastatic complete response (mCR) rate and 3-year event-free survival (EFS) compared with rapid COJEC (rCOJEC; cisplatin [C], vincristine [O], carboplatin [J], etoposide [E], and cyclophosphamide [C]). <\/jats:p><\/jats:sec><jats:sec><jats:title>PATIENTS AND METHODS<\/jats:title><jats:p> Patients (age 1-20 years) with stage 4 neuroblastoma or stage 4\/4s aged &lt; 1 year with MYCN amplification were eligible for random assignment to rCOJEC or MSKCC-N5. Random assignment was stratified according to national group and metastatic sites. Following induction, therapy comprised primary tumor resection, high-dose busulfan and melphalan, radiotherapy to the primary tumor site, and isotretinoin with ch14.18\/CHO (dinutuximab beta) antibody with or without interleukin-2 immunotherapy. The primary end points were mCR rate and 3-year EFS. <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> A total of six hundred thirty patients were randomly assigned to receive rCOJEC (n = 313) or MSKCC-N5 (n = 317). Median age at diagnosis was 3.2 years (range, 1 month to 20 years), and 16 were younger than 1 year of age with MYCN amplification. mCR rate following rCOJEC induction (32%, 86\/272 evaluable patients) was not significantly different from 35% (99\/281) with MSKCC-N5 ( P = .368), and 3-year EFS was 44% \u00b1 3% for rCOJEC compared with 47% \u00b1 3% for MSKCC-N5 ( P = .527). Three-year overall survival was 60% \u00b1 3% for rCOJEC compared with 65% \u00b1 3% for MSKCC-N5 ( P = .379). Toxic death rates with both regimens were 1%. However, nonhematologic CTC grade 3 and 4 toxicities were higher with MSKCC-N5: 68% (193\/283) versus 48% (129\/268) ( P &lt; .001); infection 35% versus 25% ( P = .011); stomatitis 25% versus 3% ( P &lt; .001); nausea and vomiting 17% versus 7% ( P &lt; .001); and diarrhea 7% versus 3% ( P = .011). <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> No difference in outcome was observed between rCOJEC and MSKCC-N5; however, acute toxicity was less with rCOJEC, and therefore rCOJEC is the preferred induction regimen for International Society of Pediatric Oncology European Neuroblastoma Group. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.20.03144","type":"journal-article","created":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T19:59:54Z","timestamp":1624305594000},"page":"2552-2563","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":76,"title":["Randomized Trial of Two Induction Therapy Regimens for High-Risk Neuroblastoma: HR-NBL1.5 International Society of Pediatric Oncology European Neuroblastoma Group Study"],"prefix":"10.1200","volume":"39","author":[{"given":"Alberto","family":"Garaventa","sequence":"first","affiliation":[{"name":"IRCCS Istituto Giannina Gaslini, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7024-7082","authenticated-orcid":false,"given":"Ulrike","family":"Poetschger","sequence":"additional","affiliation":[{"name":"Children's Cancer Research Institute, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Valteau-Couanet","sequence":"additional","affiliation":[{"name":"Gustave Roussy, Villejuif, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Luksch","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3792-0615","authenticated-orcid":false,"given":"Victoria","family":"Castel","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Unit, Hospital Universitari I Politecnic La Fe, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Elliott","sequence":"additional","affiliation":[{"name":"Leeds Teaching Hospitals, NHS Trust, Leeds, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shifra","family":"Ash","sequence":"additional","affiliation":[{"name":"Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5032-8985","authenticated-orcid":false,"given":"Godfrey C. 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