IRCCS Istituto Giannina Gaslini, Genova, Italy.
Children's Cancer Research Institute, Vienna, Austria.
J Clin Oncol. 2021 Aug 10;39(23):2552-2563. doi: 10.1200/JCO.20.03144. Epub 2021 Jun 21.
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]).
Patients (age 1-20 years) with stage 4 neuroblastoma or stage 4/4s aged < 1 year with 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.
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 amplification. mCR rate following rCOJEC induction (32%, 86/272 evaluable patients) was not significantly different from 35% (99/281) with MSKCC-N5 ( = .368), and 3-year EFS was 44% ± 3% for rCOJEC compared with 47% ± 3% for MSKCC-N5 ( = .527). Three-year overall survival was 60% ± 3% for rCOJEC compared with 65% ± 3% for MSKCC-N5 ( = .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) ( < .001); infection 35% versus 25% ( = .011); stomatitis 25% versus 3% ( < .001); nausea and vomiting 17% versus 7% ( < .001); and diarrhea 7% versus 3% ( = .011).
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.
诱导疗法是高危神经母细胞瘤治疗的重要组成部分。我们旨在评估纪念斯隆-凯特琳癌症中心（MSKCC）N5 诱导方案（MSKCC-N5）是否会提高转移性完全缓解（mCR）率和 3 年无事件生存（EFS）率，与快速 COJEC（rCOJEC；顺铂[C]、长春新碱[O]、卡铂[J]、依托泊苷[E]和环磷酰胺[C]）相比。
患有 4 期神经母细胞瘤或 4/4s 期年龄<1 岁且有扩增的患者有资格接受 rCOJEC 或 MSKCC-N5 的随机分组。随机分组根据国家组和转移部位进行分层。诱导后，治疗包括原发肿瘤切除术、大剂量白消安和马法兰、原发肿瘤部位放疗以及异维 A 酸联合 ch14.18/CHO（dinutuximab beta）抗体联合或不联合白细胞介素-2 免疫治疗。主要终点是 mCR 率和 3 年 EFS。
共有 630 名患者被随机分配接受 rCOJEC（n=313）或 MSKCC-N5（n=317）。诊断时的中位年龄为 3.2 岁（范围 1 个月至 20 岁），16 名患者年龄<1 岁且有扩增。rCOJEC 诱导后的 mCR 率（32%，272 例可评估患者中的 86 例）与 MSKCC-N5 的 35%（281 例中的 99 例）无显著差异（=.368），3 年 EFS 为 rCOJEC 的 44%±3%，MSKCC-N5 的 47%±3%（=.527）。rCOJEC 的 3 年总生存率为 60%±3%，MSKCC-N5 的为 65%±3%（=.379）。两种方案的毒性死亡率均为 1%。然而，MSKCC-N5 的非血液学 CTC 3 级和 4 级毒性更高：68%（283 例中的 193 例）与 48%（268 例中的 129 例）（<.001）；感染 35%与 25%（=.011）；口腔炎 25%与 3%（<.001）；恶心和呕吐 17%与 7%（<.001）；腹泻 7%与 3%（=.011）。
rCOJEC 和 MSKCC-N5 之间未观察到结局差异；然而，rCOJEC 的急性毒性较小，因此 rCOJEC 是国际小儿肿瘤学会欧洲神经母细胞瘤组的首选诱导方案。
