Outcome after reduced chemotherapy for intermediate-risk neuroblastoma.
Outcome after reduced chemotherapy for intermediate-risk neuroblastoma.
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DOI：
10.1056/nejmoa1001527
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发表时间：
2010-09-30
期刊：
影响因子：
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通讯作者：
Children’s Oncology Group
中科院分区：
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作者：
Baker DL;Schmidt ML;Cohn SL;Maris JM;London WB;Buxton A;Stram D;Castleberry RP;Shimada H;Sandler A;Shamberger RC;Look AT;Reynolds CP;Seeger RC;Matthay KK;Children’s Oncology Group
接受剂量密集化疗的中危神经母细胞瘤患者的生存率非常好，但接受较短时间减少剂量化疗的患者的生存率尚不清楚。我们进行了一项前瞻性、3 期、非随机试验，以确定是否可以使用基于肿瘤生物学的治疗分配，通过减少治疗持续时间和药物剂量来维持超过 90% 的 3 年估计总生存率。符合条件的患者患有新诊断的中危神经母细胞瘤，没有 MYCN 扩增；这些患者包括患有3期或4期疾病的婴儿（<365天）、患有具有良好组织病理学特征的3期肿瘤的儿童（≥365天）以及患有具有二倍体DNA指数或不利组织病理学特征的4S期疾病的婴儿。患有具有良好组织病理学特征和超二倍体的疾病的患者被分配到四个周期的化疗，而那些具有不完全反应或不利特征的患者被分配到八个周期。 1997年至2005年间，共有479名符合条件的患者参加了这项试验（270名患有3期疾病的患者，178名患有4期疾病的患者，31名患有4S期疾病的患者）。共有 323 名患者的肿瘤具有良好的生物学特征，141 名患者的肿瘤具有不利的生物学特征。倍性而非组织病理学特征可以显着预测结果。 10 名患者（2.1%）发生了没有疾病进展的严重不良事件，包括继发性白血病（3 名患者）、感染死亡（3 名患者）和手术死亡（4 名患者）。全组总生存率的 3 年估计 (±SE) 为 96±1%，其中肿瘤具有有利生物学特征的患者的总生存率为 98±1%，肿瘤具有不利生物学特征的患者的总生存率为 93±2%。与早期试验中使用的方案相比，通过基于生物学的治疗分配，包括大幅缩短化疗持续时间和减少化疗药物剂量，中危神经母细胞瘤患者的生存率非常高。这些数据为进一步减少化疗和更精细的风险分层提供了支持。 （由国家癌症研究所资助；ClinicalTrials.gov 编号，NCT00003093。）
The survival rate among patients with intermediate-risk neuroblastoma who receive dose-intensive chemotherapy is excellent, but the survival rate among patients who receive reduced doses of chemotherapy for shorter periods of time is not known. We conducted a prospective, phase 3, nonrandomized trial to determine whether a 3-year estimated overall survival of more than 90% could be maintained with reductions in the duration of therapy and drug doses, using a tumor biology-based therapy assignment. Eligible patients had newly diagnosed, intermediate-risk neuroblastoma without MYCN amplification; these patients included infants (<365 days of age) who had stage 3 or 4 disease, children (≥365 days of age) who had stage 3 tumors with favorable histopathological features, and infants who had stage 4S disease with a diploid DNA index or unfavorable histopathological features. Patients who had disease with favorable histopathological features and hyperdiploidy were assigned to four cycles of chemotherapy, and those with an incomplete response or either unfavorable feature were assigned to eight cycles. Between 1997 and 2005, a total of 479 eligible patients were enrolled in this trial (270 patients with stage 3 disease, 178 with stage 4 disease, and 31 with stage 4S disease). A total of 323 patients had tumors with favorable biologic features, and 141 had tumors with unfavorable biologic features. Ploidy, but not histopathological features, was significantly predictive of the outcome. Severe adverse events without disease progression occurred in 10 patients (2.1%), including secondary leukemia (in 3 patients), death from infection (in 3 patients), and death at surgery (in 4 patients). The 3-year estimate (±SE) of overall survival for the entire group was 96±1%, with an overall survival rate of 98±1% among patients who had tumors with favorable biologic features and 93±2% among patients who had tumors with unfavorable biologic features. A very high rate of survival among patients with intermediate-risk neuroblastoma was achieved with a biologically based treatment assignment involving a substantially reduced duration of chemotherapy and reduced doses of chemotherapeutic agents as compared with the regimens used in earlier trials. These data provide support for further reduction in chemotherapy with more refined risk stratification. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00003093.)