Princess Margaret Hospital for Children, Perth, Australia.
N Engl J Med. 2010 Sep 30;363(14):1313-23. doi: 10.1056/NEJMoa1001527.
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.)
接受强化化疗的中危神经母细胞瘤患者的存活率非常高，但接受较短时间、较低剂量化疗的患者的存活率尚不清楚。
我们进行了一项前瞻性、3 期、非随机试验，以确定在基于肿瘤生物学的治疗方案下，通过减少治疗时间和药物剂量，是否可以维持 3 年估计总生存率超过 90%。符合条件的患者为新诊断的、无 MYCN 扩增的中危神经母细胞瘤；这些患者包括患有 3 或 4 期疾病的婴儿（<365 天）、患有 3 期肿瘤且具有有利组织病理学特征的儿童（≥365 天），以及患有 4S 期疾病且具有二倍体 DNA 指数或不利组织病理学特征的婴儿。具有有利组织病理学特征和超二倍体的患者被分配接受四个周期的化疗，而不完全缓解或具有任何不利特征的患者被分配接受八个周期的化疗。
1997 年至 2005 年间，共有 479 名符合条件的患者入组该试验（320 名患有 3 期疾病，178 名患有 4 期疾病，31 名患有 4S 期疾病）。共有 323 名患者的肿瘤具有有利的生物学特征，141 名患者的肿瘤具有不利的生物学特征。倍性而不是组织病理学特征与结局显著相关。在没有疾病进展的情况下发生了 10 例严重不良事件（2.1%），包括继发性白血病（3 例）、感染性死亡（3 例）和手术死亡（4 例）。整个组的 3 年估计（±SE）总生存率为 96%±1%，具有有利生物学特征的患者的总生存率为 98%±1%，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方案，将化疗的持续时间和化疗药物的剂量大大减少，中危神经母细胞瘤患者的生存率非常高。这些数据支持进一步减少化疗剂量，并进行更精细的风险分层。（由美国国家癌症研究所资助；ClinicalTrials.gov 编号，NCT00003093。）
