De Bernardi Bruno, Nicolas Brigitte, Boni Luca, Indolfi Paolo, Carli Modesto, Cordero Di Montezemolo Luca, Donfrancesco Alberto, Pession Andrea, Provenzi Massimo, di Cataldo Andrea, Rizzo Antonino, Tonini Gian Paolo, Dallorso Sandro, Conte Massimo, Gambini Claudio, Garaventa Alberto, Bonetti Federico, Zanazzo Andrea, D'Angelo Paolo, Bruzzi Paolo
Giannina Gaslini Children's Hospital, Largo Gerolamo Gaslini 5, 16147 Genova, Italy.
J Clin Oncol. 2003 Apr 15;21(8):1592-601. doi: 10.1200/JCO.2003.05.191.
To compare the outcomes associated with modifications in three consecutive protocols employed by the Italian Co-Operative Group for Neuroblastoma (ICGNB) in disseminated neuroblastoma.
Between January 1985 and November 1997, a total of 359 children aged 1 to 15 years with newly diagnosed stage 4 neuroblastoma were enrolled in three consecutive protocols. Compared with ICGNB-85, the ICGNB-89 protocol contained two more chemotherapy cycles, and some drugs were given at greater doses, whereas in the ICGNB-92 protocol, the induction phase included a chelating agent, and individual cycles contained four drugs instead of two.
A total of 330 of 359 evaluable children were included in this analysis; 106 children were treated with ICGNB-85, 65 children were treated with ICGNB-89, and 159 children were treated with ICGNB-92 protocols. Radical resection of primary tumor was carried out in 59.4%, 50.8%, and 57.9% of the patients, respectively. Major tumor response after induction therapy was achieved in 66.7%, 69.2%, and 68.6% of the patients, respectively. A total of 218 of 232 patients received consolidation therapy consisting of conventional chemotherapy in 65 patients and of high-dose chemotherapy in 153 patients. Disease recurrence or progression occurred in 82.1%, 69.2%, and 74.8% of the patients, respectively. Therapy-related deaths occurred in 1.9%, 12.3%, and 6.9% of the patients, respectively. Five-year overall survival (OS) for the three studies was 26%, 23%, and 28%, and event-free survival (EFS) was 19%, 17%, and 17%, respectively.
The therapeutic modifications adopted in the ICGNB-89 and ICGNB-92 protocols were not associated with a significant improvement in response rate or in the 5-year OS and EFS as compared with the ICGNB-85 protocol. Attempts at intensifying chemotherapy were associated with greater toxicity.
比较意大利神经母细胞瘤协作组（ICGNB）在播散性神经母细胞瘤中采用的三个连续方案的修改所带来的结果。
1985年1月至1997年11月期间，共有359名年龄在1至15岁、新诊断为4期神经母细胞瘤的儿童参加了三个连续方案。与ICGNB - 85相比，ICGNB - 89方案多了两个化疗周期，且一些药物剂量更大，而在ICGNB - 92方案中，诱导期包括一种螯合剂，且每个周期包含四种药物而非两种。
359名可评估儿童中有330名纳入本分析；106名儿童接受ICGNB - 85治疗，65名儿童接受ICGNB - 89治疗，159名儿童接受ICGNB - 92方案治疗。分别有59.4%、50.8%和57.9%的患者进行了原发肿瘤根治性切除。诱导治疗后主要肿瘤反应分别在66.7%、69.2%和68.6%的患者中实现。232名患者中有218名接受了巩固治疗，其中65名患者接受传统化疗，153名患者接受大剂量化疗。疾病复发或进展分别发生在82.1%、69.2%和74.8%的患者中。治疗相关死亡分别发生在1.9%、12.3%和6.9%的患者中。三项研究的五年总生存率（OS）分别为26%、23%和28%，无事件生存率（EFS）分别为19%、17%和17%。
与ICGNB - 85方案相比，ICGNB - 89和ICGNB - 92方案中采用的治疗修改在缓解率或五年OS和EFS方面未带来显著改善。强化化疗的尝试与更大的毒性相关。
