Children's Hospital, University of Cologne, Cologne, Germany.
BMC Cancer. 2011 Jan 18;11:21. doi: 10.1186/1471-2407-11-21.
The treatment of high-risk neuroblastoma patients consists of multimodal induction therapy to achieve remission followed by consolidation therapy to prevent relapses. However, the type of consolidation therapy is still discussed controversial. We applied metronomic chemotherapy in the prospective NB90 trial and monoclonal anti-GD2-antibody (MAB) ch14.18 in the NB97 trial. Here, we present the long term outcome data of the patient cohort.
A total of 334 stage 4 neuroblastoma patients one year or older were included. All patients successfully completed the induction therapy. In the NB90 trial, 99 patients received at least one cycle of the oral maintenance chemotherapy (NB90 MT, 12 alternating cycles of oral melphalan/etoposide and vincristine/cyclophosphamide). In the NB97 trial, 166 patients commenced the MAB ch14.18 consolidation therapy (six cycles over 12 months). Patients who received no maintenance therapy according to the NB90 protocol or by refusal in NB97 (n = 69) served as controls.
The median observation time was 11.11 years. The nine-year event-free survival rates were 41 ± 4%, 31 ± 5%, and 32 ± 6% for MAB ch14.18, NB90 MT, and no consolidation, respectively (p = 0.098). In contrast to earlier reports, MAB ch14.18 treatment improved the long-term outcome compared to no additional therapy (p = 0.038). The overall survival was better in the MAB ch14.18-treated group (9-y-OS 46 ± 4%) compared to NB90 MT (34 ± 5%, p = 0.026) and to no consolidation (35 ± 6%, p = 0.019). Multivariable Cox regression analysis revealed ch14.18 consolidation to improve outcome compared to no consolidation, however, no difference between NB90 MT and MAB ch14.18-treated patients was found.
Follow-up analysis of the patient cohort indicated that immunotherapy with MAB ch14.18 may prevent late relapses. Finally, metronomic oral maintenance chemotherapy also appeared effective.
高危神经母细胞瘤患者的治疗包括多模式诱导治疗以达到缓解，随后进行巩固治疗以预防复发。然而，巩固治疗的类型仍存在争议。我们在前瞻性 NB90 试验中应用了节拍化疗，在 NB97 试验中应用了单克隆抗 GD2 抗体（MAB）ch14.18。在此，我们报告了该患者队列的长期结果数据。
共纳入 334 例年龄在 1 岁以上的 IV 期神经母细胞瘤患者。所有患者均成功完成诱导治疗。在 NB90 试验中，99 例患者接受了至少一个周期的口服维持化疗（NB90 MT，12 个周期的口服美法仑/依托泊苷和长春新碱/环磷酰胺交替）。在 NB97 试验中，166 例患者开始进行 MAB ch14.18 巩固治疗（12 个月内 6 个周期）。根据 NB90 方案未接受维持治疗或拒绝治疗的患者（n=69）作为对照组。
中位观察时间为 11.11 年。MAB ch14.18、NB90 MT 和无巩固治疗的 9 年无事件生存率分别为 41±4%、31±5%和 32±6%（p=0.098）。与之前的报告不同，MAB ch14.18 治疗与无额外治疗相比改善了长期结果（p=0.038）。MAB ch14.18 治疗组的总生存率（9 年 OS 为 46±4%）优于 NB90 MT 组（34±5%，p=0.026）和无巩固治疗组（35±6%，p=0.019）。多变量 Cox 回归分析显示，与无巩固治疗相比，ch14.18 巩固治疗可改善预后，但 NB90 MT 与 MAB ch14.18 治疗组之间无差异。
该患者队列的随访分析表明，MAB ch14.18 免疫治疗可能预防晚期复发。最后，节拍化疗也表现出有效。
