Pein F, Michon J, Valteau-Couanet D, Quintana E, Frappaz D, Vannier J P, Philip T, Bergeron C, Baranzelli M C, Thyss A, Stephan J L, Boutard P, Gentet J C, Zucker J M, Tournade M F, Hartmann O
Pediatric Oncology Department, Institut Gustave Roussy, Villejuif, France.
J Clin Oncol. 1998 Oct;16(10):3295-301. doi: 10.1200/JCO.1998.16.10.3295.
The three-drug combination of melphalan (M), etoposide (E), and carboplatin (C) followed by autologous stem-cell (ASC) rescue has been evaluated prospectively by the French Society of Pediatric Oncology (SFOP) in pediatric high-risk recurrent (HRR) Wilms' tumor (WT) patients with chemotherapy-responsive disease.
From October 1988 to October 1994, 29 patients with HRR WT were treated in nine SFOP centers. Two additional patients with stage IV anaplastic WT were consolidated in first complete response (CR) with the same regimen and have been studied separately. The regimen consisted of M 180 mg/m2 for 1 day, E 200 mg/m2/d for 5 days, and C at a daily targeted area under the concentration-time curve (AUC) of 4 mg x min/mL for 5 days. ASCs were reinfused 48 hours after M.
Twelve of 28 assessable patients with HRR WT are still in continuous CR at a median of 48.5 months (range, 36 to 96) after consolidation. Disease-free survival (DFS) and overall survival (OS) estimated by the Kaplan-Meier method at 3 years were 50%+/-17% and 60%+/-18%, respectively. Sixteen patients relapsed at a median of 8.5 months (range, 3 to 53) after consolidation. Toxicity data are available in 31 grafted patients. Grade III and IV toxicities included hematologic side effects (n=31), hemorrhage (n=8), mucositis (n=24), diarrhea (n=12), renal disorders (n=8), and pneumonitis (n=3).
The adverse prognostic factors (APF) used to select patients for this dose-intensive chemotherapy define children with very-poor-risk recurrent WT. Despite high treatment-related toxicity, about half of these patients remain disease-free at 3 years. Patient outcome is statistically better when high-dose chemotherapy (HDCT) is performed as early as the second CR or partial response (PR). Novel therapeutic approaches with innovative preparative regimens are warranted for the remaining high-risk patients.
法国儿科肿瘤学会（SFOP）对美法仑（M）、依托泊苷（E）和卡铂（C）三药联合方案继以自体干细胞（ASC）解救用于化疗敏感的小儿高危复发性（HRR）肾母细胞瘤（WT）患者进行了前瞻性评估。
1988年10月至1994年10月，9个SFOP中心对29例HRR WT患者进行了治疗。另外2例IV期间变型WT患者在首次完全缓解（CR）时采用相同方案巩固治疗，并单独进行了研究。该方案包括美法仑180 mg/m²，静脉滴注1天；依托泊苷200 mg/m²/天，静脉滴注5天；卡铂每日靶浓度-时间曲线下面积（AUC）为4 mg·min/mL，静脉滴注5天。在美法仑治疗后48小时回输ASCs。
28例可评估的HRR WT患者中有12例在巩固治疗后中位48.5个月（范围36至96个月）仍处于持续CR状态。采用Kaplan-Meier法估计的3年无病生存率（DFS）和总生存率（OS）分别为50%±17%和60%±18%。16例患者在巩固治疗后中位8.5个月（范围3至53个月）复发。31例接受移植的患者有毒性数据。III级和IV级毒性包括血液学副作用（n = 31）、出血（n = 8）、黏膜炎（n = 24）、腹泻（n = 12）、肾脏疾病（n = 8）和肺炎（n = 3）。
用于选择接受这种剂量密集化疗患者的不良预后因素（APF）确定了复发WT的极低危儿童。尽管治疗相关毒性高，但这些患者中约一半在3年时仍无病生存。当在第二次CR或部分缓解（PR）时尽早进行大剂量化疗（HDCT），患者的预后在统计学上更好。对于其余高危患者，需要采用创新预处理方案的新型治疗方法。
