Metzger Monika L, Stewart Clinton F, Freeman Burgess B, Billups Catherine A, Hoffer Fredric A, Wu Jianrong, Coppes Max J, Grant Ronald, Chintagumpala Murali, Mullen Elizabeth A, Alvarado Carlos, Daw Najat C, Dome Jeffrey S
St Jude Children's Research Hospital, Memphis, TN, USA.
J Clin Oncol. 2007 Jul 20;25(21):3130-6. doi: 10.1200/JCO.2007.10.9298.
A phase II study was conducted to evaluate the activity and safety of topotecan in pediatric patients with recurrent Wilms' tumor.
Patients with favorable histology Wilms' tumor (FHWT) and recurrence after at least one salvage chemotherapy regimen or with anaplastic histology Wilms' tumor (AHWT) in first or subsequent recurrence were eligible. Patients were stratified according to histology, with statistical considerations based on the FHWT stratum. Topotecan was administered intravenously over 30 minutes for 5 days on 2 consecutive weeks. Treatment dosages were adjusted to achieve a target area under the curve (AUC) of 80 +/- 10 ng/mL*h. Tumor responses were measured after two cycles of treatment.
Thirty-seven patients (26 patients with FHWT) were enrolled and received a total of 94 cycles of topotecan (range, one to six cycles). The median topotecan dosage required to achieve the target AUC was 1.8 mg/m2 (range, 0.7 to 3.2 mg/m2). Of 25 assessable patients with FHWT, 12 had partial response (PR), six had stable disease (SD), and seven had progressive disease (PD), for an overall response rate of 48% (95% CI, 27.8% to 68.7%). Of 11 assessable patients with AHWT, two had PR, one had SD, and eight had PD. The main toxicities were grade 3 and 4 neutropenia (median duration, 13 days) and thrombocytopenia (median duration, 7.5 days).
Topotecan administered on a protracted schedule is active against recurrent FHWT. Inclusion of topotecan in front-line clinical trials for patients with recurrent Wilms' tumor should be considered.
开展一项II期研究，以评估拓扑替康在复发性肾母细胞瘤儿科患者中的活性和安全性。
组织学类型良好的肾母细胞瘤（FHWT）患者在至少接受一种挽救性化疗方案后复发，或间变性组织学类型的肾母细胞瘤（AHWT）患者首次复发或后续复发，符合入组条件。患者根据组织学类型进行分层，并基于FHWT层进行统计学考量。拓扑替康在连续2周内静脉输注30分钟，共5天。调整治疗剂量以达到80±10 ng/mL*h的目标曲线下面积（AUC）。在两个周期的治疗后测量肿瘤反应。
37例患者（26例FHWT患者）入组，共接受94个周期的拓扑替康治疗（范围为1至6个周期）。达到目标AUC所需的拓扑替康中位剂量为1.8 mg/m²（范围为0.7至3.2 mg/m²）。在25例可评估的FHWT患者中，12例有部分缓解（PR），6例疾病稳定（SD），7例疾病进展（PD），总缓解率为48%（95%CI，27.8%至68.7%）。在11例可评估的AHWT患者中，2例有PR，1例SD，8例PD。主要毒性为3级和4级中性粒细胞减少（中位持续时间为13天）和血小板减少（中位持续时间为7.5天）。
延长给药方案的拓扑替康对复发性FHWT有活性。应考虑将拓扑替康纳入复发性肾母细胞瘤患者的一线临床试验。
