Shaikh Furqan, Cullen John W, Olson Thomas A, Pashankar Farzana, Malogolowkin Marcio H, Amatruda James F, Villaluna Doojduen, Krailo Mark, Billmire Deborah F, Rescorla Frederick J, Egler Rachel A, Dicken Bryan J, Ross Jonathan H, Schlatter Marc, Rodriguez-Galindo Carlos, Frazier A Lindsay
Furqan Shaikh, The Hospital for Sick Children, University of Toronto, Toronto, Canada; John W. Cullen, Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center, Denver, CO; Thomas A. Olson, Children's Healthcare of Atlanta, and Emory University, Atlanta, GA; Farzana Pashankar, Yale University School of Medicine, New Haven, CT; Marcio H. Malogolowkin, University of California Davis Comprehensive Cancer Center, Sacramento; Doojduen Villaluna and Mark Krailo, Children's Oncology Group, Monrovia; Mark Krailo, University of Southern California, Los Angeles, CA; James F. Amatruda, University of Texas Southwestern Medical Center and Children's Medical Center Dallas, Dallas, TX; Deborah F. Billmire and Frederick J. Rescorla, Riley Hospital for Children, Indianapolis, IN; Rachel A. Egler and Jonathan H. Ross, Rainbow Babies and Children's Hospital, Cleveland, OH; Bryan J. Dicken, Stollery Children's Hospital, and University of Alberta Hospital, Edmonton, Alberta, Canada; Marc Schlatter, Helen DeVos Children's Hospital at Spectrum Health, Grand Rapids, MI; Carlos Rodriguez-Galindo, St Jude Children's Research Hospital, Memphis, TN; and A. Lindsay Frazier, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA.
J Clin Oncol. 2017 Apr 10;35(11):1203-1210. doi: 10.1200/JCO.2016.67.6544. Epub 2017 Feb 27.
Purpose To investigate whether event-free survival (EFS) can be maintained among children and adolescents with intermediate-risk (IR) malignant germ cell tumors (MGCT) if the administration of cisplatin, etoposide, and bleomycin (PEb) is reduced from four to three cycles and compressed from 5 to 3 days per cycle. Patients and Methods In a phase 3, single-arm trial, patients with IR MGCT (stage II-IV testicular, II-III ovarian, I-II extragonadal, or stage I gonadal tumors with subsequent recurrence) received three cycles of PEb. A parametric comparator model specified that the observed EFS rate should not be significantly < 92%. As recommended for trials that test a reduction of therapy, a one-sided P value ≤ .10 was used to indicate statistical significance. In a post hoc analysis, we also compared results to the EFS rate of comparable patients treated with four cycles of PEb in two prior studies. Results Among 210 eligible patients enrolled from 2003 to 2011, 4-year EFS (EFS) rate was 89% (95% confidence interval, 83% to 92%), which was significantly lower than the 92% threshold of the comparison model ( P = .08). Among 181 newly diagnosed patients, the EFS rate was 87%, compared with 92% for 92 comparable children in the historical cohort ( P = .15). The EFS rate was significantly associated with stage (stage I, 100%; stage II, 92%; stage III, 85%; and stage IV, 54%; P < .001). Conclusion The EFS rate for children with IR MGCT observed after three cycles of PEb was less than that of a prespecified parametric model, particularly for patients with higher-stage tumors. These data do not support a reduction in the number of cycles of PEb from four to three. However, further investigation of a reduction in the number of cycles for patients with lower-stage tumors is warranted.
目的 探讨对于中危（IR）恶性生殖细胞肿瘤（MGCT）的儿童和青少年患者，若顺铂、依托泊苷和博来霉素（PEb）的给药周期从4个减少至3个，且每个周期的给药天数从5天压缩至3天，无事件生存期（EFS）能否得以维持。患者与方法 在一项3期单臂试验中，IR MGCT患者（II-IV期睾丸肿瘤、II-III期卵巢肿瘤、I-II期性腺外肿瘤或I期性腺肿瘤伴后续复发）接受3个周期的PEb治疗。一个参数比较模型规定，观察到的EFS率不应显著低于92%。按照检测治疗减少情况的试验的推荐，使用单侧P值≤0.10来表示统计学显著性。在一项事后分析中，我们还将结果与两项先前研究中接受4个周期PEb治疗的可比患者的EFS率进行了比较。结果 在2003年至2011年入组的210例符合条件的患者中，4年EFS率为89%（95%置信区间，83%至92%），显著低于比较模型的92%阈值（P = 0.08）。在181例新诊断患者中，EFS率为87%，而历史队列中92例可比儿童的EFS率为92%（P = 0.15）。EFS率与分期显著相关（I期，100%；II期，92%；III期，85%；IV期，54%；P < 0.001）。结论 接受3个周期PEb治疗后观察到的IR MGCT儿童患者的EFS率低于预先设定的参数模型，尤其是对于更高分期肿瘤的患者。这些数据不支持将PEb的周期数从4个减少至3个。然而，有必要进一步研究降低低分期肿瘤患者的周期数。
