Senerchia Andreza A, Macedo Carla Renata, Ferman Sima, Scopinaro Marcelo, Cacciavillano Walter, Boldrini Erica, Lins de Moraes Vera Lúcia, Rey Guadalupe, de Oliveira Claudia T, Castillo Luis, Almeida Maria Tereza, Borsato Maria Luisa, Lima Eduardo, Lustosa Daniel, Barreto José Henrique, El-Jaick Tatiana, Aguiar Simone, Brunetto Algemir, Greggiani Lauro, Cogo-Moreira Hugo, Atallah Alvaro, Petrilli Antonio Sergio
Institute of Pediatric Oncology/Support Group for Adolescents and Children With Cancer, Federal University of Sao Paulo, Sao Paulo, Brazil.
National Cancer Institute, Rio de Janeiro, Brazil.
Cancer. 2017 May 15;123(6):1003-1010. doi: 10.1002/cncr.30411. Epub 2016 Nov 7.
Metronomic chemotherapy (MC) consists of the administration of a low dose of chemotherapy on a daily or weekly basis without a long break to achieve an antitumoral effect through an antiangiogenic effect or stimulation of the immune system. The potential effect of MC with continuous oral cyclophosphamide and methotrexate in patients with high-grade operable osteosarcomas (OSTs) of the extremities was investigated.
Patients with high-grade OSTs who were 30 years old or younger were eligible for registration at diagnosis. Eligibility for randomization included 1) nonmetastatic disease and 2) complete resection of the primary tumor. The study design included a backbone of 10 weeks of preoperative therapy with methotrexate, adriamycin, and platinum (MAP). After surgery, patients were randomized between 2 arms to complete 31 weeks of MAP or receive 73 weeks of MC after MAP. The primary endpoint was event-free survival (EFS) from randomization.
There were 422 nonmetastatic patients registered (May 2006 to July 2013) from 27 sites in 3 countries (Brazil, Argentina and Uruguay), and 296 were randomized to MAP plus MC (n = 139) or MAP alone (n = 157). At 5 years, the EFS cumulative proportions surviving in the MAP-MC group and the MAP-alone group were 61% (standard error [SE], 0.5%) and 64% (SE, 0.5%), respectively, and they were not statistically different (Wilcoxon [Gehan] statistic = 0.724; P =.395). The multivariate analysis showed that necrosis grades 1 and 2, tumor size, and amputation were associated with shorter EFS.
According to the current follow-up, EFS with MAP plus MC is not statistically superior to EFS with MAP alone in patients with high-grade, resectable OSTs of the extremities. Cancer 2017;123:1003-10. © 2016 American Cancer Society.
节拍化疗（MC）是指每日或每周给予低剂量化疗且无长时间中断，通过抗血管生成作用或刺激免疫系统来达到抗肿瘤效果。本研究调查了连续口服环磷酰胺和甲氨蝶呤的节拍化疗对四肢高级别可手术骨肉瘤（OST）患者的潜在疗效。
30岁及以下的高级别OST患者在确诊时符合登记条件。随机分组的条件包括：1）无转移疾病；2）原发肿瘤完全切除。研究设计包括以甲氨蝶呤、阿霉素和铂（MAP）进行10周术前治疗的基础方案。术后，患者被随机分为两组，一组完成31周的MAP治疗，另一组在MAP治疗后接受73周的节拍化疗。主要终点是随机分组后的无事件生存期（EFS）。
来自3个国家（巴西、阿根廷和乌拉圭）27个地点的422例无转移患者进行了登记（2006年5月至2013年7月），其中296例被随机分为MAP加节拍化疗组（n = 139）或单纯MAP组（n = 157）。5年时，MAP - 节拍化疗组和单纯MAP组的EFS累积生存比例分别为61%（标准误[SE]，0.5%）和64%（SE，0.5%），两者无统计学差异（Wilcoxon[Gehan]统计量 = 0.724；P = 0.395）。多因素分析显示，坏死分级1和2、肿瘤大小以及截肢与较短的EFS相关。
根据目前的随访结果，对于四肢高级别、可切除的骨肉瘤患者，MAP加节拍化疗的EFS在统计学上并不优于单纯MAP的EFS。《癌症》2017年；123：1003 - 10。©2016美国癌症协会。
