Fousseyni Traore, Diawara Maimouna, Pasquier Eddy, André Nicolas
Service d'Oncologie Pédiatrique, Hôpital Gabriel Touré, Bamako, Mali.
J Pediatr Hematol Oncol. 2011 Jan;33(1):31-4. doi: 10.1097/MPH.0b013e3182018ab8.
Metronomic chemotherapy (MC) is defined as the frequent administration of chemotherapy at doses below the maximal tolerated dose and with no prolonged drug-free break. As off-patent chemotherapeutic drugs can be used and given the low toxicity profile of this approach, MC seems to be well adapted to low-income countries.
The aim of this study was to assess the efficacy and safety of a vincristine/cyclophosphamide/methotrexate MC regimen given to children with refractory cancer of various tumor types.
This prospective, pilot, single-center study evaluated the use of MC with a first cycle consisting of weekly vincristine (1.5 mg/m) on days 1, 8, 15, and 22, daily cyclophosphamide (25 mg/m) on days 1 to 21, and twice weekly methotrexate (15 mg/m) on days 21 to 42, followed by a 1-week break. For the following cycles, vincristine was administered only at weeks 1 and 5 of the cycle. This treatment was proposed to children with refractory cancer following treatments with the standard protocols available in our institution and to patients who were not eligible for the protocol. Adverse events were determined through laboratory analyses and investigator observations.
From November 2008 to December 2009, 12 children (median age, 3.7 y; range, 2 to 7 y) were included. The most frequent diagnoses were Wilms tumors (6) and retinoblastoma (5). No objective response was observed, but 7 patients experienced disease stabilization (58%) and continued their treatment for 15 to 24 weeks. After a median follow-up of 39 weeks, 6 patients (50%) were alive. Most importantly, in 3 patients (25%), disease remained stable for at least 6 months after completion of treatment. One grade 4 anemia was observed in 1 patient and 1 grade 4 nonfebrile neutropenia in 1 patient. No other grade 3 or 4 toxicities were noted.
The MC regimen that we report here was well tolerated and was associated with disease stabilization. Most importantly, stabilization could be maintained for over 6 additional months after completion of treatment in 3 patients. The potential of MC in children and young adults in low-income countries warrants further studies.
节拍化疗（MC）被定义为以低于最大耐受剂量的剂量频繁进行化疗且无延长的无药间歇期。由于可使用已过专利保护期的化疗药物，且该方法毒性较低，MC似乎很适合低收入国家。
本研究旨在评估长春新碱/环磷酰胺/甲氨蝶呤节拍化疗方案用于患有各种肿瘤类型难治性癌症儿童的疗效和安全性。
这项前瞻性、试点、单中心研究评估了节拍化疗的使用情况，第一个周期包括在第1、8、15和22天每周一次长春新碱（1.5mg/m²），在第1至21天每天一次环磷酰胺（25mg/m²），以及在第21至42天每周两次甲氨蝶呤（15mg/m²），随后休息1周。对于后续周期，长春新碱仅在周期的第1周和第5周给药。该治疗方案适用于在本机构接受标准方案治疗后患有难治性癌症的儿童以及不符合该方案条件的患者。通过实验室分析和研究者观察来确定不良事件。
从2008年11月至2009年12月，纳入了12名儿童（中位年龄3.7岁；范围2至7岁）。最常见的诊断是肾母细胞瘤（6例）和视网膜母细胞瘤（5例）。未观察到客观缓解，但7例患者病情稳定（58%），并持续治疗15至24周。中位随访39周后，6例患者（50%）存活。最重要的是，3例患者（25%）在完成治疗后疾病稳定至少6个月。1例患者出现1级4度贫血，1例患者出现1级4度非发热性中性粒细胞减少。未观察到其他3级或4级毒性反应。
我们在此报告的节拍化疗方案耐受性良好，且与病情稳定相关。最重要的是，3例患者在完成治疗后病情稳定可维持超过6个月。节拍化疗在低收入国家儿童和青年中的潜力值得进一步研究。
