Department of Medical Oncology, Tata Memorial Centre, Mumbai, Maharashtra, India.
Department of Oncology, Aster Malabar Institute of Medical Sciences, Kozhikode, Kerala, India.
Pediatr Blood Cancer. 2019 Sep;66(9):e27877. doi: 10.1002/pbc.27877. Epub 2019 Jun 17.
The management of osteosarcoma is challenging especially in lower-income and middle-income countries, and there is an unmet need to evolve efficient and sustainable chemotherapy regimens.
We compared the outcomes in nonmetastatic osteosarcoma patients treated with three sequential non-high-dose methotrexate-based combination chemotherapy protocols at a single tertiary care center over two decades. The first protocol, OGS-99, involved dose-intense, alternating dyads of three drugs: doxorubicin (Dox), cisplatin (CDDP), and ifosfamide (Ifo). The second protocol, OGS-99 enhanced, included OGS-99 drugs with etoposide and enhanced supportive care. The OGS-12 protocol involved dose-dense administration of eight sequential dyads of Dox, CDDP and Ifo, universal growth factor prophylaxis and targeted nutritional support. Event-free survival (EFS), overall survival (OS), and toxicity were reported using a retrospective chart review in the OGS-99 and OGS-99 enhanced protocols and prospectively in the OGS-12 protocol.
A total of 41, 94, and 385 treatment-naïve, consecutive, nonmetastatic patients with extremity osteosarcoma were treated with the OGS-99 (2000-2005), OGS-99 enhanced (2010), and OGS-12 (2011-2016), respectively. At a median follow-up of 19, 86, and 39 months, the five-year EFS rates were 38%, 50%, and 62% in the OGS-99, OGS-99 enhanced, and OGS-12, respectively. The corresponding rates of five-year OS were nonevaluable, 60% and 77%, respectively, with acceptable rates of grade 3-4 toxicities: febrile neutropenia (40%), thrombocytopenia (36%), anemia (51%), and 1% deaths related to toxicity.
Sequential selection of an intelligent, dose-dense chemotherapy regimen together with enhanced supportive care resulted in marked improvement in outcomes of nonmetastatic osteosarcoma and this "small steps-big changes" model deserves wider recognition and usage.
骨肉瘤的治疗具有挑战性，尤其是在中低收入国家，因此需要不断发展高效和可持续的化疗方案。
我们比较了在一家三级护理中心接受三种连续的非高剂量甲氨蝶呤为基础的联合化疗方案治疗的非转移性骨肉瘤患者的结果，这些方案跨越了二十年。第一个方案 OGS-99 涉及剂量密集的、交替的三种药物双联体：阿霉素（Dox）、顺铂（CDDP）和异环磷酰胺（Ifo）。第二个方案 OGS-99 增强版包括 OGS-99 药物与依托泊苷和增强的支持性护理。OGS-12 方案涉及剂量密集的八组连续的 Dox、CDDP 和 Ifo 双联体给药、通用生长因子预防和靶向营养支持。无事件生存（EFS）、总生存（OS）和毒性使用 OGS-99 和 OGS-99 增强方案的回顾性图表审查以及 OGS-12 方案的前瞻性报告。
总共 41、94 和 385 例未经治疗的、连续的、肢体骨肉瘤患者分别接受 OGS-99（2000-2005 年）、OGS-99 增强版（2010 年）和 OGS-12（2011-2016 年）治疗。在中位数随访 19、86 和 39 个月时，OGS-99、OGS-99 增强版和 OGS-12 的五年 EFS 率分别为 38%、50%和 62%。相应的五年 OS 率分别为无法评估、60%和 77%，毒性的 3-4 级发生率可接受：发热性中性粒细胞减少症（40%）、血小板减少症（36%）、贫血（51%）和 1%与毒性相关的死亡。
明智地选择剂量密集的化疗方案并辅以增强的支持性护理，显著改善了非转移性骨肉瘤的结果，这种“小步大变化”的模式值得更广泛的认可和应用。
