Ferrari Stefano, Palmerini Emanuela
Chemotherapy Department, Istituto Ortopedico Rizzoli, Bologna, Italy.
Curr Opin Oncol. 2007 Jul;19(4):341-6. doi: 10.1097/CCO.0b013e328122d73f.
The most recent developments regarding chemotherapy treatment of osteogenic sarcoma are reviewed, with special emphasis on prospective clinical trials and evaluations of late effects of chemotherapy.
In recent years, clinical research has essentially focused on possible refinements of the classic four-drug (methotrexate, cisplatin, doxorubicin and ifosfamide) therapy rather than investigating new drugs. It has been demonstrated that dose-intensification does not improve prognosis. Many investigators have evaluated late chemotherapy-related side effects, particularly in terms of cardiac, renal and auditive toxicity, risk of infertility and of second tumors. Recent findings recommend further studies to define the role of the immunostimulating agent muramyl tripeptide-phosphatidilethanolamine in osteosarcoma. Preclinical and phase II studies suggest an activity of mammalian target of rapamycin (mTOR) inhibitors in osteosarcoma, which also deserves further clinical studies.
At present, patients with nonmetastatic osteosarcoma of the extremity aged less than 40 years have an expected 5-year survival rate of 70% with a chemotherapy regimen based on methotrexate, cisplatin, doxorubicin and ifosfamide. Further improvement cannot be achieved by dose intensification of treatment and new strategies are required. Prolonged follow-up is mandatory due to the risk of late effects, second tumors and late relapse from osteosarcoma.
回顾骨肉瘤化疗治疗的最新进展,特别强调前瞻性临床试验以及化疗远期效应的评估。
近年来,临床研究主要集中在对经典四联药物(甲氨蝶呤、顺铂、阿霉素和异环磷酰胺)疗法的可能优化,而非研究新药。已证实剂量强化并不能改善预后。许多研究者评估了化疗相关的远期副作用,特别是心脏、肾脏和听觉毒性、不孕风险以及二次肿瘤风险。最新发现建议进一步开展研究,以明确免疫刺激剂胞壁酰三肽 - 磷脂酰乙醇胺在骨肉瘤中的作用。临床前和II期研究提示雷帕霉素靶蛋白(mTOR)抑制剂在骨肉瘤中有活性,这也值得进一步开展临床研究。
目前,年龄小于40岁的非转移性肢体骨肉瘤患者,采用基于甲氨蝶呤、顺铂、阿霉素和异环磷酰胺的化疗方案,其预期5年生存率为70%。通过强化治疗剂量无法实现进一步改善,需要新的策略。由于存在骨肉瘤远期效应、二次肿瘤和晚期复发的风险,长期随访是必要的。