Ferrari Stefano, Smeland Sigbjorn, Mercuri Mario, Bertoni Franco, Longhi Alessandra, Ruggieri Pietro, Alvegard Thor A, Picci Piero, Capanna Rodolfo, Bernini Gabriella, Müller Cristoph, Tienghi Amelia, Wiebe Thomas, Comandone Alessandro, Böhling Tom, Del Prever Adalberto Brach, Brosjö Otte, Bacci Gaetano, Saeter Gunnar
Chemotherapy Division of Department of Musculoskeletal Oncology, Istituti Ortopedici Rizzoli, Via C. Pupilli 1, 40136 Bologna, Italy.
J Clin Oncol. 2005 Dec 1;23(34):8845-52. doi: 10.1200/JCO.2004.00.5785. Epub 2005 Oct 24.
To explore the effect of high-dose ifosfamide in first-line treatment for patients < or = 40 years of age with nonmetastatic osteosarcoma of the extremity.
From March 1997 to September 2000, 182 patients were evaluated. Primary treatment consisted of two blocks of high-dose ifosfamide (15 g/m2), methotrexate (12 g/m2), cisplatin (120 mg/m2), and doxorubicin (75 mg/m2). Postoperatively, patients received two cycles of doxorubicin (90 mg/m2), and three cycles each of high-dose ifosfamide, methotrexate, and cisplatin (120 to 150 mg/m2). Granulocyte colony-stimulating factor support was mandatory after the high-dose ifosfamide/cisplatin/doxorubicin combination.
No disease progression was recorded during primary chemotherapy, 164 patients (92%) underwent limb-salvage surgery, four patients (2%) underwent rotation plasty, and 11 patients (6%) had limbs amputated. Three (1.6%) patients died as a result of treatment-related toxicity, and one died as a result of pulmonary embolism after pathologic fracture. Grade 4 neutropenia and thrombocytopenia followed 52% and 31% of all courses, respectively, and mild to severe nephrotoxicity was recorded in 19 patients (10%). The median received dose-intensity compared with protocol was 0.82. With a median follow-up of 55 months, the 5-year probability of event-free survival was 64% (95% CI, 57% to 71%) and overall survival was 77% (95% CI, 67% to 81%), whereas seven patients (4%) experienced local recurrence.
The addition of high-dose ifosfamide to methotrexate, cisplatin, and doxorubicin in the preoperative phase is feasible, but with major renal and hematologic toxicities, and survival rates similar to those obtained with four-drug regimens using standard-dose ifosfamide. Italian Sarcoma Group/Scandinavian Sarcoma Group study I showed that in a multicenter setting, more than 90% of patients with osteosarcoma of the extremity can undergo conservative surgery.
探讨大剂量异环磷酰胺在一线治疗40岁及以下非转移性肢体骨肉瘤患者中的疗效。
1997年3月至2000年9月，对182例患者进行了评估。初始治疗包括两个疗程的大剂量异环磷酰胺（15 g/m²）、甲氨蝶呤（12 g/m²）、顺铂（120 mg/m²）和阿霉素（75 mg/m²）。术后，患者接受两个疗程的阿霉素（90 mg/m²），以及各三个疗程的大剂量异环磷酰胺、甲氨蝶呤和顺铂（120至150 mg/m²）。在大剂量异环磷酰胺/顺铂/阿霉素联合治疗后，必须给予粒细胞集落刺激因子支持。
初始化疗期间未记录到疾病进展，164例患者（92%）接受了保肢手术，4例患者（2%）接受了旋转成形术，11例患者（6%）进行了截肢。3例（1.6%）患者因治疗相关毒性死亡，1例患者因病理性骨折后肺栓塞死亡。4级中性粒细胞减少和血小板减少分别发生在所有疗程的52%和31%，19例患者（10%）记录到轻度至重度肾毒性。与方案相比，中位接受剂量强度为0.82。中位随访55个月，5年无事件生存率为64%（95%CI，57%至71%），总生存率为77%（95%CI，67%至81%），7例患者（4%）出现局部复发。
术前在甲氨蝶呤、顺铂和阿霉素中加入大剂量异环磷酰胺是可行的，但有严重的肾和血液学毒性，生存率与使用标准剂量异环磷酰胺的四联方案相似。意大利肉瘤组/斯堪的纳维亚肉瘤组研究I表明，在多中心环境中，超过90%的肢体骨肉瘤患者可以接受保守手术。
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