Bramwell V H, Burgers M, Sneath R, Souhami R, van Oosterom A T, Voûte P A, Rouesse J, Spooner D, Craft A W, Somers R
London Regional Cancer Centre, East London, Canada.
J Clin Oncol. 1992 Oct;10(10):1579-91. doi: 10.1200/JCO.1992.10.10.1579.
A randomized pilot study was undertaken to assess the acute and chronic toxicities of two short intensive chemotherapy regimens, and to evaluate the feasibility of conservative surgery in this setting. Additional aims were to determine the clinical and radiologic response and the degree of histologic necrosis after chemotherapy. With extension of the study, eventual accrual was sufficient to compare disease-free survival (DFS) and overall survival (OS).
Between July 1983 and December 1986, the European Osteosarcoma Intergroup (EOI) entered 198 eligible patients with classic high-grade extremity osteosarcoma onto a randomized trial that compared doxorubicin (DOX) 25 mg/m2/d times three, intravenous (IV) bolus plus cisplatin (CDDP) 100 mg/m2, 24 hour infusion, every 3 weeks times six; the same combination was preceded 10 days earlier by high-dose methotrexate (HDMTX) 8 g/m2, 6-hour infusion, every 4.5 weeks times four. In the majority of patients (179), chemotherapy was commenced after biopsy; definitive surgery was scheduled at 9 weeks in both groups.
Toxicities for both regimens did not differ substantially from those that occurred in other trials of adjuvant chemotherapy in osteosarcoma. Local recurrence (9%) and surgical complications (18%) after conservative surgery were acceptable. With a median follow-up of 53 months, DFS at 5 years is superior (P = .02) for DOX/CDDP, 57% versus 41%, although OS, 64% versus 50%, is not different significantly (P = .10). In a subset of 66 patients for whom pathologic data on the resected specimen were available, DFS (P = .003) and OS (P = .008) were better for those who demonstrated > or = 90% necrosis.
A brief intensive chemotherapy regimen of DOX/CDDP has produced excellent long-term results, which are similar to those that have been achieved in cooperative group studies of longer, more complex multiagent chemotherapy, and provide the basis for a direct comparison in the next EOI study.
开展一项随机对照试验性研究，以评估两种短期强化化疗方案的急慢性毒性，并评估在这种情况下保肢手术的可行性。其他目的包括确定化疗后的临床和影像学反应以及组织学坏死程度。随着研究的扩展，最终纳入的病例数足以比较无病生存期（DFS）和总生存期（OS）。
1983年7月至1986年12月期间，欧洲骨肉瘤协作组（EOI）将198例符合条件的经典型高级别肢体骨肉瘤患者纳入一项随机试验，该试验比较了多柔比星（DOX）25mg/m²/d静脉推注3次，加顺铂（CDDP）100mg/m²静脉滴注24小时，每3周1次，共6次；另一种方案是在上述方案前10天先给予大剂量甲氨蝶呤（HDMTX）8g/m²静脉滴注6小时，每4.5周1次，共4次。大多数患者（179例）在活检后开始化疗；两组均计划在9周时进行确定性手术。
两种方案的毒性与骨肉瘤辅助化疗的其他试验中观察到的毒性无显著差异。保肢手术后的局部复发率（9%）和手术并发症发生率（18%）均可接受。中位随访53个月，多柔比星/顺铂组5年DFS更好（P = 0.02），为57%，而另一组为41%；尽管OS分别为64%和50%，差异无统计学意义（P = 0.10）。在66例有切除标本病理数据的患者亚组中，坏死率≥90%的患者DFS（P = 0.003）和OS（P = 0.008）更好。
多柔比星/顺铂短期强化化疗方案产生了优异的长期结果，与更长、更复杂的多药联合化疗的协作组研究结果相似，为下一次EOI研究中的直接比较提供了依据。
