Adjuvant chemotherapy with doxorubicin, ifosfamide, and lenograstim for resected soft-tissue sarcoma (EORTC 62931): a multicentre randomised controlled trial
Adjuvant chemotherapy with doxorubicin, ifosfamide, and lenograstim for resected soft-tissue sarcoma (EORTC 62931): a multicentre randomised controlled trial
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DOI：
10.1016/s1470-2045(12)70346-7
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发表时间：
2012-10-01
期刊：
影响因子：
51.1
通讯作者：
Hohenberger, Peter
中科院分区：
文献类型：
--
作者：
Woll, Penella J.;Reichardt, Peter;Hohenberger, Peter
背景 辅助化疗对软组织肉瘤切除术后生存的影响仍不清楚。我们研究了强化辅助化疗对高危软组织肉瘤切除后患者生存的影响。 方法 在这项多中心随机试验中，任何部位肉眼切除的 Trojani II-III 级软组织肉瘤、无转移、体能状态低于 2、年龄在 16 至 70 岁之间的患者在根治性手术后 4 周内符合资格。患者被随机分配接受辅助化疗或不接受化疗（对照组）。采用最小化技术进行随机化，按医院、原发肿瘤部位、肿瘤大小、计划放疗和孤立肢体灌注治疗进行分层。化疗包括 5 个周期的阿霉素 75 mg/m(2)、异环磷酰胺 5 g/m(2) 和每 3 周一次的来格司亭。如果切除边缘或肿瘤复发，两组患者均接受放射治疗。主要终点是总生存期，并按意向治疗进行分析。最终结果已公布。该试验已在 ClinicalTrials.gov 注册，NCT00002641。结果 1995 年 2 月至 2003 年 12 月期间，351 名患者被随机分配至辅助化疗组（175 名患者）或对照组（176 名患者）。 351 名患者中有 258 名（73%）接受了放射治疗，每组 129 名。各组之间的总生存期没有显着差异（风险比 [HR] 0.94 [95% CI 0.68-1.31]，p=0.72），无复发生存期也没有显着差异（HR 0.91 [0.67-1.22]，p=0.51）。化疗组5年总生存率为66.5%（58.8-73.0），对照组为67.8%（60.3-74.2）。化疗的耐受性良好，开始化疗的 163 名患者中有 130 名 (80%) 完成了所有五个周期。 16 名患者 (10%) 出现 3 级或 4 级发烧或感染，但没有记录因毒性作用而死亡。 解释 在切除的软组织肉瘤中使用阿霉素和异环磷酰胺辅助化疗对无复发生存期或总生存期没有益处。未来的研究应重点关注较大的 III 级和肢体肉瘤患者。
Background The effect of adjuvant chemotherapy on survival for resected soft-tissue sarcoma remains unknown. We investigated the effect of intensive adjuvant chemotherapy on survival in patients after resection of high-risk soft-tissue sarcomas.Methods In this multicentre randomised trial, patients with macroscopically resected, Trojani grade II-III soft-tissue sarcomas at any site, no metastases, performance status lower than 2 and aged between 16 and 70 years were eligible within 4 weeks of definitive surgery. Patients were randomly assigned to receive adjuvant chemotherapy or no chemotherapy (control group). Randomisation was done with a minimisation technique, stratified by hospital, site of primary tumour, tumour size, planned radiotherapy, and isolated limb perfusion therapy. Chemotherapy consisted of five cycles of doxorubicin 75 mg/m(2), ifosfamide 5 g/m(2), and lenograstim every 3 weeks. Patients in both groups received radiotherapy if the resection was marginal or the tumour recurrent. The primary endpoint was overall survival and analyses were done by intention to treat. The final results are presented. This trial is registered with ClinicalTrials.gov, NCT00002641.Findings Between February, 1995, and December, 2003, 351 patients were randomly assigned to the adjuvant chemotherapy group (175 patients) or to the control group (176). 258 (73%) of 351 patients received radiotherapy, 129 in each group. Overall survival did not differ significantly between groups (hazard ratio [HR] 0.94 [95% CI 0.68-1.31], p=0.72) nor did relapse-free survival (HR 0.91 [0.67-1.22], p=0.51). 5-year overall survival rate was 66.5% (58.8-73.0) in the chemotherapy group and 67.8% (60.3-74.2) in the control group. Chemotherapy was well tolerated, with 130 (80%) of 163 patients who started it completing all five cycles. 16 (10%) patients had grade 3 or 4 fever or infection, but no deaths due to toxic effects were recorded.Interpretation Adjuvant chemotherapy with doxorubicin and ifosfamide in resected soft-tissue sarcoma showed no benefit in relapse-free survival or overall survival. Future studies should focus on patients with larger, grade III, and extremity sarcomas.