University of Sheffield, Sheffield, UK.
Lancet Oncol. 2012 Oct;13(10):1045-54. doi: 10.1016/S1470-2045(12)70346-7. Epub 2012 Sep 4.
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.
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.
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.
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.
辅助化疗对软组织肉瘤切除术后患者的生存影响仍不清楚。我们研究了强化辅助化疗对不同风险软组织肉瘤切除术后患者生存的影响。
这是一项多中心随机试验，纳入了在根治性手术后 4 周内接受治疗的，组织学分级为 Trojani II-III 级、位于任何部位、无转移、体力状态评分＜2 分且年龄在 16 至 70 岁之间的患者。患者被随机分配至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分组，按医院、原发肿瘤部位、肿瘤大小、计划放疗和隔离肢体灌注治疗分层。化疗方案为阿霉素 75mg/m2，异环磷酰胺 5g/m2，每 3 周 1 次，共 5 个周期，同时使用粒细胞集落刺激因子。如果切除边缘阳性或肿瘤复发，两组患者均接受放疗。主要终点是总生存，分析采用意向治疗。仅报告最终结果。本试验在 ClinicalTrials.gov 注册，编号为 NCT00002641。
1995 年 2 月至 2003 年 12 月，351 例患者被随机分配至辅助化疗组（175 例）或对照组（176 例）。258 例（73%）患者接受了放疗，两组分别为 129 例。两组间总生存（风险比[HR]0.94[95%CI 0.68-1.31]，p=0.72）和无复发生存（HR 0.91[0.67-1.22]，p=0.51）差异均无统计学意义。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，163 例开始化疗的患者中，有 130 例（80%）完成了全部 5 个周期。16 例（10%）患者发生 3 级或 4 级发热或感染，但无因毒性反应而死亡的病例。
阿霉素和异环磷酰胺辅助化疗并不能改善软组织肉瘤切除术后患者的无复发生存或总生存。未来的研究应集中于更大的、组织学分级为 III 级的和肢体肉瘤患者。
