Casper E S, Gaynor J J, Harrison L B, Panicek D M, Hajdu S I, Brennan M F
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Cancer. 1994 Mar 15;73(6):1644-51. doi: 10.1002/1097-0142(19940315)73:6<1644::aid-cncr2820730616>3.0.co;2-v.
Patients with high grade soft tissue sarcoma greater than or equal to 10 cm have a 3-year disease-free survival of approximately 30%. There is no convincing evidence, however, that postoperative adjuvant chemotherapy is beneficial. Preoperative chemotherapy has theoretical advantages over postoperative chemotherapy.
Twenty-nine evaluable patients with primary or recurrent high grade, nonmetastatic, soft tissue sarcoma were treated with two preoperative cycles of cyclophosphamide 500 mg/m2, doxorubicin 60 mg/m2, and DTIC 1000 mg/m2 before definitive surgery and radiation. Clinical and radiologic assessment of response to chemotherapy was performed preoperatively, and the resected specimen was examined for treatment effects. Patients who did not progress during preoperative therapy were eligible to receive four additional cycles of chemotherapy. Disease-free and overall survival rates of study patients were compared with two cohorts of historic controls.
Although subjective changes in the firmness of some tumors were observed, only one patient met the criteria for partial response (3%, 2-sided 95% confidence interval = < 1-17%). Intratumoral hemorrhage, cystic necrosis, and liquefaction were observed regularly, and three tumors were more than 90% necrotic. Toxicity of the chemotherapy was acceptable, but patients were reluctant to receive postoperative therapy. The median time free from distant metastasis was 28 months; median survival was 35 months. These results were not superior to the experience with no chemotherapy, or with postoperative doxorubicin.
Adjuvant chemotherapy for patients with soft tissue sarcoma remains investigational. There is a strong rationale, however, for continued investigation of preoperative chemotherapy for high risk patients using doxorubicin and ifosfamide with colony stimulating factor support. Development of sensitive and specific methods to assess response to preoperative chemotherapy is needed.
肿瘤大小大于或等于10cm的高级别软组织肉瘤患者的3年无病生存率约为30%。然而，尚无令人信服的证据表明术后辅助化疗有益。术前化疗相对于术后化疗具有理论优势。
29例可评估的原发性或复发性高级别、非转移性软组织肉瘤患者在进行确定性手术和放疗前接受两个周期的术前化疗，化疗方案为环磷酰胺500mg/m²、多柔比星60mg/m²和达卡巴嗪1000mg/m²。术前对化疗反应进行临床和影像学评估，并对切除标本进行治疗效果检查。术前治疗期间未进展的患者有资格接受另外四个周期的化疗。将研究患者的无病生存率和总生存率与两组历史对照进行比较。
尽管观察到一些肿瘤硬度有主观变化，但只有1例患者符合部分缓解标准（3%，双侧95%置信区间 = <1-17%）。肿瘤内出血、囊性坏死和液化经常可见，3个肿瘤坏死率超过90%。化疗毒性可接受，但患者不愿接受术后治疗。无远处转移的中位时间为28个月；中位生存期为35个月。这些结果并不优于未进行化疗或术后使用多柔比星的情况。
软组织肉瘤患者的辅助化疗仍处于研究阶段。然而，有充分的理由继续研究使用多柔比星和异环磷酰胺并给予集落刺激因子支持的术前化疗方案，用于高危患者。需要开发敏感和特异的方法来评估术前化疗的反应。
