Department of Oncology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Cancer. 2011 Aug 1;117(15):3468-75. doi: 10.1002/cncr.25928. Epub 2011 Feb 1.
The primary goal of this trial was to evaluate the confirmed response rate of temsirolimus (CCI-779), a mammalian target of rapamycin in patients with advanced soft tissue sarcomas (STS).
Patients ≥18 years with measurable advanced STS, no prior chemotherapy for metastatic disease (adjuvant and neoadjuvant chemotherapy allowed), adequate organ function, and performance status of ≤2 were eligible. After premedication with an antihistamine, CCI-779 was given intravenously at 25 mg over 30 minutes on Days 1, 8, 15, and 22, repeated every 4 weeks. The primary endpoint was confirmed response rate per Response Evaluation Criteria in Solid Tumors.
Between June 2004 and November 2005, a total of 41 patients were enrolled and began treatment; 40 patients are evaluable for response and adverse events. The median age was 62 years (range, 28-72 years) with 56% women. Eighty percent had high-grade STS, and 22% had prior adjuvant chemotherapy. There were 2 patients (5%; 95% confidence interval [CI], 1-17) (undifferentiated fibrosarcoma and uterine leiomyosarcoma) who achieved a confirmed partial response lasting 3 and 17 months, respectively. Thirty-nine (95%) patients have progressed, with a median time to progression of 2.0 months (95% CI, 1.8-3.5). The median overall survival was 7.6 months (95% CI, 6.1-15.9). Forty-three percent experienced grade 3+ adverse events that were possibly related to therapy.
Temsirolimus in this patient population of STS had limited clinical activity and had moderate toxicities.
本试验的主要目的是评估哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂替西罗莫司（CCI-779）在晚期软组织肉瘤（STS）患者中的确认缓解率。
纳入标准为：年龄≥18 岁、有可测量的晚期 STS、无转移性疾病的既往化疗（辅助和新辅助化疗允许）、足够的器官功能和 2 分的体能状态。在给予抗组胺药预处理后，CCI-779 以 25mg/30 分钟的速度静脉滴注，第 1、8、15 和 22 天给药，每 4 周重复一次。主要终点为实体瘤反应评估标准的确认缓解率。
2004 年 6 月至 2005 年 11 月，共纳入 41 例患者并开始治疗；40 例患者可评估疗效和不良反应。中位年龄为 62 岁（范围，28-72 岁），女性占 56%。80%为高级别 STS，22%有既往辅助化疗。有 2 例患者（5%；95%置信区间[CI]，1-17）（未分化纤维肉瘤和子宫平滑肌肉瘤）获得了持续 3 个月和 17 个月的确认部分缓解。39 例（95%）患者进展，中位无进展生存期为 2.0 个月（95%CI，1.8-3.5）。中位总生存期为 7.6 个月（95%CI，6.1-15.9）。43%的患者发生 3 级或以上可能与治疗相关的不良反应。
替西罗莫司在 STS 患者人群中临床活性有限，毒性中等。
