Phase II study of temsirolimus (CCI-779), a novel inhibitor of mTOR, in heavily pretreated patients with locally advanced or metastatic breast cancer
Phase II study of temsirolimus (CCI-779), a novel inhibitor of mTOR, in heavily pretreated patients with locally advanced or metastatic breast cancer
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DOI：
10.1200/jco.2005.66.130
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发表时间：
2005-08-10
影响因子：
45.3
通讯作者：
Moore, L
中科院分区：
文献类型：
--
作者：
Chan, S;Scheulen, ME;Moore, L
目的在本研究中，评估了两种剂量的替西罗莫司 (CCI-779)（一种雷帕霉素哺乳动物靶点的新型抑制剂）在经过大量预处理的局部晚期或转移性乳腺癌患者中的疗效、安全性和药代动力学。 患者和方法患者 (n = 109) 被随机分配接受 75 或 250 mg 替西罗莫司 每周一次，静脉输注 30 分钟。对患者的肿瘤反应、肿瘤进展时间、不良事件和替西罗莫司的药代动力学进行了评估。结果在意向治疗人群中，替西罗莫司的客观缓解率为 9.2%（10 例部分缓解）。肿瘤进展的中位时间为 12.0 周。两种剂量水平的疗效相似，但较高剂量水平的毒性更常见，尤其是 3 级或 4 级抑郁症（250 mg 剂量水平的患者为 10%，75 mg 剂量水平的患者为 0%）。所有级别中最常见的替西罗莫司相关不良事件是粘膜炎（70%）、斑丘疹（51%）和恶心（43%）。最常见、临床上重要的 3 级或 4 级不良事件是粘膜炎 (9%)、白细胞减少 (7%)、高血糖 (7%)、嗜睡 (6%)、血小板减少 (5%) 和抑郁 (5%)。 结论 在接受过大量治疗的局部晚期或转移性乳腺癌患者中，75 和 250 mg 替西罗莫司显示出抗肿瘤活性，75 mg 替西罗莫司表现出总体上可耐受的安全性。
PurposeIn this study, two doses of temsirolimus (CCI-779), a novel inhibitor of the mammalian target of rapamycin, were evaluated for efficacy, safety, and pharmacokinetics in patients with locally advanced or metastatic breast cancer who had been heavily pretreated.Patients and MethodsPatients (n = 109) were randomly assigned to receive 75 or 250 mg of temsirolimus weekly as a 30-minute intravenous infusion. Patients were evaluated for tumor response, time to tumor progression, adverse events, and pharmacokinetics of temsirolimus.ResultsTemsirolimus produced an objective response rate of 9.2% (10 partial responses) in the intent-to-treat population. Median time to tumor progression was 12.0 weeks. Efficacy was similar for both dose levels but toxicity was more common with the higher dose level, especially grade 3 or 4 depression (10% of patients at the 250-mg dose level, 0% at the 75-mg dose level). The most common temsirolimus-related adverse events of all grades were mucositis (70%), maculopapular rash (51%), and nausea (43%). The most common, clinically important grade 3 or 4 adverse events were mucositis (9%), leukopenia (7%), hyperglycemia (7%), somnolence (6%), thrombocytopenia (5%), and depression (5%).ConclusionIn heavily pretreated patients with locally advanced or metastatic breast cancer, 75 and 250 mg temsirolimus showed antitumor activity and 75 mg temsirolimus showed a generally tolerable safety profile.