Moreno-Aspitia Alvaro, Morton Roscoe F, Hillman David W, Lingle Wilma L, Rowland Kendrith M, Wiesenfeld Martin, Flynn Patrick J, Fitch Tom R, Perez Edith A
Division of Hematology/Oncology, Mayo Clinic and Mayo Foundation, Jacksonville, FL 32224, USA.
J Clin Oncol. 2009 Jan 1;27(1):11-5. doi: 10.1200/JCO.2007.15.5242. Epub 2008 Dec 1.
We conducted a cooperative group phase II study to assess antitumor activity and toxicity of sorafenib in patients with metastatic breast cancer (MBC) who had received prior treatment for their disease.
Patients were eligible if they had measurable disease and had previously received an anthracycline and/or a taxane in the neoadjuvant, adjuvant, or metastatic setting. The primary end point of the study was tumor response per Response Evaluation Criteria in Solid Tumors (RECIST). The study was designed in two stages. Sorafenib was administered as 400 mg twice daily on days 1 through 28 of each 4-week cycle.
Twenty-three patients were enrolled with a median age of 54 years (range, 37 to 70 years). Twenty-two (96%) had prior anthracycline treatment and 16 (70%) had prior taxane treatment. Patients received sorafenib for a median of two cycles (range, one to 15 cycles) with a median follow-up of 2.4 years (range, 2.2 to 2.6 years). There were no grade 4 toxicities and few grade 3 toxicities. Among the 20 patients eligible for efficacy analysis, no patients experienced a partial response or complete response per RECIST criteria. Thus, the trial stopped at the end of the first stage per study design. Two patients (10%; 90% CI, 1.8% to 28.3%) achieved stable disease lasting longer than 6 months.
Sorafenib as a single agent, although well tolerated, did not exhibit activity when measured by tumor shrinkage in patients with MBC who had received prior treatment. Further research should focus on combinations with standard therapy and end points more sensitive to effects of targeted agents, such as disease stabilization.
我们开展了一项协作组II期研究，以评估索拉非尼对曾接受过转移性乳腺癌（MBC）治疗的患者的抗肿瘤活性和毒性。
如果患者有可测量的病灶，并且在新辅助、辅助或转移性治疗阶段曾接受过蒽环类药物和/或紫杉烷治疗，则符合入组条件。本研究的主要终点是根据实体瘤疗效评价标准（RECIST）评估的肿瘤反应。该研究分两个阶段设计。索拉非尼在每个4周周期的第1至28天，每日两次，每次400mg给药。
入组23例患者，中位年龄54岁（范围37至70岁）。22例（96%）曾接受过蒽环类药物治疗，16例（70%）曾接受过紫杉烷治疗。患者接受索拉非尼治疗的中位周期数为2个周期（范围1至15个周期），中位随访时间为2.4年（范围2.2至2.6年）。无4级毒性反应，3级毒性反应也很少。在符合疗效分析条件的20例患者中，根据RECIST标准，无患者出现部分缓解或完全缓解。因此，根据研究设计，试验在第一阶段结束时停止。2例患者（10%；90%CI，1.8%至28.3%）病情稳定超过6个月。
索拉非尼单药治疗尽管耐受性良好，但在曾接受过治疗的MBC患者中，以肿瘤缩小衡量时未显示出活性。进一步的研究应聚焦于与标准治疗联合，以及对靶向药物效果更敏感的终点指标，如病情稳定。
