Division of Hematology-Oncology, Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Urol Oncol. 2013 Jan;31(1):82-6. doi: 10.1016/j.urolonc.2010.09.018. Epub 2011 Mar 10.
Epidermal growth factor receptor (EGFR) and HER-2 tyrosine kinases may be involved in activation of androgen receptor and progression of prostate cancer. They represent potential therapeutic targets in prostate cancer. Lapatinib is an oral inhibitor of EGFR and HER-2. The objective of this study is to assess the preliminary clinical efficacy of lapatinib in the therapy of castration-resistant prostate cancer.
In this multicenter, open-label trial, patients with rising PSA on androgen deprivation therapy and not having received chemotherapy were eligible. They were treated with lapatinib at a dose of 1,500 mg once daily. The primary end point was a >50% confirmed PSA decline from baseline; safety, tolerability, and time to PSA progression were secondary outcomes.
Twenty-nine patients enrolled in the study had a median age of 73 years and a baseline PSA of 21.6 ng/ml. Seven patients had no radiologic evidence of metastatic disease, while the remaining patients had bone or measurable disease or both. Treatment was well tolerated with only grade 3 treatment-related toxicities being diarrhea (14%) and rash (3%). One of 21 evaluable patients had >50% reduction in PSA, while another patient had 47% reduction in PSA with an ongoing duration of response of 45+ months. The median time to PSA progression was 29 days.
Lapatinib showed single agent activity in a small subset of unselected patients with castration-resistant prostate cancer, as measured by PSA. Future trials should explore a trial design with time-to-event end points and predictive biomarkers and a combination with other agents.
表皮生长因子受体（EGFR）和 HER-2 酪氨酸激酶可能参与雄激素受体的激活和前列腺癌的进展。它们是前列腺癌潜在的治疗靶点。拉帕替尼是一种口服的 EGFR 和 HER-2 抑制剂。本研究的目的是评估拉帕替尼在去势抵抗性前列腺癌治疗中的初步临床疗效。
在这项多中心、开放标签试验中，符合条件的患者为正在接受雄激素剥夺治疗且未接受化疗的 PSA 升高的患者。他们接受每日一次 1500mg 的拉帕替尼治疗。主要终点为基线 PSA 下降>50%的确认；次要终点为安全性、耐受性和 PSA 进展时间。
29 名入组患者的中位年龄为 73 岁，基线 PSA 为 21.6ng/ml。7 名患者无影像学证据的转移性疾病，而其余患者有骨转移或可测量疾病或两者兼有。治疗耐受性良好，仅出现 3 级治疗相关毒性，包括腹泻（14%）和皮疹（3%）。21 名可评估患者中有 1 名 PSA 下降>50%，另 1 名 PSA 下降 47%，持续缓解时间为 45+个月。PSA 进展的中位时间为 29 天。
拉帕替尼在未选择的去势抵抗性前列腺癌患者中，以 PSA 为指标，显示出单药活性。未来的试验应探索具有时间事件终点和预测生物标志物的试验设计，并与其他药物联合使用。
