Princess Margaret Hospital, Toronto, ON, Canada.
Am J Clin Oncol. 2010 Dec;33(6):609-13. doi: 10.1097/COC.0b013e3181beac33.
Lapatinib (GW572016) is a selective and potent dual tyrosine kinase inhibitor of the epidermal growth factor 1 (EGFR) and 2 (HER2), approved in the treatment of HER2 positive breast cancer. Since EGFR and HER2 overexpression has also been seen in prostate cancer and appears to correlate with a worse clinical outcome, Lapatinib may represent a novel therapeutic strategy in prostate cancer. This Phase II multicenter clinical trial is the first to evaluate Lapatinib in early stage, hormonally untreated recurrent or metastatic prostate cancer.
Eligible patients received lapatinib 1500 mg PO daily until progression. The primary end point was prostate specific antigen (PSA) response. Archival tumor tissue was collected for EGFR and HER2 analysis.
A total of 23 patients, median age 67, ECOG PS 0-2, mean baseline PSA 7.5, were evaluable for response. In total, 125 cycles were administered. The most frequent adverse events were lymphopenia, fatigue, rash, dyspepsia, and diarrhea. Grade 3+ increased alanine aminotransferase (ALT) was reported in 2 patients, and grade 4 blurry vision in 1 patient. No PSA responses were seen. Median time to progression (TTP) was 4.6 months and 6 months progression-free estimate was 44.5%.
Lapatinib was well tolerated but like other EGFR- and HER2-targeted agents in advanced HRPC failed to show significant antitumor activity even in this very early stage hormonally untreated population.
拉帕替尼（GW572016）是一种选择性和有效的表皮生长因子 1（EGFR）和 2（HER2）双重酪氨酸激酶抑制剂，已被批准用于治疗 HER2 阳性乳腺癌。由于 EGFR 和 HER2 的过度表达也见于前列腺癌，并且似乎与更差的临床结局相关，拉帕替尼可能代表了前列腺癌的一种新的治疗策略。这项 II 期多中心临床试验是首次评估拉帕替尼在早期、未接受激素治疗的复发性或转移性前列腺癌中的应用。
符合条件的患者接受拉帕替尼 1500 mg PO 每日一次，直至疾病进展。主要终点是前列腺特异性抗原（PSA）反应。收集存档的肿瘤组织进行 EGFR 和 HER2 分析。
共 23 例患者，中位年龄 67 岁，ECOG PS 0-2，基线 PSA 平均为 7.5，可评估反应。共给予 125 个周期。最常见的不良反应是淋巴细胞减少、疲劳、皮疹、消化不良和腹泻。2 例患者出现 3+级丙氨酸氨基转移酶（ALT）升高，1 例患者出现 4 级视力模糊。未观察到 PSA 反应。中位无进展生存期（TTP）为 4.6 个月，6 个月无进展生存率为 44.5%。
拉帕替尼耐受性良好，但与其他针对晚期 HRPC 的 EGFR 和 HER2 靶向药物一样，即使在这种非常早期、未接受激素治疗的人群中，也未能显示出显著的抗肿瘤活性。
