Gravis G, Bladou F, Salem N, Gonçalves A, Esterni B, Walz J, Bagattini S, Marcy M, Brunelle S, Viens P
Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France.
Ann Oncol. 2008 Sep;19(9):1624-8. doi: 10.1093/annonc/mdn174. Epub 2008 May 7.
Erlotinib is an orally active small-molecule tyrosine kinase inhibitor targeted against human epidermal growth factor receptor 1/epidermal growth factor receptor (ErbB1), known to be overexpressed in a variety of cancers, including prostate cancer.
This was a phase II monocentric study of 30 patients with advanced or metastatic prostate cancer, 29 had castration-resistant prostate cancer and 23 had received prior chemotherapy. Patients received erlotinib: 150 mg/day, increased to 200 mg at week 4, and continued until progression or unacceptable toxicity. Efficacy was defined as a decrease or stabilization of prostate-specific antigen (PSA) without clinical progression. Clinical benefit was evaluated by Karnofsky performance status and pain intensity, and response was an improvement in one of these parameters without worsening in the other.
Median age was 69 years (range 51-77 years), and median PSA 102 ng/ml (range 3-1213 ng/ml). Dose escalation to 200 mg was possible in 16 (55%) patients. Moderate toxicity was observed. No patient had a decrease in PSA, 14% had stabilization, less than the >or=20% expected. PSA-doubling time, evaluated before and after erlotinib, was increased for 10 patients (P = 0.0058). Clinical benefit was achieved in 40% of patients.
Erlotinib demonstrated an improvement in clinical benefit. Future directions should include evaluating its use in less advanced prostate cancer.
厄洛替尼是一种口服活性小分子酪氨酸激酶抑制剂，靶向作用于人表皮生长因子受体1/表皮生长因子受体（ErbB1），已知该受体在包括前列腺癌在内的多种癌症中过度表达。
这是一项针对30例晚期或转移性前列腺癌患者的II期单中心研究，其中29例为去势抵抗性前列腺癌，23例曾接受过化疗。患者接受厄洛替尼治疗：150毫克/天，在第4周增加至200毫克，并持续至疾病进展或出现不可接受的毒性。疗效定义为前列腺特异性抗原（PSA）降低或稳定且无临床进展。通过卡诺夫斯基功能状态评分和疼痛强度评估临床获益，反应定义为这些参数之一有所改善且另一个参数未恶化。
中位年龄为69岁（范围51 - 77岁），中位PSA为102纳克/毫升（范围3 - 1213纳克/毫升）。16例（55%）患者能够将剂量增至200毫克。观察到有中度毒性。没有患者的PSA降低，14%的患者PSA稳定，低于预期的≥20%。对10例患者在厄洛替尼治疗前后评估的PSA倍增时间有所延长（P = 0.0058）。40%的患者实现了临床获益。
厄洛替尼显示出临床获益有所改善。未来的研究方向应包括评估其在病情不太严重的前列腺癌中的应用。
