Omuro Antonio M P, Kris Mark G, Miller Vincent A, Franceschi Enrico, Shah Neelam, Milton Daniel T, Abrey Lauren E
Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Cancer. 2005 Jun 1;103(11):2344-8. doi: 10.1002/cncr.21033.
Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor that induces an early and dramatic response in 10% of patients with advanced nonsmall cell lung carcinoma (NSCLC). Long- term outcome and patterns of disease recurrence after response have not been described.
The authors evaluated 139 patients with NSCLC treated with gefitinib at Memorial Sloan-Kettering Cancer Center (New York, NY) between 1998 and 2002. They focused on patterns of disease recurrence, risk of brain metastases (BM) and leptomeningeal metastasis (LM), and long-term outcome after initial response to gefitinib.
Of the 139 patients treated with gefitinib, 21 (15%) achieved a partial response. The median age of the responders was 64 years (range, 38-87 years), the median Karnofsky performance score was 80 (range, 60-90), and 4 of the patients were men. All responders had adenocarcinoma. The central nervous system (CNS) was the initial site of disease recurrence in 7 (33%) patients (BM in 5 and LM in 2). In 9 (43%) patients, the initial site of disease recurrence was the lung and in 1 it was the liver and bone. Four (57%) of the patients with disease recurrence in the CNS had lung disease under control. BM also developed in 2 patients who had initial disease recurrence in the lungs. The actuarial 5-year incidence of CNS metastases was 60%. The median overall survival periods were 15 months and 23 months for patients with and without CNS metastases, respectively (P = 0.24).
The CNS was a frequent site of disease recurrence in patients with NSCLC after an initial response to gefitinib, regardless of disease control in the lungs. Patients should be carefully monitored for neurologic symptoms. Intrinsic resistance of metastatic clones, incomplete CNS penetrance of the drug, and longer survival are possible explanations for this high incidence.
吉非替尼是一种表皮生长因子受体酪氨酸激酶抑制剂，在10%的晚期非小细胞肺癌（NSCLC）患者中可诱导早期且显著的反应。反应后的长期结局和疾病复发模式尚未见报道。
作者评估了1998年至2002年间在纪念斯隆凯特琳癌症中心（纽约，NY）接受吉非替尼治疗的139例NSCLC患者。他们关注疾病复发模式、脑转移（BM）和软脑膜转移（LM）风险以及吉非替尼初始反应后的长期结局。
在139例接受吉非替尼治疗的患者中，21例（15%）获得部分缓解。缓解者的中位年龄为64岁（范围38 - 87岁），中位卡诺夫斯基体能状态评分是80（范围60 - 90），且4例患者为男性。所有缓解者均为腺癌。7例（33%）患者疾病复发的初始部位是中枢神经系统（CNS）（5例为BM，2例为LM）。9例（43%）患者疾病复发的初始部位是肺，1例是肝和骨。CNS疾病复发的患者中有4例（57%）肺部疾病得到控制。BM也发生在2例初始疾病复发部位为肺的患者中。CNS转移的5年精算发病率为60%。有和无CNS转移患者的中位总生存期分别为15个月和23个月（P = 0.24）。
NSCLC患者在对吉非替尼初始反应后，CNS是疾病复发的常见部位，无论肺部疾病是否得到控制。应仔细监测患者的神经症状。转移克隆的内在耐药性、药物对CNS的穿透不完全以及生存期延长可能是这种高发病率出现的原因。
