Department of Molecular and Internal Medicine, Graduate School of Biomedical Science, Hiroshima University, 1-2-3 Kasumi Minami-ku, Hiroshima 734-8551, Japan.
Cancer Chemother Pharmacol. 2011 Jun;67(6):1465-9. doi: 10.1007/s00280-011-1555-6. Epub 2011 Jan 28.
We have treated patients with non-small-cell lung cancer (NSCLC) who developed leptomeningeal metastases (LM) during gefitinib therapy, and then found symptomatic improvement following treatment change to erlotinib. Based on this experience, we wondered whether erlotinib could be detected in cerebrospinal fluid (CSF) when it was used for NSCLC patients with LM. This study was conducted to determine erlotinib concentrations in CSF and assess responses to erlotinib in patients with NSCLC developing LM during gefitinib therapy.
Three advanced NSCLC patients with LM that developed during gefitinib therapy were treated with erlotinib. On day 28 after the initiation of erlotinib treatment, plasma and CSF were obtained and the concentrations of erlotinib in these samples were measured. Eastern Cooperative Oncology Group (ECOG) performance status (PS) and neurologic symptoms were determined.
Erlotinib CSF penetration was 6.3% ± 6.1% (mean ± SD). In cases 1 and 2, we observed improvements in ECOG PS and neurologic symptoms. In case 3, cytological improvement was seen in the CSF. In each patient, deletion of exon 19 or exon 21 L858R mutation of the epidermal growth factor receptor (EGFR) gene was detected in carcinoma cells from the CSF.
We report on 3 patients with NSCLC who had developed LM during gefitinib treatment and showed clinical improvements following change to erlotinib therapy. In all cases, small but measurable penetration of erlotinib into CSF was observed. Because EGFR mutations were detected in all cases, we suggest that erlotinib is a therapeutic option for LM carcinoma cells with EGFR mutations.
我们治疗了在吉非替尼治疗期间发生脑膜转移（LM）的非小细胞肺癌（NSCLC）患者，然后发现改用厄洛替尼治疗后症状有所改善。基于这一经验，我们想知道厄洛替尼是否可在 LM 发生于吉非替尼治疗的 NSCLC 患者时被检测到脑脊液（CSF）中。本研究旨在确定 CSF 中的厄洛替尼浓度，并评估其对接受厄洛替尼治疗的 NSCLC 患者的疗效。
对 3 例在吉非替尼治疗期间发生 LM 的晚期 NSCLC 患者进行厄洛替尼治疗。厄洛替尼治疗开始后第 28 天，采集患者的血浆和 CSF，并检测这些样本中的厄洛替尼浓度。同时，还评估了患者的东部肿瘤协作组（ECOG）表现状态（PS）和神经症状。
厄洛替尼 CSF 穿透率为 6.3%±6.1%（均值±标准差）。在病例 1 和 2 中，我们观察到 ECOG PS 和神经症状的改善。在病例 3 中，CSF 中的细胞学得到改善。在每个患者中，都在 CSF 中的肿瘤细胞中检测到了表皮生长因子受体（EGFR）基因的外显子 19 缺失或外显子 21 L858R 突变。
我们报告了 3 例在吉非替尼治疗期间发生 LM 的 NSCLC 患者，他们在改用厄洛替尼治疗后临床症状有所改善。在所有患者中，均观察到厄洛替尼进入 CSF 的程度虽小但可测量。由于所有病例均检测到 EGFR 突变，我们建议厄洛替尼是具有 EGFR 突变的 LM 癌细胞的一种治疗选择。
