吉非替尼（“易瑞沙”，ZD1839）对晚期非小细胞肺癌患者脑转移的影响。

Effect of gefitinib ('Iressa', ZD1839) on brain metastases in patients with advanced non-small-cell lung cancer.

作者信息

Hotta Katsuyuki, Kiura Katsuyuki, Ueoka Hiroshi, Tabata Masahiro, Fujiwara Keiichi, Kozuki Toshiyuki, Okada Toshiaki, Hisamoto Akiko, Tanimoto Mitsune

机构信息

Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine and Dentistry, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.

出版信息

Lung Cancer. 2004 Nov;46(2):255-61. doi: 10.1016/j.lungcan.2004.04.036.

DOI:10.1016/j.lungcan.2004.04.036

PMID:15474674

Abstract

BACKGROUND

Gefitinib ('Iressa', ZD1839), an orally active epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (EGFR-TKI), has shown antitumor activity in refractory patients with non-small-cell lung cancer (NSCLC) in clinical trials. We have retrospectively analyzed the efficacy and tolerability of gefitinib in patients with advanced NSCLC treated at Okayama University Hospital.

METHODS

We reviewed the clinical records of 57 patients with advanced NSCLC who had received 250 mg/day gefitinib at our hospital between November 2000 and May 2003. Correlations between the sensitivity of brain metastases and extracranial disease following treatment with gefitinib were also investigated.

RESULTS

Extracranial objective responses were observed in 15 (27%; 95% confidence interval 15.8-40.3%) patients. Fourteen out of 57 patients had brain metastases; six experienced objective responses (one complete response, CR and five partial responses, PR) and eight had stable disease (SD) in the brain. Seven out of 14 patients with brain metastases experienced objective responses in their extracranial tumors and, interestingly, objective responses in the brain were observed in six (86%) of these patients. Multivariate analysis found that advanced age (> or = 70 years) and the presence of brain metastases were associated with clinical response to gefitinib (P = 0.01 and 0.05, respectively), and that female patients were more likely to respond. Median survival and median duration of response were 9.1 and 7.7 months, respectively. The majority of adverse events (AEs) were mild and reversible skin and gastrointestinal disorders, with grade 3 adverse events observed in six (11%) patients.

CONCLUSIONS

This retrospective analysis has found that gefitinib is effective and well tolerated in patients with refractory NSCLC, confirming previous phase II trial data. Interestingly, gefitinib appeared to be effective for brain metastases as well as extracranial tumors. Further prospective trials are warranted to evaluate the efficacy of gefitinib in elderly patients and in patients with brain metastases.

摘要

背景

吉非替尼（“易瑞沙”，ZD1839）是一种口服活性表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（EGFR-TKI），在临床试验中已显示出对难治性非小细胞肺癌（NSCLC）患者具有抗肿瘤活性。我们回顾性分析了冈山大学医院治疗的晚期NSCLC患者使用吉非替尼的疗效和耐受性。

方法

我们回顾了2000年11月至2003年5月期间在我院接受每日250mg吉非替尼治疗的57例晚期NSCLC患者的临床记录。还研究了吉非替尼治疗后脑转移和颅外疾病敏感性之间的相关性。

结果

15例（27%；95%置信区间15.8 - 40.3%）患者出现颅外客观缓解。57例患者中有14例发生脑转移；其中6例出现客观缓解（1例完全缓解，CR，5例部分缓解，PR），8例脑内病情稳定（SD）。14例脑转移患者中有7例颅外肿瘤出现客观缓解，有趣的是，这些患者中有6例（86%）脑内出现客观缓解。多因素分析发现，高龄（≥70岁）和存在脑转移与吉非替尼的临床反应相关（P分别为0.01和0.05），女性患者更易出现反应。中位生存期和中位缓解持续时间分别为9.1个月和7.7个月。大多数不良事件（AE）为轻度且可逆的皮肤和胃肠道疾病，6例（11%）患者出现3级不良事件。