Ma Shenglin, Xu Yaping, Deng Qinghua, Yu Xinmin
Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, PR China.
Lung Cancer. 2009 Aug;65(2):198-203. doi: 10.1016/j.lungcan.2008.10.028. Epub 2008 Dec 16.
Brain metastases (BM) represent one of the most common challenges related to non-small cell lung cancer (NSCLC), with evolving treatment strategies. We have conducted a phase II clinical trial in a Chinese population to evaluate concomitant treatment with whole brain radiotherapy (WBRT) and Gefitinib in patients with BM from NSCLC. The purpose of this study is to report the efficacy and toxicity of this treatment, and assess its impact on patient Quality of Life (QoL) and survival post-treatment.
Between October 2005 and January 2007, 21 patients were enrolled and received 40Gy/20f/4w WBRT. Gefitinib was administrated orally at a dosage of 250mg/day during the radiation course and was continued for each 28-day treatment cycle until progression of the disease, unacceptable toxicity, or withdrawal of consent. The primary end point of the study was tumor response and QoL. The secondary end points were toxicity and survival. Objective response rate according to the RECIST criteria was recorded. Health-related QoL was measured using FACT-Br (V4.0) and toxicity was evaluated and recorded using the NCI Common Toxicity Criteria. The Kaplan-Meier method was used to evaluate patient survival. Univariate analysis of patient characteristics and tumor responses was conducted using the Chi-square and Fisher's exact test.
Four (19%) and 13 patients (62%) had a complete and partial response respectively, while 3 patients disease remained stable and 1 patient had progression of the disease. The overall response rate (81%, 95% confidence interval (CI): 58-95%) exceeded the goal per study design. The median progression-free survival and overall survival were 10.0 months (95% CI: 7.5-12.5 months) and 13.0 months (95% CI: 8.2-17.8 months), respectively. The most frequent toxicities included rash (86%) and diarrhea (43%), with only 3 patients developing a grade III diarrhea. Other grade II or higher toxicities occurring in about 50% of patients included nausea, vomiting, headache, and fatigue. Most side effects were grade II and well tolerated by supportive care. Gender and cigarettes/year were predictive factors for the responses found in univariate analysis. All domains of QoL were significantly improved following treatment.
Our data suggests that concomitant treatment was well tolerated, with promising activity and a significant improvement of QoL in a Chinese population with brain metastases from NSCLC. Although the data presented herewithin appears promising, more data from randomized trials are needed to further validate this regimen of WBRT/Gefitinib.
脑转移瘤（BM）是与非小细胞肺癌（NSCLC）相关的最常见挑战之一，治疗策略不断发展。我们在中国人群中进行了一项II期临床试验，以评估全脑放疗（WBRT）与吉非替尼联合治疗NSCLC脑转移患者的疗效。本研究的目的是报告这种治疗的疗效和毒性，并评估其对患者生活质量（QoL）和治疗后生存的影响。
2005年10月至2007年1月期间，招募了21例患者，接受40Gy/20次/4周的WBRT。在放疗期间，吉非替尼口服给药，剂量为250mg/天，并在每个28天的治疗周期中持续使用，直至疾病进展、出现不可接受的毒性或患者撤回同意。研究的主要终点是肿瘤反应和QoL。次要终点是毒性和生存。根据RECIST标准记录客观缓解率。使用FACT-Br（V4.0）测量健康相关QoL，并使用美国国立癌症研究所通用毒性标准评估和记录毒性。采用Kaplan-Meier方法评估患者生存情况。使用卡方检验和Fisher精确检验对患者特征和肿瘤反应进行单因素分析。
分别有4例（19%）和13例患者（62%）达到完全缓解和部分缓解，3例患者疾病稳定，1例患者疾病进展。总体缓解率（81%，95%置信区间（CI）：58-95%）超过了研究设计的目标。无进展生存期和总生存期的中位数分别为10.0个月（95%CI：7.5-12.5个月）和13.0个月（95%CI：8.2-17.8个月）。最常见的毒性包括皮疹（86%）和腹泻（43%），只有3例患者出现III级腹泻。约50%的患者出现的其他II级或更高等级的毒性包括恶心、呕吐、头痛和疲劳。大多数副作用为II级，通过支持治疗耐受性良好。在单因素分析中，性别和每年吸烟量是反应的预测因素。治疗后QoL的所有领域均有显著改善。
我们的数据表明，联合治疗耐受性良好，在NSCLC脑转移的中国人群中具有良好的活性和QoL的显著改善。尽管此处呈现的数据看起来很有前景，但仍需要更多来自随机试验的数据来进一步验证这种WBRT/吉非替尼方案。
