Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Seoul 135-710, Republic of Korea.
Lung Cancer. 2010 Sep;69(3):323-9. doi: 10.1016/j.lungcan.2009.12.002. Epub 2010 Jan 12.
Pemetrexed is one of the standard second-line therapies in advanced non-small cell lung cancer (NSCLC). Currently, there are no standard cytotoxic treatments beyond second-line therapy. We evaluated the efficacy and safety of pemetrexed as a salvage regimen in heavily pretreated NSCLC patients. We also analyzed thymidylate synthase (TS) expression in tumor tissues to determine whether TS expression is correlated with the clinical efficacy of pemetrexed.
One hundred and ten NSCLC patients who received pemetrexed as third- or fourth-line therapy at the Samsung Medical Center between June 2006 and June 2008 were retrospectively reviewed. TS expression was analyzed by immunohistochemical staining in 55 NSCLC tissue specimens. The relationships between TS expression and clinicopathological factors were evaluated. Univariate and multivariate analyses were performed to define the predictive factors and prognostic significances.
The median age of patients in this study was 59 years (range: 24-84), 50.9% were men, and 27 (24.6%) were smokers or previous smokers. Sixty-five patients (59.1%) received pemetrexed as third-line treatment, and 95 (86.4%) had non-squamous cell carcinoma. Platinum-based chemotherapy (84.6%) was the most common first-line therapy, and EGFR TKIs [erlotinib (17.3%) or gefitinib (43.6%)] were a common second-line therapy. The median time from date of diagnosis to the date of the first pemetrexed treatment was 12.8 months (range: 1.8-62.2 months) and the median number of pemetrexed treatments was 4 (range 1-22). Eighteen patients achieved PR (16.3%), 41 patients SD (37.3%), and 43 patients PD (39.1%), with a disease control rate of 53.6%. The median follow-up duration was 16.1 months, the median progression-free survival (PFS) was 3.2 months (95% CI: 1.9-4.5 months), and the median overall survival (OS) was 11.6 months (95% CI: 9.0-14.1 months). Male gender was the only independent variable for poor PFS (HR=1.673, 95% CI: 1.103-2.535), with poor performance status (HR=2.454, 95% CI: 1.405-4.287) and history of smoking (HR=1.856, 95% CI: 1.087-3.168) being independent adverse factors for OS. Thirteen of 55 tumor tissues (23.6%) showed TS expression; however, there were no significant correlations between TS expression and the clinicopathological factors.
Pemetrexed was suggested as a third- or fourth-line therapy due to its favorable efficacy and tolerable toxicity. Further studies are warranted to define the adequate sequence of salvage treatments, especially in patients with adenocarcinoma lung cancer.
培美曲塞是晚期非小细胞肺癌（NSCLC）二线标准治疗药物之一。目前，二线治疗后尚无标准的细胞毒药物治疗方案。我们评估了培美曲塞作为预处理过的晚期 NSCLC 患者三线或四线治疗方案的疗效和安全性。我们还分析了肿瘤组织中的胸苷酸合成酶（TS）表达，以确定 TS 表达是否与培美曲塞的临床疗效相关。
回顾性分析 2006 年 6 月至 2008 年 6 月在三星医疗中心接受培美曲塞三线或四线治疗的 110 例 NSCLC 患者。55 例 NSCLC 组织标本采用免疫组织化学染色法分析 TS 表达。评估 TS 表达与临床病理因素的关系。采用单因素和多因素分析确定预测因素和预后意义。
本研究患者的中位年龄为 59 岁（范围：24-84 岁），50.9%为男性，27 例（24.6%）为吸烟者或曾经吸烟者。65 例（59.1%）接受培美曲塞三线治疗，95 例（86.4%）为非鳞状细胞癌。铂类化疗（84.6%）是最常见的一线治疗方案，EGFR-TKIs[厄洛替尼（17.3%）或吉非替尼（43.6%）]是常见的二线治疗方案。从诊断日期到首次培美曲塞治疗日期的中位时间为 12.8 个月（范围：1.8-62.2 个月），培美曲塞治疗的中位次数为 4 次（范围 1-22 次）。18 例患者获得部分缓解（PR）（16.3%），41 例患者疾病稳定（SD）（37.3%），43 例患者疾病进展（PD）（39.1%），疾病控制率为 53.6%。中位随访时间为 16.1 个月，中位无进展生存期（PFS）为 3.2 个月（95%CI：1.9-4.5 个月），中位总生存期（OS）为 11.6 个月（95%CI：9.0-14.1 个月）。男性是 PFS 不良的唯一独立变量（HR=1.673，95%CI：1.103-2.535），而较差的体能状态（HR=2.454，95%CI：1.405-4.287）和吸烟史（HR=1.856，95%CI：1.087-3.168）是 OS 的独立不良因素。55 例肿瘤组织中有 13 例（23.6%）显示 TS 表达；然而，TS 表达与临床病理因素之间没有显著相关性。
培美曲塞因其良好的疗效和可耐受的毒性，被推荐作为三线或四线治疗药物。需要进一步的研究来确定适当的挽救性治疗方案，特别是在肺腺癌患者中。
