Bambury Richard M, Benjamin David J, Chaim Joshua L, Zabor Emily C, Sullivan John, Garcia-Grossman Ilana R, Regazzi Ashley M, Ostrovnaya Irina, Apollo Aryln, Xiao Han, Voss Martin H, Iyer Gopa, Bajorin Dean F, Rosenberg Jonathan E
Memorial Sloan Kettering Cancer Center, New York, New York, USA; Tulane University School of Medicine, New Orleans, Louisiana, USA
Memorial Sloan Kettering Cancer Center, New York, New York, USA; Tulane University School of Medicine, New Orleans, Louisiana, USA.
Oncologist. 2015 May;20(5):508-15. doi: 10.1634/theoncologist.2014-0354. Epub 2015 Apr 6.
Pemetrexed is a commonly used treatment for platinum-resistant advanced urothelial carcinoma (UC) based on objective response rates of 8% and 28% in two small phase II studies. To address the discrepancy in reported response rates and to assess efficacy and toxicity outside of a clinical trial setting, we performed a large retrospective analysis of pemetrexed use at Memorial Sloan Kettering Cancer Center. We also investigated candidate prognostic factors for overall survival in this setting to explore whether the neutrophil-lymphocyte ratio (NLR) had independent prognostic significance.
Patients receiving pemetrexed for platinum-resistant advanced UC between 2008 and 2013 were identified. The Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) were used to determine response rate. Kaplan-Meier and Cox regression analyses were used to examine the association of various factors with efficacy and survival outcomes. Hematologic toxicity and laboratory abnormalities were recorded.
One hundred and twenty-nine patients were treated with pemetrexed. The objective response rate was 5% (95% confidence interval: 1%-9%), and the median duration of response was 8 months. Median progression-free survival (PFS) was 2.4 months, and the 6-month PFS rate was 14%. There was no significant difference in response rate by age, Eastern Cooperative Oncology Group (ECOG) performance status, or number of prior therapies. On multivariable analysis, ECOG performance status (p < .01), liver metastases (p = .02), and NLR (p < .01) had independent prognostic significance for overall survival.
This 129-patient series is the largest reported data set describing pemetrexed use in advanced UC. Activity was modest, although discovery of molecular biomarkers predictive of response would be valuable to identify the small subset of patients who do gain significant benefit. Overall, the data highlight the urgent need to develop novel therapies for these patients.
培美曲塞是一种常用于治疗铂类耐药晚期尿路上皮癌（UC）的药物，两项小型II期研究显示其客观缓解率分别为8%和28%。为了解决报告的缓解率差异问题，并评估临床试验环境之外的疗效和毒性，我们在纪念斯隆凯特琳癌症中心对培美曲塞的使用情况进行了一项大型回顾性分析。我们还研究了该情况下总生存期的候选预后因素，以探讨中性粒细胞与淋巴细胞比值（NLR）是否具有独立的预后意义。
确定2008年至2013年间接受培美曲塞治疗铂类耐药晚期UC的患者。采用实体瘤疗效评价标准（RECIST，1.1版）确定缓解率。采用Kaplan-Meier法和Cox回归分析来检验各种因素与疗效和生存结果之间的关联。记录血液学毒性和实验室异常情况。
129例患者接受了培美曲塞治疗。客观缓解率为5%（95%置信区间：1%-9%），中位缓解持续时间为8个月。中位无进展生存期（PFS）为2.4个月，6个月PFS率为14%。年龄、东部肿瘤协作组（ECOG）体能状态或既往治疗次数对缓解率无显著差异。多变量分析显示，ECOG体能状态（p < .01）、肝转移（p = .02）和NLR（p < .01）对总生存期具有独立的预后意义。
这个包含129例患者的系列是描述培美曲塞用于晚期UC的最大报告数据集。活性适度，尽管发现预测反应的分子生物标志物对于识别确实能获得显著益处的一小部分患者将是有价值的。总体而言，数据突出了为这些患者开发新疗法的迫切需求。
