Lung cancer：培美曲塞化疗不需要因补充叶酸而延迟

对于晚期非小细胞肺癌一线化疗失败后培美曲塞化疗是二线化疗的首选。然而化疗前补充叶酸和维生素 B12的最佳持续时间迄今还未确定。针对这种情况，来韩国成均馆大学医学院首尔三星医疗中心血液肿瘤科的Young Saing Kim博士等人进行了一项研究，研究结果发表于2013年5月14日的《肺癌》（Lung cancer）杂志上。作者发现第一周期培美曲塞治疗前补充维生素的持续时间与培美曲塞相关的毒性无关，提示开始以培美曲塞为基础的化疗时不需要为适应维生素补充而延迟。

该研究对第一周期单药培美曲塞治疗的晚期非小细胞肺癌（NSCLC）患者的不良事件进行了回顾性分析，共有350 例患者入组。患者被分为两组：A组在第一周期培美曲塞治疗前开始补充维生素5-14天，B组4天。A和B组 分别包括294（84.0％）和56 例（16.0％）。在这两组患者中培美曲塞平均使用3个周期。

研究结果表明，第一周期培美曲塞治疗的A和B组患者出现白细胞减少症（分别为6.1％和5.4％，P = 1.00），中性粒细胞减少症（5.1％对3.6％，P = 1.00），血小板减少症（3.1％比7.1％，P = 0.14），中性粒细胞减少性发热（0.7％和0％，P = 1.00），乏力（20.1％比19.6％，P = 0.94）和厌食（15.0 ％对21.4％，P = 0.23）相似。A组和B之间住院时间无显着性差异（4.4％对5.4％，P = 0.73），不定期随访培美曲塞相关的不良事件无显著差异（8.2％比12.5％，P = 0.31）。多因素Logistic回归分析表明，年龄≥65岁（比值比为3.49，95％CI为1.12-10.86），体力状态（比值比为3.96，95％CI为1.12-14.03）是血液毒性3级或4级的显著预测因子。

该研究发现，第一周期培美曲塞治疗前补充维生素的持续时间与培美曲塞相关的毒性无关，提示开始以培美曲塞为基础的化疗时不需要为适应维生素补充而延迟。

The optimal duration of vitamin supplementation prior to the first dose of pemetrexed in patients with non-small-cell lung cancer.
Abstract
Although folic acid and vitamin B12 supplements are recommended during pemetrexed therapy, the optimal duration for supplementation prior to the first dose of pemetrexed has not been defined. We analyzed adverse events during the first cycle of pemetrexed therapy in 350 patients with advanced non-small-cell lung cancer (NSCLC) who had received pemetrexed monotherapy. Patients were divided into two groups: group A and group B included patients who started vitamin supplements 5-14 days versus within 4 days before the first dose of pemetrexed, respectively. Groups A and B included 294 (84.0%) and 56 (16.0%) patients, respectively. The median number of cycles of pemetrexed was three in both groups. Patients in group A and B showed similar rates of leukopenia (6.1% vs. 5.4%, respectively, P=1.00), neutropenia (5.1% vs. 3.6%, P=1.00), thrombocytopenia (3.1% vs. 7.1%, P=0.14), neutropenic fever (0.7% vs. 0%, P=1.00), fatigue (20.1% vs. 19.6%, P=0.94), and anorexia (15.0% vs. 21.4%, P=0.23) during the first cycle of pemetrexed therapy. There were no significant differences in terms of hospitalization (4.4% vs. 5.4%, P=0.73) or unscheduled visits due to pemetrexed-related adverse events (8.2% vs. 12.5%, P=0.31) between groups A and B, respectively. Multivariate logistic regression analysis demonstrated that an age of ≥65 years (odds ratio, 3.49; 95% CI 1.12-10.86) and poor performance status (odds ratio, 3.96; 95% CI 1.12-14.03) were statistically significant predictive factors for grade 3 or 4 hematologic toxicity. The duration of vitamin supplementation before the first dose of pemetrexed did not affect the development of pemetrexed-related toxicities, suggesting that the initiation of pemetrexed-based chemotherapy does not have to be delayed to accommodate a vitamin supplementation schedule.