Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Lung Cancer. 2013 Aug;81(2):231-5. doi: 10.1016/j.lungcan.2013.04.011. Epub 2013 May 14.
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.
虽然建议在培美曲塞治疗期间补充叶酸和维生素 B12，但在接受培美曲塞治疗前首次剂量之前补充的最佳持续时间尚未确定。我们分析了 350 例接受培美曲塞单药治疗的晚期非小细胞肺癌（NSCLC）患者在培美曲塞治疗第一个周期期间的不良事件。患者分为两组：A 组和 B 组分别为开始维生素补充剂 5-14 天和 4 天内的患者。A 组和 B 组分别包括 294 例（84.0%）和 56 例（16.0%）患者。两组患者培美曲塞的中位周期数均为 3 个。A 组和 B 组的白细胞减少症发生率相似（分别为 6.1%和 5.4%，P=1.00）、中性粒细胞减少症（分别为 5.1%和 3.6%，P=1.00）、血小板减少症（分别为 3.1%和 7.1%，P=0.14）、中性粒细胞发热（分别为 0.7%和 0%，P=1.00）、疲劳（分别为 20.1%和 19.6%，P=0.94）和厌食症（分别为 15.0%和 21.4%，P=0.23）。A 组和 B 组患者在培美曲塞治疗的第一个周期中，因培美曲塞相关不良事件而住院（分别为 4.4%和 5.4%，P=0.73）或计划外就诊（分别为 8.2%和 12.5%，P=0.31）的差异无统计学意义。多变量 logistic 回归分析表明，年龄≥65 岁（比值比，3.49；95%CI，1.12-10.86）和较差的体能状态（比值比，3.96；95%CI，1.12-14.03）是 3 级或 4 级血液学毒性的统计学显著预测因素。培美曲塞治疗前首次剂量前维生素补充的持续时间并不影响培美曲塞相关毒性的发展，这表明不必为了适应维生素补充计划而延迟培美曲塞为基础的化疗的开始。
