目的：Pemetrexed 是一種多重葉酸拮抗劑，可治療惡性肋膜間質細胞瘤及非鱗狀上皮型非小細胞肺癌，副作用較一般化療藥物輕，常見為疲倦和血液相關副作用，如：嗜中性球低下、貧血及血小板低下等，適時補充葉酸及維他命B12 可減少血液相關副作用，腎功能不佳或併用非固醇類抗發炎藥物 (non-steroidal anti-inflammatory drugs, NSAIDs) 會增加其發生率，卻少有pemetrexed 之安全性使用分析。本研究以某區域教學醫院pemetrexed 處方型態進行安全使用評估，期望進而建立預防機制。
方法：以回溯性世代研究2011 年1 月至2017 年12 月間曾使用pemetrexed 之病人，觀察注射pemetrexed 期間是否併用葉酸、維他命B12 與NSAIDs，以及至下次給藥前，發生血液相關副作用之機率。
結果：研究期間共納入180 位病人，合計接受pemetrexed 注射874 次，發現併用NSAIDs 病人嗜中性球低下的發生率 (29.6% vs. 20.0%, p = 0.016) 較高，而在貧血及血小板低下之發生率則無顯著差異。在pemetrexed 療程中補充葉酸 (11.2% vs. 23.5%, p = 0.001) 與維他命B12 (14.1% vs. 26.4%, p < 0.001) 明顯降低嗜中性球低下之發生；補充葉酸 (17.8% vs. 34.5%, p = 0.001) 與維他命B12 (27.3% vs. 34.5%, p = 0.025) 亦能降低血小板低下；補充維他命B12 (67.3% vs. 79.0%, p < 0.001) 則顯著降低貧血之發生率。
結論：Pemetrexed 副作用較輕微，臨床不良反應較易被輕忽，藉此研究發現在pemetrexed 療程中若能適當補充維他命B12 與葉酸並避免併用NSAIDs，可減少血液相關副作用發生，因此，建立有效預防機制才能提升pemetrexed 用藥安全。
Objective: Pemetrexed is a multitargeted antifolate indicated for malignant pleural mesothelioma and non-small cell lung cancer (NSCLC) with nonsquamous histology. Pemetrexed can induce some hematological toxicities, including fatigue, neutropenia, anemia, and thrombocytopenia, but causes fewer than other chemotherapeutic agents, while folic acid or vitamin B12 supplementation further reduces such toxicities. To further avoid toxicities, pemetrexed should not be used in renally impaired patients or with non-steroidal anti-inflammatory drugs (NSAIDs). This study evaluated the appropriateness of pemetrexed use in a regional teaching hospital.
Methods: We retrospectively investigated patients treated with pemetrexed from 2011–2017, comparing the incidences of hematological toxicities among those with or without folic acid or vitamin B12 supplementation and those also receiving NSAIDs.
Results: A total of 180 patients who received 874 pemetrexed injections were enrolled. The incidence of neutropenia, but not anemia or thrombocytopenia, was significantly higher (29.6% vs. 20.0%, p = 0.016) in patients also treated with NSAIDs. Folic acid supplementation (11.2% vs. 23.5%, p = 0.001) and vitamin B12 supplementation (14.1% vs. 26.4%, p < 0.001) significantly reduced the incidence of neutropenia during pemetrexed treatment. Folic acid supplementation (17.8% vs. 34.5%, p = 0.001) and vitamin B12 supplementation (27.3% vs. 34.5%, p = 0.025) also reduced the risk of thrombocytopenia, and vitamin B12 supplementation (67.3% vs. 79.0%, p < 0.001) also reduced the incidence of anemia.
Conclusions: Pemetrexed has mild side effects that are often overlooked. This study found that both folic acid and vitamin B12 supplementation and the avoidance of NSAIDs during pemetrexed treatment can reduce hematological toxicities. Therefore, utilizing such supplementation and avoiding NSAIDs when possible can improve the safety of pemetrexed.
