Preventing and Managing Toxicities of High-Dose Methotrexate.
Preventing and Managing Toxicities of High-Dose Methotrexate.
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DOI：
10.1634/theoncologist.2015-0164
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发表时间：
2016-12
期刊：
影响因子：
--
通讯作者：
Harvey RD
中科院分区：
文献类型：
--
作者：
Howard SC;McCormick J;Pui CH;Buddington RK;Harvey RD
高剂量甲氨蝶呤（HDMTX），定义为高于500 mg/m2的剂量，用于治疗一系列成人和儿童癌症。虽然HDMTX对大多数患者是安全的，但它会引起严重的毒性，包括急性肾损伤。本文提供了预防HDMTX毒性的全面建议，沿着详细的治疗指南，以减轻急性肾损伤和随后的毒性。高剂量甲氨蝶呤（HDMTX），定义为高于500 mg/m2的剂量，用于治疗一系列成人和儿童癌症。虽然HDMTX对大多数患者安全，但它可能导致严重的毒性，包括2%-12%的患者的急性肾损伤（阿基）。肾毒性由甲氨蝶呤在肾小管腔中结晶而引起，导致肾小管毒性。高剂量甲氨蝶呤的阿基和其他毒性可导致显著的发病率、治疗延迟和肾功能下降。蛋氨酸相关毒性的风险因素包括肾功能不全、血容量不足、酸性尿和药物相互作用史。肾毒性导致甲氨蝶呤清除受损和长期暴露于毒性浓度，这进一步恶化肾功能并加剧非肾不良事件，包括骨髓抑制、粘膜炎、皮肤毒性和肝毒性。监测血清肌酐、尿排出量和血清甲氨蝶呤浓度以评估肾清除率，同时进行水合、尿碱化和甲酰四氢叶酸补救，以预防和减轻阿基和后续毒性。尽管采取了预防性策略，但仍发生甲氨蝶呤排泄延迟或阿基时，增加水合作用、高剂量甲酰四氢叶酸和葡萄糖醛酸酶通常足以使肾脏恢复，而无需透析。阿基和相关毒性的及时识别和有效治疗可减轻进一步的毒性，促进肾脏恢复，并允许患者接受其他化疗或在需要额外疗程时恢复HDMTX治疗。高剂量甲氨蝶呤（HDMTX），定义为高于500 mg/m2的剂量，用于一系列癌症。尽管HDMTX可安全地施用于大多数患者，但其可引起显著毒性，包括急性肾损伤（阿基），这归因于甲氨蝶呤在肾小管腔中结晶，从而导致肾小管毒性。当尽管采取了预防策略但仍发生阿基时，增加水合作用、高剂量甲酰四氢叶酸和葡萄糖醛酸酶可使肾脏恢复，而无需透析。本文基于对当前相关文献的综述，提供了预防毒性的综合建议，并在必要时提供了减轻阿基和后续毒性的详细治疗指南。
High-dose methotrexate (HDMTX), defined as a dose higher than 500 mg/m2, is used to treat a range of adult and childhood cancers. Although HDMTX is safely administered to most patients, it can cause significant toxicity, including acute kidney injury. This article provides comprehensive recommendations for prevention of toxicity from HDMTX, along with detailed treatment guidance to mitigate acute kidney injury and subsequent toxicity. High-dose methotrexate (HDMTX), defined as a dose higher than 500 mg/m2, is used to treat a range of adult and childhood cancers. Although HDMTX is safely administered to most patients, it can cause significant toxicity, including acute kidney injury (AKI) in 2%–12% of patients. Nephrotoxicity results from crystallization of methotrexate in the renal tubular lumen, leading to tubular toxicity. AKI and other toxicities of high-dose methotrexate can lead to significant morbidity, treatment delays, and diminished renal function. Risk factors for methotrexate-associated toxicity include a history of renal dysfunction, volume depletion, acidic urine, and drug interactions. Renal toxicity leads to impaired methotrexate clearance and prolonged exposure to toxic concentrations, which further worsen renal function and exacerbate nonrenal adverse events, including myelosuppression, mucositis, dermatologic toxicity, and hepatotoxicity. Serum creatinine, urine output, and serum methotrexate concentration are monitored to assess renal clearance, with concurrent hydration, urinary alkalinization, and leucovorin rescue to prevent and mitigate AKI and subsequent toxicity. When delayed methotrexate excretion or AKI occurs despite preventive strategies, increased hydration, high-dose leucovorin, and glucarpidase are usually sufficient to allow renal recovery without the need for dialysis. Prompt recognition and effective treatment of AKI and associated toxicities mitigate further toxicity, facilitate renal recovery, and permit patients to receive other chemotherapy or resume HDMTX therapy when additional courses are indicated. High-dose methotrexate (HDMTX), defined as a dose higher than 500 mg/m2, is used for a range of cancers. Although HDMTX is safely administered to most patients, it can cause significant toxicity, including acute kidney injury (AKI), attributable to crystallization of methotrexate in the renal tubular lumen, leading to tubular toxicity. When AKI occurs despite preventive strategies, increased hydration, high-dose leucovorin, and glucarpidase allow renal recovery without the need for dialysis. This article, based on a review of the current associated literature, provides comprehensive recommendations for prevention of toxicity and, when necessary, detailed treatment guidance to mitigate AKI and subsequent toxicity.
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