Glucarpidase(羧肽酶g2)干预在成年和老年癌症患者肾脏功能障碍和延迟大剂量甲氨蝶呤治疗后甲氨蝶呤消除。

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施瓦茨,波尔纳K,穆勒K, Martus P,费舍尔L, Korfel, Auton T,泰尔E

Glucarpidase(羧肽酶g2)干预在成年和老年癌症患者肾脏功能障碍和延迟大剂量甲氨蝶呤治疗后甲氨蝶呤消除。

肿瘤学家。2007年11月,12 (11):1299 - 308。doi: 10.1634 / theoncologist.12 - 11 - 1299。

PubMed ID

18055849 (在PubMed

]

文摘

目的:甲酰四氢叶酸和体外清除甲氨蝶呤(MTX)疗效有限在延迟MTX消除后大剂量甲氨蝶呤(HD-MTX)治疗。Glucarpidase(羧肽酶G2)劈开MTX成无毒的代谢物,但这种酶是有限的经验在成人患者。我们评估的影响glucarpidase干预成年和老年患者延迟MTX消除。病人和方法:对43例(年龄18 - 78岁)与MTX血清中浓度(sMTX) 1 - 1187 micromol / l收到glucarpidase,甲酰四氢叶酸救援指导下MTX免疫测定,和标准支持性护理。血清中MTX和MTX代谢物中量化(24例)和尿液的高效液相色谱(8例)。分摊风险因素、毒性和生存都记录在所有的病人。结果:Glucarpidase耐受性良好,导致立即> sMTX减少97%,0.2% -35%尿总剂量MTX的复苏不活跃的MTX代谢物。四十43(93%)的患者规范化(n = 25)或改善他们的血清肌酐(n = 15)。频繁的等级iii iv MTX毒性是血液中(60%)和粘膜炎(35%);只有8个(19%)病人发达iii iv级肾毒性。 Ten (23%) of 43 patients experienced fatal complications associated with HD-MTX therapy. Patients with three or more contributory risk factors for delayed MTX elimination had a significantly poorer survival than patients with fewer than three risk factors (hazard ratio, 3.64; confidence interval, 1.14-17.54). CONCLUSIONS: Glucarpidase is well tolerated and produces a rapid inactivation of substantial amounts of MTX. However, overall results are still unsatisfactory in adult and elderly patients, suggesting that earlier recognition of delayed MTX elimination and more rapid intervention are needed.

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药物

Glucarpidase