一种bstract
Even in the era of immuno- and personalised therapy, optimal use of old-fashioned chemotherapy is of utmost importance, also for patients with renal insufficiency or declining renal functionhttp://ow.ly/rdlH30m4V1N
Even in the era of immunotherapy and personalised medicine, chemotherapy remains a cornerstone in the treatment of nonsmall cell lung cancer (NSCLC) [1]。化疗提高了患有肿瘤的患者的患者的长度和质量,无论是肿瘤的肿瘤,都没有致癌司机。化学疗法与检查点抑制剂的组合即将成为NSCLC最有效的一线治疗[2]。同样在佐剂设置中,即。adding chemotherapy after surgery, chemotherapy improves survival with an absolute increase of 4% at 5 years [3.]。
化疗的最佳用途是优化患者预后的重要因素。对或实际发生的恐惧可能会干扰其最佳用途。化疗的常见并发症是肾衰竭的发展。肾功能的下降可以作为化学治疗剂的直接毒性效果,也可以发生患者相关和其他药物相关因素发挥关键作用[4.]。肾毒性往往是治疗停止或剂量降低的原因,导致次优处理时间表[5.]。The fact that about 60% of the people with cancer have underlying compromised renal function stresses the importance of this topic [6.]。
在这个问题中欧洲呼吸杂志nal那V.isser等等。[7.] describe the impact of pemetrexed on the renal function of patients with NSCLC. Pemetrexed is a therapeutic option for many patients. It is currently approved for treatment of nonsquamous NSCLC and mesothelioma. The approval for nonsquamous NSCLC involves first-line therapy in combination with cisplatin, and more recently in combination with carboplatin and pembrolizumab, as continuation and switch maintenance treatment and second-line therapy. In mesothelioma, the pemetrexed–cisplatin combination is the only approved regimen [8.]。
在目前批准的500 mg·m的剂量-2那pemetrexed pharmacokinetics are linear. It is eliminated通过肾脏,70%-90%的尿液中尿液中的24小时内回收[9.],它显示了双相消除,并且培养基的间隙与肌酐清除线性相关[10那11]。S.ystemic exposure is importantly correlated with toxicity and efficacy [12那13.],曝光更高,导致剂量限制血液学毒性的发病率更高[10]。Renal function and dose of pemetrexed are the sole determinants for total systemic exposure [10那14.那15.]。
一种lthough nephrotoxicity is not amongst the list of dose-limiting toxicities of pemetrexed [16.], it is commonly encountered. Pemetrexed enters the proximal tubule cells both通过基石和顶端侧。在细胞内部的聚戊酰胺化是聚谷淀粉化,其损害了磷酸盐的磷酸盐输出并导致升高的细胞内浓度。通过培养基,损害DNA和小管细胞的植物途径涉及叶酸途径的酶的抑制作用进一步增加了Pemetrexed的肾毒性作用[4.]。
Presently, Visser等等。[7.] showed in their prospective study, which was performed in a standard hospital setting, that patients with an estimated glomerular filtration rate (eGFR) of <90 mL·min-1在用磷酸盐治疗之前,在发育急性肾病的风险上升。作者能够在独立回顾性的NSCLC患者队列中确认这种观察。两个队列还表明,在维修期间肾脏疾病的发展期间肾功能减少了肾功能期间的肾病。在维护治疗过程中,近30%的患者在肾功能下降,其中60%不得不停止化疗。作者还注意到疗法剂量的疗效和肾毒性之间存在统计学上不切实际的关系。
It is obvious that renal toxicity has more impact on patients with a pre-existing impaired renal function. Whether this patient population also were more likely to develop significant nephrotoxicity has already been suggested in other studies. The paper by Visser等等。[7.),然而,是第一个显示预测公关operties of baseline reduced eGFR and reduced renal function during therapy for a (further) reduction in renal function due to pemetrexed. This is in line with a similar French study which had shown that renal toxicity was the main reason for interruption of treatment with pemetrexed and bevacizumab [17.]。
The study by Visser等等。[7.] has limitations, related to its partially retrospective design, the fact that the effect of pemetrexed was studied when given in combination with the nephrotoxic agents carboplatin and cisplatin, the lack of data on concomitant medication, and the relatively small number of patients. Nonetheless, the study paves the way for new strategies and research ideas and once again underlines the importance of optimal treatment for all patients, including those with a renal impairment.
一种改善这种易碎人群的方法可能是我们标准给药练习的变化。肾功能不考虑肾功能的植物表面积的目前,标准实践,将临床医生面临两个主要问题:1)从EGFR <45毫升·min的患者中扣留潜在有效的治疗方法-1[11];2)肾功能的肾功能劣化,导致培养基治疗,导致治疗的不利影响和停止[11那18.], might prevent optimal anti-tumour therapy, as is also shown by Visser等等。[7.]。This applies both to those patients with normal renal function and to those patients with a diminished renal function at the start of therapy [4.那9.]。
New studies on individualised pemetrexed dosing in patients with NSCLC and mesothelioma based on their renal function are, therefore, being eagerly awaited, also in the new immunotherapy era, in which triple combinations of chemotherapy and immunotherapy are about to become standard of NSCLC care.
Footnotes
Conflict of interest: R. Boosman has nothing to disclose.
Conflict of interest: J.A. Burgers reports advisory board work for Roche, Boehringer Ingelheim and AstraZeneca, outside the submitted work.
- Received2018年9月5日。
- 公认S.eptember 7, 2018.
- Copyright ©ERS 2018