Institute of Experimental and Clinical Pharmacology and Toxicology, Chair of Clinical Pharmacology and Clinical Toxicology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Fahrstraße 17, 91054, Erlangen, Germany.
Pharmacy Department, Erlangen University Hospital, Palmsanlage 3, 91054, Erlangen, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 2018 Feb;391(2):219-229. doi: 10.1007/s00210-017-1456-2. Epub 2018 Jan 2.
Clearance of cisplatin, etoposide, and ifosfamide depends on kidney function and dosages should be adjusted in patients with renal impairment. However, there is still limited data on the adherence of physicians to dosing recommendations for these drugs in cancer patients with renal impairment. Three thousand four hundred forty-eight prescriptions to 369 patients, treated in the Comprehensive Cancer Center of a German university hospital, were retrospectively evaluated. The administered relative doses of cisplatin, etoposide, and ifosfamide were compared with relative doses recommended at the time of prescription according to the patients' creatinine clearance. Cisplatin is contraindicated according to two German summary of product characteristics (SmPC) in patients with a creatinine clearance < 60 mL/min. Nevertheless, 37 cisplatin prescriptions were made for this group of patients (i.e., 2.0% of all cisplatin prescriptions). According to one German SmPC (valid in the year of data analysis), etoposide dosage should be reduced in patients with a creatinine clearance from 15 to 50 mL/min, while it is contraindicated below 15 mL/min. Thirteen etoposide prescriptions were without dose reduction in patients with creatinine clearance from 15 to 50 mL/min (1.5% of all etoposide prescriptions); one patient received etoposide with creatinine clearance below 15 mL/min. In 8.9% of ifosfamide prescriptions, patients did not receive a reduced dose in spite of respective recommendations. Dosages of cisplatin, etoposide, and ifosfamide are not always adjusted as recommended in patients with renal impairment. Consistent international dosing recommendations (e.g., in SmPCs), preferentially included in clinical decision support systems, should be developed to tackle this problem.
顺铂、依托泊苷和异环磷酰胺的清除率取决于肾功能，肾功能损害患者应调整剂量。然而，对于肾功能损害的癌症患者，医生在这些药物的剂量推荐方面的依从性仍然有限。回顾性评估了德国一所大学医院综合癌症中心治疗的 369 名患者的 3448 份处方。根据患者的肌酐清除率，将给予的顺铂、依托泊苷和异环磷酰胺的相对剂量与处方时推荐的相对剂量进行比较。根据两份德国药品说明书（SmPC），肌酐清除率<60 mL/min 的患者禁用顺铂。然而，仍有 37 例为该组患者开具顺铂处方（即所有顺铂处方的 2.0%）。根据一份德国 SmPC（在数据分析当年有效），肌酐清除率为 15 至 50 mL/min 的患者需要减少依托泊苷的剂量，而肌酐清除率<15 mL/min 的患者则禁用依托泊苷。在肌酐清除率为 15 至 50 mL/min 的患者中，有 13 例处方未减少依托泊苷剂量（即所有依托泊苷处方的 1.5%）；一名患者在肌酐清除率<15 mL/min 的情况下接受了依托泊苷治疗。在 8.9%的异环磷酰胺处方中，尽管有相应的推荐，但患者没有接受减量。在肾功能损害患者中，顺铂、依托泊苷和异环磷酰胺的剂量并未按照推荐进行调整。应制定一致的国际剂量推荐（例如，在 SmPC 中），并优先纳入临床决策支持系统，以解决这一问题。
