Anticancer Dose Adjustment for Patients with Renal and Hepatic Dysfunction: From Scientific Evidence to Clinical Application

Abstract

Most anticancer agents exhibit a narrow therapeutic index, i.e., a small change in plasma concentrations can lead to a less efficacious treatment or an unacceptable degree of toxicity. This study aimed at providing health professionals with a feasible and time-saving tool to adapt the dose of anticancer agents for patients with renal or hepatic dysfunction. A guideline for anticancer agents was developed based on a literature search. An algorithm was generated to enhance the efficiency of the dose adaptation process. Finally, the dosing guideline was converted into an easy-to-use ExcelTM tool. The concept was applied to a total of 105 adult patients at the Centre for Integrated Oncology, Bonn, Germany. In total, 392 recommendations for dose adaptation were made and 320 (81.6%) recommendations were responded to by the oncologists. 98.4% of the recommendations were accepted. The algorithm simplifies the decision and screening process for high-risk patients. Moreover, it provides the possibility to quickly decide which laboratory tests are required and whether a dose adjustment for a particular anticancer drug is needed. The ExcelTM tool provides a recommended individual dose for patients with renal or hepatic dysfunction. The effectiveness of this strategy to reduce toxicity should be investigated in further studies before being adopted for routine use.

Keywords: anticancer; dose adjustment; hepatic dysfunction; renal dysfunction.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1

Algorithm of dose adjustment of anticancer agents for a patient with renal dysfunction. TDM, therapeutic drug monitoring; SCr, serum creatinine; T.Bil, total bilirubin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; CrCl, creatinine clearance; CG, Cockcroft & Gault formula; MDRD, simplified Modification of Diet in Renal Disease formula; * use full dose if not contraindicated; (1) contraindicated if CrCl < 40 mL∙min−1; (2) contraindicated if CrCl < 30 mL∙min−1; (3) contraindicated if CrCl < 10 mL∙min−1; (4) contraindicated if CrCl < 15 mL∙min−1; (5) contraindicated if CrCl < 45 mL∙min−1.

Figure 2

Algorithm of dose adjustment of anticancer agents for a patient with hepatic dysfunction. TDM, therapeutic drug monitoring; SCr, serum creatinine; T.Bil, total bilirubin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ULN, upper limit normal; * use full dose if not contraindicated; (1) contraindicated if T.Bil > 3 ULN; (2) contraindicated if T.Bil > 5 ULN; (3) contraindicated if T.Bil > 7 ULN; (4) for Paclitaxel, 24-h infusion and first course of therapy, contraindicated if T.Bil > 7.5 ULN; (5) contraindicated if AST > 6 ULN; (6) contraindicated if transaminase > 10 ULN.

Figure 3

Easy-to-use Excel tool.