International consensus guideline for anticancer drug dosing in kidney dysfunction (ADDIKD): A standardized approach to assessing kidney function in cancer patients and its application to anticancer drug dosing.

Abstract

e13518 Background: Anticancer drug dosing recommendations in kidney dysfunction are often empirical, based on non-standardised creatinine assays calculated via the Cockcroft-Gault equation, and lack applicability to globally accepted kidney dysfunction classifications. ADDIKD aims to provide a standardised approach to assessing kidney function in cancer patients, and to apply evidence and consensus-based recommendations to anticancer drug dosing in kidney dysfunction. Methods: An expert international multidisciplinary working group was established to develop anticancer drug dosing recommendations. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to critically appraise the quality and strength of evidence and formulate recommendations. The working group participated in workshops to achieve > 80% consensus for a standardised approach to assessing and classifying levels of kidney function, its application to anticancer drug dosing in kidney dysfunction, and dosing recommendations for individual drugs. Upcoming public consultation will refine these recommendations and facilitate acceptance as an international benchmark. Results: Three key recommendations formed the basis of ADDIKD: Application of estimated glomerular filtration rate via the Chronic Kidney Disease-Epidemiology Collaboration equation (eGFRCKD-EPI) to guide the assessment of kidney function, except where directly measured glomerular filtration rate (mGFR) is clinically necessary. Where the anticancer drug dose is dependent on kidney function and mGFR is not clinically necessary, eGFRCKD-EPI is suggested to guide dosing. Application of the Kidney Disease Improving Global Outcomes (KDIGO) Chronic Kidney Disease categories to guide stepwise dose adjustments of anticancer drugs in kidney dysfunction. A review of 2263 published articles and 177 registered product information monographs enabled 127 GRADE assessments by the working party, resulting in evidence and consensus-based dosing recommendations for 59 anticancer drugs. 'Quick reference’ dosing tables incorporated a traffic light system for alerting clinicians to caution around levels of kidney function and specific patient risk factors for consideration. Conclusions: eGFRCKD-EPI is the most accurate and convenient method for assessing kidney function in diverse populations (including cancer patients) and accounts for the standardisation of the creatinine assay. ADDIKD’s expert acceptance of this standardised approach, together with anticancer drug dosing recommendations in kidney dysfunction, provides a practical tool to establish clinically relevant dosing in this patient population.

Estimation of kidney function for medication dosing in adult patients with chronic kidney disease: a practice update

“…Direct measured GFR (mGFR) testing is the gold standard and is recommended to be used in a select group of anticancer medications, including carboplatin, cisplatin and methotrexate (≥500 mg/m 2 ), as well as in patients with extremes of body size or muscle mass, amputees or persons with paraplegia or conditions of skeletal muscle. 46 However, access to mGFR in cancer care is currently limited due to capacity in larger centres and the unavailability of mGFR at smaller services, so it is often reserved for situations that necessitate a more accurate dose (e.g. carboplatin dosing).…”

“…26,47 In line with the newly developed International Consensus Guideline for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) by eviQ and Cancer Institute NSW, it is recommended to use eGFR CKD-EPI as the standard and routine estimate of kidney function, and to use BSA-adjusted eGFR CKD-EPI for carboplatin dosing using the Calvert equation. 46 The ADDIKD was developed after an extensive and in-depth review of published literature. For individual guidance on specific medications and special populations (e.g.…”

“…For individual guidance on specific medications and special populations (e.g. obesity, AKI) practitioners should refer directly to the ADDIKD and related protocols 46 …”

“…If medications require dosing on BSA, such as chemotherapy, currently there is no evidence‐based recommendation for calculating BSA in patients with amputations 54 . For anticancer medications, the consensus recommendation by the ADDIKD is to use mGFR 46 …”

Prior cancer history and suitability for kidney transplantation

“…However, establishment of the appropriate estimation of kidney function has been challenging. The recently published international consensus guideline for anticancer drug dosing recommends the use of estimated glomerular filtration rate (eGFR) calculated via the Chronic Kidney Disease Epidemiology Collaboration (eGFR CKD-EPI ) equation to guide the assessment of kidney function in adult cancer patients, except where directly measured glomerular filtration rate (mGFR) is clinically necessary [ 13 ]. Directly measured GFR, expressed in mL/min, refers to a direct measurement of the clearance of exogenous markers (filtered by the glomerulus and neither reabsorbed nor secreted by the kidney tubules), such as iohexol, iothalamate, 51Cr-EDTA or 99mTc-DTPA.…”