A methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney function

Geeta Sandhu^{1

2

3}, Evangeline Armstrong Gordon², Josephine Adattini², Niamh O'Neill², Pinkie Chambers⁴, David W Johnson^{5

6

7}, Aisling Kelly², Winston Liauw^{8

9}, Andrew J Mallett^{10

11

12}, Michael Michael^{13

14}, Sanja Mirkov¹⁵, Carla Scuderi^{16

17}, Julia Shingleton², Jim Siderov¹⁸, Ben Sprangers^{19

20}, Brian N Stein^{21

22}, David J Tunnicliffe^{23

24}, Robyn L Ward^{1

2}; ADDIKD Working Group

Affiliations

¹ Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
² eviQ, Cancer Institute NSW, St Leonards, NSW, Australia.
³ Pharmacy Department, St Vincent's Hospital, Sydney, NSW, Australia.
⁴ University College London School of Pharmacy and University College London Hospital-University College London Centre for Medicines Optimisation Research and Education, London, United Kingdom.
⁵ Australasian Kidney Trials Network, The University of Queensland, Brisbane, QLD, Australia.
⁶ Department of Kidney and Transplant Services, Princess Alexandra Hospital, Brisbane, QLD, Australia.
⁷ Translational Research Institute, Brisbane, QLD, Australia.
⁸ Cancer Care Centre, St George Hospital, Kogarah, NSW, Australia.
⁹ School of Clinical Medicine, The University of New South Wales, Sydney, NSW, Australia.
¹⁰ Department of Renal Medicine, Townsville University Hospital, Townsville, QLD, Australia.
¹¹ College of Medicine & Dentistry, James Cook University, Townsville, QLD, Australia.
¹² Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
¹³ Peter MacCallum Cancer Centre, Parkville, VIC, Australia.
¹⁴ The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia.
¹⁵ Pharmacy Department, Cairns and Hinterland Hospital and Health Service, Cairns, QLD, Australia.
¹⁶ Kidney Health Service, Metro North Hospital and Health Service, Brisbane, QLD, Australia.
¹⁷ School of Pharmacy, University of Queensland, Brisbane, QLD, Australia.
¹⁸ Pharmacy Department, Austin Health, Melbourne, VIC, Australia.
¹⁹ Division of Nephrology, Ziekenhuis Oost-Limburg, Genk, Belgium.
²⁰ Department of Immunology and Infection, Biomedical Research Institute, UHasselt, Diepenbeek, Belgium.
²¹ ICON Cancer Centre, Adelaide, SA, Australia.
²² University of Adelaide, Adelaide, SA, Australia.
²³ Sydney School of Public Health, The University of Sydney, Sydney, NSW, Australia.
²⁴ Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, NSW, Australia.

PMID: 40290846
PMCID: PMC12034072
DOI: 10.1016/j.eclinm.2025.103101

Review

A methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney function

Geeta Sandhu et al. EClinicalMedicine. 2025.

. 2025 Mar 25:82:103101.

doi: 10.1016/j.eclinm.2025.103101. eCollection 2025 Apr.

Authors

Affiliations

¹ Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
² eviQ, Cancer Institute NSW, St Leonards, NSW, Australia.
³ Pharmacy Department, St Vincent's Hospital, Sydney, NSW, Australia.
⁴ University College London School of Pharmacy and University College London Hospital-University College London Centre for Medicines Optimisation Research and Education, London, United Kingdom.
⁵ Australasian Kidney Trials Network, The University of Queensland, Brisbane, QLD, Australia.
⁶ Department of Kidney and Transplant Services, Princess Alexandra Hospital, Brisbane, QLD, Australia.
⁷ Translational Research Institute, Brisbane, QLD, Australia.
⁸ Cancer Care Centre, St George Hospital, Kogarah, NSW, Australia.
⁹ School of Clinical Medicine, The University of New South Wales, Sydney, NSW, Australia.
¹⁰ Department of Renal Medicine, Townsville University Hospital, Townsville, QLD, Australia.
¹¹ College of Medicine & Dentistry, James Cook University, Townsville, QLD, Australia.
¹² Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
¹³ Peter MacCallum Cancer Centre, Parkville, VIC, Australia.
¹⁴ The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia.
¹⁵ Pharmacy Department, Cairns and Hinterland Hospital and Health Service, Cairns, QLD, Australia.
¹⁶ Kidney Health Service, Metro North Hospital and Health Service, Brisbane, QLD, Australia.
¹⁷ School of Pharmacy, University of Queensland, Brisbane, QLD, Australia.
¹⁸ Pharmacy Department, Austin Health, Melbourne, VIC, Australia.
¹⁹ Division of Nephrology, Ziekenhuis Oost-Limburg, Genk, Belgium.
²⁰ Department of Immunology and Infection, Biomedical Research Institute, UHasselt, Diepenbeek, Belgium.
²¹ ICON Cancer Centre, Adelaide, SA, Australia.
²² University of Adelaide, Adelaide, SA, Australia.
²³ Sydney School of Public Health, The University of Sydney, Sydney, NSW, Australia.
²⁴ Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, NSW, Australia.

PMID: 40290846
PMCID: PMC12034072
DOI: 10.1016/j.eclinm.2025.103101

Abstract

Reduced kidney function (or kidney dysfunction) is commonly an exclusion criterion for randomised controlled trials (RCTs) in cancer. Consequently, high quality evidence for anticancer drug dosing in reduced kidney function is limited and no internationally agreed guidelines exist to inform prescribing decisions in this population. A methodology for guideline development was applied which did not require availability of RCTs but used critical appraisal of existing observational literature and group consensus. An international multidisciplinary working group (n = 38) established consensus recommendations in two parts to form the International Consensus Guideline on Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD). The approach enabled virtual participation worldwide. In Part 1 we developed a standardised approach for assessment and classification of kidney function in patients with cancer using global nephrology standards and working group expertise. Part 2 involved a comprehensive literature search of 59 anticancer drugs followed by a critical appraisal of the evidence certainty through the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process and development of dosing recommendations in reduced kidney function. Key external stakeholders (n = 9) invited expert contributors (n = 25), and the working group participated in virtual interactive workshops to vote on the acceptability of these recommendations. The participants were provided with evaluation of the literature, and they engaged in several rounds of virtual discussion (involving robustness of the evidence behind recommendations and their real-world application) and anonymous consensus voting. Adapting the ADDIKD guideline development process to a virtual format enabled engagement with a very broad base of specialised international experts especially during the global pandemic. Combining GRADE methodology with consensus-building approaches was an effective method of producing recommendations (in an area lacking RCTs) by merging critical review of the literature with expert opinion and clinical practice.

Funding: Development of the ADDIKD guideline is funded by the Cancer Institute NSW as part of the NSW Government and received no funding from external commercial sources.

Keywords: Chemotherapy; Drug dosing; Haematology; Kidney dysfunction; Oncology; Pharmacokinetics; Renal.

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Conflict of interest statement

AJM reports a relationship with National Health and Medical Research Council that includes: funding grants. AJM reports a relationship with Townsville Hospital and Health Service that includes: funding grants. AJM reports a relationship with Australian Government Medical Research Future Fund that includes: funding grants. AJM reports a relationship with Queensland Government that includes: funding grants. AJM reports a relationship with Otsuka Pharmaceutical Co Ltd that includes: travel reimbursement. AJM reports a relationship with GSK that includes: travel reimbursement. AJM reports a relationship with Australia and New Zealand Society of Nephrology that includes: board membership. BS reports a relationship with Omeros Corporation that includes: consulting or advisory. BS reports a relationship with AstraZeneca Pharmaceuticals LP that includes: speaking and lecture fees and travel reimbursement. BS reports a relationship with Vifor Pharma Switzerland SA that includes: speaking and lecture fees. BS reports a relationship with Janssen Pharmaceuticals Inc that includes: speaking and lecture fees. BS reports a relationship with Boehringer Ingelheim Canada Ltd that includes: board membership and speaking and lecture fees. BS reports a relationship with MorphoSys US Inc that includes: board membership. JS reports a relationship with Roche that includes: speaking and lecture fees. JS reports a relationship with Amgen Inc that includes: speaking and lecture fees. JS reports a relationship with AbbVie Inc that includes: speaking and lecture fees. JS reports a relationship with Pfizer Inc that includes: speaking and lecture fees. JS reports a relationship with Mundipharma International Limited that includes: speaking and lecture fees. JS reports a relationship with Bristol Myers Squibb Co that includes: speaking and lecture fees. JS reports a relationship with Baxter Health that includes: speaking and lecture fees. JS reports a relationship with Becton Dickinson and Company that includes: speaking and lecture fees. JS reports a relationship with Juniper Pharmaceuticals Inc that includes: board membership. JS reports a relationship with Antengene Corporation Limited that includes: board membership. DWJ reports a relationship with Baxter Health that includes: speaking and lecture fees. DJT reports a relationship with National Health and Medical Research Council that includes: funding grants. PC reports a relationship with Pfizer Inc that includes: funding grants. PC reports a relationship with Gilead Sciences Inc that includes: funding grants, speaking and lecture fees, and travel reimbursement. SM reports a relationship with Advanced Pharmacy Australia that includes: board membership. RLW reports a relationship with Cancer Institute that includes: board membership. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

**Fig. 1**
Summary of ADDIKD guideline development.

**Fig. 2**
PRISMA diagram of studies included from the literature search.

**Fig. 3**
Example of a dose recommendations table according to kidney function.

See this image and copyright information in PMC

References

1. Canter D., Kutikov A., Manley B., et al. Utility of the R.E.N.A.L. nephrometry scoring system in objectifying treatment decision-making of the enhancing renal mass. Urology. 2011;78(5):1089–1094. - PMC - PubMed
1. Christiansen C.F., Johansen M.B., Langeberg W.J., Fryzek J.P., Sørensen H.T. Incidence of acute kidney injury in cancer patients: a Danish population-based cohort study. Eur J Intern Med. 2011;22(4):399–406. - PubMed
1. Iff S., Craig J.C., Turner R., et al. Reduced estimated GFR and cancer mortality. Am J Kidney Dis. 2014;63(1):23–30. - PubMed
1. Janus N., Launay-vacher V., Byloos E., et al. Cancer and renal insufficiency results of the BIRMA study. Br J Cancer. 2010;103(12):1815–1821. - PMC - PubMed
1. Kidney Disease Improving Global Outcomes (KDIGO) 2012. KDIGO Clinical Practice Guideline for acute kidney injury.kdigo.org/wpcontent/uploads/2016/10/KDIGO-2012-AKI-Guideline-English.pdf

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A methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney function

Affiliations

A methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney function

Authors

Affiliations

Abstract

Conflict of interest statement

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References

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