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

Area of Science:

• Oncology
• Nephrology
• Clinical Pharmacology

Background:

• Reduced kidney function is a common exclusion criterion in cancer clinical trials, leading to limited evidence for anticancer drug dosing.
• No internationally agreed guidelines exist for prescribing anticancer medications to cancer patients with impaired kidney function.
• This gap necessitates the development of evidence-based recommendations to ensure safe and effective cancer treatment in this vulnerable population.

Purpose of the Study:

• To develop the International Consensus Guideline on Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD).
• To establish standardized methods for assessing kidney function in cancer patients.
• To provide dosing recommendations for anticancer drugs in patients with reduced kidney function, utilizing available evidence and expert consensus.

Main Methods:

• A guideline development methodology was employed, critically appraising observational literature and utilizing group consensus due to the lack of randomized controlled trials (RCTs).
• An international multidisciplinary working group (n=38) developed recommendations in two parts: kidney function assessment and anticancer drug dosing.
• The Grading of Recommendations Assessment, Development and Evaluation (GRADE) process was used to appraise evidence certainty, followed by virtual consensus voting by experts.

Main Results:

• A standardized approach for assessing and classifying kidney function in cancer patients was established.
• A comprehensive literature search identified evidence for 59 anticancer drugs.
• Consensus-based dosing recommendations for anticancer drugs in reduced kidney function were developed, integrating critical literature review with expert opinion.

Conclusions:

• The ADDIKD guideline provides crucial recommendations for anticancer drug dosing in patients with reduced kidney function, addressing a significant evidence gap.
• The virtual guideline development process facilitated broad international expert engagement, particularly during the COVID-19 pandemic.
• Combining GRADE methodology with consensus-building proved effective for generating recommendations in an area lacking RCTs, merging literature review with clinical expertise.