Inclusion of Participants with CKD and Other Kidney-Related Considerations during Clinical Drug Development

Butrovich, Morgan A.; Reaves, Allison C; Heyward, Jamie; Moore, Thomas J.; Alexander, G. Caleb; Inker, Lesley A.; Nolin, Thomas D.

doi:10.2215/cjn.0000000000000105

Cited by 10 publications

(17 citation statements)

References 19 publications

(38 reference statements)

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“…This is likely because the original trials of chemotherapeutics determine dose thresholds were based on CG estimations of CrCl. Oncology research continues to use CG in trials today 5 . For example, a 2017 research letter described a random sample of active, Phase I‐III, cisplatin‐based clinical trials and showed that only 2% of studies used eGFR to define kidney function thresholds 23 .…”

Section: Practical Considerations For Estimating Gfr In Oncologymentioning

confidence: 99%

“…While a large proportion of the studies (61%) used CG‐based estimation of CrCl or serum creatinine alone, 33% did not articulate any kidney function threshold for trial inclusion 23 . These data expose the imprecision and inconsistency of methods used to estimate kidney function in cancer clinical trials 5,23 …”

Section: Practical Considerations For Estimating Gfr In Oncologymentioning

confidence: 99%

“…Oncology research continues to use CG in trials today. 5 For example, a 2017 research letter described a random sample of active, Phase I-III, cisplatin-based clinical trials and showed that only 2% of studies used eGFR to define kidney function thresholds. 23 While a large proportion of the studies (61%) used CG-based estimation of CrCl or serum creatinine alone, 33% did not articulate any kidney function threshold for trial inclusion.…”

Section: Current Standards In Oncology Researchmentioning

confidence: 99%

“…Alternatively, under‐estimating kidney function can lead to inappropriately low drug doses or inappropriate exclusion from first‐line chemotherapies, risking poorer outcomes. Patients with chronic kidney disease (CKD), as defined by an eGFR <60 mL/min/1.73 m 2 , are commonly excluded from cancer‐related clinical trials despite representing a large fraction of patients with cancer 5 . Those with CKD were excluded from nearly 85% of recent, high‐impact chemotherapy drug trials for common malignancies 6 .…”

Section: Introductionmentioning

confidence: 99%

“…Patients with chronic kidney disease (CKD), as defined by an eGFR <60 mL/ min/1.73 m 2 , are commonly excluded from cancer-related clinical trials despite representing a large fraction of patients with cancer. 5 Those with CKD were excluded from nearly 85% of recent, high-impact chemotherapy drug trials for common malignancies. 6 This compounds the risk involved with treating cancer in patients with kidney disease, as little evidence exists.…”

Section: Introductionmentioning

confidence: 99%

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Estimating kidney function in patients with cancer: A narrative review

et al. 2023

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Aim Accurate evaluation of glomerular filtration rate (GFR) is crucial in Oncology as drug eligibility and dosing depend on estimates of GFR. However, there are no clear guidelines on the optimal method of determining kidney function in patients with cancer. We aimed to summarize the evidence on estimation of kidney function in patients with cancer. Methods We searched PubMed for literature discussing the performance of GFR estimating equations in patients with malignancy to create a table of the evidence for creatinine‐ and cystatin c‐based equations. We further reviewed novel estimation techniques such as panel eGFR, real‐time measured GFR, and functional magnetic resonance imaging. Results The commonly used GFR estimating equations were derived from populations of patients without cancer. These equations may be less applicable in Oncology due to severe sarcopenia, inflammation, and other physiologic changes in patients with cancer. The Cockcroft‐Gault equation currently dominates in clinical Oncology despite significant limitations and accumulating evidence for use of the CKD‐EPICr formula. Additional considerations in the practice of Oncology include a recently developed equation (CamGFRv2, also called the Janowitz formula) and the use of cystatin c‐based equations to overcome some of the barriers to accurate GFR estimation based on creatinine alone. Conclusion Overall, we suggest using the CKD‐EPI equations (either cystatin c or creatinine‐based) among patients with cancer in routine clinical practice and measured GFR for patients at a critical threshold for treatment decisions.

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Section: Practical Considerations For Estimating Gfr In Oncologymentioning

confidence: 99%

Section: Practical Considerations For Estimating Gfr In Oncologymentioning

confidence: 99%

Section: Current Standards In Oncology Researchmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Estimating kidney function in patients with cancer: A narrative review

et al. 2023

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Dose Optimization Informed by PBPK Modeling: State‐of‐the Art and Future

Rowland Yeo,

Gil Berglund,

Chen

2024

Clin Pharma and Therapeutics

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Model‐informed drug development (MIDD) is a powerful quantitative approach that plays an integral role in drug development and regulatory review. While applied throughout the life cycle of the development of new drugs, a key application of MIDD is to inform clinical trial design including dose selection and optimization. To date, physiologically‐based pharmacokinetic (PBPK) modeling, an established component of the MIDD toolkit, has mainly been used for assessment of drug–drug interactions (DDIs) and consequential dose adjustments in regulatory submissions. As a result of recent scientific advances and growing confidence in the utility of the approach, PBPK models are being increasingly applied to provide dose recommendations for subjects with differing ages, genetics, and disease states. In this review, we present our perspective on the current landscape of regulatory acceptance of PBPK applications supported by relevant case studies. We also discuss the recent progress and future challenges associated with expanding the utility of PBPK models into emerging areas for regulatory decision making, especially dose optimization in highly vulnerable and understudied populations and facilitating diversity in clinical trials.

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