Narrow Therapeutic Index Chemotherapy Dosing With eGFR: Safeguards for Oncology Pharmacists

In this National Kidney Foundation (NKF) panel, Andrew Bzowyckyj, PharmD, BCPS, CDCES, senior scientific director and learning consultant at NKF, is joined by 2 clinical pharmacists:

• Angie Maynard, PharmD, MS, BCOP, assistant professor at the Lipscomb University College of Pharmacy and Health Sciences in Nashville, Tennessee;
• and Rachel Pokorny, PharmD, BCPS, BCOP, clinical pharmacy specialist in neuro-oncology and the director of the PGY2 oncology pharmacy residency program at Vanderbilt University Medical Center in Nashville, Tennessee.

In this second segment, the 3 experts discussed how the shift to race-agnostic estimated glomerular filtration rate (eGFR) affects narrow therapeutic index agents, such as carboplatin, cisplatin, and methotrexate, as well as supportive care drugs such as acyclovir and trimethoprim-sulfamethoxazole. Maynard suggested that pharmacists should compare results from the new and old equations and look for differences of more than 10%. They should also consider whether a new dose fits the patient’s history of dose delays or cytopenias, whether it moves the patient across a dose-adjustment threshold, a chronic kidney disease category, or a clinical trial eligibility cutoff, and whether efficacy could suffer.

Pokorny described 3 safeguards:

First, cross-compare estimates. When values are similar and kidney function is stable, eGFR can likely be used in place of Cockcroft-Gault. For narrow therapeutic index drugs, though, pharmacists should check the primary literature. Carboplatin is a good example of mixed guidance: National Comprehensive Cancer Network guidelines recommend Cockcroft-Gault in the Calvert formula, whereas the International Consensus Guideline for Anticancer Drug Dosing in Kidney Dysfunction recommends non–race-based eGFR.

Second, when data are limited or the estimates disagree, decide the dose together with the treating team.

Third, use caution in patients who are more likely to get an inaccurate estimate, including those who have underweight or overweight, have had amputations, have muscle wasting, or have rapidly changing kidney function. Pokorny recommended that pharmacists should clearly document which equation they used so the dose stays consistent from one clinician to the next.

The panel also covered cystatin C, which eGFR-based dosing makes easier to use. Maynard said her safety-net hospital does not currently collect it, because it is a send-out lab with an extra fee. She sees it as a possible baseline lab, especially for those with multiple myeloma. More than 40% of patients with myeloma have altered kidney function at diagnosis, and some data link cystatin C levels to myeloma outcomes. She noted that cancer itself can falsely raise cystatin C. Pokorny said she has used cystatin C to tell whether a rise in serum creatinine caused by an oral tyrosine kinase inhibitor reflects true kidney decline. Bzowyckyj noted that rapid cell turnover and systemic inflammation also affect cystatin C. He said labs should be ordered with care, and only when the results will change management.

Learn more about the National Kidney Foundation at kidney.org and at this link.