Key result
A multivariable model including body surface area, age, glomerular filtration rate, and albumin explained 17.1% of the variation in cyclophosphamide exposure (assessed via PAM-Hb), significantly outperforming body surface area alone.
Why the study?
Cyclophosphamide dosing by body surface area has been questioned as a predictor for individual drug exposure.
Does a multivariable model including BSA, age, GFR, and albumin better predict cyclophosphamide exposure (PAM-Hb) than BSA alone in breast cancer patients?
Observational (n=135)
Yes
Does a multivariable model including BSA, age, GFR, and albumin better predict cyclophosphamide exposure (PAM-Hb) than BSA alone in breast cancer patients?
Effect estimate: 17.1% explained variance
p-value: p=<0.001
Cyclophosphamide dosing based solely on body surface area results in significant inter-individual variation in exposure, which can be better predicted by incorporating age, GFR, and albumin.
Substantial PAM-Hb variability despite BSA dosing supports considering age, GFR and albumin for initial CPA dosing; leaves open impact on outcomes in breast cancer.
Cyclophosphamide (CPA) dosing by body surface area (BSA, m 2 ) has been questioned as a predictor for individual drug exposure. This study investigated phosphoramide mustard-hemoglobin (PAM-Hb, pmol g −1 Hb) as a biomarker of CPA exposure in 135 female breast cancer patients receiving CPA during three courses based on BSA: 500 mg/m 2 (C500 group, n = 67) or 600 mg/m 2 (C600 group, n = 68). The inter-individual difference was calculated for both groups by dividing the highest through the lowest PAM-Hb value of each course. The inter-occasion difference was calculated in percentage for each individual by dividing their PAM-Hb value through the group mean per course, and subsequently dividing this ratio of the latter through the previous course. A multivariable linear regression (MLR) was performed to identify factors that explained the variation of PAM-Hb. During the three courses, the inter-individual difference changed from 3.5 to 2.1 and the inter-occasion difference ranged between 13.3% and 11.9% in the C500 group. In the C600 group, the inter-individual difference changed from 2.7 to 2.9 and the inter-occasion difference ranged between 14.1% and 11.7%. The MLR including BSA, age, GFR, and albumin explained 17.1% of the variation of PAM-Hb and was significantly better then the model including only BSA. These factors should be considered when calculating the first dose of CPA for breast cancer patients.
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Gernaat et al. (2021) conducted an observational in Breast cancer (n=135). Cyclophosphamide vs. Body surface area alone was evaluated on Variation of PAM-Hb explained by multivariable linear regression model (17.1% explained variance, p=<0.001). A multivariable model including body surface area, age, glomerular filtration rate, and albumin explained 17.1% of the variation in cyclophosphamide exposure (assessed via PAM-Hb), significantly outperforming body surface area alone.
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