Evaluation for pharmacokinetic exposure of cytotoxic anticancer drugs in elderly patients receiving (R-)CHOP therapy

Abstract

(R-)miniCHOP therapy, which delivers approximately half-doses of the (R-)CHOP regimen, has shown efficacy and safety in patients who are more than 80 years old. This study aimed to compare the area under the plasma concentration-time curves (AUCs) of vincristine (VCR), doxorubicin (DXR), and cyclophosphamide (CPA) between (R-)CHOP and (R-)miniCHOP regimens. The AUCs were compared between patients aged 65-79 years receiving (R-)CHOP therapy and those aged 80 years and older receiving (R-)miniCHOP therapy. Age was not an independent variable for predicting the dose-adjusted AUCs (AUC/Ds) of cytotoxic anticancer drugs. The median AUCs of DXR and CPA were significantly smaller in the (R-)miniCHOP group than in the (R-)CHOP group (168.7 vs. 257.9 ng h/mL, P = 0.003, and 219.9 vs. 301.7 µg h/mL, P = 0.020, respectively). The median AUCs of VCR showed the same trend but the difference was not significant (24.83 vs. 34.85 ng h/mL, P = 0.135). It is possible that the AUCs of VCR, DXR, and CPA in patients aged 80 years and older receiving (R-)miniCHOP therapy may be lower than those in patients 65-79 years old receiving (R-)CHOP therapy.

Figure 1

Concentration–time curve of cytotoxic anticancer drugs. (a) Linear- and (b) logarithmic-scale concentration–time curves of vincristine (circle), doxorubicin (triangle), and cyclophosphamide (square). Each point is presented as a mean ± standard deviation.

Figure 2

Comparison of AUC of cytotoxic anticancer drugs between (R-)CHOP and (R-)miniCHOP groups. a vincristine; b doxorubicin; c cyclophosphamide. The box spans data between 2 quartiles (interquartile range [IQR]), with the median represented as a bold horizontal line. The ends of the whiskers (vertical lines) represent the smallest and largest values that were not outliers. Outliers (circles) are values between 1.5 and 3 IQRs from the end of the box. Values more than 3 IQRs from the end of the box are defined as extreme (asterisk). AUC, area under the plasma concentration–time curve; AUC of vincristine and doxorubicin, AUC_1.5–25.5; AUC of cyclophosphamide, AUC_1–25; ^☨P < 0.05.

Figure 3

CHOP regimen and blood sampling protocol. AUC, area under the plasma concentration–time curve; CPA, cyclophosphamide; dIV, drip infusion into vein; DXR, doxorubicin; PSL, prednisolone; VCR, vincristine.