Plasma concentrations of doxorubicin and cyclophosphamide during anthracycline-based chemotherapy in a pregnant breast cancer patient: evaluation of gestational changes.

PURPOSE: Anthracycline-based chemotherapy with doxorubicin plus cyclophosphamide (AC) is commonly used for breast cancer during the second and third trimesters of pregnancy, yet pharmacokinetic data for these drugs in pregnant patients are limited. This case report evaluates changes in the plasma concentrations of doxorubicin and cyclophosphamide during pregnancy in a breast cancer patient undergoing AC to clarify the influence of gestation on drug pharmacokinetics.

METHODS

A 39-year-old woman with stage IIA breast cancer diagnosed at 16 weeks of gestation received four cycles of AC, with doses based on her pre-pregnancy body surface area. Plasma concentrations of doxorubicin and cyclophosphamide were measured by LC-MS/MS 24 h after administration during the first and third cycles.

RESULTS

Doxorubicin concentrations were 5.5 and 8.2 ng/mL in the first and third cycles, respectively, which were lower than reported in non-pregnant patients. Cyclophosphamide concentrations were respectively 1.3 and 1.1 µg/mL, which were comparable to non-pregnant levels. No serious maternal or fetal adverse events were observed, and plasma concentrations remained stable over time.

CONCLUSION

Doxorubicin concentrations during pregnancy were 30%-60% lower than those reported in non-pregnant patients. We did not observe a gestational decline in doxorubicin concentrations between the two sampling points in this patient, likely due to gestational changes in factors that can influence pharmacokinetic parameters (e.g., persistent P-glycoprotein upregulation). Cyclophosphamide pharmacokinetics remained unchanged. Although further studies are needed to confirm the optimal dosing and safety, these findings suggest that AC with pre-pregnancy body surface area-based dosing may be feasible in pregnant patients.