Purpose: We report a patient with renal insufficiency
(creatinine clearance, CLcr = 38 mL/min) who received
high-dose chemotherapy with cyclophosphamide (1,500
mg/m2 day-1), thiotepa (120 mg/m2 day-1) and carboplatin
(AUC = 5 mg min/mL day-1) for four consecutive days.
Methods: Blood samples were collected on day 1 and 3
and plasma levels of cyclophosphamide, its active metabolite
4-hydroxycyclophosphamide, thiotepa, its main metabolite
tepa and carboplatin were determined.
Results: Pharmacokinetic analyses indicated that the
elimination of cyclophosphamide, thiotepa, carboplatin, but
especially tepa was strongly reduced in this patient,
resulting in increased exposures to these compounds of 67,
43, 30 and 157%, respectively, compared to a reference
population (n = 24) receiving similar doses. Exposure to
4-hydroxycyclophosphamide increased 11%.
Conclusion: These results suggest that it may not be necessary
to alter the dose of cyclophosphamide in patients
with moderate renal impairment. However, because high
exposures to thiotepa and tepa have been correlated with
increased toxicity, caution should be applied when administering
thiotepa to patients with renal insuYciency