Doxorubicin and cyclophosphamide have no clinically relevanteffects on pharmacokinetics of oral or intravenous etoposide.Methotrexate and procarbazine do not affect pharmacokinetics of oral etoposide
Clinical evidence,mechanism, importance and management
A pharmacokinetic study in 7 patients with small-cell lung cancer (SCLC) treated with cyclophosphamide 800 mg/m(See reference number 2), doxorubicin 40 mg/m(See reference number 2) and etoposide 100 mg/m(See reference number 2) (all given intravenously) found that protein binding, metabolism and renal clearance of etoposide were unaffected by other antineoplastics (See reference number 1). Similarly, another study found only modest changes in pharmacokinetics of intravenous etoposide when it was given with cyclophosphamide and doxorubicin, compared with use alone, and these changes were considered unlikely to be clinically relevant. Specifically, AUC of etoposide was 9 % higher and clearance was 10 % lower on day 1 of CAE cycle (cyclophosphamide, doxorubicin, and etoposide) compared with days 2 and 3 (etoposide alone) (See reference number 2). This is a commonly used regimen,and these data suggest there is no pharmacokinetic interaction.
Similarly,no changes in etoposide pharmacokinetics were seen when oral etoposide 100mg was given immediately after oral cyclophosphamide 100 mg/m(See reference number 2) and methotrexate 12.5 mg/m(See reference number 2)in 8 patients with SCLC. In addition, no changes were seen when same dose of oral etoposide was given 15 minutes after intravenous doxorubicin 35 mg/m(See reference number 2) and oral procarbazine 60 mg/m(See reference number 2).(See reference number 3) Oral etoposide pharmacokinetics appear not to be affected by these antineoplastics.
For lack of effect of platinum derivatives, see Etoposide + Cisplatin or Carboplatin interaction.
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