The pharmacokinetics of two etoposide (E) formulations were evaluated in patients with refractory hematologic malignancies receiving high-dose conditioning with autologous stem cell transplantation. Patients were randomized to either E at 800 mg/m2 (containing polysorbate 80 and polyethylene glycol) or etoposide phosphate (EP) at 910mg/m2 on days -7 and -5, prior to melphalan, 80 mg/m2 on day -5. On day -3, EP was repeated. Plasma E was analyzed after each formulation on days -7 and -5 to compare intrapatient pharmacokinetics. In total, 10 patients were treated: four each with multiple myeloma or Hodgkin's disease and two with non-Hodgkin's lymphoma. Mucositis was the major toxicity with seven patients. EP first produced grade 3 mucositis. There was no procedure-related mortality and eight patients remained alive 1 year post-transplant. Cumulative etoposide exposure (AUC) was slightly greater with EP (P = 0.056). Conversely, the volume of distribution was slightly, 33%, larger (P = 0.052) and clearance was increased with the E infusion (P = 0.14). As none of the differences reached statistical significance, both E formulations appear to be pharmacokinetically equivalent in the high-dose transplant setting. The combination of high-dose EP with melphatan is an active preparative regimen prior to ABMT for hematologic malignancies.
- Hematologic malignancies
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