Comparative pharmacokinetic study of high-dose etoposide and etoposide phosphate in patients with lymphoid malignancy receiving autologous stem cell transplantation.
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/m(2) (containing polysorbate 80 and polyethylene glycol) or etoposide phosphate (EP) at 910 mg/m(2) on days -7 and -5, prior to melphalan, 80 mg/m(2) 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 melphalan is an active preparative regimen prior to ABMT for hematologic malignancies.
Dorr
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Department of Pharmacology, The University of Arizona, Tucson, AZ, USA.
Briggs
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Kintzel
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Meyers
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Chow
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List
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D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D005047:Etoposide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006689:Hodgkin Disease / Q000188:drug therapy / Q000628:therapy; D006801:Humans; D008017:Life Expectancy; D008223:Lymphoma / Q000188:drug therapy / Q000628:therapy*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000628:therapy; D008558:Melphalan / Q000493:pharmacokinetics; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000628:therapy; D009943:Organophosphorus Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use; D033581:Stem Cell Transplantation; D013997:Time Factors; D014182:Transplantation, Autologous
D000970:Antineoplastic Agents; D009943:Organophosphorus Compounds; C061400:etoposide phosphate; D005047:Etoposide; D008558:Melphalan