title: Comparative pharmacokinetic study of high-dose etoposide and etoposide phosphate in patients with lymphoid malignancy receiving autologous stem cell transplantation.
abstract: 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.
authors.affiliation: Department of Pharmacology, The University of Arizona, Tucson, AZ, USA.
authors.forename: R T
authors.initials: RT
authors.lastname: Dorr
authors.forename: A
authors.initials: A
authors.lastname: Briggs
authors.forename: P
authors.initials: P
authors.lastname: Kintzel
authors.forename: R
authors.initials: R
authors.lastname: Meyers
authors.forename: H-H S
authors.initials: HH
authors.lastname: Chow
authors.forename: A
authors.initials: A
authors.lastname: List
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D009943:Organophosphorus Compounds; C061400:etoposide phosphate; D005047:Etoposide; D008558:Melphalan