Comparative pharmacokinetic study of high-dose etoposide and etoposide phosphate in patients with lymphoid malignancy receiving autologous stem cell transplantation

Robert T Dorr, A. Briggs, P. Kintzel, R. Meyers, Hsiao-Hui Chow, A. List

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5 Citations (Scopus)

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/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.

Original languageEnglish (US)
Pages (from-to)643-649
Number of pages7
JournalBone Marrow Transplantation
Volume31
Issue number8
DOIs
StatePublished - Apr 2003

Fingerprint

Stem Cell Transplantation
Etoposide
Pharmacokinetics
Mucositis
Hematologic Neoplasms
Neoplasms
Transplants
Melphalan
Polysorbates
Multiple Myeloma
Hodgkin Disease
Non-Hodgkin's Lymphoma
Area Under Curve
etoposide phosphate
Mortality

Keywords

  • Etoposide
  • Hematologic malignancies
  • Pharmacokinetics

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

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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/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.",
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author = "Dorr, {Robert T} and A. Briggs and P. Kintzel and R. Meyers and Hsiao-Hui Chow and A. List",
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T1 - Comparative pharmacokinetic study of high-dose etoposide and etoposide phosphate in patients with lymphoid malignancy receiving autologous stem cell transplantation

AU - Dorr, Robert T

AU - Briggs, A.

AU - Kintzel, P.

AU - Meyers, R.

AU - Chow, Hsiao-Hui

AU - List, A.

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N2 - 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.

AB - 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.

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