Summary:
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 910 mg/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 melphalan is an active preparative regimen prior to ABMT for hematologic malignancies.
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Acknowledgements
This study was supported in part by a grant from Bristol Myers Oncology Division, Plainsboro, NJ and by Grant CA-23074 from the National Cancer Institute, Bethesda, MD and supported in part by a grant from Bristol Myers Squibb, Oncology Section, Princeton, NJ USA (AB) and by Grants CA17094 (RTD), CA23078 (RTD) from National Cancer Institute, National Institutes of Health, Bethesda, MD USA.
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Dorr, R., Briggs, A., Kintzel, P. et al. Comparative pharmacokinetic study of high-dose etoposide and etoposide phosphate in patients with lymphoid malignancy receiving autologous stem cell transplantation. Bone Marrow Transplant 31, 643–649 (2003). https://doi.org/10.1038/sj.bmt.1703906
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DOI: https://doi.org/10.1038/sj.bmt.1703906