Daily busulfan plus melphalan and autologous stem cell transplantation for high-risk solid tumors: pharmacokinetic studies and clinical results

A. M. Yeager, C. Qsowski, R. Mullins, C. Kaplan, M. Bover, S. Devine, K. Forte, M. Lauer, M. Mogul, E. Oison, T. Oison, C. Turner, R. Vega

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Abstract

The lack of effective preparative regimens limits the treatment of highrisk solid tumors by autologous stem cell transplantation (ASCT). We evaluated ASCT after single dairy dose busulfan (BU; 160 mg/W/dose p.o. x 4 days) and melphalan (MEL; 140 mg/m2 i.v. x 1) and determined BU pharmacokinetics in 10 patients (pis) (median age, 15 yr; range, 3-47) with relapsed or refractory Ewing's sarcoma (2), neuroblastoma (1), osteosarcoma (1), ovarian dysgerminoma (1), seminoma (1), testicular carcinoma (1), primitive neuroectodermal tumor (1), Wilms' tumor (1), or hepatoblastoma (1). Pts received ASCT with bone marrow (3 pts), peripheral blood progenitor cells (4 pts), or both (3 pts). Median peak BU concentrations were 6.96 umol/L (range, 3.77-11.31) in the 4 pédiatrie pts and 12.63 umol/L (range, 6.55-18.23) in the 6 adult pts (P=NS; Wilcoxon rank-sum test). Median BU area under the curve (AUC) was 1S36 umol/L.min (range, 1623-3SS8) in pédiatrie pts and 4856 umol/L.min (range, 2571-7470) in adult pts (P<0.01, Wilcoxon rank-sum test). Median BU half-life was 129 min (range, 114-148) in pédiatrie pts and 174 min (range, 102-214) in adults (P=NS). All pts developed mucositis but none developed hepatic veno-occlusive disease. Median time to ANOO.S x lO'/L was 11 days (range, 10-17) and to platelets >20 x lO'/L was 17 days (range, 11-21) post-ASCT. Two pts (1 neuroblastoma, 1 osteosarcoma) relapsed at 3 and 5 months, respectively, after ASCT and died with progressive tumor. Eight pts remain in remission at a median of 8 months (range, 1.5-17.5+) after ASCT. Our findings demonstrate significantly different BU AUCs between pédiatrie and adult pts given daily body surface area-based BU dosing. Daily BU plus MEL and ASCT is a well-tolerated regimen that may provide durable relapsefree survival in pts with refractory solid tumors.

Original languageEnglish (US)
Number of pages1
JournalExperimental Hematology
Volume25
Issue number8
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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    Yeager, A. M., Qsowski, C., Mullins, R., Kaplan, C., Bover, M., Devine, S., Forte, K., Lauer, M., Mogul, M., Oison, E., Oison, T., Turner, C., & Vega, R. (1997). Daily busulfan plus melphalan and autologous stem cell transplantation for high-risk solid tumors: pharmacokinetic studies and clinical results. Experimental Hematology, 25(8).