Busulfan dosing (Q6 or Q24) with adjusted or actual body weight, does it matter?

Amber Bradley Clemmons, Sarah Evans, David L. Deremer, Farrukh T. Awan

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background In hematopoietic stem cell transplantation (HSCT), patients receive individualized treatment planning in conditioning regimens to prevent unwarranted toxicities while maximizing desired outcomes. The dose of a widely studied agent in this setting, busulfan, can be adjusted based on area under the curve (AUC); however, choice of actual body weight (ABW) versus adjusted body weight (DBW) weight to calculate the initial dose may be critical in attaining goal AUC. Objective To determine which weight best correlates with achievement of goal AUC for patients receiving busulfan conditioning for HSCT. Secondary objectives include evaluation of AUC results with clinical outcomes such as toxicity and survival. Methods An institutional review board-approved retrospective analysis was performed on 31 allogeneic HSCT recipients who received intravenous busulfan (Q6H with cyclophosphamide [Bu/Cy] or once daily with fludarabine [Flu/Bu]). Results Eighteen patients received Flu/Bu (50% ABW, 50% DBW) and 13 received Bu/Cy (23% ABW, 77% DBW). Overall, patients dosed by DBW were more likely to undershoot goal AUC ('12.8% vs. +19.5%, p = 0.018) and require dose increases (+20% vs. '19.9%, p = 0.012) versus those dosed by ABW. Subgroup analysis confirmed these results for Bu/Cy ('23.6% vs. +2.2%, p < 0.001 for goal AUC; +36.2% vs. '4.5%, p = 0.008 for busulfan dose increase), but not Flu/Bu ('0.8% vs. +25.3%, p = 0.123 for goal AUC; +3.4% vs. '25.1%, p = 0.174 for busulfan dose increase). Time to engraftment, progression-free survival, and overall survival were not different between dosing groups (p > 0.05). No patient experienced busulfan-related toxicity. Conclusions Further prospective studies are warranted to elucidate which weight is most likely to achieve goal AUC and subsequent optimal patient outcomes.

Original languageEnglish (US)
Pages (from-to)425-432
Number of pages8
JournalJournal of Oncology Pharmacy Practice
Volume21
Issue number6
DOIs
StatePublished - Dec 1 2015
Externally publishedYes

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Busulfan
Area Under Curve
Body Weight
Hematopoietic Stem Cell Transplantation
Weights and Measures
Research Ethics Committees
Cyclophosphamide
Prospective Studies
Survival

Keywords

  • Busulfan
  • obesity
  • pharmacokinetics
  • weight-based dosing

ASJC Scopus subject areas

  • Oncology
  • Pharmacology (medical)

Cite this

Busulfan dosing (Q6 or Q24) with adjusted or actual body weight, does it matter? / Clemmons, Amber Bradley; Evans, Sarah; Deremer, David L.; Awan, Farrukh T.

In: Journal of Oncology Pharmacy Practice, Vol. 21, No. 6, 01.12.2015, p. 425-432.

Research output: Contribution to journalArticle

Clemmons, Amber Bradley ; Evans, Sarah ; Deremer, David L. ; Awan, Farrukh T. / Busulfan dosing (Q6 or Q24) with adjusted or actual body weight, does it matter?. In: Journal of Oncology Pharmacy Practice. 2015 ; Vol. 21, No. 6. pp. 425-432.
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abstract = "Background In hematopoietic stem cell transplantation (HSCT), patients receive individualized treatment planning in conditioning regimens to prevent unwarranted toxicities while maximizing desired outcomes. The dose of a widely studied agent in this setting, busulfan, can be adjusted based on area under the curve (AUC); however, choice of actual body weight (ABW) versus adjusted body weight (DBW) weight to calculate the initial dose may be critical in attaining goal AUC. Objective To determine which weight best correlates with achievement of goal AUC for patients receiving busulfan conditioning for HSCT. Secondary objectives include evaluation of AUC results with clinical outcomes such as toxicity and survival. Methods An institutional review board-approved retrospective analysis was performed on 31 allogeneic HSCT recipients who received intravenous busulfan (Q6H with cyclophosphamide [Bu/Cy] or once daily with fludarabine [Flu/Bu]). Results Eighteen patients received Flu/Bu (50{\%} ABW, 50{\%} DBW) and 13 received Bu/Cy (23{\%} ABW, 77{\%} DBW). Overall, patients dosed by DBW were more likely to undershoot goal AUC ('12.8{\%} vs. +19.5{\%}, p = 0.018) and require dose increases (+20{\%} vs. '19.9{\%}, p = 0.012) versus those dosed by ABW. Subgroup analysis confirmed these results for Bu/Cy ('23.6{\%} vs. +2.2{\%}, p < 0.001 for goal AUC; +36.2{\%} vs. '4.5{\%}, p = 0.008 for busulfan dose increase), but not Flu/Bu ('0.8{\%} vs. +25.3{\%}, p = 0.123 for goal AUC; +3.4{\%} vs. '25.1{\%}, p = 0.174 for busulfan dose increase). Time to engraftment, progression-free survival, and overall survival were not different between dosing groups (p > 0.05). No patient experienced busulfan-related toxicity. Conclusions Further prospective studies are warranted to elucidate which weight is most likely to achieve goal AUC and subsequent optimal patient outcomes.",
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N2 - Background In hematopoietic stem cell transplantation (HSCT), patients receive individualized treatment planning in conditioning regimens to prevent unwarranted toxicities while maximizing desired outcomes. The dose of a widely studied agent in this setting, busulfan, can be adjusted based on area under the curve (AUC); however, choice of actual body weight (ABW) versus adjusted body weight (DBW) weight to calculate the initial dose may be critical in attaining goal AUC. Objective To determine which weight best correlates with achievement of goal AUC for patients receiving busulfan conditioning for HSCT. Secondary objectives include evaluation of AUC results with clinical outcomes such as toxicity and survival. Methods An institutional review board-approved retrospective analysis was performed on 31 allogeneic HSCT recipients who received intravenous busulfan (Q6H with cyclophosphamide [Bu/Cy] or once daily with fludarabine [Flu/Bu]). Results Eighteen patients received Flu/Bu (50% ABW, 50% DBW) and 13 received Bu/Cy (23% ABW, 77% DBW). Overall, patients dosed by DBW were more likely to undershoot goal AUC ('12.8% vs. +19.5%, p = 0.018) and require dose increases (+20% vs. '19.9%, p = 0.012) versus those dosed by ABW. Subgroup analysis confirmed these results for Bu/Cy ('23.6% vs. +2.2%, p < 0.001 for goal AUC; +36.2% vs. '4.5%, p = 0.008 for busulfan dose increase), but not Flu/Bu ('0.8% vs. +25.3%, p = 0.123 for goal AUC; +3.4% vs. '25.1%, p = 0.174 for busulfan dose increase). Time to engraftment, progression-free survival, and overall survival were not different between dosing groups (p > 0.05). No patient experienced busulfan-related toxicity. Conclusions Further prospective studies are warranted to elucidate which weight is most likely to achieve goal AUC and subsequent optimal patient outcomes.

AB - Background In hematopoietic stem cell transplantation (HSCT), patients receive individualized treatment planning in conditioning regimens to prevent unwarranted toxicities while maximizing desired outcomes. The dose of a widely studied agent in this setting, busulfan, can be adjusted based on area under the curve (AUC); however, choice of actual body weight (ABW) versus adjusted body weight (DBW) weight to calculate the initial dose may be critical in attaining goal AUC. Objective To determine which weight best correlates with achievement of goal AUC for patients receiving busulfan conditioning for HSCT. Secondary objectives include evaluation of AUC results with clinical outcomes such as toxicity and survival. Methods An institutional review board-approved retrospective analysis was performed on 31 allogeneic HSCT recipients who received intravenous busulfan (Q6H with cyclophosphamide [Bu/Cy] or once daily with fludarabine [Flu/Bu]). Results Eighteen patients received Flu/Bu (50% ABW, 50% DBW) and 13 received Bu/Cy (23% ABW, 77% DBW). Overall, patients dosed by DBW were more likely to undershoot goal AUC ('12.8% vs. +19.5%, p = 0.018) and require dose increases (+20% vs. '19.9%, p = 0.012) versus those dosed by ABW. Subgroup analysis confirmed these results for Bu/Cy ('23.6% vs. +2.2%, p < 0.001 for goal AUC; +36.2% vs. '4.5%, p = 0.008 for busulfan dose increase), but not Flu/Bu ('0.8% vs. +25.3%, p = 0.123 for goal AUC; +3.4% vs. '25.1%, p = 0.174 for busulfan dose increase). Time to engraftment, progression-free survival, and overall survival were not different between dosing groups (p > 0.05). No patient experienced busulfan-related toxicity. Conclusions Further prospective studies are warranted to elucidate which weight is most likely to achieve goal AUC and subsequent optimal patient outcomes.

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KW - pharmacokinetics

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