title: Busulfan dosing (Q6 or Q24) with adjusted or actual body weight, does it matter?
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.
authors.affiliation: Department of Clinical and Administrative Pharmacy, University of Georgia College of Pharmacy, Augusta, GA, USA Georgia Regents Cancer Center, Augusta, GA, USA aclemmons@gru.edu.
authors.forename: Amber Bradley
authors.initials: AB
authors.lastname: Clemmons
authors.affiliation: Department of Clinical and Administrative Pharmacy, University of Georgia College of Pharmacy, Augusta, GA, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Evans
authors.affiliation: Department of Clinical and Administrative Pharmacy, University of Georgia College of Pharmacy, Augusta, GA, USA Georgia Regents Cancer Center, Augusta, GA, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: DeRemer
authors.affiliation: Bone Marrow Transplant Program, Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
authors.forename: Farrukh T
authors.initials: FT
authors.lastname: Awan
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D001835:Body Weight; D002066:Busulfan / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007166:Immunosuppressive Agents; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine
keywords: Busulfan; obesity; pharmacokinetics; weight-based dosing