title: Characterization of the long-term pharmacokinetics of bevacizumab following last dose in patients with resected stage II and III carcinoma of the colon.
abstract: OBJECTIVE
  The study characterizes the long-term pharmacokinetics (PK) following last dose of bevacizumab as adjuvant therapy in patients with resected stage II and III colon carcinoma in a Phase III clinical study (AVF3077s).
  
  
  METHODS
  Patients in AVF3077s received bevacizumab (5 mg/kg every 2 weeks) as adjuvant therapy for 1 year. Following the last dose bevacizumab concentration, data at 3 and 6 months were used to characterize long-term bevacizumab PK based on the population-modeling approach.
  
  
  RESULTS
  The long-term bevacizumab PK were consistent with previously reported results based on short-term bevacizumab PK. The clearance (CL), central volume of distribution (V(1)), intercompartmental clearance (Q), and the peripheral volume of distribution (V(2)) were 214 mL/day, 2,830 mL, 636 mL/day, and 2,490 mL, which correspond to a disposition and elimination half-life of 1.33 and 19.1 days, respectively. The empirical Bayes estimates of median post-treatment bevacizumab drug levels at 3 and 6 months were 6.14 and 0.23 μg/mL, respectively. For test covariates, the change in CL and V(1) of bevacizumab was less than 20% of the typical value. Body weight is the important covariate explaining the inter-individual variability on CL and V(1).
  
  
  CONCLUSIONS
  Long-term bevacizumab PK in this study was predictable based on short-term PK data from metastatic settings in other tumor types. An exploratory analysis demonstrated no apparent association of the tested covariates with bevacizumab PK. Further, the extended serum persistence of bevacizumab following last dose should be considered in clinical study designs and post-treatment evaluations that may be affected by bevacizumab.
authors.affiliation: Genentech, Inc., South San Francisco, CA, USA. jingli101@gmail.com
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Manish
authors.initials: M
authors.lastname: Gupta
authors.forename: Denise
authors.initials: D
authors.lastname: Jin
authors.forename: Yan
authors.initials: Y
authors.lastname: Xin
authors.forename: Jennifer
authors.initials: J
authors.lastname: Visich
authors.forename: David E
authors.initials: DE
authors.lastname: Allison
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001499:Bayes Theorem; D000068258:Bevacizumab; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000601:surgery; D003131:Combined Modality Therapy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D002955:Leucovorin; D005472:Fluorouracil