title: A dynamic model of hand-and-foot syndrome in patients receiving capecitabine.
abstract: For the purpose of developing a longitudinal model to predict hand-and-foot syndrome (HFS) dynamics in patients receiving capecitabine, data from two large phase III studies were used. Of 595 patients in the capecitabine arms, 400 patients were randomly selected to build the model, and the other 195 were assigned for model validation. A score for risk of developing HFS was modeled using the proportional odds model, a sigmoidal maximum effect model driven by capecitabine accumulation as estimated through a kinetic-pharmacodynamic model and a Markov process. The lower the calculated creatinine clearance value at inclusion, the higher was the risk of HFS. Model validation was performed by visual and statistical predictive checks. The predictive dynamic model of HFS in patients receiving capecitabine allows the prediction of toxicity risk based on cumulative capecitabine dose and previous HFS grade. This dose-toxicity model will be useful in developing Bayesian individual treatment adaptations and may be of use in the clinic.
authors.affiliation: Université de Lyon, Lyon, France.
authors.forename: E
authors.initials: E
authors.lastname: Hénin
authors.forename: B
authors.initials: B
authors.lastname: You
authors.forename: E
authors.initials: E
authors.lastname: VanCutsem
authors.forename: P M
authors.initials: PM
authors.lastname: Hoff
authors.forename: J
authors.initials: J
authors.lastname: Cassidy
authors.forename: C
authors.initials: C
authors.lastname: Twelves
authors.forename: K P
authors.initials: KP
authors.lastname: Zuideveld
authors.forename: F
authors.initials: F
authors.lastname: Sirzen
authors.forename: C
authors.initials: C
authors.lastname: Dartois
authors.forename: G
authors.initials: G
authors.lastname: Freyer
authors.forename: M
authors.initials: M
authors.lastname: Tod
authors.forename: P
authors.initials: P
authors.lastname: Girard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000453:epidemiology; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005533:Foot Dermatoses / Q000139:chemically induced* / Q000145:classification / Q000453:epidemiology; D006229:Hand Dermatoses / Q000139:chemically induced* / Q000145:classification / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015203:Reproducibility of Results; D013577:Syndrome; D055815:Young Adult
chemical_list: D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil