Fixed-dose capecitabine is feasible: Results from a pharmacokinetic and pharmacogenetic study in metastatic breast cancer

Michelle A. Rudek, Roisin M. Connolly, Janelle M. Hoskins, Elizabeth Garrett-Mayer, Stacie C. Jeter, Deborah K. Armstrong, John H. Fetting, Vered Stearns, Laurie A. Wright, Ming Zhao, Stanley P. Watkins, Howard L. McLeod, Nancy E. Davidson, Antonio C. Wolff

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


The pro-drug capecitabine is approved for treatment of anthracycline- and paclitaxel-resistant metastatic breast cancer. However, toxicity and large interpatient pharmacokinetic variability occur despite body surface area (BSA)-dosing. We hypothesized that a fixed-dose schedule would simplify dosing and provide an effective and safe alternative to BSA-based dosing. We conducted an open label, single-arm, two-stage study of oral capecitabine with fixed starting dose (3,000 mg total daily dose in two divided doses × 14 days q21 days) in patients with metastatic breast cancer. We correlated pharmacodynamic endpoints [e.g., efficacy (response) per RECIST and toxicity], adherence and pharmacokinetics/pharmacogenetics. Sample size of 45 patients was required to detect a 25 % response rate from null response rate of 10 % using a Simon two-stage design. Twenty-six patients were enrolled in the first-stage and 21 were evaluable after a median of four cycles of capecitabine. Two thirds of patients received either the same dose or a dose 500 mg lower than what would have been administered with a commonly used 2,000 mg/m2 BSA-dosing schedule. Eight patients had stable disease but progressed after a median of seven cycles. Despite a clinical benefit rate of 19 %, no RECIST responses were observed following the first stage and the study was closed. Dose-reductions were required for grade 2 hand-foot syndrome (28 %) and vomiting (5 %). Adherence was similar when using both patient-reported and Medication Event Monitoring System methods. High interpatient variability was observed for capecitabine and metabolite pharmacokinetics, but was not attributed to observed pharmacogenetic or BSA differences. Single agent activity of capecitabine was modest in our patients with estrogen receptor-positive or -negative metastatic breast cancer and comparable to recent studies. BSA was not the main source of pharmacokinetic variability. Fixed-dose capecitabine is feasible, and simplifies dosing.

Original languageEnglish (US)
Pages (from-to)135-143
Number of pages9
JournalBreast Cancer Research and Treatment
Issue number1
StatePublished - May 2013


  • Breast cancer
  • Capecitabine
  • Pharmacogenetics
  • Pharmacokinetics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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