title: Concomitant Administration of Proton Pump Inhibitors and Capecitabine is Associated With Increased Recurrence Risk in Early Stage Colorectal Cancer Patients.
abstract: Capecitabine is used to treat colorectal (CRC) cancer. TRIO-013, a study examining capecitabine/oxaliplatin ± lapatinib in metastatic gastro-esophageal cancer did not show increases in overall survival (OS) with lapatinib. An analysis showed concurrent proton pump inhibitor (PPI) usage negatively impacted recurrence-free survival (RFS). We retrospectively studied PPI effects on capecitabine efficacy in early stage CRC and how capecitabine adjustments impacted RFS.
  
  
  
  Early stage CRC patients taking monotherapy capecitabine treated from 2008 to 2012 were reviewed for demographics, medications, toxicities, and patient outcomes.
  
  
  
  Of 298 identified patients, 25.8% (n = 77) received concurrent PPIs. Five-year RFS was 74% versus 83% (hazard ratio [HR], 1.89; 95% confidence interval [CI], 1.07-3.35; P = .03) in PPI versus non-PPI patients respectively. OS was 81% versus 78%, respectively (HR, 1.13; 95% CI, 0.60-2.14; P = .7). After accounting for gender, stage, age, and performance status, PPI patients tended toward decreased RFS (HR, 1.65; 95% CI, 0.93-2.94; P = .09). Capecitabine dose modifications affected outcomes. Five-year RFS was 84% in the control group, 100% in the treatment-delay group (P = .99), 67% in the dose reduction group (HR, 2.46; 95% CI, 1.23-4.93; P = .01), and 64% in the discontinuation group (HR, 2.27; 95% CI, 0.93-5.53; P = .07). Five-year OS was significantly less in the discontinuation group than control group (59% vs. 82%; HR, 3.27; 95% CI, 1.44-7.45; P = .005).
  
  
  
  PPIs appear to impact RFS; this may be due to PPIs preventing capecitabine tablet dissolution and absorption. Patients with dose reductions or who stopped treatment had worse outcomes than patients who continued with treatment at starting doses.
authors.affiliation: Department of Medical Oncology, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta, Canada.
authors.forename: Julia
authors.initials: J
authors.lastname: Sun
authors.affiliation: Pharmacy Department, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta, Canada.
authors.forename: Alastair I
authors.initials: AI
authors.lastname: Ilich
authors.affiliation: Department of Medical Oncology, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta, Canada.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Kim
authors.affiliation: Department of Medical Oncology, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta, Canada.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Chu
authors.affiliation: Pharmacy Department, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta, Canada.
authors.forename: Grace G
authors.initials: GG
authors.lastname: Wong
authors.affiliation: Clinical Trials Unit, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta, Canada.
authors.forename: Sunita
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Pharmacy Department, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta, Canada.
authors.forename: Melanie
authors.initials: M
authors.lastname: Danilak
authors.affiliation: Department of Medical Oncology, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta, Canada.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Mulder
authors.affiliation: Department of Medical Oncology, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta, Canada.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Spratlin
authors.affiliation: Pharmacy Department, Tom Baker Cancer Centre, Calgary, Alberta, Canada.
authors.forename: Carole R
authors.initials: CR
authors.lastname: Chambers
authors.affiliation: Department of Medical Oncology, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta, Canada. Electronic address: michael.sawyer@albertahealthservices.ca.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Sawyer
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000069287:Capecitabine / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000401:mortality; D016016:Proportional Hazards Models; D054328:Proton Pump Inhibitors / Q000009:adverse effects*; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents; D054328:Proton Pump Inhibitors; D000069287:Capecitabine
keywords: Adjuvant chemotherapy; Dose modification; Pharmacokinetics; Toxicity; pH dependent solubility