Effects of Proton Pump Inhibitors on FOLFOX and CapeOx Regimens in Colorectal Cancer

Grace G Wong; Vincent Ha; Michael P Chu; Deonne Dersch-Mills; Sunita Ghosh; Carole R Chambers; Michael B Sawyer

doi:10.1016/j.clcc.2018.11.001

Effects of Proton Pump Inhibitors on FOLFOX and CapeOx Regimens in Colorectal Cancer

Clin Colorectal Cancer. 2019 Mar;18(1):72-79. doi: 10.1016/j.clcc.2018.11.001. Epub 2018 Nov 16.

Authors

Grace G Wong¹, Vincent Ha¹, Michael P Chu², Deonne Dersch-Mills³, Sunita Ghosh⁴, Carole R Chambers⁵, Michael B Sawyer⁶

Affiliations

¹ Pharmacy Department, Cross Cancer Institute, Edmonton, Alberta, Canada.
² Department of Medical Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada.
³ Pharmacy Department, Alberta Children's Hospital, Calgary, Alberta, Canada.
⁴ Clinical Trials Unit, Cross Cancer Institute, Edmonton, Alberta, Canada.
⁵ Pharmacy Department, Tom Baker Cancer Centre, Calgary, Alberta, Canada.
⁶ Department of Medical Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada. Electronic address: michael.sawyer@albertahealthservices.ca.

PMID: 30551953
DOI: 10.1016/j.clcc.2018.11.001

Abstract

Background: First-line adjuvant chemotherapy options for early-stage colorectal cancer (CRC) include CapeOx (capecitabine, intravenous oxaliplatin) and FOLFOX (intravenous 5-fluorouracil, leucovorin, oxaliplatin). Capecitabine is an oral prodrug analog of 5-fluorouracil, and recent studies have suggested that proton pump inhibitors (PPIs) may detrimentally affect capecitabine efficacy. Conversely, some literature suggests that PPIs may negatively affect CRC itself. To gain insight into the nature of PPIs' effect on capecitabine and CRC, we investigated their effects on effectiveness of CapeOx versus FOLFOX chemotherapy.

Patients and methods: We conducted a retrospective chart review of 389 patients with stage II-III CRC who received adjuvant CapeOx or FOLFOX from 2004 to 2013. Information regarding PPI receipt, chemotherapy, and patient outcomes from medical records was analyzed.

Results: Three-year recurrence-free survival was significantly lower in CapeOx-treated PPI recipients than non-PPI recipients (69.5 vs. 82.6%; P = .029). Unadjusted analysis showed that CapeOx-treated PPI recipients were twice as likely to experience cancer recurrence or death as CapeOx-treated non-PPI recipients (hazard ratio = 2.03; 95% confidence interval, 1.06-3.88; P = .033). FOLFOX-treated PPI recipients had a non-statistically significant difference in 3-year recurrence-free survival versus non-PPI recipients (82.9 vs. 61.7%; P = .066) and a non-statistically significant difference in recurrence/death (hazard ratio = 0.51; 95% confidence interval, 0.25-1.06; P = .071). No significant differences were seen in overall survival between groups.

Conclusion: Our results suggest PPIs negatively affected recurrence-free survival in CapeOx-treated CRC patients and yielded no significant effects among FOLFOX-treated patients, potentially implicating a pharmacokinetic interaction between PPIs and capecitabine. No overall survival effects were seen. Given PPIs' widespread use, further studies are required to corroborate our findings.

Keywords: Absorption; Adjuvant chemotherapy; Capecitabine; Drug interaction; pH-dependent solubility.

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Capecitabine / administration & dosage
Colorectal Neoplasms / drug therapy*
Colorectal Neoplasms / pathology
Drug Interactions*
Drug Therapy, Combination
Female
Fluorouracil / administration & dosage
Follow-Up Studies
Humans
Leucovorin / administration & dosage
Male
Middle Aged
Neoplasm Recurrence, Local / drug therapy*
Neoplasm Recurrence, Local / pathology
Oxaliplatin / administration & dosage
Prognosis
Proton Pump Inhibitors / therapeutic use*
Retrospective Studies
Survival Rate

Substances

Proton Pump Inhibitors
Oxaliplatin
Capecitabine
Leucovorin
Fluorouracil