498P Association between capecitabine efficacy and proton pump inhibitors in patients with stage II-III colorectal cancer: A retrospective multicenter study

621 Title: Effects of Proton Pump Inhibitors (PPIs) on FOLFOX and XELOX Regimens in Colorectal Cancer (CRC) Background: First-line adjuvant chemotherapy options for stage II-III CRC include XELOX (capecitabine (cape), oxaliplatin) and FOLFOX (oxaliplatin, leucovorin, 5FU). Cape is an oral 5FU prodrug, and recent studies suggested that PPIs may detrimentally affect cape efficacy. Conversely, some literature posits that PPIs may negatively impact CRC itself. Our primary objective was to compare 3-year recurrence-free survival (RFS) rates between XELOX-treated PPI-users and non-PPI users, and FOLFOX-treated PPI users and non-PPI users. Our main secondary objective was to compare overall survival (OS). Methods: We conducted a retrospective chart review of 389 stage II-III CRC patients (pts) who received adjuvant XELOX or FOLFOX from a tertiary cancer center in Alberta, Canada between 2004-2013. Information regarding PPI use, cancer treatment, and pt outcomes were gathered and analyzed from pharmacy databases. Results: 23.4% of XELOX-treated pts and 28.0% of FOLFOX -treated pts used PPIs concurrently with treatment. 3-year RFS was significantly lower in XELOX-treated PPI pts than non-PPI pts (69.5 vs. 82.6%, P=0.029). Unadjusted analysis showed that XELOX-treated PPI pts were twice as likely to experience cancer recurrence or death as XELOX-treated non-PPI pts (HR 2.03, P=0.033). FOLFOX-treated PPI pts had a non-significant increase in three-year RFS versus non-PPI pts (82.9 vs. 61.7%, P=0.066), and no significant difference in recurrence or death (HR 0.51, P=0.071). No significant differences were seen in OS. Conclusions: Our results suggest that PPIs negatively impacted RFS in early-stage XELOX-treated CRC pts, and yielded no significant effect amongst FOLFOX-treated patients. Further studies are required to corroborate our findings. [Table: see text]

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Bevacizumab Efficacy Is Influenced by Primary Tumor Resection in First-Line Treatment of Metastatic Colorectal Cancer in a Retrospective Multicenter Study

Clinical Colorectal Cancer ◽

10.1016/j.clcc.2016.04.009 ◽

2016 ◽

Vol 15 (4) ◽

pp. e165-e174 ◽

Cited By ~ 4

Author(s):

Mathilde Cabart ◽

Jean-Sébastien Frénel ◽

Loïc Campion ◽

Jean-François Ramée ◽

Olivier Dupuis ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Multicenter Study ◽

Primary Tumor ◽

Tumor Resection ◽

Primary Tumor Resection ◽

Line Treatment ◽

First Line ◽

Retrospective Multicenter Study ◽

First Line Treatment

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Clinical and oncologic outcomes of laparoscopic versus open surgery in elderly patients with colorectal cancer: a retrospective multicenter study

International Journal of Clinical Oncology ◽

10.1007/s10147-021-02009-4 ◽

2021 ◽

Author(s):

Il Tae Son ◽

Jeong Yeon Kim ◽

Min Jeong Kim ◽

Byung Chun Kim ◽

Byung Mo Kang ◽

...

Keyword(s):

Colorectal Cancer ◽

Elderly Patients ◽

Multicenter Study ◽

Open Surgery ◽

Oncologic Outcomes ◽

Retrospective Multicenter Study ◽

Surgery In Elderly

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Effect of Proton Pump Inhibitors on Colorectal Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms21113877 ◽

2020 ◽

Vol 21 (11) ◽

pp. 3877 ◽

Cited By ~ 2

Author(s):

Takamitsu Sasaki ◽

Shiori Mori ◽

Shingo Kishi ◽

Rina Fujiwara-Tani ◽

Hitoshi Ohmori ◽

...

Keyword(s):

Oxidative Stress ◽

Colorectal Cancer ◽

Colon Cancer ◽

Liver Metastasis ◽

Cyclin D1 ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

Aged People ◽

Mitochondrial Volume ◽

Risk Of Cancer

Proton pump inhibitors (PPIs) are administered commonly to aged people; however, their effect on colorectal cancer (CRC) has still not been fully elucidated. Here, we examined the effect of PPIs and consequent alkalization on CRC cells. PPI administration alkalized the fecal pH and increased serum gastrin concentration. PPI and pH8 treatment (alkalization) of CMT93 mouse colon cancer cells inhibited cell growth and invasion, increased oxidative stress and apoptosis, and decreased mitochondrial volume and protein levels of cyclin D1 and phosphorylated extracellular signal-regulated kinase (pERK) 1/2. In contrast, gastrin treatment enhanced growth and invasion, decreased oxidative stress and apoptosis, and increased mitochondrial volume and cyclin D1 and pERK1/2 levels. Concurrent treatment with a PPI, pH8, and gastrin increased aldehyde dehydrogenase activity and also enhanced liver metastasis in the BALB/c strain of mice. PPI administration was associated with Clostridium perfringens enterotoxin (CPE) in CRC lesions. CPE treatment activated yes-associated protein (YAP) signals to enhance proliferation and stemness. The orthotopic colon cancer model of CMT93 cells with long-term PPI administration showed enhanced tumor growth and liver metastasis due to gastrin and YAP activation, as indicated by gastrin receptor knockdown and treatment with a YAP inhibitor. These findings suggest that PPI promotes CRC growth and metastasis by increasing gastrin concentration and YAP activation, resulting in gut flora alteration and fecal alkalization. These findings suggest that PPI use in colorectal cancer patients might create a risk of cancer promotion.

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