What are the guidelines for using Proton Pump Inhibitors (PPIs) in patients with esophageal cancer?

PPI Use in Patients with Oesophageal Cancer

Proton pump inhibitors (PPIs) should be used in patients with oesophageal cancer primarily for symptom control of gastro-oesophageal reflux, with regular dose review to minimize potential long-term side effects, rather than for cancer prevention. 1

Indications for PPI Use in Oesophageal Cancer Patients

Definite Indications

• PPIs are indicated for control of reflux symptoms in patients with oesophageal cancer, particularly those with Barrett's oesophagus (BE), which is a precursor to oesophageal adenocarcinoma 1
• Patients with severe erosive esophagitis (Los Angeles Classification grade C/D) or GERD-related complications should generally continue PPI therapy 1
• Barrett's oesophagus patients should not be considered for PPI discontinuation, as PPIs may help manage the underlying condition 1

Chemopreventive Effects

• Despite some cohort studies suggesting PPI-treated patients with Barrett's oesophagus have lower rates of dysplasia and oesophageal adenocarcinoma, high-quality evidence from randomized trials (AspECT) showed high-dose PPIs had no clinically important effect on outcomes including all-cause mortality, progression to dysplasia or cancer 1
• The current evidence does not support a recommendation for using PPIs specifically to prevent progression to dysplasia and oesophageal cancer 1
• Meta-analyses have not demonstrated statistically significant chemopreventive effects of PPIs in patients with Barrett's oesophagus 2

Dosing Considerations

• Standard PPI dosing should be used for symptom control, as high-dose PPIs have not demonstrated superior outcomes in preventing cancer progression 1
• PPI dose should be reviewed regularly to assess for side effects and prevent potential long-term complications 1
• Most patients on twice-daily dosing should be considered for step down to once-daily PPI when appropriate 1

Monitoring and Safety Considerations

Important Monitoring Parameters

• Regular endoscopic surveillance is still recommended for Barrett's oesophagus patients on PPI therapy due to the risk of disease progression 1
• Symptomatic response to PPI therapy does not preclude the presence of gastric malignancy, so additional follow-up and diagnostic testing should be considered in patients with suboptimal response 3, 4
• Monitor for potential long-term side effects of PPIs, including:
  • Bone fractures (especially with high-dose, long-term therapy) 3, 4
  • Hypomagnesemia (particularly after a year of therapy) 3, 4
  • Vitamin B12 deficiency (with treatment longer than three years) 3, 4
  • Clostridium difficile-associated diarrhea 3, 4

Drug Interactions

• PPIs may decrease the efficacy of some antineoplastic agents through drug-drug interactions 5
• Consider potential interactions with chemotherapy agents when prescribing PPIs to cancer patients 5

Special Considerations

• Patients with eosinophilic esophagitis may benefit from PPI therapy as a first-line pharmacologic option, with histologic response rates of approximately 42% 1
• For patients with idiopathic pulmonary fibrosis, low-quality evidence suggests PPIs may reduce disease progression, so these patients should generally not be considered for PPI de-prescribing 1

Pitfalls and Caveats

• Long-term PPI use has been associated with increased risk of oesophageal adenocarcinoma in some observational studies, but this likely represents confounding by indication rather than causation 6
• The incidence of oesophageal adenocarcinoma appears to be low in PPI-treated Barrett's oesophagus patients compared with published series (0.31% in one long-term study) 7
• Prolonged use of PPIs and good adherence have been associated with a reduced risk of neoplastic progression in some studies, but these findings must be interpreted cautiously due to potential confounding factors 8
• PPIs should be used at the lowest effective dose for the shortest duration appropriate to the condition being treated 3, 4