Acid Reflux Medicines Improve Survival for Patients With Head and Neck Squamous Cell Carcinoma

“Proton-pump inhibitors and histamine receptor-2 antagonists are commonly and regularly administered to HNSCC patients at the University of Michigan as part of their cancer treatment to manage acid reflux and complications from conventional therapies,” said Silvana M. Papagerakis, MD, PhD, a research assistant professor in the Department of Otolaryngology-Head and Neck Surgery at the University of Michigan, Ann Arbor. “While we had suspicions that these medications might have favorable secondary effects, our study suggests that they improve overall survival after treatment for HNSCC. However, validation of these results in randomized, prospective trials is needed before we can recommend that all patients with HNSCC be treated with acid reflux medication.”

Analysis of overall survival after a median follow-up of 55 months that took into account other variables that can affect survival (including age, smoking history, and treatment) showed that patients with HNSCC taking a proton-pump inhibitor had a 45 percent decreased risk of death compared with those not taking a proton-pump inhibitor. Among those taking a histamine receptor-2 antagonist, risk of death at this time was decreased by 33 percent, compared with those not taking these acid reflux medicines.

“Although we saw differences in the degree to which overall survival was improved by proton-pump inhibitors and histamine receptor-2 antagonists, patients should not change their medications without consulting a physician,” said Papagerakis. “Moreover, histamine receptor-2 antagonists improved overall survival for patients with oral cavity cancer more than proton-pump inhibitors did.”

Papagerakis and colleagues retrospectively analyzed data from 596 patients diagnosed with HNSCC at the University of Michigan from January 2003 to November 2007. All patients had received no prior treatment for HNSCC. Among the patients, 191 used only proton-pump inhibitors after diagnosis, 83 used only histamine receptor-2 antagonists, and 136 used both at some point after diagnosis.

Although the association between treatment with histamine receptor-2 antagonists and overall survival was statistically significant when all types of histamine receptor-2 antagonist were considered together (p=0.0479), the association was lost when each histamine receptor-2 antagonist was considered individually. For the proton-pump inhibitors, a statistically significant association with overall survival was seen for omeprazole and esomeprazole (p=0.0008 and p=0.001, respectively), a trend was seen for lansoprazole (p=0.06), and no association was seen for pantoprazole (p=0.67).

“We think that the different types of proton-pump inhibitors and histamine receptor-2 antagonists may affect survival of HNSCC patients through different mechanisms,” said Papagerakis. “We are currently investigating this, and need to understand this if we are to design the optimal prospective clinical trials.”

The study was supported by funds from the National Cancer Institute/National Institute of Dental and Craniofacial Research, the American Cancer Society, and the Undergraduate Research Opportunity Program at the University of Michigan, Ann Arbor. Papagerakis declares no conflicts of interest.


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