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Long-Term Use of Valproic Acid May Reduce the Risk of Head and Neck Cancer

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Key Points

  • Patients taking the anticonvulsive agent valproic acid for at least 1 year had a 34% lower risk of developing head and neck cancer compared with those who did not take the medication.
  • Higher doses of the drug over a longer duration were associated with additional benefit.
  • The magnitude of the observed potential benefit of valproic acid warrants further investigation of the agent as a cancer chemoprevention therapy.

The antiseizure medication and mood stabilizer valproic acid was associated with a significant reduction in head and neck cancer risk, according to a study recently published in Cancer. The large retrospective cohort study by Kang et al was conducted to evaluate the effects of the drug, a histone deacetylase inhibitor, on the risk of developing cancers of the lung, head and neck, prostate, bladder, and colon.

Study Details

The researchers analyzed data from the U.S. Department of Veterans Affairs (VA) 2002-2008 Medical SAS Dataset linked to the VA Central Cancer Registry. Inclusion criteria for the main cohort were as follows: the presence of at least one diagnosis of a psychiatric or neurologic disease for which long-term valproic acid has an accepted clinical indication, including bipolar disorder, post-traumatic stress disorder (PTSD), migraines, or seizures; clinical follow-up of at least 1 year; current smoker or former smoker status; and at least 40 years of age at the inclusion of the cohort.

The final cohort consisted of 439,628 patients, of which 49% were current smokers and 51% were former smokers. Of these patients, 26,911 had filled prescriptions for valproic acid for bipolar disorder, PTSD, migraines, and seizures.

Multivariable Cox proportional hazards models were used to estimate hazards ratios (HR) and 95% confidence intervals (CI) reflecting the association between use of valproic acid and cancer incidence. Results from the researchers’ analysis found that veterans who took valproic acid for at least 1 year had a 34% lower risk of developing head and neck cancer compared with those who did not take the medication (HR = 0.66; 95% CI = 0.48–0.92).

Additional association was noted with the duration of treatment and median valproic acid drug levels. No significant differences were observed for lung, bladder, colon, and prostate cancer incidences.

Potential Use as a Chemoprevention Agent

“A 34% risk reduction for the development of head and neck cancer with [valproic acid] use could result in the prevention of up to approximately 16,000 new cases and 3,000 to 4,000 annual deaths in the U.S. alone,” Johann Christoph Brandes, MD, PhD, from the Atlanta Veterans Affairs Medical Center and Emory University and a coauthor of the study, said in a statement. “Head and neck cancer is an important global health crisis, and low-cost, low-toxicity prevention strategies like [valproic acid] use have a high potential impact on pain, suffering, costs, and mortality associated with this disease.”

“The extensive preclinical and clinical evidence and the magnitude of the observed potential benefit warrant further investigation of valproic acid as a cancer chemoprevention agent, possibly in patients with premalignant lesions of the head and neck,” concluded the researchers.

According to the National Cancer Institute, head and neck cancers account for approximately 3% of all cancers in the United States. These cancers are nearly twice as common among men as they are among women and are diagnosed more often in people over age 50. Alcohol and tobacco use are the two most important risk factors for head and neck cancers.

Dr. Brandes is the corresponding author for the Cancer article.

Funding for this study was supported by grants from the Department of Veterans Affairs, the Veterans Health Administration, and Office of Research and Development; the National Cancer Institute, a CHEST Foundation/LUNGevity Foundation Clinical Lung Cancer Research award, a Uniting Against Lung Cancer/LUNGevity Foundation research award, and a Sun Trust Scholar Award. Suresh S. Ramalingam, MD, received personal fees from Aveo, Ariad, Boehringer Ingelheim, Genentech, Lilly, Teva, Novartis, and AstraZeneca.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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