Researchers find that certain cancer cell lines are more sensitive to NSAID treatment

Nonsteroidal anti-inflammatory drugs, or NSAIDs, improved the overall five-year survival rate from 25% to 78% for patients whose cancer contained a specific altered gene, known as PIK3CA, report the researchers. The survival of patients whose gene was not altered in their tumor was not affected by the use of NSAIDs.

This is the first study to show a strong clinical benefit of regular NSAID use in patients with head and neck cancer with mutations in the PIK3CA gene and may indicate a clear biological reason to implement NSAID therapy in some cases of the disease, the authors said.

The article is published on January 25, 2019 in the Journal of Experimental Medicine.

“Our results suggest that the use of NSAIDs could significantly improve outcomes not only for patients with head and neck cancer, but also for patients with other cancers containing the PIK3CA mutation,” said Jennifer R. Grandis, MD, UCSF professor of otolaryngology, head, and neck surgery and senior author of the paper.

“The magnitude of the apparent benefit is strong and could potentially positively impact human health,” Grandis said.

In squamous cell carcinoma of the head and neck, PIK3CA is the most commonly altered oncogene, with 34% of all tumors harboring mutations that activate the PIK3CA uncomfortable. In head and neck cancer associated with human papillomavirus (HPV), PIK3CA is mutated in more than half of tumors.

Squamous cell carcinoma of the head and neck is a complex malignancy with a poor prognosis: the five-year survival rate is approximately 45%. According to the American Cancer Society, head and neck cancer accounts for about 4% of all cancers in the United States, with approximately 65,000 people developing it each year.

Although the disease can occur in young people, most patients are over 50 at the time of diagnosis. Major risk factors include smoking, alcohol consumption, and HPV infection.

NSAIDs, which include over-the-counter medications such as ibuprofen and aspirin, are known to relieve pain and reduce inflammation, fever, and blood clots. These are the most commonly prescribed medications for conditions such as arthritis.

In the new research, 266 patients at the University of Pittsburgh Medical Center whose tumors were surgically removed were studied by the study authors. The majority (84%) smoked and 67% received postoperative chemotherapy and/or radiotherapy. Median overall survival was 66 months.

A total of 75 tumors (28%) in the study had an activating alteration of PIK3CA uncomfortable.

Of the patients who regularly used NSAIDs, 93% used aspirin as a component of the NSAID regiment and 73% took aspirin exclusively. Most regular users started aspirin therapy after their diagnosis of head and neck cancer.

Investigators learned that regular use of NSAIDs for at least six months provided “significantly prolonged” improved survival compared to no use for patients whose PIK3CA The gene was mutated or amplified – in these patients, NSAIDs increased five-year overall survival by 25-78%. However, patients without impairment of their PIK3CA gene were not better off taking NSAIDs.

Through analysis of cell line and mouse studies, the researchers hypothesized that NSAIDs likely block tumor growth by reducing the production of an inflammatory molecule called prostaglandin E2.

The researchers stressed that their findings needed to be corroborated by a prospective trial. Additionally, they noted limitations, including the small size of the study group, and the type, timing, and doses of NSAIDs taken by patients.

“The use of NSAIDs probably confers a statistically and clinically significant advantage in terms of overall survival in PIK3CA-altered cancer of the head and neck by direct interaction between PI3K and coxswain pathways,” said Grandis, a member of UCSF’s Helen Diller Family Comprehensive Cancer Center.

“Given the marked mortality of this disease,” she said, “researchers designed a prospective randomized clinical trial to address the limitations of the original study and assess the clinical significance of this therapeutic use.”