Dr Feigin on the Effect of Benzodiazepines on Survival Outcomes in Pancreatic Cancer

Michael Feigin, PhD, associate professor, pharmacology and therapeutics, Roswell Park Comprehensive Cancer Center, discusses findings from a retrospective study investigating the association between benzodiazepines and survival outcomes in patients with pancreatic cancer.

Investigators found an association between progression-free survival and specific types of benzodiazepines administered to patients with pancreatic cancer, Feigin says. Patients with cancer who are treated at Roswell Park and other cancer centers are commonly prescribed benzodiazepines, and the highest percentage of patients who are prescribed these drugs are those with pancreatic cancer, Feigin notes. Although lorazepam (Ativan) and alprazolam (Xanax) are both intermediate-acting benzodiazepines with similar structures, investigators found that patients with pancreatic cancer who received lorazepam tended to have worse disease outcomes, and those who received alprazolam tended to have better disease outcomes.

To determine the cause of this difference in outcomes, investigators treated mouse models with lorazepam and alprazolam. They found that the tumor microenvironment in mice treated with lorazepam was different than the tumor microenvironment in those treated with alprazolam. The tumor microenvironments in the lorazepam-treated mice had changes associated with poor disease outcomes, such as increased deposition of collagen, which is a protein that can lead to tumor hardening, Feigin explains.

In vitro studies demonstrated that lorazepam activated the GPR68 protein on cancer-associated fibroblasts, which led to secretion of the pro-inflammatory molecule IL6. Conversely, alprazolam decreased IL6 secretion. These findings may explain the differences in survival outcomes observed between patients who received lorazepam and alprazolam because the presence of IL6 affects responses to therapy in patients with pancreatic cancer.

Investigators then determined whether these findings were generalizable beyond pancreatic cancer. An analysis of patient outcomes with these agents across different cancer types showed that patients receiving lorazepam generally had worse survival outcomes than those receiving alprazolam, Feigin explains.

These findings indicate that there are clear distinctions between different benzodiazepines, Feigin emphasizes. Further research is needed to understand how these drugs perform in pancreatic cancer and other cancers, Feigin concludes