Choice of anxiety treatment may affect pancreatic cancer outcomes
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Key takeaways:
- Patients who used any benzodiazepine exhibited a 30% lower risk for pancreatic cancer-related death.
- Researchers observed considerable differences in outcomes based on the specific agent used.
Use of any benzodiazepine appeared associated with reduced risk for pancreatic cancer-related death, according to study results published in Clinical Cancer Research.
However, outcomes varied greatly based on which agent patients used, with researchers noting striking differences in outcomes between those who took alprazolam or lorazepam compared with nonusers.
“I was really surprised that no one had ever made these connections before,” Abigail Cornwell, pre-doctoral trainee at Roswell Park Comprehensive Cancer Center, told Healio. “A lot of data exists about how drugs such as benzodiazepines can bind to receptors that are known to be expressed by tumors and these receptors are known to influence the characteristics of the tumors in ways that could impact [survival for patients with cancer] in positive or negative ways.”
Background and methodology
Patients with pancreatic cancer or other malignancies often are prescribed benzodiazepines — which suppress central nervous system activity — to ease symptoms of insomnia, anxiety or seizures.
Evidence about the potential effect these agents may have on cancer outcomes is limited, according to study background.
Cornwell and colleagues used prescription records to retrospectively assess the association between benzodiazepines and survival outcomes among patients with pancreatic cancer treated at Roswell Park.
Results
Overall, analyses adjusted for race, age, sex, disease stage and progression, and treatment received showed use of any benzodiazepine appeared linked to a 30% reduced risk for pancreatic cancer-related death.
However, outcomes varied greatly based on the agent used.
Aside from short-acting benzodiazepines used as a component of surgical anesthesia, the two most frequently used benzodiazepines were lorazepam (n = 40) and alprazolam (n = 27).
Patients who took alprazolam (n = 27) exhibited a 62% reduced risk for disease progression or death (HR = 0.38; 95% CI, 0.16-0.92) compared with those who did not take the agent (n = 42).
However, those who took lorazepam (n = 40) exhibited a 3.83-fold (95% CI, 1.53-9.57) increased risk for disease progression or death compared with those who did not take the agent (n = 29).
Additionally, researchers noted that lorazepam stimulates fibrosis and inflammatory signaling, and promotes desmoplasia and ischemic necrosis.
Cornwell and colleagues also examined the associations between lorazepam and alprazolam use and outcomes among individuals with other types of cancer.
They determined alprazolam rarely appeared associated with significant differences in outcomes. However, use of lorazepam appeared associated with significantly poorer survival among individuals with ovarian, prostate, head and neck, colon, uterine or breast cancers, as well as melanoma. The effects ranged from a 25% elevated risk to a 116% elevated risk depending on malignancy.
Researchers conducted mechanistic studies with mice to assess the effects of lorazepam on pancreatic tumors at a cellular level.
Results revealed lorazepam may activate GPR68, a protein that is highly expressed on fibroblasts that support the tumor. GPR68 increases expression of IL-6, which promotes inflammation in the pancreatic tumor microenvironment, resulting in tumor growth.
Researchers acknowledged study limitations, including differences in optimal dosing of benzodiazepines between humans and mice, as well as the inability to account for differences in benzodiazepine doses administered to humans for different indications. In addition, investigators performed some mouse experiments on subcutaneously implanted tumors. These have different microenvironments than tumors that develop within the pancreas.
Next steps
The findings demonstrate that psychiatric medications can affect long-term patient outcomes, Cornwell and colleagues concluded.
Additional research is necessary to better understand the relationship.
“Pancreatic cancer has been linked with depression and anxiety since the early 1900s,” Christos Fountzilas, MD, FACP, medical oncologist at Roswell Park Comprehensive Cancer Center, told Healio. “Management of depression and anxiety in patients with pancreatic cancer can be very challenging. Before our report, we thought that the psychiatric medications we used for symptom management in pancreatic cancer have no effect in long-term patient outcomes, but our findings challenge this notion.
“Additionally, our research findings have uncovered the significance of a new target for cancer therapeutics — GPR68,” Fountzilas added. “I hope that drugs designed to block GPR68 — without the unwanted side effects of benzodiazepines — will be evaluated as anticancer agents soon.”
References:
- Cornwell AC, et al. Clin Cancer Res. 2023;doi:10.1158/1078-0432.CCR-23-0547.
- Lorazepam treatment may be linked to worse outcomes for pancreatic cancer patients (press release). Available at: https://www.aacr.org/about-the-aacr/newsroom/news-releases/lorazepam-treatment-may-be-linked-to-worse-outcomes-for-pancreatic-cancer-patients/. Published Aug. 17, 2023. Accessed Aug. 17, 2023.
For more information:
Abigail Cornwell and Christos Fountzilas, MD, FACP, can be reached at Roswell Park Comprehensive Cancer Center, 665 Elm St., Buffalo, NY 14203.
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