Investigators have found that the antiseizure/pain drug gabapentin may be associated with improved survival in patients with glioblastoma, according to a recent study published by Bernstock et al in Nature Communications.
Background
With about 12,000 new cases diagnosed annually in the United States, glioblastoma accounts for most primary brain tumors in adults and is known to be highly aggressive. Overall survival rates among patients with the disease has hardly improved over the past several decades, with most patients living only 12 to 14 months after diagnosis and 5.5 months following cancer recurrence.
A previous study published by Krishna et al in Nature identified thrombospondin-1—a protein involved in neural circuit development and remodeling—as a key mediator of interactions between neurons and tumor cells that promote glioma growth. In mouse models, this neuron-tumor axis was successfully targeted using gabapentin, suggesting a potential therapeutic strategy.
Study Methods and Results
In this retrospective study, the investigators analyzed the outcomes of 693 patients with glioblastoma, many of whom were already receiving gabapentin to treat issues such as nerve pain. The investigators found that the patients who received gabapentin survived an average of 16 months compared with 12 months among those who did not receive the drug. The 4-month survival benefit was deemed statistically significant.
The investigators then examined the outcomes among a separate data set of 379 patients newly diagnosed with glioblastoma. They discovered that they were able to replicate the results of their initial analysis. For instance, the patients who received gabapentin survived an average of 20.8 months, whereas those who did not receive the drug survived an average of 14.7 months.
Further, the investigators revealed that the patients who received gabapentin had lower levels of serum thrombospondin-1, indicating the protein may serve as a marker of treatment response. However, the relationship between thrombospondin-1 levels and gabapentin may require further assessment in future studies.
Conclusions
“This study is an exciting step forward,” suggested lead study author Joshua Bernstock, MD, PhD, a clinical fellow in the Department of Neurosurgery at Brigham and Women’s Hospital. “[Glioblastoma] is a relentlessly progressive and nearly universally fatal disease. The discovery that an already approved [drug] with a favorable safety profile can extend overall survival represents a meaningful and potentially practice-changing advance,” he highlighted.
Despite the positive findings, the investigators noted that the retrospective nature of the study did not allow them to administer gabapentin in a controlled way to better understand its effects. As a result, larger, randomized clinical trials are needed to confirm the results and explore the role of gabapentin and thrombospondin-1 in glioblastoma progression.
“There have been very few advances in survival [among] patients [with glioblastoma] since the early 2000s,” Dr. Bernstock underscored. “We need to think more creatively about the emerging biology in these tumors and how to target them,” he concluded.
Disclosure: The research in this study was funded in part by the DFCI/Kiki Leptomeningeal Disease Grant. For full disclosures of the study authors, visit nature.com.
