Exth-61. Celecoxib Improves Outcome of Patients Treated With Tumor Treating Fields
Year: 2019
Type: conference-abstract
Abstract: Tumor Treating Fields (TTFields) are known to cause mitotic catastrophe resulting in aberrant mitotic exit. However, there is accumulating evidence that the clinical effectiveness of TTFields requires immune competence. Exposure of cells to TTFields induced signs of cellular stress including cytoskeletal changes, surface expression of calreticulin and secretion of HMGB1 suggesting that TTFields may promote anti-tumor immunity that leads to subsequent tumor regression. Many tumor-protective mechanisms require immunosuppressive cell types within the tumor microenvironment whose development and suppressive functions are supported by prostaglandin E2 (PGE2). The rate limiting enzyme for PGE2 production is Cyclooxygenases-2 (COX-2) whose upregulation has been correlated with poor survival in glioma patients. Therefore, we reasoned that reduction of PGE2 production within the tumor microenvironment might improve response to TTFields therapy. Previous data from our group indicated that dexamethasone use interfered with TTFields-efficacy. When our population having low dexamethasone usage (n=42) was dichotomized according to celecoxib use, those without celecoxib (n = 14) had a median overall survival (OS) of 8.1 months while those receiving celecoxib had a median OS of 12.9 months (chi-square 5.42, p=0.002, HR = 2.1, 95% CI = 1.19–5.59). Patients not receiving celecoxib were treated with TTFields for a median of 3.8 months while those receiving celecoxib were treated for a median of 8.2 months (Chi-square = 6.75, p = 0.01, HR = 2.3, CI = 1.33–6.47). These data suggest that the addition of celecoxib improved the efficacy of TTFields against glioblastoma in this cohort. However, celecoxib did not sensitize TTFields-induced killing of cells in vitro suggesting an indirect mechanism of action. Together with our in vitro data, the results support an immune mechanism of action underlying TTFields’ anti-tumor efficacy. These findings concerning the effects of celecoxib on patient outcomes need to be confirmed in a prospective clinical trial.
Source: Neuro-Oncology
Institution: Beth Israel Deaconess Medical Center
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2986596748