Viraj Master Leads Study of NSAID as Potential Agent for Blocking Recurrence
August 2020
Viraj Master, MD, PhD, is principal investigator of a new pilot study of biomarker evaluation and safety of pre-incisional ketorolac for patients undergoing surgical resection for non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC). The study is funded by the Morningside Center for Innovative and Affordable Medicine, an interdisciplinary unit within the Woodruff Health Sciences Center at Emory University that seeks to promote research, education, and advocacy for effective and affordable medical treatments.
Surgery induces inflammation, immunosuppression, and angiogenesis. Although these processes are important for wound healing in response to tissue injury caused by surgery, they also support the survival, growth, and dissemination of any remaining cancer cells and can lead to systemic recurrence soon after surgery.
Surgical trauma also increases the production of prostaglandins and thromboxanes, which have tumor-promoting and immunosuppressive activities, and reduces the activity of natural killer cells, which impairs the ability of the immune system to keep cancer cells in check.
However, if given just before tissue injury, non-steroidal anti-inflammatory drugs (NSAIDs) may be able to block the production of prostaglandins/thromboxanes and boost the activity of natural killer cells, thereby decreasing the risk of cancer recurrence. NSAIDs such as ketorolac are already routinely given to cancer patients postoperatively for pain management and are sometimes given intraoperatively to prevent postoperative pain. A retrospective clinical analysis found that intraoperative intravenous ketorolac or diclofenac (another NSAID), when added to standard of care for patients with stage I/II NSCLC, was associated with decreased risks of distant recurrence and mortality.
For the study, participants will be randomized to either a preoperative ketorolac group or a concurrent control group who will not receive preincisional ketorolac. The latter group will obtain untreated biologic samples for biologic correlative studies and secondary endpoints, and will not be compared to the investigational cohort in regards to the primary endpoint of safety. Patients will be randomized on the day of surgery to either the experimental or control arms and participants will be followed for 28 days. Medical records will be reviewed at one and two years post-surgery for survival assessment.
"This research will advance scientific knowledge by studying the safety of a preoperative dose of ketorolac prior to major surgical resection, which needs to be assessed prior to proceeding with a larger phase II study designed to evaluate traditional efficacy endpoints such as recurrence and overall survival," says Dr. Master.
Dr. Master's co-investigators and collaborators on the study are Haydn Kissick, PhD; Onkar Khullar, MD (Department of Surgery); Manoj Bhasin, PhD, MS (Department of Pediatrics and Department of Biomedical Informatics); and Yuan Liu, PhD, MS (Department of Bioinformatics).
