A Population Based Study of Ketorolac and Ovarian Cancer Survival

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Ovarian cancer is the most deadly gynecologic cancer in the U.S. and most patients still die of chemo-resistant, recurrent disease. We propose that a FDA-approved analgesic may also have anti-tumor properties that will reduce recurrent disease and improve survival if given during or closely following ovarian cancer surgery. Racemic R,S-ketorolac (Toradol® or a generic equivalent) is an strong non-steroidal anti-inflammatory drug (NSAID) used in conjunction with surgeries. We have been investigating ketorolac since 2008 and have compelling preliminary evidence to support the hypothesis that ketroloac can help reduce ovarian cancer mortality. Our work is supported further by reported recurrence and mortality reduction with surgery-associated ketorolac administration in breast and lung cancer patients. Combined, this compelling evidence suggests that ketorolac will confer an anti-tumor benefit; however, a reduction in ovarian cancer mortality with surgery- associated ketorolac (vs. none) has not been demonstrated. We propose to address this gap in our knowledge with a population-based cohort study of ovarian cancer cases. We hypothesize that ovarian cancer cases that are given ketorolac as an analgesic during ovarian cancer surgery will have better overall survival than those who do not receive ketorolac, after accounting for factors such as co-morbidities, stage of disease and received treatment. In addressing this hypothesis, we will use an existing cohort of population-based ovarian cancer cases from Alberta and British Columbia, Canada, who were diagnosed from 2002 to 2012 with mortality followed through 2020, providing between 8 and 18 years of follow-up. We will complete de novo medical record reviews to ascertain co-morbidities and all analgesics and anesthesia used during surgery for ovarian cancer. Existing data/resources that are already in hand includes: details of cancer treatments received, standardized pathology review to classify the tumors by contemporary criteria, and tissue micro-arrays (TMAs) (all histotypes). Using these TMAs, we will use immunohistochemical staining of markers that may define subsets of patients to address our mechanistic hypothesis. If ketorolac given in the surgical period makes a substantial improvement in survival, then the use of ketorolac would be an efficient and widely applicable method to improve survival within normal medical practice.