From the Journals

Intensive nonaspirin NSAID use linked to reduced ovarian cancer mortality



Intensive use of nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with improved survival of patients with serous ovarian cancer in a recent population-based study.

By contrast, any use of nonaspirin NSAIDs was not associated with survival benefit, according to the authors of the study, which was based on records for more than 4,000 patients in the Danish Cancer Registry.

“More intensive use of nonaspirin NSAIDs appears necessary to obtain a prognostic benefit,” wrote Freija Verdoodt, PhD, postdoctoral researcher with the Danish Cancer Society Research Center, Copenhagen and her coauthors. The report was published in Gynecologic Oncology.

In addition, there was a suggestion that use of these drugs was associated with increased mortality in patients that with nonserous ovarian cancer, Dr. Verdoodt and her colleagues noted.

The study population comprised 4,117 women who were alive 1 year after a diagnosis of epithelial ovarian cancer. Ovarian cancer–specific mortality, the primary outcome of the analysis, was evaluated in relation to postdiagnosis use of nonaspirin NSAIDs.

The investigators found that any postdiagnosis use of nonaspirin NSAIDs was not associated with a difference in mortality, with a hazard ratio of 0.97 (95% confidence interval, 0.87-1.08) after adjusting for factors such as age, clinical stage, and year of diagnosis.

“Nonaspirin NSAIDs are typically used sporadically, and thus limited use among a substantial proportion of the postdiagnosis users may have attenuated the mortality risk estimates of our main analysis,” Dr. Verdoodt and her coauthors wrote.

However, increasing cumulative dose was associated with decreases in mortality, with hazard ratios of 1.03, 0.96, and 0.75 for low, medium, and high cumulative doses, respectively.

Likewise, the intensity of use, defined as cumulative dose divided by the number of days between the first and most recent postdiagnosis NSAID prescription, was associated with decreased mortality, with hazard ratios of 1.04, 0.98, and 0.86 for low, medium, and high use intensity, the reported data show.

When stratified by tumor histology, the data showed an association between reduced ovarian cancer–specific mortality and serous ovarian tumors (hazard ratio, 0.87; 95% CI, 0.77-0.99), and post hoc analyses confirmed further reductions in mortality based on high cumulative doses, with a hazard ratio of 0.62, and high intensity of use, with a hazard ratio of 0.79.

Conversely, other histologies were associated with increases in ovarian cancer mortality, though the numbers of patients in these subgroups were small, limiting interpretation of the results, investigators said.

Prior to this study, there were few epidemiologic investigations of the impact of nonaspirin NSAIDs on ovarian cancer prognosis, and of those, most did not include separate estimates based on histological subtypes, according to the investigators.

Although this study suggests intensive nonaspirin NSAID use comes with a potential prognostic benefit, these drugs also have potential adverse effects, including serious cardiovascular adverse events, the investigators said.

“A consideration of such risks in the light of a survival benefit among poor-prognosis serous ovarian cancer patients should guide further research,” they wrote.

The study was supported by the Sapere Aude program of the Independent Research Fund Denmark and the Mermaid project. The authors declared no conflicts of interest.

SOURCE: Verdoodt F et al. Gynecol Oncol. 2018 Jun 27. doi: 10.1016/j.ygyno.2018.06.018.

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