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Intermittent ADT may improve quality of life in men with prostate cancer
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Intermittent androgen deprivation therapy appeared noninferior to continuous therapy with respect to OS among patients with advanced or recurrent prostate cancer, according to the results of a systemic review and meta-analysis.
Further, intermittent ADT improved certain quality-of-life criteria, the researchers reported.
ADT serves as the standard of care for patients with advanced or recurrent prostate cancer. However, it can produce adverse events and diminish quality of life, as well as lead to the development of castration-resistant disease in most recipients, according to study background.
Sindy Magnan, MD, MSc, FRCPC, a radiation oncologist at Laval University in Quebec City, Quebec, and colleagues sought to determine the efficacy of intermittent ADT, which has been proposed as an alternative to continuous therapy in this patient population.
The researchers conducted a systemic review and meta-analysis to compare the efficacy and tolerability of intermittent vs. continuous therapy. They searched eight databases — including Cochrane CENTRAL and Google Scholar — for guidelines, reviews and other relevant articles that compared intermittent and continuous ADT in patients with prostate cancer published up to March 2014. Researchers also conducted a bias assessment of the trials.
OS and quality of life served as the primary endpoints. Secondary endpoints included disease-specific survival (DSS), PFS, time to castration resistance, skeletal-related events and adverse events.
The study included data from 22 articles from 15 trials published between 2000 and 2013, comprising 6,856 patients. All but one study had an unclear or high risk for bias.
The researchers did not observe a significant difference between treatment modalities regarding OS (HR = 1.02; 95% CI, 0.93-1.11; data from 8 trials, n = 5,352), DSS (HR = 1.02; 95% CI, 0.84-1.19; data from 5 trials, n = 3,613) or PFS (HR = 0.94; 95% CI, 0.84-1.05; data from 4 trials, n = 1,774). The upper boundary of the HR for OS was less than the prespecified 1.15 limit, meaning intermittent therapy was noninferior to continuous therapy for OS outcomes.
Self-reported quality of life appeared similar between patients who received either treatment modality. However, patients in seven trials experienced improved quality of life with intermittent ADT in certain domains, the most frequent of which related to physical and sexual functioning.
Further, pooled point estimates appeared to favor reduced drug-related adverse events with intermittent ADT.
In addition to the high risk for bias, the researchers acknowledge a lack of available data — which precluded the conducting of pooled analyses or the inclusion of all trials in certain analyses in some cases — as a study limitation.
“Intermittent ADT can be considered as an alternative therapeutic option in patients with prostate cancer,” Magnan and colleagues wrote. “However, the high risk for bias observed in some trials, the unclear optimal approach to the duration of treatment and off-treatment periods and criteria on which it should be based, and the unknown magnitude of effect according to the disease stage warrant further research before it becomes the mandatory standard of care.”
The available data from clinical trials studying intermittent vs. continuous ADT are too variant to be applied to large patient populations, Christopher J. Sweeney, MBBS, associate professor of medicine at Harvard Medical School and member of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, wrote in an accompanying editorial.
Christopher J. Sweeney
“The meta-analysis conducted by Magnan and colleagues is exhaustive, and the team is to be commended for the extensive work and appropriate use of established methodological guidelines,” Sweeney wrote. “However, I propose that there is clinical uncertainty in the data. The fact that one of the largest and most robust phase 3 studies, S9346, begins the conclusions section with ‘our findings were statistically inconclusive’ could be construed as emblematic of this fact. It is with this uncertainty in mind that I propose the following question: Can population science guide well-informed individual treatment recommendations for who should, and who should not, undergo intermittent ADT? My answer to this question is no.” – by Cameron Kelsall
Disclosure: One researcher reports honoraria from Abbvie, Amgen, Astellas, Janssen, Peladin and Sanofi. The other researchers and Sweeney report no relevant financial disclosures.
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