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Risks of Major Long‐Term Side Effects Associated with Androgen‐Deprivation Therapy in Men with Prostate Cancer
Author(s) -
Nguyen Chi,
Lairson David R.,
Swartz Michael D.,
Du Xianglin L.
Publication year - 2018
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/phar.2168
Subject(s) - medicine , androgen deprivation therapy , prostate cancer , hazard ratio , proportional hazards model , myocardial infarction , diabetes mellitus , retrospective cohort study , cancer , dementia , prostatectomy , cohort , cohort study , confidence interval , surgery , disease , endocrinology
Study Objective To examine the risks and compare the occurrences of major long‐term side effects (sexual dysfunction, bone fractures, diabetes, cardiovascular morbidity, acute myocardial infarction [MI], and dementia) in patients with prostate cancer who received androgen‐deprivation therapy (ADT) with those who did not. Design Propensity score–matched retrospective cohort study using Medicare claims data. Data Source National Cancer Institute's Surveillance, Epidemiology, and End Results Program–Medicare linked database. Patients A total of 201,797 patients 66 years or older who were diagnosed with any stage of prostate cancer between 1992 and 2009; of these, 94,528 patients received ADT; 107,269 patients did not. Measurements and Main Results We identified receipt of ADT and number of claims for ADT, and ascertained the long‐term treatment‐related side effects that occurred during 19 years of follow‐up, from 1992–2010, from Medicare claims data. Cox proportional hazards models were used to estimate the incidences and hazard ratios (HRs) of newly developed side effects. Among all potential long‐term side effects, the risk of bone fractures was highest (HR 1.39, 95% confidence interval [CI] 1.35–1.43), followed by diabetes (HR 1.21, 95% CI 1.18–1.24), dementia (HR 1.16, 95% CI 1.13–1.20), coronary heart disease (HR 1.12, 95% CI 1.09–1.14), and acute MI (HR 1.11, 95% CI 1.08–1.15) in those who received ADT compared with those who did not. The HRs for bone fractures and diabetes increased steadily as the number of ADT doses increased, indicating a linear trend in the dose‐response relationship. Compared with patients who received active surveillance, ADT was associated with a 12% increased risk of sexual dysfunction (HR 1.12, 95% CI 1.05–1.20). The HR for sexual dysfunction increased to 1.68 (95% CI 1.59–1.77) when ADT was combined with radiation therapy and to 3.54 (95% CI 3.26–3.85) when ADT was combined with radiation and surgery. Conclusion The results of this study demonstrated that in men with prostate cancer, receipt of ADT was associated with higher risks of bone fractures, diabetes, dementia, coronary heart disease, acute MI, and sexual dysfunction than in those who did not receive ADT.