Publications by authors named "Amy K Darke"

23 Publications

  • Page 1 of 1

Association of Osteonecrosis of the Jaw With Zoledronic Acid Treatment for Bone Metastases in Patients With Cancer.

JAMA Oncol 2021 Feb;7(2):246-254

University of Washington, Seattle, Cancer Care Alliance, Seattle.

Importance: Osteonecrosis of the jaw (ONJ) affects patients with cancer and metastatic bone disease (MBD) treated with bone-modifying agents (BMAs), yet the true incidence is unknown.

Objective: To define the cumulative incidence of ONJ at 3 years in patients receiving zoledronic acid for MBD from any malignant neoplasm.

Design, Setting, And Participants: This multicenter, prospective observational cohort study (SWOG Cancer Research Network S0702) included patients with MBD with either limited or no prior exposure to BMAs and a clinical care plan that included use of zoledronic acid within 30 days of registration. Medical, dental, and patient-reported outcome forms were submitted at baseline and every 6 months. Follow-up was 3 years. Osteonecrosis of the jaw was defined using established criteria. Data were collected from January 30, 2009, to December 13, 2013, and analyzed from August 24, 2018, to August 6, 2020.

Interventions/exposures: Cancer treatments, BMAs, and dental care were administered as clinically indicated.

Main Outcomes And Measures: Cumulative incidence of confirmed ONJ, defined as an area of exposed bone in the maxillofacial region present for more than 8 weeks with no concurrent radiotherapy to the craniofacial region. Risk factors for ONJ were also examined.

Results: The SWOG S0702 trial enrolled 3491 evaluable patients (1806 women [51.7%]; median age, 63.1 [range, 2.24-93.9] years), of whom 1120 had breast cancer; 580, myeloma; 702, prostate cancer; 666, lung cancer; and 423, other neoplasm. A baseline dental examination was performed in 2263 patients (64.8%). Overall, 90 patients developed confirmed ONJ, with cumulative incidence of 0.8% (95% CI, 0.5%-1.1%) at year 1, 2.0% (95% CI, 1.5%-2.5%) at year 2, and 2.8% (95% CI, 2.3%-3.5%) at year 3; 3-year cumulative incidence was highest in patients with myeloma (4.3%; 95% CI, 2.8%-6.4%). Patients with planned zoledronic acid dosing intervals of less than 5 weeks were more likely to experience ONJ than patients with planned dosing intervals of 5 weeks or more (hazard ratio [HR], 4.65; 95% CI, 1.46-14.81; P = .009). A higher rate of ONJ was associated with fewer total number of teeth (HR, 0.51; 95% CI, 0.31-0.83; P = .006), the presence of dentures (HR, 1.83; 95% CI, 1.10-3.03; P = .02), and current smoking (HR, 2.12; 95% CI, 1.12-4.02; P = .02).

Conclusions And Relevance: As the findings show, the cumulative incidence of ONJ after 3 years was 2.8% in patients receiving zoledronic acid for MBD. Cancer type, oral health, and frequency of dosing were associated with the risk of ONJ. These data provide information to guide stratification of risk for developing ONJ in patients with MBD receiving zoledronic acid.
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http://dx.doi.org/10.1001/jamaoncol.2020.6353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747039PMC
February 2021

Age-related macular degeneration in a randomized trial of selenium and vitamin E in men: the Select Eye Endpoints (SEE) study (SWOG S0000B).

Acta Ophthalmol 2021 Mar 23;99(2):e285-e287. Epub 2020 Jul 23.

Department of Urology, Cancer Therapy and Research Center, University of Texas Health Science Center, San Antonio, TX, USA.

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http://dx.doi.org/10.1111/aos.14538DOI Listing
March 2021

Design, data linkage, and implementation considerations in the first cooperative group led study assessing financial outcomes in cancer patients and their informal caregivers.

Contemp Clin Trials 2020 08 30;95:106037. Epub 2020 May 30.

Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America; University of Washington, Department of Medicine, Seattle, WA, United States of America.

Background: Few studies have assessed the financial impact of cancer diagnosis on patients and caregivers in diverse clinical settings. S1417CD, led by the SWOG Cancer Research Network, is the first prospective longitudinal cohort study assessing financial outcomes conducted in the NCI Community Oncology Research Program (NCORP). We report our experience navigating design and implementation barriers.

Methods: Patients age ≥ 18 within 120 days of metastatic colorectal cancer diagnosis were considered eligible and invited to identify a caregiver to participate in an optional substudy. Measures include 1) patient and caregiver surveys assessing financial status, caregiver burden, and quality of life and 2) patient credit reports obtained from the credit agency TransUnion through a linkage requiring social security numbers and secure data transfer processes. The primary endpoint is incidence of treatment-related financial hardship, defined as one or more of the following: debt accrual, selling or refinancing home, ≥20% income decline, or borrowing money. Accrual goal was n = 374 patients in 3 years.

Results: S1417CD activated on Apr 1, 2016 and closed on Feb 1, 2019 after reaching its accrual goal sooner than anticipated. A total of 380 patients (median age 59.7 years) and 155 caregivers enrolled across 548 clinical sites. Credit data were not obtainable for 76 (20%) patients due to early death, lack of credit, or inability to match records.

Conclusions: Robust accrual to S1417CD demonstrates patients' and caregivers' willingness to improve understanding of financial toxicity despite perceived barriers such as embarrassment and fears that disclosing financial status could influence treatment recommendations.
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http://dx.doi.org/10.1016/j.cct.2020.106037DOI Listing
August 2020

Effect of Acupuncture vs Sham Acupuncture or Waitlist Control on Joint Pain Related to Aromatase Inhibitors Among Women With Early-Stage Breast Cancer: A Randomized Clinical Trial.

JAMA 2018 07;320(2):167-176

University of Utah Huntsman Cancer Institute, Salt Lake City.

Importance: Musculoskeletal symptoms are the most common adverse effects of aromatase inhibitors and often result in therapy discontinuation. Small studies suggest that acupuncture may decrease aromatase inhibitor-related joint symptoms.

Objective: To determine the effect of acupuncture in reducing aromatase inhibitor-related joint pain.

Design, Setting, And Patients: Randomized clinical trial conducted at 11 academic centers and clinical sites in the United States from March 2012 to February 2017 (final date of follow-up, September 5, 2017). Eligible patients were postmenopausal women with early-stage breast cancer who were taking an aromatase inhibitor and scored at least 3 on the Brief Pain Inventory Worst Pain (BPI-WP) item (score range, 0-10; higher scores indicate greater pain).

Interventions: Patients were randomized 2:1:1 to the true acupuncture (n = 110), sham acupuncture (n = 59), or waitlist control (n = 57) group. True acupuncture and sham acupuncture protocols consisted of 12 acupuncture sessions over 6 weeks (2 sessions per week), followed by 1 session per week for 6 weeks. The waitlist control group did not receive any intervention. All participants were offered 10 acupuncture sessions to be used between weeks 24 and 52.

Main Outcomes And Measures: The primary end point was the 6-week BPI-WP score. Mean 6-week BPI-WP scores were compared by study group using linear regression, adjusted for baseline pain and stratification factors (clinically meaningful difference specified as 2 points).

Results: Among 226 randomized patients (mean [SD] age, 60.7 [8.6] years; 88% white; mean [SD] baseline BPI-WP score, 6.6 [1.5]), 206 (91.1%) completed the trial. From baseline to 6 weeks, the mean observed BPI-WP score decreased by 2.05 points (reduced pain) in the true acupuncture group, by 1.07 points in the sham acupuncture group, and by 0.99 points in the waitlist control group. The adjusted difference for true acupuncture vs sham acupuncture was 0.92 points (95% CI, 0.20-1.65; P = .01) and for true acupuncture vs waitlist control was 0.96 points (95% CI, 0.24-1.67; P = .01). Patients in the true acupuncture group experienced more grade 1 bruising compared with patients in the sham acupuncture group (47% vs 25%; P = .01).

Conclusions And Relevance: Among postmenopausal women with early-stage breast cancer and aromatase inhibitor-related arthralgias, true acupuncture compared with sham acupuncture or with waitlist control resulted in a statistically significant reduction in joint pain at 6 weeks, although the observed improvement was of uncertain clinical importance.

Trial Registration: ClinicalTrials.gov Identifier: NCT01535066.
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http://dx.doi.org/10.1001/jama.2018.8907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583520PMC
July 2018

Response to H. Nabi et al.

J Natl Cancer Inst 2018 12;110(12):1424-1425

Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY.

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http://dx.doi.org/10.1093/jnci/djy069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658869PMC
December 2018

Smoking, Sex, and Non-Small Cell Lung Cancer: Steroid Hormone Receptors in Tumor Tissue (S0424).

J Natl Cancer Inst 2018 07;110(7):734-742

Department of Cancer Prevention and Control and Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY.

Background: To what extent steroid hormones contribute to lung cancer in male and female never smokers and smokers is unclear. We examined expression of hormone receptors in lung tumors by sex and smoking.

Methods: Patients with primary non-small cell lung cancer were recruited into an Intergroup study in the United States and Canada, led by SWOG (S0424). Tumors from 813 cases (450 women and 363 men) were assayed using immunohistochemistry for estrogen receptor (ER)-α, ER-β, progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Linear regression was used to examine differences in expression by sex and smoking status. Cox proportional hazard models were used to estimate survival associated with the receptors. All statistical tests were two-sided.

Results: In ever smokers, postmenopause and oral contraceptive use were associated with lower nuclear ER-β (P = .02) and total (nuclear + cytoplasmic) PR expression (P = .02), respectively. Women had lower cytoplasmic ER-α (regression coefficient [β], or differences in H-scores = -15.8, P = .003) and nuclear ER-β (β = -12.8, P = .04) expression than men, adjusting for age, race, and smoking. Ever smokers had both higher cytoplasmic ER-α (β = 45.0, P < .001) and ER-β (β = 25.9, P < .001) but lower total PR (β = -42.1, P < .001) than never smokers. Higher cytoplasmic ER-α and ER-β were associated with worse survival (hazard ratio = 1.73, 95% confidence interval [CI] = 1.15 to 2.58, and HR = 1.59, 95% CI = 1.08 to 2.33, respectively; quartiles 4 vs 1).

Conclusions: Lower expression of nuclear ER-β in women supports the estrogen hypothesis in lung cancer etiology. Increasing cytoplasmic ER-α and ER-β and decreasing PR protein expression may be mechanisms whereby smoking disrupts hormone pathways.
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http://dx.doi.org/10.1093/jnci/djx260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6037104PMC
July 2018

Association of Antioxidant Supplement Use and Dementia in the Prevention of Alzheimer's Disease by Vitamin E and Selenium Trial (PREADViSE).

JAMA Neurol 2017 05;74(5):567-573

Sanders-Brown Center on Aging, University of Kentucky, Lexington2Alzheimer's Disease Center, University of Kentucky, Lexington9Department of Neurology, College of Medicine, University of Kentucky, Lexington.

Importance: Oxidative stress is an established dementia pathway, but it is unknown if the use of antioxidant supplements can prevent dementia.

Objective: To determine if antioxidant supplements (vitamin E or selenium) used alone or in combination can prevent dementia in asymptomatic older men.

Design, Setting, And Participants: The Prevention of Alzheimer's Disease by Vitamin E and Selenium (PREADViSE) trial began as a double-blind randomized clinical trial in May 2002, which transformed into a cohort study from September 2009 to May 2015. The PREADViSE trial was ancillary to the Selenium and Vitamin E Cancer Prevention Trial (SELECT), a randomized clinical trial of the same antioxidant supplements for preventing prostate cancer, which closed in 2009 owing to findings from a futility analysis. The PREADViSE trial recruited 7540 men, of whom 3786 continued into the cohort study. Participants were at least 60 years old at study entry and were enrolled at 130 SELECT sites, and Cox proportional hazards models were used in a modified intent-to-treat analysis to compare hazard rates among the study arms.

Interventions: Participants were randomized to vitamin E, selenium, vitamin E and selenium, or placebo. While taking study supplements, enrolled men visited their SELECT site and were evaluated for dementia using a 2-stage screen. During the cohort study, men were contacted by telephone and assessed using an enhanced 2-stage cognitive screen. In both phases, men were encouraged to visit their physician if the screen results indicated possible cognitive impairment.

Main Outcomes And Measures: Dementia case ascertainment relied on a consensus review of the cognitive screens and medical records for men with suspected dementia who visited their physician for an evaluation or by review of all available information, including a functional assessment screen.

Results: The mean (SD) baseline age of the 7540 participants was 67.5 (5.3) years, with 3936 (52.2%) reporting a college education or better, 754 (10.0%) reporting black race, and 505 (6.7%) reporting Hispanic ethnicity. Dementia incidence (325 of 7338 men [4.4%]) was not different among the 4 study arms. A Cox model, which adjusted incidence for participant demographic information and baseline self-reported comorbidities, yielded hazard ratios of 0.88 (95% CI, 0.64-1.20) for vitamin E, 0.83 (0.60-1.13) for selenium, and 1.00 (0.75-1.35) for the combination compared with placebo.

Conclusions And Relevance: Neither supplement prevented dementia. To our knowledge, this is the first study to investigate the long-term association of antioxidant supplement use and dementia incidence among asymptomatic men.
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http://dx.doi.org/10.1001/jamaneurol.2016.5778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5506489PMC
May 2017

Colorectal Adenomas in Participants of the SELECT Randomized Trial of Selenium and Vitamin E for Prostate Cancer Prevention.

Cancer Prev Res (Phila) 2017 Jan 24;10(1):45-54. Epub 2016 Oct 24.

University of Arizona Cancer Center, Tucson, Arizona.

Selenium and vitamin E micronutrients have been advocated for the prevention of colorectal cancer. Colorectal adenoma occurrence was used as a surrogate for colorectal cancer in an ancillary study to the Selenium and Vitamin E Cancer Prevention Trial (SELECT) for prostate cancer prevention. The primary objective was to measure the effect of selenium (as selenomethionine) on colorectal adenomas occurrence, with the effect of vitamin E (as α-tocopherol) supplementation on colorectal adenoma occurrence considered as a secondary objective. Participants who underwent lower endoscopy while in SELECT were identified from a subgroup of the 35,533 men randomized in the trial. Adenoma occurrence was ascertained from the endoscopy and pathology reports for these procedures. Relative Risk (RR) estimates and 95% confidence intervals (CI) of adenoma occurrence were generated comparing those randomized to selenium versus placebo and to vitamin E versus placebo based on the full factorial design. Evaluable endoscopy information was obtained for 6,546 participants, of whom 2,286 had 1+ adenomas. Apart from 21 flexible sigmoidoscopies, all the procedures yielding adenomas were colonoscopies. Adenomas occurred in 34.2% and 35.7%, respectively, of participants whose intervention included or did not include selenium. Compared with placebo, the RR for adenoma occurrence in participants randomized to selenium was 0.96 (95% CI, 0.90-1.02; P = 0.194). Vitamin E did not affect adenoma occurrence compared with placebo (RR = 1.03; 95% CI, 0.96-1.10; P = 0.38). Neither selenium nor vitamin E supplementation can be recommended for colorectal adenoma prevention. Cancer Prev Res; 10(1); 45-54. ©2016 AACR.
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http://dx.doi.org/10.1158/1940-6207.CAPR-16-0104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5510661PMC
January 2017

Opportunities and challenges in incorporating ancillary studies into a cancer prevention randomized clinical trial.

Trials 2016 08 12;17:400. Epub 2016 Aug 12.

University of California at Irvine, Orange, CA, USA.

Background: The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was a randomized, double-blind, placebo-controlled, prostate cancer prevention study funded by the National Cancer Institute and conducted by SWOG (Southwest Oncology Group). A total of 35,533 men were assigned randomly to one of four treatment groups (vitamin E + placebo, selenium + placebo, vitamin E + selenium, placebo + placebo). At the time of the trial's development, NIH had invested substantial resources in evaluating the potential benefits of these antioxidants. To capitalize on the knowledge gained from following a large cohort of healthy, aging males on the effects of selenium and/or vitamin E, ancillary studies with other disease endpoints were solicited.

Methods: Four ancillary studies were added. Each drew from the same population but had independent objectives and an endpoint other than prostate cancer. These studies fell into two categories: those prospectively enrolling and following participants (studies of Alzheimer's disease and respiratory function) and those requiring a retrospective medical record review after a reported event (cataracts/age-related macular degeneration and colorectal screening). An examination of the challenges and opportunities of adding ancillary studies is provided. The impact of the ancillary studies on adherence to SELECT was evaluated using a Cox proportional hazards model.

Results: While the addition of ancillary studies appears to have improved participant adherence to the primary trial, this did not come without added complexity. Activation of the ancillary studies happened after the SELECT randomizations had begun resulting in accrual problems to some of the studies. Study site participation in the ancillary trials varied greatly and depended on the interest of the study site principal investigator. Procedures for each were integrated into the primary trial and all monitoring was done by the SELECT Data and Safety Monitoring Committee. The impact of the early closure of the primary trial was different for each of the ancillary trials.

Conclusions: The ancillary studies allowed study sites to broaden the research opportunities for their participants. Their implementation was efficient because of the established infrastructure of the primary trial. Implementation of these ancillary trials took substantial planning and coordination but enriched the overall primary trial.

Trial Registration: NCT00006392-S0000 : Selenium and Vitamin E in Preventing Prostate Cancer (SELECT) (4 October 2000). NCT00780689-S0000A :  Prevention of Alzheimer's Disease by Vitamin E and Selenium (PREADVISE) (25 June 2002). NCT00784225-S0000B : Vitamin E and/or Selenium in Preventing Cataract and Age-Related Macular Degeneration in Men on SELECT SWOG-S0000 (SEE) (31 October 2008). NCT00706121-S0000D : Effect of Vitamin E and/or Selenium on Colorectal Polyps in Men Enrolled on SELECT Trial SWOG-S0000 (ACP) (26 June 2008). NCT00063453-S0000C : Vitamin E and/or Selenium in Preventing Loss of Lung Function in Older Men Enrolled on SELECT Clinical Trial SWOG-S0000 (26 June 2003).
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http://dx.doi.org/10.1186/s13063-016-1524-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4983010PMC
August 2016

Selenium- or Vitamin E-Related Gene Variants, Interaction with Supplementation, and Risk of High-Grade Prostate Cancer in SELECT.

Cancer Epidemiol Biomarkers Prev 2016 07 6;25(7):1050-1058. Epub 2016 May 6.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston MA.

Background: Epidemiologic studies and secondary analyses of randomized trials supported the hypothesis that selenium and vitamin E lower prostate cancer risk. However, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed no benefit of either supplement. Genetic variants involved in selenium or vitamin E metabolism or transport may underlie the complex associations of selenium and vitamin E.

Methods: We undertook a case-cohort study of SELECT participants randomized to placebo, selenium, or vitamin E. The subcohort included 1,434 men; our primary outcome was high-grade prostate cancer (N = 278 cases, Gleason 7 or higher cancer). We used weighted Cox regression to examine the association between SNPs and high-grade prostate cancer risk. To assess effect modification, we created interaction terms between randomization arm and genotype and calculated log likelihood statistics.

Results: We noted statistically significant (P < 0.05) interactions between selenium assignment, SNPs in CAT, SOD2, PRDX6, SOD3, and TXNRD2, and high-grade prostate cancer risk. Statistically significant SNPs that modified the association of vitamin E assignment and high-grade prostate cancer included SEC14L2, SOD1, and TTPA In the placebo arm, several SNPs, hypothesized to interact with supplement assignment and risk of high-grade prostate cancer, were also directly associated with outcome.

Conclusion: Variants in selenium and vitamin E metabolism/transport genes may influence risk of overall and high-grade prostate cancer, and may modify an individual man's response to vitamin E or selenium supplementation with regards to these risks.

Impact: The effect of selenium or vitamin E supplementation on high-grade prostate cancer risk may vary by genotype. Cancer Epidemiol Biomarkers Prev; 25(7); 1050-8. ©2016 AACR.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5086806PMC
http://dx.doi.org/10.1158/1055-9965.EPI-16-0104DOI Listing
July 2016

Age-related cataract in men in the selenium and vitamin e cancer prevention trial eye endpoints study: a randomized clinical trial.

JAMA Ophthalmol 2015 Jan;133(1):17-24

Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio.

Importance: Observational studies suggest a role for dietary nutrients such as vitamin E and selenium in cataract prevention. However, the results of randomized clinical trials of vitamin E supplements and cataract have been disappointing and are not yet available for selenium.

Objective: To test whether long-term supplementation with selenium and vitamin E affects the incidence of cataract in a large cohort of men.

Design, Setting, And Participants: The Selenium and Vitamin E Cancer Prevention Trial (SELECT) Eye Endpoints Study was an ancillary study of the Southwest Oncology Group-coordinated SELECT, a randomized placebo-controlled 4-arm trial of selenium and vitamin E conducted among 35,533 men, 50 years and older for African American participants and 55 years and older for all other men, at 427 participating sites in the United States, Canada, and Puerto Rico. A total of 11,267 SELECT participants from 128 SELECT sites participated in the SELECT Eye Endpoints ancillary study.

Interventions: Individual supplements of selenium (200 μg per day from L-selenomethionine) and vitamin E (400 IU per day of all rac-α-tocopheryl acetate).

Main Outcomes And Measures: Incident cataract was defined as a lens opacity, age related in origin, and responsible for a reduction in best-corrected visual acuity to 20/30 or worse based on self-reports confirmed by medical record review. Cataract extraction was defined as the surgical removal of an incident cataract.

Results: During a mean (SD) of 5.6 (1.2) years of treatment and follow-up, 389 cases of cataract were documented. There were 185 cataracts in the selenium group and 204 in the no selenium group (hazard ratio, 0.91; 95 % CI, 0.75-1.11; P = .37). For vitamin E, there were 197 cases in the treated group and 192 in the placebo group (hazard ratio, 1.02; 95 % CI, 0.84-1.25; P = .81). Similar results were observed for cataract extraction.

Conclusions And Relevance: These data from a large cohort of apparently healthy men indicate that long-term daily supplementation with selenium and/or vitamin E is unlikely to have a large beneficial effect on age-related cataract.

Trial Registration: ClinicalTrials.gov Identifier: NCT00784225.
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http://dx.doi.org/10.1001/jamaophthalmol.2014.3478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4395006PMC
January 2015

A functional variant in NKX3.1 associated with prostate cancer risk in the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

Cancer Prev Res (Phila) 2014 Sep 3;7(9):950-7. Epub 2014 Jun 3.

Departments of Pathology, Microbiology and Immunology, Cancer Biology, and Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois

NKX3.1 is an androgen-regulated prostate tumor suppressor protein. We previously found that antioxidant administration (N-acetylcysteine) in the Nkx3.1 knockout mouse model promoted prostate epithelial proliferation, suggesting that NKX3.1 activity modifies the effect of antioxidant administration on prostate carcinogenesis. Interestingly, administration of the antioxidant vitamin E significantly increased prostate cancer risk in the Selenium and Vitamin E Cancer Prevention Trial (SELECT), suggesting that our animal experiments may be relevant to humans. To determine whether NKX3.1 played a role in increased human prostate cancer risk associated with antioxidant administration in SELECT, we investigated the joint risk of antioxidant administration and NKX3.1 genotypes previously found to be associated with decreased NKX3.1 mRNA expression (rs11781886) or DNA-binding activity in vitro (rs2228013) in the SELECT biomarker case-cohort substudy (1,866 cases; 3,135 non-cases). Multivariable COX regression models were developed to determine the joint association of NKX3.1 genotypes with administration of vitamin E, selenium, or the combination, compared with placebo. The CC genotype at rs11781886 combined with selenium administration was associated with increased overall prostate cancer risk [HR, 1.676; 95% confidence interval (CI), 1.011-2.777; P = 0.045] and low-grade prostate cancer risk (HR, 1.811; 95% CI, 1.016-3.228; P = 0.0441). Similarly, the rs11781886 minor allele (CC+CT) combined with vitamin E administration was significantly associated with increased prostate cancer risk (HR, 1.450; 95% CI, 1.117-1.882; P = 0.0052). Our results indicate that variation in NKX3.1 expression combined with selenium or vitamin E treatment modifies the risk of prostate cancer. Genetic background may modulate the effects of antioxidant supplementation thought to act as chemoprevention agents.
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http://dx.doi.org/10.1158/1940-6207.CAPR-14-0075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4154984PMC
September 2014

Baseline selenium status and effects of selenium and vitamin e supplementation on prostate cancer risk.

J Natl Cancer Inst 2014 Mar 22;106(3):djt456. Epub 2014 Feb 22.

Affiliations of authors: Cancer Prevention Program (ARK) and SWOG Statistical Center (AKD, CMT, PJG), Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Epidemiology (ARK, GEG) and Department of Environmental Health (GEG), University of Washington, Seattle, WA; University of Missouri, Research Reactor Center, Columbia, MO (JSM); Harry S. Truman Memorial Veterans Hospital, Columbia, MO (JSM); Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, TX (IMT); Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, CA (FLM); Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD (LMM, HLP); Moores Cancer Center, University of California San Diego, San Diego, CA (SML); Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH (EAK).

Background: The Selenium and Vitamin E Cancer Prevention Trial found no effect of selenium supplementation on prostate cancer (PCa) risk but a 17% increased risk from vitamin E supplementation. This case-cohort study investigates effects of selenium and vitamin E supplementation conditional upon baseline selenium status.

Methods: There were 1739 total and 489 high-grade (Gleason 7-10) PCa cases and 3117 men in the randomly selected cohort. Proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for effects of supplementation within quintiles of baseline toenail selenium. Cox proportional hazards models were used to estimate hazard ratios, and all statistical tests are two-sided.

Results: Toenail selenium, in the absence of supplementation, was not associated with PCa risk. Selenium supplementation (combined selenium only and selenium + vitamin E arms) had no effect among men with low selenium status (<60th percentile of toenail selenium) but increased the risk of high-grade PCa among men with higher selenium status by 91% (P = .007). Vitamin E supplementation (alone) had no effect among men with high selenium status (≥40th percentile of toenail selenium) but increased the risks of total, low-grade, and high-grade PCa among men with lower selenium status (63%, P = .02; 46%, P = .09; 111%, P = .008, respectively).

Conclusions: Selenium supplementation did not benefit men with low selenium status but increased the risk of high-grade PCa among men with high selenium status. Vitamin E increased the risk of PCa among men with low selenium status. Men should avoid selenium or vitamin E supplementation at doses that exceed recommended dietary intakes.
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http://dx.doi.org/10.1093/jnci/djt456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975165PMC
March 2014

Plasma phospholipid fatty acids and prostate cancer risk in the SELECT trial.

J Natl Cancer Inst 2013 Aug 10;105(15):1132-41. Epub 2013 Jul 10.

Department of Internal Medicine, Division of Cancer Prevention and Control, The Ohio State University College of Medicine, Columbus, OH, USA.

Background: Studies of dietary ω-3 fatty acid intake and prostate cancer risk are inconsistent; however, recent large prospective studies have found increased risk of prostate cancer among men with high blood concentrations of long-chain ω-3 polyunsaturated fatty acids ([LCω-3PUFA] 20:5ω3; 22:5ω3; 22:6ω3]. This case-cohort study examines associations between plasma phospholipid fatty acids and prostate cancer risk among participants in the Selenium and Vitamin E Cancer Prevention Trial.

Methods: Case subjects were 834 men diagnosed with prostate cancer, of which 156 had high-grade cancer. The subcohort consisted of 1393 men selected randomly at baseline and from within strata frequency matched to case subjects on age and race. Proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals (CI) for associations between fatty acids and prostate cancer risk overall and by grade. All statistical tests were two-sided.

Results: Compared with men in the lowest quartiles of LCω-3PUFA, men in the highest quartile had increased risks for low-grade (HR = 1.44, 95% CI = 1.08 to 1.93), high-grade (HR = 1.71, 95% CI = 1.00 to 2.94), and total prostate cancer (HR = 1.43, 95% CI = 1.09 to 1.88). Associations were similar for individual long-chain ω-3 fatty acids. Higher linoleic acid (ω-6) was associated with reduced risks of low-grade (HR = 0.75, 95% CI = 0.56 to 0.99) and total prostate cancer (HR = 0.77, 95% CI = 0.59 to 1.01); however, there was no dose response.

Conclusions: This study confirms previous reports of increased prostate cancer risk among men with high blood concentrations of LCω-3PUFA. The consistency of these findings suggests that these fatty acids are involved in prostate tumorigenesis. Recommendations to increase LCω-3PUFA intake should consider its potential risks.
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http://dx.doi.org/10.1093/jnci/djt174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3735464PMC
August 2013

Moving a randomized clinical trial into an observational cohort.

Clin Trials 2013 Feb 12;10(1):131-42. Epub 2012 Oct 12.

SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Background: The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was a randomized, double-blind, placebo-controlled prostate cancer prevention study funded by the National Cancer Institute (NCI) and conducted by the Southwest Oncology Group (SWOG). A total of 35,533 men were assigned randomly to one of the four treatment groups (vitamin E + placebo, selenium + placebo, vitamin E + selenium, and placebo + placebo). The independent Data and Safety Monitoring Committee (DSMC) recommended the discontinuation of study supplements because of the lack of efficacy for risk reduction and because futility analyses demonstrated no possibility of benefit of the supplements to the anticipated degree (25% reduction in prostate cancer incidence) with additional follow-up. Study leadership agreed that the randomized trial should be terminated but believed that the cohort should be maintained and followed as the additional follow-up would contribute important information to the understanding of the biologic consequences of the intervention. Since the participants no longer needed to be seen in person to assess acute toxicities or to be given study supplements, it was determined that the most efficient and cost-effective way to follow them was via a central coordinated effort.

Purpose: A number of changes were necessary at the local Study Sites and SELECT Statistical Center to transition to following participants via a Central Coordinating Center. We describe the transition process from a randomized clinical trial to the observational Centralized Follow-Up (CFU) study.

Methods: The process of transitioning SELECT, implemented at more than 400 Study Sites across the United States, Canada, and Puerto Rico, entailed many critical decisions and actions including updates to online documents such as the SELECT Workbench and Study Manual, a protocol amendment, reorganization of the Statistical Center, creation of a Transition Committee, development of materials for SELECT Study Sites, development of procedures to close Study Sites, and revision of data collection procedures and the process by which to contact participants.

Results: At the time of the publication of the primary SELECT results in December 2008, there were 32,569 men alive and currently active in the trial. As of 31 December 2011, 17,761 participants had been registered to the CFU study. This number is less than had been anticipated due to unforeseen difficulties with local Study Site institutional review boards (IRBs). However, from this cohort, we estimate that an additional 580 prostate cancer cases and 215 Gleason 7 or higher grade cancers will be identified. Over 109,000 individual items have been mailed to participants. Active SELECT ancillary studies have continued. The substantial SELECT biorepository is available to researchers; requests to use the specimens are reviewed for feasibility and scientific merit. As of April 2012, 12 proposals had been approved.

Limitations: The accrual goal of the follow-up study was not met, limiting our power to address the study objectives satisfactorily. The CFU study is also dependent on a number of factors including continued funding, continued interest of investigators in the biorepository, and the continued contribution of the participants. Our experience may be less pertinent to investigators who wish to follow participants in a treatment trial or participants in prevention trials in other medical areas.

Conclusions: Extended follow-up of participants in prevention research is important to study the long-term effects of the interventions, such as those used in SELECT. The approach taken by SELECT investigators was to continue to follow participants centrally via an annual questionnaire and with a web-based option. The participants enrolled in the CFU study represent a large, well-characterized, generally healthy cohort. The CFU has enabled us to collect additional prostate and other cancer endpoints and longer follow-up on the almost 18,000 participants enrolled. The utility of the extensive biorepository that was developed during the course of the SELECT is enhanced by longer follow-up.
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http://dx.doi.org/10.1177/1740774512460345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636982PMC
February 2013

Health-related quality-of-life findings for the prostate cancer prevention trial.

J Natl Cancer Inst 2012 Sep 12;104(18):1373-85. Epub 2012 Sep 12.

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, M3-C102 1100 Fairview Ave North, PO Box 19024 Seattle, WA 98109-1024, USA.

Background: The Prostate Cancer Prevention Trial (PCPT)-a randomized placebo-controlled study of the efficacy of finasteride in preventing prostate cancer-offered the opportunity to prospectively study effects of finasteride and other covariates on the health-related quality of life of participants in a multiyear trial.

Methods: We assessed three health-related quality-of-life domains (measured with the Health Survey Short Form-36: Physical Functioning, Mental Health, and Vitality scales) via questionnaires completed by PCPT participants at enrollment (3 months before randomization), at 6 months after randomization, and annually for 7 years. Covariate data obtained at enrollment from patient-completed questionnaires were included in our model. Mixed-effects model analyses and a cross-sectional presentation at three time points began at 6 months after randomization. All statistical tests were two-sided.

Results: For the physical function outcome (n = 16 077), neither the finasteride main effect nor the finasteride interaction with time were statistically significant. The effects of finasteride on physical function were minor and accounted for less than a 1-point difference over time in Physical Functioning scores (mixed-effect estimate = 0.07, 95% confidence interval [CI] = -0.28 to 0.42, P = .71). Comorbidities such as congestive heart failure (estimate = -5.64, 95% CI = -7.96 to -3.32, P < .001), leg pain (estimate = -2.57, 95% CI = -3.04 to -2.10, P < .001), and diabetes (estimate = -1.31, 95% CI = -2.04 to -0.57, P < .001) had statistically significant negative effects on physical function, as did current smoking (estimate = -2.34, 95% CI = -2.97 to -1.71, P < .001) and time on study (estimate = -1.20, 95% CI = -1.36 to -1.03, P < .001). Finasteride did not have a statistically significant effect on the other two dependent variables, mental health and vitality, either in the mixed-effects analyses or in the cross-sectional analysis at any of the three time points.

Conclusion: Finasteride did not negatively affect SF-36 Physical Functioning, Mental Health, or Vitality scores.
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http://dx.doi.org/10.1093/jnci/djs359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3529595PMC
September 2012

Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

JAMA 2011 Oct;306(14):1549-56

Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.

Context: The initial report of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) found no reduction in risk of prostate cancer with either selenium or vitamin E supplements but a statistically nonsignificant increase in prostate cancer risk with vitamin E. Longer follow-up and more prostate cancer events provide further insight into the relationship of vitamin E and prostate cancer.

Objective: To determine the long-term effect of vitamin E and selenium on risk of prostate cancer in relatively healthy men.

Design, Setting, And Participants: A total of 35,533 men from 427 study sites in the United States, Canada, and Puerto Rico were randomized between August 22, 2001, and June 24, 2004. Eligibility criteria included a prostate-specific antigen (PSA) of 4.0 ng/mL or less, a digital rectal examination not suspicious for prostate cancer, and age 50 years or older for black men and 55 years or older for all others. The primary analysis included 34,887 men who were randomly assigned to 1 of 4 treatment groups: 8752 to receive selenium; 8737, vitamin E; 8702, both agents, and 8696, placebo. Analysis reflect the final data collected by the study sites on their participants through July 5, 2011.

Interventions: Oral selenium (200 μg/d from L-selenomethionine) with matched vitamin E placebo, vitamin E (400 IU/d of all rac-α-tocopheryl acetate) with matched selenium placebo, both agents, or both matched placebos for a planned follow-up of a minimum of 7 and maximum of 12 years.

Main Outcome Measures: Prostate cancer incidence.

Results: This report includes 54,464 additional person-years of follow-up and 521 additional cases of prostate cancer since the primary report. Compared with the placebo (referent group) in which 529 men developed prostate cancer, 620 men in the vitamin E group developed prostate cancer (hazard ratio [HR], 1.17; 99% CI, 1.004-1.36, P = .008); as did 575 in the selenium group (HR, 1.09; 99% CI, 0.93-1.27; P = .18), and 555 in the selenium plus vitamin E group (HR, 1.05; 99% CI, 0.89-1.22, P = .46). Compared with placebo, the absolute increase in risk of prostate cancer per 1000 person-years was 1.6 for vitamin E, 0.8 for selenium, and 0.4 for the combination.

Conclusion: Dietary supplementation with vitamin E significantly increased the risk of prostate cancer among healthy men.

Trial Registration: Clinicaltrials.gov Identifier: NCT00006392.
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http://dx.doi.org/10.1001/jama.2011.1437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4169010PMC
October 2011

Transparency and reproducibility in data analysis: the Prostate Cancer Prevention Trial.

Biostatistics 2010 Jul 19;11(3):413-8. Epub 2010 Feb 19.

Biometry Research Group, Division of Cancer Prevention, National Cancer Institute, 6130 Executive Boulevard, Bethesda, MD 20892-7354, USA.

With the analysis of complex, messy data sets, the statistics community has recently focused attention on "reproducible research," namely research that can be readily replicated by others. One standard that has been proposed is the availability of data sets and computer code. However, in some situations, raw data cannot be disseminated for reasons of confidentiality or because the data are so messy as to make dissemination impractical. For one such situation, we propose 2 steps for reproducible research: (i) presentation of a table of data and (ii) presentation of a formula to estimate key quantities from the table of data. We illustrate this strategy in the analysis of data from the Prostate Cancer Prevention Trial, which investigated the effect of the drug finasteride versus placebo on the period prevalence of prostate cancer. With such an important result at stake, a transparent analysis was important.
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http://dx.doi.org/10.1093/biostatistics/kxq004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883301PMC
July 2010

Pathologic characteristics of cancers detected in The Prostate Cancer Prevention Trial: implications for prostate cancer detection and chemoprevention.

Cancer Prev Res (Phila) 2008 Aug 18;1(3):167-73. Epub 2008 May 18.

University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA.

The Prostate Cancer Prevention Trial (PCPT) showed a risk of prostate cancer at prostate-specific antigen (PSA) <4.0 ng/mL and that prostate cancer risk is reduced by finasteride. A major concern about early detection by PSA and prevention by finasteride is that they may involve biologically inconsequential tumors. We reviewed the pathologic characteristics of prostate biopsies from men in the placebo and finasteride groups of the PCPT. We examined tumor pathology characteristics stratified by level of PSA for men in the placebo group who underwent radical prostatectomy. Seventy-five percent of all cancers and 62% of Gleason score or=7) tumors for the same PSA strata were 15.6%, 37.9%, 49.1%, and 52.4%, respectively. These data highlight the dilemma of PSA when used for screening: Lower cutoff levels increase detection of insignificant disease, but cure is more likely, whereas higher cutoff levels make detection of significant cancer more likely, but cure is less likely. Therefore, the effectiveness of finasteride in preventing prostate cancer, including Gleason score
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http://dx.doi.org/10.1158/1940-6207.CAPR-08-0078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985428PMC
August 2008

Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

JAMA 2009 Jan 9;301(1):39-51. Epub 2008 Dec 9.

Division of Cancer Medicine, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.

Context: Secondary analyses of 2 randomized controlled trials and supportive epidemiologic and preclinical data indicated the potential of selenium and vitamin E for preventing prostate cancer.

Objective: To determine whether selenium, vitamin E, or both could prevent prostate cancer and other diseases with little or no toxicity in relatively healthy men.

Design, Setting, And Participants: A randomized, placebo-controlled trial (Selenium and Vitamin E Cancer Prevention Trial [SELECT]) of 35,533 men from 427 participating sites in the United States, Canada, and Puerto Rico randomly assigned to 4 groups (selenium, vitamin E, selenium + vitamin E, and placebo) in a double-blind fashion between August 22, 2001, and June 24, 2004. Baseline eligibility included age 50 years or older (African American men) or 55 years or older (all other men), a serum prostate-specific antigen level of 4 ng/mL or less, and a digital rectal examination not suspicious for prostate cancer.

Interventions: Oral selenium (200 microg/d from L-selenomethionine) and matched vitamin E placebo, vitamin E (400 IU/d of all rac-alpha-tocopheryl acetate) and matched selenium placebo, selenium + vitamin E, or placebo + placebo for a planned follow-up of minimum of 7 years and a maximum of 12 years.

Main Outcome Measures: Prostate cancer and prespecified secondary outcomes, including lung, colorectal, and overall primary cancer.

Results: As of October 23, 2008, median overall follow-up was 5.46 years (range, 4.17-7.33 years). Hazard ratios (99% confidence intervals [CIs]) for prostate cancer were 1.13 (99% CI, 0.95-1.35; n = 473) for vitamin E, 1.04 (99% CI, 0.87-1.24; n = 432) for selenium, and 1.05 (99% CI, 0.88-1.25; n = 437) for selenium + vitamin E vs 1.00 (n = 416) for placebo. There were no significant differences (all P>.15) in any other prespecified cancer end points. There were statistically nonsignificant increased risks of prostate cancer in the vitamin E group (P = .06) and type 2 diabetes mellitus in the selenium group (relative risk, 1.07; 99% CI, 0.94-1.22; P = .16) but not in the selenium + vitamin E group.

Conclusion: Selenium or vitamin E, alone or in combination at the doses and formulations used, did not prevent prostate cancer in this population of relatively healthy men.

Trial Registration: clinicaltrials.gov identifier: NCT00006392.
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http://dx.doi.org/10.1001/jama.2008.864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682779PMC
January 2009

Finasteride and high-grade prostate cancer in the Prostate Cancer Prevention Trial.

J Natl Cancer Inst 2007 Sep 11;99(18):1375-83. Epub 2007 Sep 11.

Department of Pathology, University of Colorado Denver and Health Sciences Center, 4200 E Ninth Ave, Box B-216, Denver, CO 80262, USA.

Background: The Prostate Cancer Prevention Trial (PCPT) reported a decreased incidence of prostate cancer overall but an increase in the incidence of high-grade prostate cancer with finasteride compared with placebo. We assessed whether the increased high-grade prostate cancer associated with finasteride in the PCPT was due to finasteride's potential effects on tumor morphology or prostate size.

Methods: Prostate biopsies with Gleason score 8-10 (n = 90, finasteride; n = 52, placebo) were examined histologically for hormonal effects, and those with Gleason score 7-10 (n = 282, finasteride; n = 244, placebo) were examined for pathologic surrogates of disease extent. Prostate volumes were measured at biopsy. Samples from radical prostatectomies (n = 222, finasteride; n = 306, placebo) were examined for tumor grade and extent, and, where possible, grades at biopsy and prostatectomy were compared between the groups. Logistic regression was used to analyze differences between treatment groups with respect to pathologic criteria. All statistical tests were two-sided.

Results: Degenerative hormonal changes in high-grade biopsies were equivalent between the finasteride and placebo groups, but prostate volumes were lower in the finasteride group (median = 25.1 versus 34.4 cm3, P<.001). Pathologic surrogates for tumor extent were lower with finasteride than with placebo, including mean percentage of positive cores (34% versus 38%, P = .016), mean tumor linear extent (greatest [4.4 versus 4.8 mm, P = .19] and aggregate [7.6 versus 9.2 mm, P = .13]), bilaterality (22.8% versus 30.6%, P = .046), and perineural invasion (14.2% versus 20.3%, P = .07). Among patients who had prostatectomy, the finasteride-associated increase in high-grade disease (Gleason score > or = 7) at biopsy (42.7% finasteride versus 25.4% placebo, P<.001) was diminished at prostatectomy (46.4% finasteride versus 38.6% placebo, P = .10). Biopsy identified a greater proportion of patients with high-grade disease present at prostatectomy in the finasteride group than in the placebo group (69.7% versus 50.5%, P = .01). The rate of upgrading (from low-grade cancer at biopsy to high-grade cancer at prostatectomy) and pathologic stage at prostatectomy were similar in both groups.

Conclusions: Effects of finasteride on prostate volume and selective inhibition of low-grade cancer, rather than effects on tumor morphology, may have contributed to the increase in high-grade cancers with finasteride in the PCPT. Although induction of high-grade cancer cannot be excluded, the results suggest that high-grade cancer was detected earlier and was less extensive in the finasteride group than in the placebo group.
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http://dx.doi.org/10.1093/jnci/djm117DOI Listing
September 2007

Longitudinal analysis of sexual function reported by men in the Prostate Cancer Prevention Trial.

J Natl Cancer Inst 2007 Jul 27;99(13):1025-35. Epub 2007 Jun 27.

Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center/M3-C102, 1100 Fairview Ave North, Box 19024, Seattle, WA 98109-1024, USA.

Background: The Prostate Cancer Prevention Trial (PCPT) was a randomized, double-blind, placebo-controlled study of the efficacy of finasteride in preventing prostate cancer in 18,882 men aged 55 years or older. The PCPT offered an opportunity to prospectively study the effects of finasteride and other covariates on sexual dysfunction.

Methods: We assessed sexual dysfunction in 17,313 PCPT participants during a 7-year period. A battery of questionnaires assessed sexual dysfunction (Sexual Activity Scale score); age; race; SF-36 Mental Health Inventory-5, Physical Function, and Vitality scores; body mass index; smoking status; and the presence of diabetes and hypertension. Assessments began at month 6 after random assignment and included the Sexual Activity Scale score at randomization as a covariate. Two-sided general t tests, with a cutoff of P value less than .05, were used to determine the statistical significance for mixed model effects with correlated random time slopes and intercepts. The changing impact of covariates on sexual dysfunction was also assessed at 6 months, 3.5 years, and 6.5 years after randomization.

Results: Finasteride increased sexual dysfunction only slightly and its impact diminished over time; the increase in the Sexual Activity Scale score relative to placebo of 3.21 points (95% confidence interval [CI] = 2.83 to 3.59 points; P<.001) at the first assessment decreased to 2.11 points (95% CI = 1.44 to 2.81 points; P<.001) at the end of study. These Sexual Activity score values were small on a scale of 0-100, the range observed in the study, and in comparison with individual variation. After adjustment for all covariates, mean sexual dysfunction increased in both arms from baseline (6 months after randomization) by 1.26 Sexual Activity points (95% CI = 1.16 to 1.36 points; P<.001) per year, corresponding to a cumulative increase of 8.22 points (95% CI = 7.52 to 8.92 points; P<.001) over the study period.

Conclusions: The effect of finasteride on sexual functioning is minimal for most men and should not impact the decision to prescribe or take finasteride.
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http://dx.doi.org/10.1093/jnci/djm023DOI Listing
July 2007