The use of selenium and vitamin E supplementation to prevent recurrence of non-muscle-invasive bladder cancer: results of the SELENIB trial


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Richard Bryan1,Sarah Pirrie1,Ben Abbotts1,Vinnie During1,Carolyn Langford1,Margaret Grant1,Deborah Bird1,Adam Devall1,Gareth Bicknell1,D Michael A Wallace1,Nicholas James1,Lucinda Billingham1,Maurice Zeegers2,Kar Keung Cheng1
1University of Birmingham,2University of Birmingham & University of Maastricht

Abstract

Background

The SELENIB trial aimed to determine whether selenium or vitamin E could prevent recurrence in non-muscle-invasive bladder cancer (NMIBC) patients.

Method

A double-blind randomized placebo-controlled 2x2 factorial trial aimed to recruit 515 newly-diagnosed NMIBC patients between 17/07/2007 and 10/10/2011. Eligibility included a new diagnosis of NMIBC; randomisation within 12months of initial transurethral resection of bladder tumour was required. Four possible interventions were oral selenium (200mcg/day high-selenium yeast) and matched vitamin E placebo, vitamin E (200IU/day d-alpha-tocopherol) and matched selenium placebo, selenium and vitamin E, or placebo and placebo for 5 years. Patients were otherwise treated according to contemporaneous EAU NMIBC guidelines. Primary outcome was recurrence-free interval. Secondary outcomes included progression-free interval and overall survival. A stratified log rank test was performed for comparing each supplement to placebo while stratifying for the other; hazard ratios were obtained using Cox’s regression model.

Results

We recruited 270 patients, with median follow-up of 5.4yrs and median duration of treatment of 1.5yrs. For selenium versus no selenium, no statistically significant difference in recurrence-free interval was observed, HR 0.92 (95% CI 0.65, 1.32, p=0.655). For vitamin E versus no vitamin E, the overall recurrence-free rate was 41% versus 60%, respectively. Vitamin E was associated with a statistically significant increase in risk of recurrence, HR 1.46 (95% CI 1.02, 2.09, p=0.039). No significant differences were observed for progression-free interval or overall survival with either supplement. A total of 85 unrelated SAEs and 27 grade ≥3 toxicities were reported.

Conclusion

Selenium supplementation did not influence recurrence, progression or survival. Vitamin E supplementation was associated with an increased risk of recurrence in NMIBC patients, but did not influence progression or overall survival. Despite being underpowered, the findings are in line with those from the Selenium and Vitamin E Cancer Prevention Trial. The effects of vitamin E on bladder carcinogenesis require further investigation.