Multicenter, phase-III study comparing selenium supplementation with observation in gynecologic radiation oncology

Abstract

9539 Background: To assess prospectively whether supplementation of selenium [Se] can compensate a pre-existing selenium deficiency and decrease radiation-induced diarrhea in adjuvant radiotherapy (RT) for gynecological cancer. Methods: A prospective, randomized phase III study was conducted across 10 radiotherapy institutions in Germany. Patients [pts.] with cervical (n=10) or uterine (n=72) cancer and whole blood selenium deficiency after curative surgical treatment were randomized before entering radiation therapy [RT] to receive Se (as sodium selenite; selenase) per os (500 mcg on the days of RT and 300 mcg on the days without RT), or observation till the last day of RT. Whole blood selenium levels were measured before RT, after completing 50% of RT and at the end of RT. The primary endpoint was to compensate the selenium deficiency, the secondary endpoint was to decrease radiation-induced diarrhea. The study was approved by the International Ethics Committee in Freiburg, Germany. Results: From 2001–2006, a total of 82 pts. (age: 31–80) were randomized. Of these pts., 39 were in the Se group [SG] and 43 in the control group [CG]. FIGO-stages between the study groups were well balanced. Before RT, the mean selenium level was 65.5 mcg/l (39.6–86.8) in the SG and 64.5 mcg/l (36.9–83.6) in the CG (p=0.481, t-test). At the end of RT, the mean selenium level in the SG was 86.9 mcg/l (59.9–144.9) and in the CG 62.8 mcg/l (36.9–98.3) (p<0.001, t-test). The actuarial incidence of radiation-induced diarrhea of at least CTC 2 was 21.0% (95%CI: 14.4–27.6%) in the SG compared to 46.6% (95%CI: 38.5–54.7%) in the CG (p=0.039, log-rank). After a median follow-up of 38 months (1–72), the actuarial 5-year overall survival rate [OS] was 94.1% (95%CI: 90.1–98.2%) in the SG compared to 86.1% (95%CI: 80.2–92.0%) in the CG (p=0.308, log-rank). During supplementation, no selenium-related side effects were observed. Conclusions: For the first time, the significant benefit of sodium selenite with regard to selenium deficiency and radiotherapy-induced diarrhea in patients with cervical and uterine cancer could be shown in a prospective randomized trial. Overall survival rates show that supplementation of selenium does not interfere with the positive biological effects of RT. No significant financial relationships to disclose.