No Additional Benefit of Venlafaxine or Soy Protein vs Placebo on Hot Flashes in Men With Prostate Cancer
Hot flashes occur in approximately 80% of androgen-deprived men. In a randomized study reported in the Journal of Clinical Oncology by Mara Z. Vitolins, DrPH, MPH, RD, of Wake Forest School of Medicine, and colleagues, neither venlafaxine nor soy protein—both of which have been used to treat menopausal symptoms in women—improved hot flashes in men with prostate cancer more than placebo. Soy protein vs no soy protein was found to have a beneficial impact on quality of life.
Study Details
In the study, 120 androgen-deprived men were randomly assigned to one of four daily regimens for 12 weeks in a 2×2 factorial design: milk protein powder (20 g, one packet per day) and placebo pill (n = 30), venlafaxine (75 mg once daily in the morning) and milk protein powder (n = 30), soy protein powder (20 g with 160-mg isoflavones, one packet per day) and placebo (n = 30), or venlafaxine and soy protein powder (n = 30). The primary endpoint was hot flash symptom severity score. Patients recorded the total number of hot flashes or night sweats daily and averaged their severity (1 = mild, 2 = moderate, 3 = severe). Daily hot flash symptom severity score was calculated as the number of hot flashes times the severity ratings, and a weekly mean score was calculated. Quality of life was also assessed, using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and FACT-General (FACT-G) scales; the FACT-P scale consists of the FACT-G scale plus a prostate-specific subscale.
Patient groups were generally well matched for age (median, 67–71 years), body mass index (80%–90% overweight or obese), race/ethnicity (73%–83% white), stratification by disease stage/hot flash severity (eg, metastatic/severe in 3%–10%, nonmetastatic/moderate in 50%–57%), Eastern Cooperative Oncology Group performance status (0 in 70%–97%), and treatments (eg, luteinizing hormone-releasing hormone in 77%–87%).
Significant Improvements in All Groups
Overall, significant decreases (all P < .001) were observed in mean number of hot flashes in all groups (from 8.8–10.0 to 4.1–5.9), mean severity in all groups (from 2.1–2.4 to 1.6–1.8), and mean hot flash symptom severity score in all groups (from 21.3–22.9 to 9.2–13.6) at 12 weeks with no significant differences among groups. At week 12, hot flash symptom severity score was reduced by 28% in the venlafaxine plus soy group, 35% in the venlafaxine group, 31% in the soy group, and 55% in the placebo group.
There were no significant differences among groups in number of hot flashes at any time point, although patients who received venlafaxine tended to have fewer hot flashes during the initial 2 weeks. There were no significant differences in severity between the soy and placebo groups at any time point, with the venlafaxine group tending to have lower scores at weeks 1 to 4. With regard to hot flash symptom severity score, although the placebo group initially did poorly, the group had the greatest percentage decline from baseline to 12 weeks, resulting in early termination of the trial by the Data Safety Monitoring Board due to lack of effect.
An interaction between venlafaxine and visit was significant (P = .014), with an initial greater effect of venlafaxine being lost over time. Hot flash symptom severity score was decreased by 28% at week 2 in patients receiving venlafaxine compared with 2% in those not receiving venlafaxine (P = .005); by week 12, the decreases were 29% vs 36% (P = .723).
Quality-of-Life Results
Quality-of-life results according to whether patients did or did not receive venlafaxine or soy showed no significant effect of venlafaxine vs no venlafaxine on subscales or total FACT-P or FACT-G scores. Compared with patients not receiving soy protein, those receiving soy protein had significant improvements in emotional (P = .029) and functional (P = .041) subscales and in total FACT-G (P = .025) and FACT-P scores (P = .048).
Toxicity was minimal and did not differ among groups. Of 19 adverse events reported, 2 were considered probably and 2 were considered possibly related to study treatment.
The investigators concluded, “In androgen-deprived men, neither venlafaxine nor soy proved effective in reducing hot flashes. Interventions that appear effective for decreasing hot flashes in women may not always turn out to be effective in men.”
The study was supported by the National Cancer Institute/Division of Cancer Prevention, National Center for Complementary and Alternative Medicine, and Physicians Pharmaceuticals.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
