Enzalutamide in prostate cancer after chemotherapy

In the randomized trial reported by Scher et al. (Sept. 27 issue),1 the administration of enzalutamide, an androgen-receptor–signaling inhibitor, was associated with an increased incidence of headache, as compared with placebo, in patients with castration-resistant prostate cancer. Androgens are implicated in the pathogenesis of migraine; thus, it is important to understand whether the headache associated with enzalutamide could be classified as migraine. Moreover, a deeper understanding of the pathophysiology of this side effect is clinically relevant, since a relationship between migraine and the presence of either hot flashes or seizures has been described previously.2,3 Migraine and epilepsy have pathophysiological characteristics in common,3 so patients who have migraine during enzalutamide therapy may be at increased risk for seizures. Notably, headache was not reported as a clinically relevant symptom in patients with castration- resistant prostate cancer who received abiraterone, 4 a drug that deeply reduces circulating androgen levels. Abiraterone was administered in association with prednisone, and glucocorticoids are efficacious in preventing migraine.5 It would be interesting to know whether glucocorticoids were used in the management of enzalutamide- induced headache and whether they were effective.