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.
