Recurrent Prostate Cancer Treatment
As noted above, studies have shown that chemotherapy with docetaxel or cabazitaxel and immunotherapy with sipuleucel-T can prolong OS in patients with hormone-resistant metastatic prostate cancer. Nevertheless, hormonal therapy has also been shown to improve survival even in men who have progressed after other forms of hormonal therapy as well as chemotherapy.
Evidence (hormonal approaches):
- Abiraterone inhibits androgen biosynthesis by blocking cytochrome P450 c17 (CYP17). Men with metastatic prostate cancer who had biochemical or clinical progression after treatment with docetaxel (N = 1,195) were randomly assigned in a 2:1 ratio to receive either abiraterone acetate (1,000 mg) (n = 797) or placebo (n = 398) orally once a day (COU-AA-301 [NCT00638690]). Both groups received prednisone (5 mg) orally twice a day.[Level of evidence; 1iA]
- After a median follow-up of 12.8 months, the trial was stopped when an interim analysis showed an OS advantage in the abiraterone group. The final report of the trial was published after a median follow-up of 20.2 months.
- Median OS was 15.8 months in the abiraterone group versus 11.2 months in the placebo group (HRdeath of 0.74; 95% CI, 0.64–0.86; P < .0001).
- Abiraterone has mineralocorticoid effects, producing an increased incidence of fluid retention and edema, hypokalemia, and hypertension.
- Enzalutamide, an androgen-receptor signaling inhibitor, has been shown to increase survival in patients with progressive prostate cancer who received prior androgen deprivation therapy as well as docetaxel. In a double-blind, placebo-controlled trial, 1,129 men were randomly assigned in a 2:1 ratio to receive enzalutamide (160 mg orally per day) versus placebo.[Levels of evidence; 1iA, 1iC]
- After a median follow-up of 14.4 months, the study was stopped at the single-planned interim analysis because improved OS, the primary endpoint, was found in the enzalutamide study group (median OS, 18.4 months; 95% CI, 17.3 to not yet reached vs. 13.6 months; 95% CI, 11.3–15.8; HRdeath of 0.63; 95% CI, 0.53–0.75; P < .001). In addition, quality of life, measured by the FACT-P questionnaire, was superior in the enzalutamide arm.
A seizure was reported in five of the 800 men in the enzalutamide study group, versus none in the placebo group; however, the relationship to enzalutamide is not clear. Of the reported seizures, two patients had brain metastases, one patient had just received intravenous lidocaine, and one seizure was not witnessed.