Enzalutamide-Induced Acute Maculopapular Rash in Treatment of Metastatic Prostate Cancer: First Case Report from a...

Enzalutamide is a new potent inhibitor of the signaling pathway for the androgen receptor with a half-life of 5.8 days. It has been on the market for the treatment of metastatic castration-resistant prostate cancer since November 2013. We report a case of acute generalized exanthematous maculopapular rash induced by enzalutamide. In summary, newer androgen receptor blockers have a propensity to cause skin related adverse effects. Most common among these are apalutamide. Enzalumatamide, per se, is a safe drug and has not been associated frequently in causing maculopapular rash. Few cases has been reported. In all these cases, the drug was discontinued and 2nd line therapy was instituted. In this report, Enzalutamide was withheld for 10 days and anti-histaminics was instituted. After a full recovery, Enzalutamide was reinstituted in treatment. A 62-year-old male patient with no significant medical history, was diagnosed in March 2020 with metastatic prostatic adenocarcinoma. Baseline PSA was 456 ng/ml. PSMA PET scan showed evidence of multiple bony metastasis. He was started on Degarelix subcutaneous injection with oral abiraterone initially. PSA level showed initial decreasing trend till September 2021 followed by sudden increase. Intramuscular Injection leuprolide was started and initial responses were good followed by later rise of PSA from January. Tab Xtandi (Enzalutamide) was added to the regimen from 31.1.22. Three days after starting enzalutamide treatment, the patient experienced an acute skin reaction. It is about of the plaques covered with widespread millimetric non-follicular papules. Enzalutamide was stopped after appearance of rashes to avoid further serious adverse effects. Anti-histaminics were started. Complete resolution of skin lesions occurred within 10 days. Tab Enzalutamide was reinstituted on 11th day after stoppage and on complete resolution of skin resolutions. According to the CTCAE 5.0 criteria, these skin rash was graded as grade 2. In view of evidence in literature and clinical improvement after stoppage, the acute drug reaction was attributed to enzalutamide. Uro oncologist can be confronted with adverse skin drug reactions attributable to new therapeutic molecules. The slow resolution of symptoms seems be due to the long half-life of enzalutamide. It should not be withdrawn from therapy owing to these effects. Rather, it should be with stopped for 10-14 days. Basic treatment with anti-histaminics or topical steroids may be enough to warranty the resolution of symptoms, and the drug (Enzalutamide) can be continued thereafter.