Medical Oncology Biochemical and Objective Response to Abiraterone Acetate Withdrawal: Incidence and Clinical Relevance of a New Scenario for Castration-resistant Prostate Cancer Orazio Caffo, Antonio Palermo, Antonello Veccia, Francesca Maines, Franca Chierichetti, Alfredo Berruti, and Enzo Galligioni OBJECTIVE To describe the incidence and clinical relevance of biochemical and objective responses to abiraterone acetate (AA) withdrawal (AAWD) in patients with castration-resistant prostate cancer (CRPC). MATERIALS AND METHODS Twenty-six patients with progressive CRPC treated with first-line docetaxel-based chemotherapy were administered with AA at the standard dose of 1000 mg/day in combination with prednisone until progression. The patients were regularly followed up during treatment and after AAWD. RESULTS Nineteen of the 26 patients discontinued AA because of progression. Three of the patients undergoing AAWD experienced a biochemical response, which was accompanied by a metabolic and radiological response as revealed by choline positron emission tomography in 2 cases. CONCLUSION Regardless of the underlying molecular bases, AAWD response does not occur rarely. It is sometimes long-lasting and accompanied by a metabolic and radiographic improvement. AAWD response should be taken into account when further therapeutic strategies are planned in patients with CRPC with progressive disease during abiraterone therapy. UROLOGY 82: 1090e1093, 2013. Ó 2013 Elsevier Inc. A biraterone acetate (AA) is an irreversible, potent, and selective CYP17 inhibitor. 1 As CYP17 is present in adrenal, prostate, and intratumoral tissues, AA can interfere with androgen production to a greater extent than traditional androgen deprivation using luteinizing hormone releasing hormone (LHRH) analogs, which only affect gonadal androgen synthesis. After phase II trials had shown that AA was active in patients with castration-resistant prostate cancer (CRPC) progressing after first-line docetaxel therapy, 2-4 the drug efficacy was demonstrated by the results of a phase III placebo-controlled trial, that clearly showed a survival benefit of abiraterone plus prednisone vs placebo plus prednisone at the initial interim analysis (median survival 14.8 vs 10.9 months) 5 and the end of the study (median overall survival 15.8 vs 11.2 months). 6 Despite the good efficacy of AA, some patients might show primary drug resistance and fail to respond, and the majority is destined to become resistant to the drug after an initial durable response. Under these conditions, other drugs active against CRPC can be proposed if they have not been previously administered, as it has been shown that cabazitaxel (a new-generation taxane) and enzalu- tamide (which acts by means of a triple androgen receptor [AR] blockade) are both active after docetaxel failure and lead to a gain in survival. 7,8 However, it has been recently observed that AA withdrawal (AAWD) itself may induce a transient biochemical response 9,10 and reproduce the clinical scenario that has been described with withdrawal syndrome after antiandrogen therapy. 11 To our knowledge, the frequency and duration of AAWD in CRPC with disease progression during AA therapy are not known. This article describes the inci- dence and clinical relevance of AAWD in a consecutive series of CRPC followed up in a single institution. PATIENTS AND METHODS AA has recently been approved by the Italian regulatory authorities and will soon be available for daily clinical practice in Italy. However, in the last months, the drug was made available by means of an expanded access or named patient program supervised by local ethics committees to allow patients with CRPC to receive it after docetaxel failure. In September 2011, our hospital started an AA NNP that continued until September 2012. All the patients were affected Financial Disclosure: The authors declare that they have no relevant financial interests. From the Medical Oncology Department, Santa Chiara Hospital, Trento, Italy; the Nuclear Medicine Department, Santa Chiara Hospital, Trento, Italy; and the Depart- ment of Medical and Surgical Specialties, Radiological Sciences and Public Health, Medical Oncology, University of Brescia, Brescia, Italy Reprint requests: Orazio Caffo, M.D., Medical Oncology Department, Santa Chiara Hospital, Largo Medaglie d’Oro, 38100 Trento, Italy. E-mail: orazio.caffo@apss.tn.it Submitted: June 16, 2013, accepted (with revisions): July 18, 2013 1090 ª 2013 Elsevier Inc. 0090-4295/13/$36.00 All Rights Reserved http://dx.doi.org/10.1016/j.urology.2013.07.029