61 Background: AA prolongs survival in mCRPC and is used pre- and post-chemotherapy. In the phase I trial, AA showed anti-tumor activity at 250 or 500 mg daily (‘low doses’). In addition, pharmacokinetic analysis showed that when AA was administered with a high-fat meal vs the fasting state, drug exposure was increased by 4.4-fold [ Attard G et al. Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven. J Clin Oncol 2008; 26: 4563-4571.]. Based on this, at our cancer centre low-dose AA is sometimes prescribed with high-fat meals to men who otherwise cannot access the drug due to funding constraints, particularly in the pre-chemotherapy setting. Our aim was to study the association between AA dose, PSA response and progression-free survival (PFS). Methods: All men receiving AA at PM (Nov2009-Mar2013) were reviewed retrospectively. PSA response rate (PSA-RR) was defined according to PCWG2 criteria as a confirmed decrease ≥50% in PSA. PFS was defined from start of AA to PSA progression, clinical progression, drug cessation or death. Associations between dose, PSA-RR and PFS were assessed using chi-square and logrank tests, respectively, for all patients and for the sub-group of chemo-naive patients. Results: 109 men were treated with AA, 89 at a full dose of 1000 mg in the fasting state, 20 at low doses with high-fat meals. There was no significant difference in PFS between the two dose levels for all men. PSA-RR was non-significantly lower in chemo-naive men treated with low doses compared to full dose (p=0.09; table). Conclusions: Administration of low dose AA with high-fat meals is not associated with shorter PFS despite a trend to lower PSA-RR. These results are clinically relevant in resource-limited settings and warrant further prospective clinical research. [Table: see text]
A Phase I Study of Everolimus and Docetaxel in Patients With Castration-Resistant Prostate Cancer