Background: Abiraterone acetate (AA) has recently been approved for men with metastatic castration-resistant prostate cancer (CRPC) following docetaxel chemotherapy. AA inhibits CYP17, reducing androgen production and thereby impacting androgen receptor (AR) signalling. Recent evidence suggests taxanes also impact AR signalling, raising concerns about potential cross-resistance. We have previously shown that docetaxel has no antitumor activity in AA refractory patients. We have now evaluated the antitumor activity of AA post-docetaxel to determine the activity of AA in docetaxel refractory patients. Methods: Forty four men with CRPC treated with docetaxel (75 mg/m2 every 21 days) followed by post-chemotherapy AA at the Royal Marsden Hospital were identified. Radiological response by RECIST, PSA response by PSAWG2 criteria and symptomatic benefit were evaluated. Results: An average of 9 cycles of docetaxel were given (range 3-17); 7 patients discontinued chemotherapy due to progression of disease and 10 for toxicity. Of 40 patients with PSA data available, 26 (65%) had a PSA decline of at least 50%. At commencement of AA, median age was 68 years. Bone, nodal and visceral metastases were present in 38 (86%), 23 (52%) and 6 (14%) of the cohort respectively. An average of 5 months of treatment were delivered and 23 patients continue on AA. Of the 44, 7 (16%) patients had a 50% or greater PSA decline on AA. None of the 7 patients who were docetaxel refractory had a subsequent PSA, radiological or clinical response to AA. Of the 6 patients who received less than 5 cycles of docetaxel due to toxicity, 2 had subsequent PSA response on AA. There was no relationship between length of time on LHRH agonist and PSA response to AA. Conclusions: Our data suggest that patients who are refractory to docetaxel do not respond to AA. Overall, in conjunction with our other evidence that in AA-refractory patients docetaxel has no antitumor activity, these data provide further evidence for cross-resistance between these two agents.