Antitumour activity of docetaxel following treatment with the CYP17A1 inhibitor abiraterone: clinical evidence for cross-resistance?

BACKGROUND: Abiraterone and docetaxel are both approved treatments for men with metastatic castration-resistant prostate cancer (mCRPC). Abiraterone pre-docetaxel is currently undergoing evaluation in a phase III study. In vitro studies indicate that taxanes may act by disrupting androgen receptor signalling. We hypothesised that prior abiraterone exposure would adversely impact docetaxel efficacy. PATIENTS AND METHODS: We retrospectively evaluated activity of docetaxel in mCRPC patients previously treated with abiraterone, using Prostate Cancer Working Group and radiological criteria. RESULTS: Of the 54 patients treated with abiraterone, 35 subsequently received docetaxel. Docetaxel resulted in a prostate-specific antigen (PSA) decline of ≥50% in nine patients [26%, 95% confidence interval (CI) 13% to 43%], with a median time to PSA progression of 4.6 months (95% CI 4.2% to 5.9%). PSA declines ≥30% were achieved by 13 patients (37%, 95% CI 22% to 55%). The median overall survival was 12.5 months (95% CI 10.6-19.4). All patients who failed to achieve a PSA fall on abiraterone and were deemed abiraterone-refractory were also docetaxel-refractory (N = 8). In the 24 patients with radiologically evaluable disease, partial responses were reported in four patients (11%), none of whom were abiraterone-refractory. CONCLUSION: The activity of docetaxel post-abiraterone appears lower than anticipated and no responses to docetaxel were observed in abiraterone-refractory patients.

[Fertility disturbances in males working as professional computer operators]. / Zaburzenia plodnosci u mezczyzn profesjonalnie obslugujacych komputery.

From 2376 patients who were diagnosed as infertile between 1986-1991, 20 professional computer operator males in the age of 26-40 were chosen (0.8%). Their working time was at least 5 hours daily and they have been working for 2-12 years (mean 7.7 +/- 3.3 years). The mean number of spermatozoa in 1 ml of sperm was 45.5 +/- 23.7 X 10(6)/ml, the percentage of properly motile spermatozoa equaled 21.5 +/- 12.2% and the percentage of pathological forms equaled 26.6 +/- 6.1%. The percentage of properly motile spermatozoa was decreased in all patients. There was not significant tendency of decreasing of the number of spermatozoa in 1 ml of sperm and percentage of properly motile spermatozoa dependent on the years of working in front of computer monitors. Whereas percentage of pathological forms increases statistically significantly in dependency of the years of working.