Docetaxel-rechallenge in castration-resistant prostate cancer: defining clinical factors for successful treatment response and improvement in overall survival.

Abstract

The purpose of the study was to define clinical factors for successful treatment response and re-exposure to docetaxel in metastatic castration-resistant prostate cancer (mCRPC). An mCRPC database of patients receiving first-line docetaxel and rechallenge courses was established. Several clinical factors were evaluated for prediction of treatment response. Multivariate cox-regression analysis was used to define pre-treatment and treatment factors for survival. Between 2005 and 2013, 94 patients with mCRPC were treated with docetaxel. Full data set and follow-up were available for 62 patients. Median follow-up was 84m [interquartile range (IQR) 64-104m]. Median biochemical progression-free survival (bPFS) and overall survival under docetaxel were 9m (IQR 5-16m) and 20m (IQR 16-26m), respectively. Partial PSA-response at first docetaxel-sequence (n = 62), rechallenge (n = 32), and third-sequence (n = 22) docetaxel was 48.4%, 31.6%, and 34.8%, respectively. Time from start of primary androgen deprivation to CRPC > 47m was the only independent pre-treatment parameter to predict improved overall survival (Hazard Ratio 0.48, p = 0.015). Interestingly, there was a strong trend for improved overall survival in patients with high Gleason Score (Hazard Ratio 0.58; p = 0.08). Partial PSA-response at docetaxel-rechallenge (Hazard Ratio 0.31; p = 0.008) and treatment-free interval > 3m (Hazard Ratio 3.49; p = 0.014) were the only independent predictive factors under taxane treatment for overall survival. Despite novel hormonal drugs, docetaxel still plays an important role in the treatment of mCRPC. Patients with partial-PSA-response at rechallenge or a treatment-free interval > 3m benefit most from docetaxel re-exposure.