Docetaxel in the Treatment of Metastatic Castration-resistant Prostate Cancer (mCRPC): an Observational Study in a Single Institution

Background: Treatment with docetaxel in combination with prednisone is the standard first-line treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). For patients failing first-line docetaxel no standard has emerged. Objectives: The outcome in routine daily clinical practice of a cohort of unselected chemotherapy-naive mCRPC patients treated with docetaxel plus methylprednisolone as first- and further-line treatment in a single institution was investigated. Patients and Methods: Data from the medical records of patients treated with docetaxel plus methylprednisolone either in a three-weekly (75 mg/m 2 ) (D3) or a three-of-four-weekly (35 mg/m 2 )(D1) schedule as first- or further-line treatment were analysed with respect to clinical and prostate-specific antigen (PSA) response, time-on-treatment (TOT), treatment-free interval (TFI), overall survival time (OS) and toxicity and were compared to the results of the registration study TAX 327. Results: Out of 41 patients, 28 and 13 received first-line docetaxel according to the D3 and the D1 schedules respectively. An overall PSA response ≥50% was achieved in thirty patients (73%). In ten patients (24%) the PSA level was normalised. The median OS of the total population was 18.7 months. No significant differences were observed between the D3 and the D1 regimens with respect to PSA response, duration of PSA response, TOT, TFI and OS. Patients obtaining a normalisation of PSA level achieved a significantly superior OS, TOT and TFI compared to those without normalisation of PSA. Second-line treatment with docetaxel in nine patients induced a normalisation in PSA level in two (22%). The TOT and TFI from the start of second-line treatment, was significantly superior in docetaxel compared to non-docetaxel treated patients. Treatment with docetaxel was well-tolerated and only two patients were withdrawn for non-haematological toxicity during first- and further-line treatment. There were no differences in either subjective or objective side-effects between both treatment schedules. Conclusion: The results of the retrospective analysis of non-selected patients with mCRPC treated with docetaxel chemotherapy are in line with the data from TAX 327. Normalisation of PSA during first-line treatment with docetaxel is associated with a better survival irrespective of second- or further-line treatment used. Retreatment with docetaxel in second- or further-line remains a treatment option in docetaxel-sensitive patients. Prostate cancer is the second most common cause of cancer death in men in the US (1) and the third most common cause of death in developed countries (2). In patients with metastatic prostate cancer, androgen deprivation therapy improves symptoms and quality of life, but patients eventually develop metastatic castration-resistant prostate cancer (mCRPC) leading to death (3). Docetaxel in combination with prednisolone has been demonstrated to improve survival and quality of life in patients with mCRPC (4-6) and is accordingly considered as the standard first-line treatment in these patients. However, in this treatment setting, a number of issues still remain to be solved, such as the optimal number of cycles: a fixed number of cycles until best response or intermittent treatment to avoid excessive toxicity. In patients progressing after docetaxel treatment, no standard second-line treatment has emerged and mitoxantrone in combination with prednisone have been proposed based on reports of their favourable effects on quality-of-life outcomes (7, 8). More recently, cabazitaxel, a tubulin-binding taxane drug in combination with prednisone has been shown in a large randomized study to produce significantly superior clinical activity compared with mitoxantrone plus prednisone in patients with mCRPC failing first-line treatment with docetaxel (9). Treatment with abiraterone, an inhibitor of the 17 alpha hydroxylase/c17-20-lyase complexes responsible for androgen synthesis, has shown a substantial decline in