Chemotherapy for hormone refractory cancer prostate: DO we really have something good ?

The classic scenario of metastatic Prostatic cancer treatment entails very rapid early response to androgen suppression that lasts for a median of 15-24 months followed by a hormone refractory phase with a fatal outcome within few months. During the last two decades, several small sized studies using different chemotherapeutic drugs could show an extremely modest response rate (less than 10%) with no impact on survival. In addition to the lack of effective drugs, patients with HRPC suffered from being an unfavourable patient population because of old age, poor performance, significant co-morbidity and lack of objective response criteria (90% have predominant osseous metastasis).
In a randomized phase II study, mitoxantrone/prednisone was the first combination that could show significant improvement in palliative benefit with prolongation of symptomatic control compared to prednisone alone. However, there was no significant advantage of MP neither in terms of PSA decline nor overall survival. Following this study (1996), MP was considered as the standard treatment for HRPC.
Recently, it has been demonstrated that HRPC has two important molecular features which may explain its chemo-resistance:

1. Over-expression of BCL2 (65% in HRPC versus 25% in hormone naïve cases)

2. Presence of mutant P53 gene in more than 75% of HRPC

Accordingly, Taxanes with their ability to induce tumour cell apoptosis independent on P53 may stand as a reasonable approach to treat HRPC.
Furthermore, Taxanes especially Docetaxel have a unique feature being able to inactivate BCL-2 (via phosphorylation). In phase II studies, both Taxanes could demonstrate a response rate ranging from 20-45% in HRPC.
On the other hand, Estramustine (Estrogenic molecular conjugated with non-nitrogen mustard) has been shown to inhibit microtubular proteins with significant synergy with Taxanes.