A systematic review of the effectiveness of docetaxel and mitoxantrone for the treatment of metastatic hormone-refractory prostate cancer

Abstract

A systematic review was performed to evaluate the clinical effectiveness of docetaxel in combination with prednisolone (docetaxel is licensed in the UK for use in combination with prednisone or prednisolone for the treatment of patients with metastatic hormonerefractory prostate cancer. Prednisone is not used in the UK, but it is reasonable to use docetaxel plus prednisone data in this review of docetaxel plus prednisolone) for the treatment of metastatic hormone-refractory prostate cancer. A scoping search identified a trial of docetaxel plus prednisone vs mitoxantrone plus prednisone, but did not identify any trials comparing docetaxel plus prednisolone/prednisone with any other treatments. Therefore, we considered additional indirect evidence that would enable a comparison of docetaxel plus prednisolone/prednisone with other chemotherapy regimens and active supportive care. Systematic searching (upto April 2005) identified seven randomised controlled trials. One large well-conducted trial assessed docetaxel plus prednisone vs mitoxantrone plus prednisone; this showed statistically significant improvements with 3-weekly docetaxel in terms of overall survival, quality of life, pain response and PSA decline. Two other chemotherapy regimens that included docetaxel with estramustine also showed improved outcomes in comparison with mitoxantrone plus prednisone. Three trials that compared mitoxantrone plus corticosteroids with corticosteroids alone were identified and their results for overall survival combined, which showed very little difference between the two groups. The addition of clodronate to mitoxantrone plus prednisone showed no significant differences in comparison with mitoxantrone plus prednisone alone. The evidence suggests that chemotherapy regimens containing 3-weekly docetaxel are superior to mitoxantrone or corticosteroids alone.

USP11-dependent selective cIAP2 deubiquitylation and stabilization determine sensitivity to Smac mimetics

“…In addition, the type II topoisomerase inhibitor mitoxantrone, which is widely used for the treatment of various tumor types, was recently identified as an USP11 inhibitor. Although mitoxantrone involves various pathways, such as inhibition of topoisomerase and induction of immunogenic cell death, to suppress tumor growth, [45][46][47] our data suggest that inhibition of the USP11-cIAP2 pathway by mitoxantrone contributes to its anticancer effects. Thus, combination treatment with mitoxantrone and Smac mimetics and/or TRAIL may synergistically enhance the desired antitumor effects.…”

Docetaxel–ST1481 sequence exerts a potent cytotoxic activity on hormone‐resistant prostate cancer cells by reducing drug resistance‐related gene expression

“…It has been seen that Doc induces apoptosis through the mitotic catastrophe mechanism in different experimental models [18,19]. In fact, it was previously demonstrated that this taxane induces mitotic catastrophe in PC3 and DU145 lines, triggering the onset and development of a proliferating aneuploid cell population characterized by significantly altered DNA content [15]. In our preclinical model it is reasonable to suppose that the cells damaged by Doc but still proliferating represented a suitable target for the effect of a DNA-damaging agent such as ST1481, with the consequent increase in apoptotic cells.…”

KLK5 gene expression is severely upregulated in androgen-independent prostate cancer cells after treatment with the chemotherapeutic agents docetaxel and mitoxantrone

“…Docetaxel, which belongs to the family of taxanes, exerts its key mode of therapeutic action through the suppression of microtubule dynamic assembly and disassembly and, thus, the disruption of mitotic cell division, finally leading to apoptosis (Van Poppel, 2005). Mitoxantrone, is an anthracenedione, which through targeting and inhibiting topoisomerase II, impedes DNA and RNA synthesis, produces DNA strand breaks and, ultimately, induces apoptotic phenomena (Boland et al, 2000;Collins et al, 2006). Previous work from our research group has demonstrated that a broad range of chemotherapeutic agents, including anthracenediones and taxanes, cause distinct modulations of apoptosis-related genes, in a variety of human cancer cell lines.…”

“…Several clinical trials have demonstrated that employment of chemotherapeutic compounds docetaxel and mitoxantrone increases the survival of HRPC patients. These data lead to the approval of these regimens for standard HRPC treatment (Berry, 2005;Collins et al, 2006;Lassi and Dawson, 2009). However, it is believed that administration of a proper treatment scheme could only confront the disease temporarily, and thus should be accompanied by accurate tools for monitoring each cancer patient's response to it (Pienta and Smith, 2005;Hadaschik and Gleave, 2007;Lassi and Dawson, 2009).…”

“…The most effective approach for HRPC treatment, to date, appears to be the administration of the FDAapproved chemotherapy compounds docetaxel and mitoxantrone. These anticancer drugs have been proven to palliate the symptoms of the disease and to extend patients' survival periods (Berry, 2005;Pienta and Smith, 2005;Van Poppel, 2005;Collins et al, 2006). Nevertheless, the application of various chemotherapy schemes does not necessarily engender the same effects in every individual.…”