Chemotherapy in hormone-sensitive metastatic prostate cancer: Evidences and uncertainties from the literature

Abstract

Data from the literature support with strong evidence the addition of docetaxel to androgen-deprivation therapy (ADT) for men with metastatic prostate cancer, and starting therapy for the first time. A meta-analysis of three randomized controlled trials showed a significant improvement of overall survival when ADT was combined with docetaxel when compared to ADT alone (HR=0.77; 95% CI: 0.68-0.87; p<0.0001). Consequently, combination therapy should be considered presently as the new standard of care, using 6 cycles of docetaxel, without prednisone. However, candidates for this upfront combination therapy in whom the balance between its side effects and benefits is favorable are still to be identified more precisely. Patients' stratification according to Gleason score, previous local treatment and age or performance status were shown to have a prognostic impact. The volume of metastases, as defined in the CHAARTED study for instance, could be an interesting predictive factor. However, data accumulated until now remain only hypothesis generating and further analysis and studies are needed to establish any potential discriminating factors. Several new efficient therapeutic options are now available in prostate cancer management and should be evaluated against a chemo-hormonal combination therapy. Other trials are warranted to establish the role of docetaxel in earlier stages of the disease, the combination with the new hormonal therapies as well as the best management options after docetaxel.

Treatment effects in prostate cancer

“…4 Men with localized or metastatic high-risk disease will typically be treated with RT with or without hormonal therapy, while patients with recurrent or metastatic, castratesensitive or -resistant disease can be offered chemotherapy. [5][6][7][8] The potential of targeted therapies based on leveraging of the patient's immune system to treat the cancer is currently being actively evaluated. 9,10 Most of the aforementioned nonsurgical treatments can have marked effects on the histological appearance of tumor and non-tumor prostate tissue, which have been well described.…”

Novel treatment options in the management of metastatic castration-naïve prostate cancer; which treatment modality to choose?

“…Additionally, several meta-analyses have made some cautious, indirect comparisons on the best treatment of mCNPC patients in terms of OS and other end points [25][26][27][28][29][30][31][32]. A 23-27% reduction in the risk of death was observed when ADT was combined with docetaxel compared with ADT alone with pooled HRs of 0.73-0.77, and the addition of abiraterone to ADT resulted in a 37%-40% reduction in risk of death with pooled HRs of 0.60-0.63 (Table 4).…”

“…In general, patients with previous local treatment had longer OS compared with those with newly diagnosed metastatic disease [33]. In CHAARTED a preplanned subgroup analysis was conducted, showing no statistically significant benefit by the addition of docetaxel to ADT in the patient group with recurrent disease after prior local therapy (HR ¼ 0.55, 95% CI 0.23-1.31, P > 0.05) [10,19]; however, the trial was not sufficiently powered for a subset analysis of this much smaller subgroup (27%) [10,27]. Since patients recurring after local therapy are not well represented, the benefit of early docetaxel in this patient group is not known.…”

Chelerythrine induced cell death through ROS-dependent ER stress in human prostate cancer cells

“… 2 Despite advances in clinical treatment, by antihormonal therapy, radiotherapy, and chemotherapy, prostate cancer remains a major cause of cancer-related morbidity and mortality. 3 – 5 Over 70% of cancer metastasis from prostate cancer develops bone metastases because of the insensitivity with the abovementioned clinical treatments. An increasing number of patients experience tumor progression to hormone-refractory prostate cancer, resulting in serious problems in the treatment of prostate cancer.…”