Combining therapies early in advanced prostate cancer

This review examined the benefit of adding docetaxel (Taxotere) or bisphosphonates to androgen deprivation therapy (ADT) in advanced prostate cancer. Authors reported a significant benefit when combining docetaxel with ADT in advanced metastatic prostate cancer. There is less evidence to suggest an advantage of bisphosphonates plus ADT.

ADT is a type of hormone therapy that targets androgens, the male sex hormones (such as testosterone), that can be invovled in cancer growth. Reducing androgen levels can improve survival among prostate cancer patients. ADT is currently the standard of care for advanced prostate cancer.

Chemotherapy, such as docetaxel, is often added in patients with cancer that is progressing despite hormonal therapy (called castration-resistant prostate cancer). However, recent evidence suggests that survival may be increased if chemotherapy is added to ADT to begin with, instead of waiting until the cancer progresses.

Bisphosphonates have also been under the focus of investigation as a possible additive treatment to ADT. Bisphosphonates are often used to treat bone damage in cases of metastatic prostate cancer (cancer that has spread). The benefit of combining docetaxel or bisphosphonates with ADT for advanced prostate cancer is still under exam. 

This study included 40 separate randomized trials, involving a combined total of 16,513 men with castration-resistant prostate cancer. 6,315 of these men had metastatic prostate cancer. 10,198 had locally advanced prostate cancer (spread to the nearby tissues). Treatment outcomes with either docetaxel plus ADT or bisphosphonates plus ADT were compared to ADT alone.

Adding docetaxel to ADT significantly improved overall survival among men with metastatic prostate cancer. 4-year overall survival (time from treatment until death from any cause) was improved by 23%, when compared to ADT alone. Docetaxel in combination with ADT also reduced disease progression by 36% relative to ADT alone.

Docetaxel plus ADT was less effective among men with locally advanced prostate cancer. No significant benefit in overall survival was noted. However, disease progression was reduced by 30% when docetaxel was added to ADT compared to ADT alone.

Overall, no treatment benefit was noted when bisphosphonates was added to ADT. This applied to men with metastatic, as well as locally advanced, prostate cancer. However, one specific type of bisphosphonate (called sodium clodronate) improved survival in men with metastatic prostate cancer by 23% in one trial studied. 

The authors concluded that the early addition of docetaxel to ADT should be considered as the standard-of-care for men with metastatic prostate cancer. There is currently no evidence to suggest an advantage of bisphosphonates plus ADT in advanced prostate cancer.