What is the Current Role of Taxanes in the Treatment of Metastatic Prostate Cancer?

Since it FDA approval in 2004, docetaxel (a taxane based chemotherapy) has been the standard first-line chemotherapy for men with metastatic prostate cancer (mCRPC).

Other than the trial of Provenge all the successful phase III trials conducted in mCRPC focused on men experiencing cancer progression after first-line docetaxel chemotherapy. The implication is that improving the outcome of these men was the most critical unmet need facing men with prostate cancer. Additionally, men at this stage provided an opportunity to demonstrate an overall survival improvement more rapidly over a shorter time frame.

Since the approval of docetaxel four different drugs have been shown to provide an overall survival benefit on top of other clinical improvements for men whose disease progressed after their having had docetaxel: cabazitaxel (Jevtana), abiraterone (Zytiga), radium-223 (Xofigo), and enzalutamide (Xtandi).

Prior to 2010 the best standard of care after docetaxel failure was considered another round of docetaxel a few months after the initial failure (there is no evidence that this second round provided any survival advantage). Then mitoxantrone with prednisone was used which only provided palliative benefit (no survival advantage).

Now, given the fact that they supply a survival advantage, it is clear that these other, new drugs should be the next treatment steps after docetaxel failure.

Cabazitaxel (Jevtana), which is a newly approved “second-generation” taxane was shown to improve overall survival when added to prednisone compared with mitoxantrone plus prednisone in the TROPIC trial (hazard ratio

[HR] 0.72, 95% CI 0.61 to 0.84; median overall survival, 15.1 vs. 12.7 months; p < 0.0001) in 745 patients with mCRPC progressing after treatment with docetaxel. Progression-free survival (PFS) was also improved with cabazitaxel and prednisone (HR 0.75, 95% CI 0.65 to 0.87). Additionally, preliminary data suggested that some antitumor activity from cabazitaxel remained in men whom both docetaxel and abiraterone failed, with a prostate-specific antigen (PSA) response rate of approximately 50%. Not surprising there are now two ongoing phase III trials with the goal of evaluating the use of cabazitaxil in men with mCRPC compared with docetaxel in the first-line chemotherapy setting (FIRSTANA, NCT01308567). There is also another large phase III trial (PEACE 2) scheduled to evaluate cabazitaxel in men with localized prostate cancer and at a very high-risk of relapse. To date, all prior attempts to development of non-taxane chemotherapy have ended in failures. Clearly, despite the development of new drugs to treat mCRPC, taxane based chemotherapy still has a major role in the treatment protocol. Additionally, the very real possibility is that taxane based therapy could take on an even larger role in the future. Joel T. Nowak, M.A., M.S.W. [/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]

2 Comments

Cliff Dweller July 5, 2013 at 12:17 pm

“I have also become aware of the lack of understanding by clinicians and survivors that this treatment is meant to be used along side of other treatments, not in a sequence.”

I’m curious to know what ‘other treatments’ can be used along w/Xofigo. This is the first mention of this encountered. My husband has mCRPC w/PSA 796 and hopes to start Xofigo ‘ASAP’ (after not qualifying for early access–low hemoglobin). In the meantime, on Monday, he’ll start weekly Andriamycin. Previous treatments include radiation, SBRT, Taxotere, Provenge, and Xtandi, among others. Many thanks.
Joel July 5, 2013 at 3:52 pm

Using the results from the clinical trial that brought about the FDA approval one should couple Xofigo with the best standard of care included local EBRT, corticosteroids, antiandrogens, estrogens, estramustine or ketoconazole. The trials were designed prior to Zytiga and Xtandi so we do not have any information about what effect they might have when used together with Xofigo.

Additionally, men with Crohn’s disease, ulcerative colitis, prior hemibody radiation or untreated imminent spinal cord compression were excluded from the study. In men with bone fractures, orthopedic stabilization was performed before starting or resuming treatment with Xofigo. Xofigo is secreted through the gut, so it makes sense that it should not be used in men with gut issues.

At ASCO it was reported that Dr Sartor said that Xofigo should not be coupled with chemotherapy because of the significant toxicity that resulted in a small trial. I do not have any references about this that I can report.

The bottom-line is that during the trial Xofigo was coupled with the best standard of care has referenced above, not as a sole agent given independently of anyother treatemnt