Findings from a federally funded phase III study supported by the National Cancer Institute (NCI) indicate that adding the chemotherapy drug docetaxel (Taxotere?; Sanofi, Bridgewater, NJ 08807, USA)to standard hormone therapy extends survival for men with newly diagnosed hormone-sensitive prostate cancer by roughly 13 months. The survival benefit is even greater for the subset of men with extensive disease spread or high-extent disease. [1][2] The study results were presented as part of the Plenary Session at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO), which was being held May 30 – June 3, 2014 in Chicago, Ill.
?Hormone therapy has been a standard treatment for prostate cancer since the 1950s,? explained lead study author Christopher Sweeney, MBBS, associate professor, department of medicine, Harvard Medical School and a medical oncologist at the Lank Center of Genitourinary Oncology at the Dana-Farber Cancer Institute in Boston, MA. ?This is the first study to identify a strategy that prolongs survival in newly diagnosed metastatic prostate cancer. The benefit is substantial and warrants this being a new standard treatment for men who have high-extent disease and are fit for chemotherapy.?
The results of this trial shows a remarkable and meaningful prolongation in survival for advanced prostate cancer. It also shows that we can continue to learn more even about older treatments…
Androgen deprivation
Androgen hormones, testosterone and dihydrotestosterone (DHT), fuel prostate cancer growth. Hormonal therapy, also called androgen deprivation therapy (ADT) or androgen suppression therapy, alone is the standard first-line treatment for hormone-sensitive prostate cancer. The primary goal with this kind of therapy is to reduce levels of male hormones in the body or to prevent them from reaching prostate cancer cells. Androgens stimulate the growth of prostate cancer cells, hence, while hormone therapy does not ‘cure’ prostate cancer, lowering androgen levels or stopping them from getting 
into prostate cancer cells may results in prostate cancers shrinkage.
Although ADT is effective, the disease eventually becomes resistant to the therapy in most patients. About 30,000 patients die of hormone-resistant prostate cancer in the United States every year. Chemotherapy is typically initiated only after the disease progresses despite ADT.
Clinical Study
In this National Cancer Institute-led study, 790 men with newly diagnosed metastatic prostate cancer were randomly assigned to receive either ADT alone or ADT with docetaxel over a period of 18 weeks.
Approximately two-thirds of patients had high-extent disease, meaning that the cancer had spread to major organs and/or the patient had bone metastases. When the disease worsened, 45 patients in the ADT plus docetaxel group received additional docetaxel. In the ADT only group, 123 patients received docetaxel at disease progression.
Trial results
At a median follow-up of 29 months, there were 136 deaths in the ADT-alone group vs. 101 in the ADT plus docetaxel group. The median overall survival was 44 months in the ADT group and 57.6 months in the ADT plus docetaxel group. The relative improvement in median overall survival was even larger among the 520 patients with high-extent disease (32.2 months vs. 49.2 month. The relative improvement in median overall survival was even larger among the 520 patients with high-extent disease (32.2 months vs. 49.2 months). The median overall survival for the subset with low-extent disease takes longer to reach as these patients respond better to ADT, and the median survival has not yet been reached.
Docetaxel also delayed disease progression, assessed by either PSA rise or appearance of new metastases or symptom worsening. At one year, the proportion of patients with PSA levels less than 0.2 ng/mL (a PSA level of less than 0.2 is considered a sign of a better remission) was 11.7% in the ADT group vs. 22.7% in the ADT plus docetaxel group. The median time to clinical progression (new symptoms or metastases detected on a scan) was 19.8 months in the ADT group vs. 32.7 months in the ADT plus docetaxel grou new metastases or symptom worsening.
At one year, the proportion of patients with PSA levels less than 0.2 ng/mL (a PSA level of less than 0.2 is considered a sign of a better remission) was 11.7% in the ADT group vs. 22.7% in the ADT plus docetaxel group. The median time to clinical progression (new symptoms or metastases detected on a scan) was 19.8 months in the ADT group vs. 32.7 months in the ADT plus docetaxel group.
New treatment paradigm
This new treatment paradigm will entail earlier, multidisciplinary care involving the collaboration of both urologists and oncologists, who both commonly treat men with prostate cancer, Dr. Sweeney said. Follow-up of patients will continue to assess survival benefits for patients with low-extent disease. Health Related Quality-of-Life (hrQoL) data from this study will be analyzed and reported at a later time.
Remarkable and Meaningful: Federally Supported Studies
?This study shows a remarkable and meaningful prolongation in survival for advanced prostate cancer. It shows that we can continue to learn more even about older treatments,” said 2013 – 2014 ASCO president Clifford A. Hudis, MD, FACP., Chief, Breast Cancer Medicine Service, at Memorial Sloan Kettering, New York, NY. ?Importantly, this study is yet another example of the large impact of the federally funded research system. These results answer critical questions faced by people with cancer and their doctors every day. There is no doubt that patients will live longer and better because of these studies. These major advances ? and many others in the history of cancer research ? were only possible thanks to our nation?s long-standing commitment to funding clinical cancer research. That commitment must be sustained.”
For more information:
[1] Sweeney C, Chen YH, Carducci MA, Liu G, Jarrard DF, Eisenberger MA, Wong YN, Hahn NM et al. Impact on overall survival (OS) with chemohormonal therapy versus hormonal therapy for hormone-sensitive newly metastatic prostate cancer (mPrCa): An ECOG-led phase III randomized trial. Plenary Session, Sunday June 1, 1:00 PM to 4:00 PM, Abstract No: LBA2 [Abstract]
[2] CHAARTED: ChemoHormonal Therapy versus Androgen Ablation Randomized Tri-al for Extensive Disease in Prostate Cancer/E3805 physician INFORMATION [Fact Sheet]
Photo: Christopher Sweeney, MBBS, Plenary Session. Photo Courtesy: ?ASCO/Phil McCarten.
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