Category: Treatment Information

In a recent interview, Dr. Mario Eisenberger, Professor of Urology and oncology at Johns Hopkins, summarized a group of on-going clinical trials for patients with metastatic, hormone-resistant prostate cancer.  Trials are ongoing combining agents targeting the androgen receptor such as abiraterone (Zytiga®) with chemotherapies such as docetacel® (taxotere) or cabazitaxel (Jevtana®). Other trials such as the Alliance trial, combines abiraterone with enzalutamide (Xtandi®).  An on-going phase III trial combines abiraterone with radium -223 (alpha-radin, Xofigo®) in men with metastaic disease who have not received chemotherapy.  Dr. Eisenberger states that there are a number of trials combining approved drugs with chemotherapy and hormonal therapy and radiopharmaceuticals such as radium-223.  There are also trials using combinations of PARP inhibitors (s0 far un-approved for prostate cancer) with standard, second line hormonal therapies. Also there are antitumor PI3K  and AKT inhibitors some of which inhibit more than one pathway which are over-expressed in prostate cancer patients who progress on androgen receptor-targeted compounds such as abiraterone or enzalutamide.  The question is whether PI3K or AKT inhibitors will enhance the effects of abiraterone or enzalutamide.  Dr. Eisenberger also discusses trials involving approved agents for metastatic disease as well as unapproved agents like TAK-700 (Ortoronel®) and ARN509 being tested in men with metastatic, hormone-naive cancer.  In addition, chemotherapy trials such as CHAARTED and STAMPEDE are discussed.  This post is primarily aimed at physicians.  If you are a patient with metastatic disease, I suggest you discuss these trials with your physician to see if any one would apply to your specific situation.

In a follow up to earlier website posts, British researchers have found that starting the chemotherapy drug docetaxel® at the same time as hormone therapy can improve survival for men with newly diagnosed, advanced prostate cancer.  The full article describing the study was published in the Prostate Cancer Foundation June 1 issue of NewsPulse.  Currently, chemotherapy is generally given after hormone therapy stops working.  But the new study found that when the two therapies were paired at the start of treatment, patients lived an average of 10 months longer. The combination had even greater benefits for men whose prostate cancer had spread to other parts of their bodies — known as “metastatic” cancer. These men experienced an average 22-month improvement in their overall survival, the findings showed.  Men treated with hormone therapy alone lived an average of 67 months. Those treated with docetaxel® and hormone therapy ended up surviving an average of 77 months, a relative improvement of 24 percent.  Those with invasive prostate cancer survived an average 65 months when they received docetaxel® and hormone therapy together, compared with 43 months for men who received just hormone therapy, the investigators found.  The chemotherapy drug appeared to benefit men by holding their cancer at bay.  Docetaxel® extended the time to relapse by 38 percent in all patients.  Hormone therapy can cause fatigue, anemia, brittle bones, decreased muscle mass and loss of sexual function, while chemotherapy drugs open the body to a host of debilitating side effects.  But the researchers noted that the addition of chemotherapy to hormone therapy in this study was well-tolerated. Very few men dropped out due to side effects from the chemotherapy, they added.  The researchers state that is hoped that these findings will encourage doctors to offer docetaxel® to men newly diagnosed with metastatic cancer.

Similar studies have been discussed in the website posts dated  June 9th and May 14th, 2015.

A new study suggests that adding radiation therapy to hormone therapy improves the chances of survival for men with prostate cancer that has spread to nearby lymph nodes.  Investigators at Massachusetts General Hospital’s Cancer Center focused on 318 patients treated with hormone therapy alone and 318 who received hormone therapy and radiation therapy. The five-year death risk among those who received the combination therapy was 50 percent lower than among those who received hormone therapy alone, the findings showed.  The study was published online May 11 in the Journal of the National Cancer Institute.  A summary was published in the Prostate Cancer Foundation June NewsPulse.  “It appears that more aggressive local management of prostate cancer confined to the pelvis can offer more durable disease control, prevent the disease from spreading further and, for some patients, even provide a potential cure,” senior study author Dr. Jason Efstathiou, of Massachusetts General Hospital’s Cancer Center and department of radiation oncology, said in a hospital news release.

The self-adjuvanted RNActive vaccine (CV9103) appears to be well-tolerated and immunogenic in men with advanced castration-resistant prostate cancer, according to a new phase I/IIa study. German researchers have been studying this new vaccine approach and they believe it has the potential to improve outcomes in men with resistant disease.

CV9103 is a sequence-optimized, chemically unmodified mRNA immunotherapy targeting four antigens: prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), prostate stem cell antigen (PSCA), and six-transmembrane epithelial antigen of the prostate 1 (STEAP1). These antigens are frequently and almost exclusively expressed in the prostate and over-expressed in prostate cancer. However, they noted that PSMA is also over-expressed in other cancers.   These antigens were picked for the vaccine because they are mainly found on residual prostate cancer cells after radical prostatectomy or radiation.  German researchers conducted a study with CV9103 in 44 patients with advanced castration-resistant prostate cancer.  The primary endpoint of the study was safety and tolerability, and the secondary endpoints included induction of antigen specific immune responses monitored at baseline and at weeks 5, 9, and 17.  Of the 33 evaluable patients treated at 1280 μg, a cellular immune response could be detected in 76% of the patients (n= 25). The researchers, who published their findings in the Journal for ImmunoTherapy of Cancer, found that immune responses against all four antigens could be induced, indicating the versatility of the platform.  The study demonstrated that CV9103 was well-tolerated and the majority of treatment-related adverse events were mild to moderate.

“The data generated by this phase I/IIa clinical study demonstrate that CV9103 mRNA was well-tolerated and immunogenic.  Furthermore, a trend towards longer survival time was also observed in immune responders,” said senior author of the paper Arnulf Stenzl, MD, who is the Medical Director of the Department of Urology, University of Tübingen Medical School, Tübingen, Germany. “Based on these results, it is evident that this mRNA technology warrants further clinical investigation.”  The researchers are now conducting a randomized, placebo-controlled, phase IIb study in 197 prostate cancer patients with the next generation experimental vaccine CV9104.  This second vaccine (CV9104) targets six antigens, including the additional antigens prostatic acid phosphatase (PAP) and MUC1.

If you have metastatic, hormone-resistant prostate cancer and are concerned about metastases to bone, the following short articles could be of interest to you and especially to your medical practitioner, with whom they should be shared.  They are written for physicians and come from a website called Cancer Network – Oncology.  Prostate cancer’s unique affinity for metastasis to the bone creates a unique need to prevent skeletal-related events (SREs) in order to maximize mobility and quality of life.  These articles describe the use of bone supportive agents such as denosumab (Xgeva®) and zoledronic acid (Reclast®) as well as life-extending anticancer therapies such as enzalutamide (Xtandi®), abiraterone (Zytiga®) and radium-223 chloride (alpharadin or Xofigo®). The linked articles are as follows: a) “Reducing Skeletal-Related Events in Metastatic, Castration (Hormone) Resistant Prostate Cancer” ; b) “Hitting Prostate Cancer Where It Hurts: Maximizing Control of Osseous Metastases”; and, c) “Progress in Prostate Cancer – at Last”, an encouraging article that contrasts progress in breast cancer with prostate cancer.  Remember to share these with your physician if they apply to your situation.

The recent national meeting of the American Society of Clinical Oncology (ASCO) contained several important presentations of interest to prostate cancer patients two of which are summarized below.

The plant-derived drug, docetaxel® (taxotere) had  been usually reserved for men whose tumors had become refractory (hormone-insensitive) and who had failed other therapies.  In a follow-up to earlier studies from Johns Hopkins and elsewhere, now researchers from Cedars Sinai Medical Center in Los Angeles reported that administration of docetaxel® (taxotere) in men with localized, high-risk, hormone-sensitive, prostate cancer led to a statistically-significant improvement in overall survival with a median follow-up of more than five (5)years. The cumulative incidence of distant metastases was also reduced. In the phase III study, 562 men with median age of 66 years with high-risk, localized prostate cancer were randomly assigned to treatment with radiation plus hormone therapy or standard therapy followed by docetaxel® chemotherapy.  Half of the men had high Gleason scores of 9-10.  See the following link for details.  Early administration of docetaxel® (taxotere) has also been discussed on this website, see May 14th, 2015 and September 20th, 2014.  For more information, see the story as covered by the BBC (see link).

In another presentation, according to Columbia University researchers, men undergoing intermittent androgen-deprivation (hormonal) therapy experienced more ischemic and thrombotic events than did men assigned to continuous hormonal therapy.