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.
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.
When men are newly diagnosed with prostate cancer, they are split into three broad categories: Low-Risk, Intermediate-Risk and High-Risk. This system, which was invented by Dr. Anthony D’Amico, is helpful for the proper selection of optimal treatment; men with more favorable types of prostate cancer can receive milder therapy and still maintain normal survival rates. In a recent e mail message from prostatesnatchers, below) these categories are defined and appropriate therapeutic options given. A major conclusion cited is that “the cancer of men with the favorable type of Intermediate-Risk prostate cancer behaves the same as Low-Risk. Analysis provides further clinical evidence that men with the favorable type of Intermediate-Risk prostate cancer can forego immediate radical therapy and embark on active surveillance.”
As far as treatment selection is concerned, as a general rule of thumb, men with Low-Risk disease are encouraged to simply monitor the disease, withholding therapy altogether unless tumor growth is detected on subsequent testing. At the other extreme, men with High-Risk disease typically undergo combination treatment with three forms of therapy: seed radiation, IMRT and hormone therapy, which is continued for a year and a half.
Treatment recommendations for men with Intermediate-Risk range widely from surgery, to the many types of radiation—IMRT, seed implants, SBRT and Proton therapy to focal therapy, as well as the alternative of simply giving hormone therapy by itself. This wide variety of treatment options is not merely a result of physician bias. It turns out that the types of cancer that occur in the Intermediate-Risk category also vary widely. At the “good” end of the spectrum, men with the favorable type of Intermediate-Risk disease have a condition that behaves more like Low-Risk while cancers men at the unfavorable end of the Intermediate-Risk spectrum have a condition that behaves more like High-Risk.
The indicators that define an unfavorable type of Intermediate-Risk disease are multiple intermediate characteristics rather than having a single Intermediate-Riskfactor. For example, it is considered unfavorable when the PSA is over ten and the Gleason is 4 + 3 (instead of 3 + 4) and there are more than 50% of the biopsy cores containing cancer. At the other extreme are men with the favorable type of Intermediate-Risk disease. These men are characterized by having all the Low-Risk factors in combination with only a single Intermediate-Risk factor.
Making a proper distinction between the favorable and unfavorable types of intermediate risk disease can be monumentally important as it relates to treatment selection. Studies show that men with favorable Intermediate-Risk disease are potential candidates for active surveillance. A recently published report at this year’s Genitourinary ASCO meeting bears directly on this issue:
In an abstract from the ASCO meeting authored by Ann Caroline Raldow from Harvard, 6500 newly-diagnosed men treated with radiation and hormone therapy at the Chicago Prostate Cancer Center between 1997 and 2013 were evaluated. Dr. Raldow calculated their survival rate after treatment based on their risk category: low, favorable-intermediate, unfavorable-intermediate, and high. Eight years after treatment 820 men had died, 72 of them from prostate cancer. Men in the favorable Intermediate-Risk category had the same survival rates as men in the Low-Risk category. Men in either the High-Risk category or in the unfavorable Intermediate-Risk category demonstrated an increased mortality rate from prostate cancer.
Bottom line, the cancer of men with the favorable type of Intermediate-Risk prostate cancer behaves the same as Low-Risk. Dr. Raldow’s analysis provides further clinical evidence that men with the favorable type of Intermediate-Risk prostate cancer can forgo immediate radical therapy and embark on active surveillance.
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.
I have some medical prostate cancer news forthcoming but I saw the following short article by Dr. Charles Stanley, Pastor of 1st Baptist Church of Atlanta, and published in his “In Touch” devotional dated June 30th. The familiar theme verse cited is from Romans 8:28 which says, “and we know that God causes all things to work together for good to those who love God, to those who are called according to His purpose.”
“Think about a circumstance in your life that you would change if you could.” (Prostate cancer perhaps?) “Are you frustrated? Worried? Angry? To experience the freedom of contentment in the midst of it, …..you must accept the situation as having been allowed by God, even if He didn’t cause it.”
“In those situations, I (Dr. Stanley) often pray, ‘Lord, I choose to accept this as though it’s coming from you. No matter what I see, I’m choosing to look to You.’ Then I can rest in His omnipotence and the knowledge that I am a child of the living God. Instead of feeling like a helpless, hopeless victim of my circumstance, I know I’m cared for and guided by my sovereign Father through whatever may come.”
“The second crucial decision is total submission. This does not mean approaching God insincerely and saying ‘Well Lord, I just want to thank you for this!’ No, it’s not. Be honest and admit ‘this is painful and I don’t like it. But I choose to submit to You because You are trustworthy and loving. I’m willing to persevere until You accomplish in me whatever You want. I choose to draw from Your strength for everything I need.’ If you make this decision and follow through, your fears will lose their power. Either you believe Romans 8:28 or you don’t. And if you do, you can entrust yourself to the Lord, knowing that He has your best interest at heart, will take care of you, and won’t ever leave your side. When you embrace these truths, you’ll have no reason to be anxious.”
P.S. If you are not sure of your relationship with God, and how Romans 8:28 applies to you individually, please see the website section entitled “How to enter into a personal relationship with God.”