Biochemical recurrence of prostate cancer after primary therapy (PSA only) remains a significant problem. Deciding on the best treatment options for men who have failed primary therapy without documented evidence of metastatic disease remains limited and controversial.
Androgen deprivation therapy (ADT), the usual next step for biochemical recurrence does prolong the time to further disease progression. The use of ADT is strongly associated with very bothersome and some potentially fatal dangerous side effects. Side effects include metabolic syndrome, hot flashes, confusion, erectile dysfunction, cardiovascular disease, and type 2 diabetes and insulin resistance (Traish et al., 2009a,b,c). Clearly, nontoxic and economical therapeutic alternatives that prolong the interval between primary treatment failure and initiation of ADT would clearly be beneficial to both improving the quality of life and possibly extending survival.
In a Phase II study, low-dose, sustained delivery of glyceryl trinitrate (an alternate name for the chemical nitroglycerin, which has been used to treat angina and heart failure) (GTN) was used to treat men after failure of primary therapy for their clinically localized prostate cancer (Siemens et al., 2009). The researchers compared the PSA doubling time (PSADT) before and after GTN treatment initiation, as well as with a matched control group (assignment to the groups was not randomized) who received no immediate treatment for their PSA recurrence.
This rational for this trial using low-dose nitric oxide (NO) is supported by preclinical in vitro and in vivo evidence which confirmed the absence of cytotoxic activity against neoplastic cells, but revealed that its use decreased the emergence of a more malignant phenotype, including invasion and metastases induced by a hostile tumor micro-environment.
Seventeen of the 29 men enrolled in the study (58%) completed the 24 months of the study treatment. Results suggest a significant inhibition of disease progression, with the mean PSADT increasing to 31.8 months from 13.2 months before starting the investigational treatment. For the 17 men who completed the study, there was no evidence of asymptomatic metastases on the end-of-study bone scans.
When the treatment group was compared with the matched group of men a similar significant difference in PSADT was observed between the two groups.
The data is supported by results of another retrospective study using data from the HealthFacts™ database, which compared the time to “Nadir PSA + 2 ng/mL” and the time to “2X Baseline PSA” between prostate cancer patients who had had radical prostatectomy and GTN exposure (n=29) and attribute-matched control patients who had had radical prostatectomy and no GTN exposure (n=29). Results of this study were suggestive of GTN efficacy in delaying disease progression in post-radical prostatectomy prostate cancer patients (data on file, Nometics Inc, Ottawa ON; available at: www.nometicsinc.com).
This Phase II study is the first report of the clinical use of NO donors for the treatment of prostate cancer. Recently, Yasuda et al. (2006) published a Phase II trial demonstrating the benefit of GTN as an adjuvant to chemotherapy for nonsmall cell lung cancer.
Despite the seemingly significant effects on the PSADT as well as the lack of any adverse events suffered by any of the men in the study with the low-dose GTN patch in men with recurrent prostate cancer, these results must be interpreted with great caution. Remember, there has not been any evidence that slowing PSADT necessarily result in long-term clinical benefit or survival benefit with men who have recurrent prostate cancer.
Siemens DR, Heaton JP, Adams MA, Kawakami J, Graham CH. Phase II study of nitric oxide donor for men with increasing prostate-specific antigen level after surgery or radiotherapy for prostate cancer. Urology. 2009 Oct;74(4):878-83.
Traish AM, Guay A, Feeley R, Saad F. The dark side of testosterone deficiency: I. Metabolic syndrome and erectile dysfunction. J Androl. 2009a Jan-Feb;30(1):10-22.
Traish AM, Saad F, Guay A. The dark side of testosterone deficiency: II. Type 2 diabetes and insulin resistance. J Androl. 2009b Jan-Feb;30(1):23-32.
Traish AM, Saad F, Feeley RJ, Guay A. The dark side of testosterone deficiency: III. Cardiovascular disease. J Androl. 2009c Sep-Oct;30(5):477-94.
Yasuda H, Yamaya M, Nakayama K, Sasaki T, Ebihara S, Kanda A, Asada M, Inoue D, Suzuki T, Okazaki T, Takahashi H, Yoshida M, Kaneta T, Ishizawa K, Yamanda S, Tomita N, Yamasaki M, Kikuchi A, Kubo H, Sasaki H. Randomized phase II trial comparing nitroglycerin plus vinorelbine and cisplatin with vinorelbine and cisplatin alone in previously untreated stage IIIB/IV non-small-cell lung cancer. J Clin Oncol. 2006 Feb 1;24(4):688-94.
Joel T Nowak, M.A., M.S.W.
Just wondering if the Viagra like drugs would do the same as they increase the availability of nitric oxide and may help improve endothelial health.
A great question, but I don’t know the answer. – Joel
I have a high psa one doctor needs a biopsy another doctor say’s no another doctor put me on avodart I have no symtoms but I am impotent, I would like to take l,arginine/nitricoxide
is that a good advise can you please advise me, I am self treated.
You have not given me enough information. Have you had a DRE, what is the history of your PSA etc. – Joel
I am very lucky to have stumbled on to your website. I will come back often for the wealth of information you have here.
I have had my prostate removed but the PSA did not go to zero. It was .16. Over the last two years it has climbed to 7 and my Mayo Clinic doctor has put me on a hormone. I will see him again in October 2014 to see how effective this is for me. I would like to take one of the OTC Nitric Oxide products, since apparently L-Arginine (my former choice for a NO source) is not good for me from what I have read. I am understanding from your discussion that this could be of some benefit for me. If I am correct what kind of dosage should I be looking at and are you in a position to suggest a product in which you have confidence?
Thank you so much.
I HAD A RADICAL PROSTATECTOMY AT HOPKINS IN 1999. GLEASON 7 ,3.8 PSA.CANCER WAS CONFINED. TEN YRS LATER IN 2010 PSA WENT TO 0.7. GOT RADIATED 38 DAYS,NO HORMONE. PSA WENT TO 1.8 . FOR THE PAST 5+YEARS I CHECK EVERY 3 MONTHS. 1.8 TO 1.6.RIGHT NOW 1.7. HOWEVER FOR THE PAST 6 -7 YRS I TAKE GENISTEIN WHICH KILLS PROSTATE CANCER . AND FOR PAST 10 YRS HAVE BEEN TAKING D3 AND AHCC ( A MUSHROOM PRODUCT OUT OF JAPAN ,GREAT STUFF ). I HAVE NO SIDE EFFECTS FROM SURGERY SUCH AS ED OR URINARY BUT DO TAKE CIALIS ONCE IN AWHILE. BEING A PHYSICIAN I GET VERY MAD THAT WE DO NOT DO ENOUGH ALTERNATIVE MEDICINE. I GUESS THE PHARMACEUTICAL CO. SHY AWAY.
And yes I think taking 5 mg of cialis every day is a good idea especially with the drugs I mentioned in my prior comments.