Originally published 5/8/2019
If it shrinks BPH, can it kill prostate cancer (PCa)? That’s the question that sparked “the first long-term prospective randomized-controlled study of an intraprostatic molecular injectable treatment for low grade localized PCa to be reported.”[i]
The authors of the study include luminaries from sites such as Johns Hopkins and Mt. Sinai/Icahn School of Medicine. 146 participants with Grade Group 1 PCa were divided into three groups: 2 groups were administered a single fexapotide triflutate (FT) prostatic injection of either 15 mg or 2.5 mg, and the third served as a control group on Active Surveillance (AS). Patients were followed for 5 years using repeat biopsies, plus urologic exams and PSA every 6 months. (Those whose grade increased or who sought definitive treatment exited the study.) The results showed that a single FT treatment at the higher strength (15 mg) brought statistically significant inhibition of PCa progression both in terms of PSA and as evidenced by biopsy.
Since multiple treatments over time were not included, it’s not possible to determine if FT has the possibility to destroy PCa tumors. However, as a “non-toxic molecular approach,” FT for low-grade PCa offers “(1) the possibility to delay treatment interventions which may be associated with undesirable secondary effects, and (2) the option to continue an ongoing AS strategy yet offer patients an opportunity for potential cancer ablation.” The authors note this might help patients on AS who would otherwise feel anxious over wondering if their disease is progressing.
That said, one study does not make FT ready for “prime time” management of low-grade PCa.
The 18th century French writer and philosopher Voltaire was known for his wit. One remark is especially apt for this blog: “In the case of news, we should always wait for the sacrament of confirmation.”
In January, 2018 the Nymox Pharmaceutical Corporation made a big urology news splash with the announcement that the World Journal of Urology (WJU) would be publishing the results of a Phase III clinical study of BPH treatment using injectable fexapotide triflutate (FT). The May, 2018 WJU carried the full article by 17 urologists from U.S. study sites that enrolled 995 BPH patients between 2009-2016.[2] The study was a placebo-controlled double-bind randomized trial. For every 3 patients who received FT, 2 patients received placebo. Follow-up, defined as long term, ranged from 2-6.75 years.
The summary of study results included the following points:
- There were no significant safety differences between FT and placebo
- Urinary symptom scores were more favorable in the FT group than the placebo group
- Long-term follow up revealed less incidence of acute urinary retention in the FT group
- Long-term follow up showed less incidence of prostate cancer in the FT group
- At 12 months, FT patients chose no further treatment, oral medications, BPH interventional treatment, or another FT treatment.
BPH background
Some background on benign prostatic hyperplasia (BPH) will explain why FT is so promising. BPH is a non-cancerous enlarging of the prostate as men age. It is not a disease. Most men don’t know it’s there until urinary symptoms appear (more frequent night urination, sense of urgency more often, difficulty starting urination, weaker stream, incomplete bladder emptying, etc.) These symptoms can lead to complications like urinary tract infections, or retaining so much urine that a trip to the emergency room is necessary (acute urinary retention). These are due to the growing prostate bulk compressing the passageway (urethra) through the gland that carries urine from the bladder out to the penis.
When symptoms become aggravated, treatment is necessary. Conventional BPH treatments include oral medication, widening the urethra using surgery or ablation (tissue destruction), implanting a device to widen the urethra, and reducing prostate bulk using Focal Laser Ablation (FLA). Depending on the side effects of any of these, their success and durability, researchers have long been looking for a “silver bullet” that would be quick, economical, safe, and effective for everyone. In the words of Ralph Waldo Emerson, “Build a better mousetrap and the world will beat a path to your door.
FT – a better mousetrap?
By now, you’re wondering what FT treatment consists of. It’s a 3-5 minute process of injecting the drug fexapotide triflutate directly into the prostate, through the rectal wall. The injection is guided by ultrasound. One half of the dose is placed in the left transition zone of the prostate, and the other in the right. The procedure is done in the doctor’s office, and “does not require a urethral catheter, intravenous or general anesthetic, and apart from a standard transrectal ultrasound (TRUS) requires no specialized equipment or instrumentation.”[iii]
The drug FT works by causing cell destruction and death – but it is selective. It only works against prostate glandular tissue, and does not affect nerves or blood vessels. As Shore, et al. (2019) describe it, “The architecture of the injected glands becomes distorted as cells die and eventually the majority of cells in the injected areas have been depleted.”[iv] It also does not appear to circulate outside of the prostate nor can it be detected in the blood. Because it is delivered transrectally, an antibiotic must be administered, but it is considered to have less infection risk due to the small needle size and only two punctures, as compared with the larger needles used to capture 12-16 tissue samples in a prostate biopsy. In the clinical studies, there were no serious infections reported.
Of note, there were also no reported adverse effects on sexual function, no doubt because FT does not affect the nerves. As for the reduced incidence of prostate cancer, the authors theorize that FT may disperse somewhat from the targeted transition zone into the peripheral zone where most prostate cancers arise. They theorize that FT has “…an inhibitory effect on clinically undetected low-grade PCa microfoci or precursor cells and lesions…”[v]
A word of caution
There is considerable excitement about FT. Nymox is applying for U.S. FDA approval as well as other agencies in Europe. However, the authors remind everyone of the need for more investigation:
The efficacy and safety of FT combination treatments, of FT used in different patient study populations, comparative studies versus other treatments, and the variability of dosing schedules remain to be answered by future investigations. Patients who have intractable severe LUTS but are poor surgical candidates are another important group where investigation may be warranted. Further studies will be needed to determine the impact of FT in relation to the gold standard of TURP.[vi]
At our Center, we will be eagerly watching in hopes that the “sacrament of confirmation” will bless FT with proof of its safety and effectiveness. It certainly may offer a rosy future to men with BPH!
NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.[i] Shore N, Kaplan SA, Tutrone R, Levin R et al. Prospective evaluation of fexapotide triflutate injection treatment of Grade Group 1 prostate cancer: 4-year results. [ii] Shore N, Tutrone R, Efros M, Bidair M, Wachs B et al. Fexapotide triflutate: results of long-term safety and efficacy trials of a novel injectable therapy for symptomatic prostate enlargement. World J Urol. 2018 May;36(5):801-809. [iii]Shore N, Tutrone R, Roehrbom CG. Efficacy and safety of faxapotide trifulutate in outpatient medical treatment of male lower urinary tract symptoms associated with benign prostatic hyperplasia. Ther Adv Urol. 2019 Jan-Dec; 11:1756287218820807. [iv] Ibid. [v] Ibid. [vi] Ibid.
About Dr. Dan Sperling
Dan Sperling, MD, DABR, is a board certified radiologist who is globally recognized as a leader in multiparametric MRI for the detection and diagnosis of a range of disease conditions. As Medical Director of the Sperling Prostate Center, Sperling Medical Group and Sperling Neurosurgery Associates, he and his team are on the leading edge of significant change in medical practice. He is the co-author of the new patient book Redefining Prostate Cancer, and is a contributing author on over 25 published studies. For more information, contact the Sperling Prostate Center.
