Bedford Research Foundation scientists have collaborated with Dr. Robert Eyre on studies of male genital tract diseases for over 20 years.

Many of the studies have focused on diseases of the prostate, especially novel approaches to early detection of prostatitis and cancer. Taken together, the results of the studies suggest that prostate diseases may be reliably diagnosed by detailed examination of the cells in semen specimens, since half the volume of a semen specimen comes from the prostate. Examination of the types of cells in semen specimens is not routinely performed by cancer pathologists, so the current need is to define the cell parameters important to cancer, especially to defining the stage of prostate cancer if it is detected. Some prostate cancers grow so slowly, no treatment is necessary when first detected. Others grow rapidly, and surgery should be considered at the time of diagnosis. Distinguishing the types of prostate cancer is an area of active clinical research. The thrust for our current research is to use new sensitive molecular biology techniques that can detect all the genes expressed in a semen specimen to identify cancer-specific genes. By correlating cancer-specific genes in semen with the stage of cancer determined by a cancer pathologist, it will be possible to develop a test panel to help diagnose, and stage, prostate cancer. Bedford Research Foundation, Prostate Cancer Project

In addition, Bedford Research Foundation scientists have partnered with OncoTx, a Massachusetts biotech company, to develop a novel therapeutic approach to cancer treatment. The following is an application for funding for that project.

The Project to Prevent and Cure Prostate Cancer

Summary

The Bedford Research Foundation, a Massachusetts-based 501(c)(3) nonprofit institution, will work in conjunction with the Center for Prostate Disease Research located at Walter Reed Army Medical Center and with a private company, OncoTx, LLC, to expedite clinical trials on a fundamentally new approach to the prevention and treatment of prostate cancer.

The approach involves the outpatient injection of a drug into the prostate under ultrasound guidance. It is anticipated that a single round of treatment will be sufficient in most cases. The drug works by permanently abolishing the potential for cell proliferation. Cell proliferation is required for the development and progression of prostate cancer. Since proliferating cells in the normal prostate are rare, the drug is not expected to cause tissue damage, erectile dysfunction, or other serious quality-of-life side effects.

This approach could provide a means to prevent prostate cancer in high-risk men, and a way to cure early-stage, localized prostate cancer without the risks of prostatectomy and radiation therapy.

Please help support this potentially breakthrough project by giving a tax-deductible* donation to the Bedford Research Foundation, Prostate Cancer Project.

* (Consult your tax adviser to ascertain the extent of deductibility of any particular contribution)

Rationale (based on data from 2008)

1. Prostate cancer is the second leading cause of cancer deaths in men.
   – Approximately 186,000 new cases will occur in the US during 2008.¹
   – An estimated 28,660 men will die of prostate cancer in 2008.
2. Most men develop prostate cancer.
   – Autopsy studies show that prostate cancer can be found in 55% of men in their 50s and 64% of men in their 70s.²
   – Prostate cancer is detected in 24% of all men age 55 and older by biopsy.³
   – 15% of all men over age 62 with normal PSA levels have prostate cancer.⁴
3. Most men with detectable prostate cancer will remain symptom free.
   – For every 100 men diagnosed with prostate cancer:
   – 62 will remain symptom free without any treatment
   – 38 will develop symptoms
   – 8 will ultimately die from prostate cancer.⁵
4. All current therapies1 have frequent side effects that impact quality of life.^6,7
   – Erectile / sexual dysfunction
   – Urinary incontinence
   – Bowel urgency
5. Watchful waiting or the withholding of therapy
   – Can cause significant anxiety and stress
   – Less then 10% of men elect watchful waiting
   – Over 70% of these men change their minds within 4 years and have treatment.⁸
6. Prostate cancer can metastasize early.
   – Cancer cells can be detected in blood of approximately 30% of patients with early-stage prostate cancer before prostatectomy or radiation therapy. – In one study, the detection rate in bone marrow using PCR was approximately 50%.⁹
7. Current therapies for prostate cancer do not adequately address the problem of metastatic prostate cancer.
   – Indications of residual cancer (e.g., a rising PSA), occur after prostatectomy for early stage disease in approximately 35% of men.
   – In one study, 3% of low risk patients, who at prostatectomy had only “organ-confined” disease, died of metastatic prostate cancer. ¹⁰
   – The ideal solution is to prevent prostate cancer in the first place.
8. The prevention of prostate cancer is currently problematic.
   – Prostate cancer evolves from the precancerous condition: HGPIN2
   – 114,000 men are diagnosed in the U.S. each year with HGPIN
   – In one study, 31% of men diagnosed with HGPIN developed prostate cancer within one year¹¹
   – There are currently no approved treatments for HGPIN. However, the drug finasteride may reduce the risk of developing prostate cancer by about 25%.¹²
9. Cell proliferation is an absolute requirement for the evolution and progression of prostate cancer. Abolishing the potential for cell proliferation within the prostate would:
   – Completely prevent the evolution of prostate cancer
   – Halt the progression of existing cancer within the prostate
   – Prevent the development and progression of benign prostatic hypertrophy (BPH)
   – Cell proliferation, although vital in many tissues, is not required in the prostate gland for general health, well-being and sexual function.
10. A drug exists that can permanently abolish the potential for cell proliferation without killing cells.
    – The drug is active against essentially all cells.
    – The drug rapidly enters cells.
    – It is retained locally and poorly absorbed into the circulatory system.
    – The drug has been tested as in intravenous anticancer agent in clinical trials.
11. The method
    – Minute, sub-toxic quantities of drug will be injected directly into the prostate gland under ultrasound guidance.
    – The entire gland will be treated.
    – One treatment should be adequate to permanently abolish the potential for cell proliferation within the prostate.
    – The approach is minimally invasive and comparable to prostate biopsies, which are routinely done in men.
    – The approach could provide an alternative to radical prostatectomy and radiation therapy for the treatment of localized early stage prostate cancer.
    – The approach could eradicate HGPIN and prevent prostate cancer in men at high risk of developing the disease.
12. Potential advantages of the method
    Safety
    – The approach is not expected to cause local tissue destruction, impotence, erectile dysfunction, incontinence, or other severe side effects.
    – The treatment will cause gradual prostate atrophy, and reduce the volume of ejaculate fluid by about 25-50%, but should not impair quality of life or general well being.
    – The dose of drug will be far below that which produces systemic toxicity.
    – The treatment could provide a less invasive alternative to prostatectomy and radiation therapy for most men diagnosed with prostate cancer.
    Efficacy
    – The efficacy of the drug in abolishing the potential for cell proliferation is well established. It is one of the most potent agents known against cell proliferation.
    – Clinical trials are needed to evaluate the efficacy of the drug given as intraprostatic injection.
    – The approach has the potential to:
    • Eradicate HGPIN
    • Prevent the evolution of prostate cancer
    • Halt the progression of localized prostate cancer
    • Treat localized prostate cancer after radiation therapy failure
    • Arrest the development and progression of BPH
13. Most importantly, the eradication of HGPIN could prevent prostate cancer and its metastatic complications.
14. Cost
    – Treatment costs are expected to be a fraction of that for current therapies:
    • Medicare currently pays $50,000 to treat prostate cancer with proton beam therapy¹³
    • Three-dimensional conformal radiation therapy (3D-CRT) of the prostate costs approximately $22,000¹⁴
    • Radical prostatectomy costs approximately $10,700.¹⁵
    • Brachytherapy (radioactive seed implants) costs approximately $9,000
15. Timing
    – Phase I/II trials could begin in approximately 18-24 months for the treatment of HGPIN.
16. Participating organizations – This multi-institutional project involves leaders in the field of prostate cancer and drug development from academia, industry and the government.
17. Related projects for brain, breast and ocular cancers, and for diabetic proliferative retinopathy – The Project to Prevent and Cure Prostate Cancer is part of a larger initiative being organized by the Bedford Research Foundation to expedite clinical trials based on a similar approach involving the local administration of agents that target cell proliferation:
    • As an alternative to bilateral prophylactic mastectomy for the prevention of breast cancer in women with BRCA1 and BRCA2 gene mutations
    • For the treatment of ductal carcinoma in situ
    • For the treatment of brain cancer and metastatic lesions to the brain
    • For the prevention and treatment of ocular melanoma
    • For the treatment of diabetic proliferative retinopathy

References and Notes

1. American Cancer Society, “Cancer Facts and Figures 2008” https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2008/cancer-facts-and-figures-2008.pdf
2. Sakr WA, Grignon DJ, Crissman JD, Heilbrun LK, Cassin BJ, Pontes JJ, Haas GP. “High grade prostatic intraepithelial neoplasia (HGPIN) and prostatic adenocarcinoma between the ages of 20-69: an autopsy study of 249 cases.” In Vivo. 1994 May-Jun;8(3):439-43
3. Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, Lieber MM, Cespedes RD, Atkins JN, Lippman SM, Carlin SM, Ryan A, Szczepanek CM, Crowley JJ, Coltman CA Jr. “The influence of finasteride on the development of prostate cancer.” N Engl J Med. 2003 Jul 17;349(3):215-24.
4. Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes HL, Minasian LM, Ford LG, Lippman SM, Crawford ED, Crowley JJ, Coltman CA Jr. “Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter.” N Engl J Med. 2004 May 27;350(22):2239-46
5. Peter T. Scardino, M.D, “Predictive Markers, Biomarkers and Clinical Decision Making” presented at the 2006 13th Annual Prostate Cancer Foundation Retreat
6. Prostatectomy, radiation therapy, radioactive seed implants, high intensity ultrasound, and hormone therapyii. F, Harlan LC; “Five-year outcomes after prostatectomy or radiotherapy for prostate cancer: the prostate cancer outcomes study.” J Natl Cancer Inst. 2004 Sep 15;96(18):1358-67
7. Raina R, Agarwal A, Goyal KK, Jackson C, Ulchaker J, Angermeier K, Klein E, Ciezki J, Zippe CD “Long-term potency after iodine-125 radiotherapy for prostate cancer and role of sildenafil citrate.”; Urology. 2003 Dec;62(6):1103-8
8. Carter CA, Donahue T, Sun L, Wu H, McLeod DG, Amling C, Lance R, Foley J, Sexton W, Kusuda L, Chung A, Soderdahl D, Jackmaan S, Moul JW. “Temporarily deferred therapy (watchful waiting) for men younger than 70 years and with low-risk localized prostate cancer in the prostate-specific antigen era.” J Clin Oncol. 2003 Nov 1;21(21):4001-8
9. Melchior SW, Corey E, Ellis WJ, Ross AA, Layton TJ, Oswin MM, Lange PH, Vessella RL. “Early tumor cell dissemination in patients with clinically localized carcinoma of the prostate.” Clin Cancer Res. 1997 Feb;3(2):249-56
10. Swanson GP, Riggs M, Hermans M., “Pathologic findings at radical prostatectomy: risk factors for failure and death.” Urol Oncol. 2007 Mar-Apr;25(2):110-4.
11. Bostwick DG, Qian J. “High-grade prostatic intraepithelial neoplasia.” Mod Pathol. 2004 Mar;17(3):360-79.
12. Price D, Stein B, Sieber P, Tutrone R, Bailen J, Goluboff E, Burzon D, Bostwick D, Steiner M.; “Toremifene for the prevention of prostate cancer in men with high grade prostatic intraepithelial neoplasia: results of a double-blind, placebo controlled, phase IIB clinical trial.” J Urol. 2006 Sep;176(3):965-70;
13. Kramer BS, et al;, “Use of 5-alpha-reductase inhibitors for prostate cancer chemoprevention: American Society of Clinical Oncology/American Urological Association 2008 Clinical Practice Guideline.” J Clin Oncol. 2009 Mar 20;27(9):1502-16.i. http://www.nytimes.com/2007/12/26/health/25cnd-proton.html?pagewanted=1&ref=business
14. Konski A, Watkins-Bruner D, Feigenberg S, Hanlon A, Kulkarni S, Beck JR, Horwitz EM, Pollack A. “Using decision analysis to determine the cost-effectiveness of intensity-modulated radiation therapy in the treatment of intermediate risk prostate cancer.” Int J Radiat Oncol Biol Phys. 2006 Oct 1;66(2):408-15.
15. Mouraviev V, Nosnik I, Sun L, Robertson CN, Walther P, Albala D, Moul JW, Polascik TJ. “Financial comparative analysis of minimally invasive surgery to open surgery for localized prostate cancer: a single-institution experience.”; Urology. 2007 Feb;69(2):311-4