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EP-3426310-B1 - PROSTATIC LIQUID BIOPSY FOR THE DETECTION OF PROSTATE CANCER AND BENIGN PROSTATIC HYPERPLASIA

EP3426310B1EP 3426310 B1EP3426310 B1EP 3426310B1EP-3426310-B1

Inventors

  • FEISTEL, CHRISTOPHER

Dates

Publication Date
20260506
Application Date
20170307

Claims (14)

  1. A debulking agent or cytoreduction agent from the group of 5-alpha reductase inhibitors for use in a method of diagnosis in vivo of bladder cancer, and/or squamous cell carcinoma, and/or kidney cancer, and/or prostate cancer; wherein the agent is used for isolating and collecting prostatic epithelial cells situated within the prostate of an individual not being treated for benign prostate hypertrophy; wherein said debulking agent or cytoreduction agent from the group of 5-alpha reductase inhibitors is effective to detach said prostatic epithelial cells from within the prostate; wherein a portion of said detached prostatic epithelial cells are operative to migrate to the prostatic urethra via prostatic ducts.
  2. The agent for use of claim 1 wherein said 5-alpha reductase inhibitor comprises Finasteride.
  3. The agent for use of claim 2 wherein the use for isolating and collecting prostatic epithelial cells comprises collecting said specimen at a time from 72 hours to 6 months or more from administration of Finasteride.
  4. The agent for use of claim 1 wherein collecting prostatic epithelial cells comprises collecting an ejaculate from said individual; or wherein said collection comprises collecting an express prostatic secretion from said individual.
  5. The agent for use of claim 1 wherein said use for isolating and collecting comprises collecting a urine specimen from said individual; preferably wherein prior to collecting said urine specimen, an internal prostatic massage is performed upon said individual; or wherein prior to collecting said urine specimen, an external prostatic massage is performed upon said individual; or wherein prior to collecting said urine specimen, a digital rectal examination is performed upon said individual.
  6. The agent for use of claim 1 wherein collecting prostatic epithelial cells comprises collecting said specimen at a time when said prostate assumes a debulking physiological state following administration of said agent.
  7. The agent for use of claim 6 wherein the determination of when said prostate assumes said debulking state is made by palpitation; or wherein the determination of when said prostate assumes said debulking state is determined by visual examination; or wherein the determination of when said prostate assumes said debulking state is determined by an imaging modality selected from the group consisting of MRI and ultrasound.
  8. The agent for use of claim 1 wherein collecting prostatic epithelial cells comprises collecting said specimen at a time corresponding to when a biomarker is present in a concentration indicative of when said prostate assumes a debulking physiological state following administration of said agent.
  9. The agent for use of claim 8 wherein said biomarker consists of PSA and wherein said PSA is present in a concentration indicative as to when said prostate assumes said debulking state.
  10. The agent for use of claim 3 wherein collecting prostatic epithelial cells comprises collecting said specimen at a time from 72 hours to 30 days from said administration of Finasteride.
  11. The agent for use of claim 2 wherein said Finasteride is provided in a dose ranging from 5 mg/day to 8 mg/day.
  12. The agent for use of claim 11 wherein said Finasteride is provided in a dose of 5 mg/day.
  13. The agent for use of claim 1 further comprising a second agent, said second agent comprising Doxazosin.
  14. The agent for use of claim 1 wherein the agent is provided as a single dose of Finasteride ranging from 80 mg to 600 mg.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS Not Applicable STATEMENT RE: FEDERALLY SPONSORED RESEARCH/DEVELOPMENT Not Applicable BACKGROUND Prostate cancer is the most common cancer found in men and it is the second leading cause of death among men who die from cancer. By the age of 50, very few men have symptoms of prostate cancer, yet some precancerous or cancer cells may be present. More than half of all American men have some cancer in their prostate glands by the age of 80. Most of these cancers never pose a problem. See, National Cancer Institute Understanding Prostate Changes: A Health Guide for Men (http://wwwdotcancerdotgov/types/prostate/understanding-prostate-changes) current website guide 1/26/16. The American Cancer Society's estimates for prostate cancer in the United States for 2015 are approximately 220,800 new cases of prostate cancer; and 27,540 deaths from prostate cancer. See, American Cancer Society Prostate Cancer Guide (Ref: http://wwwdotcancerdotorg/acs/groups/cid/documents/ webcontent/003134-pdf.pdf.) In 2012, the World Health Organization (WHO) estimated that 1.1 million men worldwide were diagnosed with prostate cancer (Ref: World Health Organization Prostate Cancer Fact Sheet. See, GloboCan 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. (http://globocandotiarcdotfr/Pages/fact_sheets_cancer.aspx)). That number was 15% of all cancers diagnosed in men. Also in 2012, WHO estimated that there were 307,000 deaths representing 6.6% of total men cancer deaths. To illustrate such disease, there is depicted, in Figures 1 and 2, in cross-sectional view, a prostate 10 in proximity to other organs and anatomical structures, and how a cancerous growth within the prostate progresses through Stages I, II, III and IV. As shown in Figure 1, the prostate is located just below the bladder 40 and in front of the rectum 50. The prostate 10 further surrounds a portion of the urethra 60 and further produces seminal fluid that nourishes and transports sperm as part of the male reproductive system. The progression of prostate cancer, like other forms of cancer, is characterized by four categories of staging that describe the local extent of a prostate tumor, ranging from Stage I or T1 to Stage IV or T4. With respect to Stage I, the tumor 20 typically cannot be felt or even seen with imaging equipment, such as transrectal ultrasound. Although highly ideal, the detection of cancer at such stage is considered almost accidental and is typically incidental to a separate transurethral resection of the prostate (TURP). Detection at such stage can also occur by needle biopsy performed as a result in increased prostate specific antigen (PSA), discussed more fully below. Stage II is characterized as becoming enlarged to the point where the cancer 20 can be felt per a digital rectal exam (DRE) or can be seen with imaging such as transrectal ultrasound. The cancer 20 at such stage however, continues to be confined to the prostate gland 10. In Stage III, the cancer 20 has grown outside of the prostate 10 and may have further grown into the seminal vesicle 30. In Stage IV, the cancer 20 has grown into tissue adjacent to the prostate (i.e., other than the seminal vesicles) and can extend into such structures such as the urethral sphincter, rectum 50, bladder 40 and/or the wall of the pelvis. The treatment of prostate cancer can vary significantly depending on factors such as how fast the cancer is growing, how much it has spread, the patient's overall health, and the benefits and potential side effects of treatment. As is true for virtually all types of cancers, early detection is always preferred, with the treatment options available having substantially fewer side effects and significantly greater patient outcome compared to detection at later stages. Given the anatomical positioning of the prostate, however, coupled with numerous drawbacks associated with the accurate diagnosis of prostate cancer, the ability to detect prostate cancer at its earliest stages is elusive and well-known to result in the implementation of harmful, sub-optimal care, as discussed below. I. Disadvantages Associated with Current Prostate Cancer Screening Methods Management and treatment of prostate cancer is limited by access to an adequate sample of prostate tissue. See, Presti, J. Prostate Biopsy: Current Status and Limitations. Rev Urol. 2007, Summer, 9(3): 93-98. In this regard, the definitive diagnosis of prostate cancer is hampered by the limitations of acquiring prostate gland tissue using an invasive surgical procedure known as a prostate core needle biopsy. See, Shariat et.al. Using Biopsy to Detect Prostate Cancer. Reviews in Urology, 2008 Fall; 10(4): 262-280; and Taneja, et al. AUA/Optimal Techniques of Prostate Biopsy and Specimen Handling: White Paper for the American Urological Association, Inc. in https://wwwdotananetdotorg/common/pdf/education/clinical-guidance/Prostate-Biopsy-WhitePaper.pdf as of 1