September, 1997

Prostascint ^tmExplained

Last month we reviewed the subject of hormonal therapies for advanced stage and hormone refractory prostate cancer. But the issue that remains a subliminal fear in all of us who have faced the beast is how to deal with either the potential, or actual, recurrence of the disease. But, before we can attack it, we must know where it is and the extent of its presence within our system. The recently FDA approved diagnostic imaging agent, ProstaScint, appears to be an effective weapon in achieving that objective.

This month we talk with Dr. Graham May, Vice President of Medical Affairs at CYTOGEN, the makers of ProstaScint.

VHS: Dr. May, your news release describes ProstaScint as a diagnostic imaging agent. In laymans terms, what does this actually mean?

GM: ProstaScint (Kit for the Preparation of Indium In111 Capromab Pendetide) is an antibody which targets an antigen produced by prostate cells, known as Prostate Specific Membrane Antigen (PSMA). Before ProstaScint is injected, it is combined with Indium In111, which is a radioisotope. When the combination of ProstaScint and Indium is injected into a patient's bloodstream, the antibody attaches itself to sites of PSMA. The patient can then be photographed or scanned with a gamma camera to view, or image, the areas that have large amounts of the antibody.

VHS: Can we assume that this process can be used as a primary diagnostic tool along with, for example, the endo-rectal MRI and the RT-PCR blood test to better determine whether extra-capsular penetration has occurred and the extent of cancer cell migration?

GM: No. ProstaScint is not a screening test. It should be used in patients with a known diagnosis of prostate cancer who are at high risk of having metastatic spread based on clinical staging, the PSA level, and the Gleason score.

VHS: Another use for ProstaScint is in those cases post-prostatectomy wherein there is a high suspicion of undetected cancer recurrence. Since we all live and die emotionally and psychologically on our latest PSA numbers as an indication of our being cancer free, what are those circumstances that should cause us to utilize the ProstaScint scan to detect the cancer's progression?

GM: If a patientís PSA begins to rise following prostatectomy, it is an indication that the prostate cancer has recurred. In such cases, a ProstaScint scan may show whether the recurrence is local (in the prostatic bed) or distant (in lymph nodes), thus helping physicians and patients with their choice of treatment.

VHS: If ProstaScint is viable post-prostatectomy for determining cancer recurrence, does it have the same reliability following other treatment modalities such as, radiation therapy (both external beam and seed implant) or cryosurgery?

GM: Studies to specifically evaluate the use of ProstaScint in post-radiation therapy and post-cryosurgery have not been conducted. However, patients have been imaged with ProstaScint following those treatments. Radiation and cryosurgery should not prevent ProstaScint from targeting PSMA. Physicians need to understand how radiation therapy may affect the pelvic structures in order to best interpret the scans following radiation therapy.

VHS: Now that we understand what ProstaScint can tell us, please discuss how the test is administered and the results determined.

GM: ProstaScint is first combined with Indium In111 in a radiopharmacy or nuclear medicine laboratory. ProstaScint and Indium In111 is then given intravenously to the patient over a five minute interval. An immediate image is obtained using a gamma camera to demonstrate the patientís vascular anatomy, so normal asymmetries wonít be mistaken for disease. On days four or five following the infusion, the patient will return for a second imaging session. The night before, the patient may be instructed to take an oral cathartic and an enema to eliminate stool which can obscure the results. During the imaging session, the bladder is often catheterized and irrigated. After the images are obtained, they are processed by a computer and read by a nuclear medicine physician who has been trained in the interpretation of ProstaScint scans.

VHS: The monoclonal antibody used is a mouse antibody. Itís been reported that in certain cases HAMA (human anti-mouse antibodies) can be created which can result in elevated PSA levels. What procedures have you included in your test protocol to account for this situation?

GM: HAMA occurs at very low frequencies and generally at low levels in patients imaged with ProstaScint. Although the presence of HAMA may interfere with antibody based immunoassays (such as PSA), there are such tests available which are resistant to HAMA interference. PSA assays that have been found to be resistant to HAMA interference include the Hybritech Tandem-R and Abbott IMX.

VHS: It's also been asserted that after a ProstaScint procedure has been performed the patient may no longer be a candidate for any therapy that uses mouse monoclonal antibodies or cytotoxic therapy. Please comment.

GM: Patients should notify their physician if they have received ProstaScint or any other murine-based products so their HAMA status can be determined, if necessary. While in most cases any increased HAMA levels are temporary, if a patient's HAMA level remains elevated, he may not be eligible to receive another murine-based product.

VHS: If the patient is on a form of hormonal therapy, is there any effect on the results derived from the procedure, or effect on the efficacy of the treatment itself?

GM: The effect of surgical and/or medical androgen ablation on the imaging performance of ProstaScint has not been studied. Preliminary data suggest hormone ablation may actually increase PSMA expression, with a concurrent decrease in PSA.

VHS: Prior to FDA approval there were some concerns expressed about the failure rate (number of false positives or negatives) for the test. Are there more study results available detailing current levels?

GM: While it is impractical to conduct another near term study to obtain new accuracy information, CYTOGEN is investing in assuring that the highest quality images are obtained and interpreted to the greatest accuracy through the PIE( (Partners in Excellence) Program. Proper training and experience helps ensure the most optimal accuracy, and the PIE Program trains technologists and physicians in the acquisition and interpretation of ProstaScint scans and provides an overread service, so scans are evaluated both by the local physician and by a recognized expert.

VHS: Relative to the ability to target the specific locations of metastasis or cell migration, has the test proven more significant in identifying soft tissue versus bone sites.

GM: A ProstaScint scan provides a soft tissue survey for occult metastatic lymph node disease. Although ProstaScint may sometimes demonstrate bony involvement in some prostate cancer patients, a radionuclide bone scan is more sensitive for detecting skeletal metastases.

VHS: Your current marketing plan has the product licensed to Bard Urological for sale to their primary clients which are office and hospital based urologists. Is there a rationale for the exclusion of medical and radiation oncologists?

GM: Our market research tells us that the majority of prostate cancer patients are managed by urologists. This is the physician group seen daily by the Bard Urological Division and thus, our copromotion alliance. CYTOGEN also recognizes the key role of medical and radiation oncologists and has initiated programs to reach these important specialties through our own efforts.

VHS: CYTOGEN has established a network of qualified nuclear medicine physicians to administer the test. How can our readers obtain a copy of that list?

GM: The number of sites in our PIE Program has almost doubled in the six months since we introduced ProstaScint and now stands at 144. An up-to-date list is always available on CYTOGEN's worldwide web site at www.cytogen.com or patients and physicians can call us directly.

VHS: How can our readers obtain more information on ProstaScint and CYTOGEN?

GM: Patients wanting additional information about our company can contact our Corporate Communications department via Internet (cytoinfo@corpcomm.cytogen.com), fax (1-800-758-5804 ext. 224650), voicemail (609-987-6467), or phone (609-987-8221). If specific product information is desired, contact Marketing Communications via e-mail (rschayow@cytogen.usa.com), phone (609-520-3082), or fax (609-987-6477).

VHS: What other products do you have currently in trial or in the lab that will be of benefit to cancer patients or survivors?

GM: Through our partners at DuPont Merck Radiopharmaceuticals, we recently introduced Quadramet( (samarium Sm 153 Lexidronam Injection), a radiopharmaceutical to treat severe bone pain resulting from a number of metastatic cancer tumors. A Phase III trial of Autolymphocyte Therapy (ALT) for renal cell carcinoma was completed earlier this year and a Biologics License Application (BLA) will be submitted to the FDA in the near future. CYTOGEN is developing other products which are earlier in development, but you can see that we have a focused effort to help cancer patients through a variety of therapeutic and diagnostic products and services.