Maybe we are about to have another new treatment for advanced prostate cancer that will earn the coveted descriptor, “ON THE HORIZON.” OncoGenex Pharmaceuticals Inc. (OGXI) has said that they will be presenting preliminary data from their phase 2 trials evaluating their investigational compound OGX-427, in prostate and bladder cancer. The data will be presented at the American Society of Clinical Oncology ( ASCO) 2012 Genitourinary Cancers Symposium which will be held on February 2-4, in San Francisco.
OGX-427 is a novel compound designed to reduce levels of Heat Shock Protein 27 (Hsp27) – a cell-survival protein expressed in many types of cancers including prostate, bladder, breast and non-small cell lung cancer. Over expression of Hsp27 is believed to be an important factor leading to the development of treatment resistance and is associated with negative clinical outcomes in patients with various tumor types, including men with advanced prostate cancer.
The trial was a randomized Phase 2 study of OGX-427 plus prednisone versus prednisone alone in men with advanced prostate cancer who were also chemotherapy-naïve.
• The data will be presented by the study’s principal investigator, Dr. Kim Chi, medical oncologist from British Columbia Cancer Agency. The data will be presented as Abstract # 121 in the General Poster Session B on Feb. 2, 2012.
• OncoGenex also stated that it will host an investigator panel to review the preliminary OGX-427 data and the on-going development program for the compound on February 2, 2012 at 6:35 p.m. P.T. at the conference. The event will also be made available via live webcast. To access the event, log on to the Investor Relations page of the OncoGenex website at www.oncogenex.com. A replay will be made available for approximately 90 days following the event.
Joel T Nowak, M.A., M.S.W.
The use of the PSA as a prostate cancer screening tool has been a controversial issue for many years. Within the last year the issue has again come to the forefront of the public awareness, especially because of the recent move of the U.S Preventative Task Force to discourage using the PSA as a screening tool . One of the ways that has been used to approach this question is to develop a better bio-marker to serve both as a screening tool and as a predictor of the responsiveness to treatment. If such a marker could be identified, we could make better decisions about who should be treated and for how long a specific treatment should be continued. This better biomarker could reduce the suffering brought about by unnecessary treatment as well as save many dollars.
Recently, circulating tumor cells (CTC’s) have been evaluated to serve as this possible marker. Studies have shown that in early stages of cancer it can begin the process of shedding cancer cells into the circulatory system. (Okegawa T, Nutahara K, etal; Prognostic Significance of Circulating Tumor Cellsin Patients with Hormonal Refractory Cancer, J Urol, March 2009. 181:1091-1097). These CTC’s can provide a handle into the intrinsic property of the tumors offering valuable information that can inform patient management (Danila, D, Heller G, etal, Circulating Tumor Cell Number in Progression, castrate-Resistant Prostate Cancer, Clinical Cancer Res, December 2007; 13(23) 7053-7).
Little known and never discussed is the decision of the FDA in 2008 to approve the CellSearch (Verdix, NH) System to count these circulating tumor cells to predict survival and monitor treatment in men with advanced prostate cancer. The Bono, etal trial (de Bono, Schere H, etal. Circulating Tumor Cells Predict Survival Benefit from Treatment in Metastatic Castrate Resistant Prostate Cancer. Clin Cancer Res 2008;(19) 6302-6309) that actually led to the CellSearch FDA approval showed that CTC numbers is a very strong predictor of survival for men who are castrate resistant. Additional research showed that when compared to PSA scores, CTC scores were clearly a more robust system to measure progression than was the PSA ( Scher, H, Jia X, etal. Circulating Tumor Cellsas as Prognostic markers in Progressive, Castrate resistant Prostate Cancer; a reanalysis of IMMC338 trial data, The Lancet Oncology, March 2009; 10(3) 233-239).
At the last ASCO Conference (June 2011) the final analysis of the Abiraterone/prednisone (Zytiga) trial concluded that both baseline and the intermediate data that CTC levels after initiating therapy were key predictors of overall survival.
So why are our oncologists continued to be married to the PSA test?
Joel T. Nowak, M.A., M.S.W.
Bavarian Nordic A/S (BAVA) announced on November 15, that its subsidiary, BN ImmunoTherapeutics has started the pivotal Phase 3 trial of PROSTVAC® for men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. The trial is being conducted under a Special Protocol Assessment agreement with the FDA. Notice this trial has the same criteria as the phase 3 trial of Provenge.
Although there are a number of on-going phase 2 trials, BAVA has now opened their first site in the U.S. for this phase 3 trial. There will be a number of other sites and countries to follow soon.
PROSTVAC® is an “off-the-shelf” therapeutic vaccine candidate that has the potential to extend the lives of people with advanced prostate cancer (according to the data presented from the phase 2 trials). Provenge is the only currently approved cancer vaccine but it is not an “off the shelf” product.
James L. Gulley, M.D., Ph.D., Director of the Clinical Trials Group at the Laboratory of Tumor Immunology and Biology at the National Cancer Institute (NCI), and Philip Kantoff M.D., Professor of Medicine at Harvard Medical School, will act as principal investigators on the trial.
According to Dr. Gulley, the Phase 2 clinical trial data of PROSTVAC® demonstrated a very promising 44% reduction in the rate of death with an 8.5 month improvement in median overall survival, a level of clinical benefit that compares favorably to other currently approved agents for advanced prostate cancer. Dr. Gulley hopes to confirm this improvement in survival in the trial.
For more information about the trial, visit: http://www.bavarian-nordic.com/prostvac.
Joel T Nowak, M.A., M.S.W.
According to a an article published in the January 2012 issue of Cancer Prevention Research, estrogen may play a role in Melanoma recurrences!
The article described a large cohort study of women who were put on an anti-estrogen therapy. The study concluded that those women on the anti-estrogen therapy had a lower risk of melanoma.
About the Study:
• It included 7,360 women who were diagnosed with breast cancer between 1980 and 2005.
• Fifty four percent (54% ) of the women were given supplemental anti-estrogen therapy.
• The surprise finding was that the rate of melanoma was 60% higher for those women not taking anti-estrogen supplements compared with the expected rate of melanoma incidence based on age and other factors.
What is the take home concern about this study for men with advanced prostate cancer?
• Those of us who become castrate resistant normally should consider a second line hormone therapy, however, many of these possible therapies can include an estrogen basis. Clearly, those of us who also have a history of Melanoma should give hard and serous consideration to this study prior to embarking on an estrogen based treatment (patches, DES etc.).
• Those of us advanced prostate cancer survivors who have not had melanoma should also consider the possible risk of developing melanoma. This is especially true of men who have a family history of melanoma.
Joel T. Nowak, M.A., M.S.W.
Neulasta (Pegfilgrastim) is used to reduce the chance of infection in people who have certain cancers and are also receiving chemotherapy medications, including taxotere for men being treated for advanced prostate cancer.
Chemotherapy is designed to kill fast growing cells. However, it can’t tell the difference between cancer cells and fast-growing healthy cells, including red and white blood cells. (This is why men can lose their hair and have damage to their nails since they are among the faster growing of our healthy cells). As a result, one of the most serious potential side effects of taxotere for men with advanced prostate cancer is to develop a low white blood cell count (neutropenia). Developing neutropenia can place men at risk for infections which can cause interruptions in receiving their chemotherapy on schedule.
Neulasta is a white blood cell booster to help support your natural defenses and help reduce the risk of infection. Neulasta is in a class of medications called colony stimulating factors which works by helping the body make more neutrophils by stimulating the bone marrow. These white blood cells help the body fight infections.
Neulasta comes as a solution (liquid) which is injected subcutaneously (under the skin). It is usually given as a single dose for each chemotherapy cycle, no sooner than 24 hours after the last dose of chemotherapy of the cycle is given and more than 14 days before beginning the next chemotherapy cycle.
Neulasta may be given to you by a healthcare provider, or you may be told to inject the medication yourself at home. If you will be injecting Neulasta at home follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. It is vital that you use it exactly as directed. Do not use more or less of it or use it more often than prescribed by your doctor and never shake the bottle. Don’t forget to ask your healthcare professional how to dispose of the used syringes and needles.
As with all medications there comes with them a risk of significant side effects. They include:
• Spleen Rupture. Your spleen may become enlarged and can rupture while taking Neulasta. A ruptured spleen can cause death. The spleen is located in the upper left section of your stomach area. Call your doctor right away if you have pain in the left upper stomach area or left shoulder tip area. This pain could mean your spleen is enlarged or ruptured.
• A serious lung problem called acute respiratory distress syndrome (ARDS). Call your doctor or seek emergency care right away if you have shortness of breath, trouble breathing, or a fast rate of breathing.
• Serious Allergic Reactions. Neulasta can cause serious allergic reactions. These reactions can cause shortness of breath, wheezing, dizziness, swelling around the mouth or eyes, fast pulse, sweating, and hives. If you start to have any of these symptoms, call your doctor or seek emergency care right away. If you have an allergic reaction during the injection of Neulasta, stop the injection. Call your doctor right away.
• Sickle Cell Crises. You may have a serious sickle cell crisis if you have a sickle cell disorder and take Neulasta. Serious and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders receiving Neulasta. Call your doctor right away if you have symptoms of sickle cell crisis such as pain or difficulty breathing.
The most common side effect you may experience is aching in the bones and muscles. If this happens, it can usually be relieved with a non-aspirin pain reliever, such as acetaminophen.
What else do I need to know about receiving Neulasta?
• Occasionally pain and redness may occur at the injection site. If there is a lump, swelling, or bruising at the injection site that does not go away, talk to the doctor.
• Neulasta should only be injected on the day the doctor has determined and should not be injected until approximately 24 hours after receiving chemotherapy.
• The needle cover on the single-use prefilled syringe contains dry natural rubber (latex), which should not be handled by persons sensitive to this substance.
If you have any questions about this information, be sure to discuss them with your doctor. As with all drugs you are encouraged to report negative side effects of prescription drugs to the FDA. You can do this by going to: www.fda.gov/medwatch or by calling 1-800-FDA-1088.
How to use Neulasta
• Read the Patient Information Leaflet provided by your pharmacist before you start using Neulasta and each time you get a refill. If you have any questions regarding the information, consult your doctor or pharmacist.
• Avoid shaking this medication; doing so may make the drug ineffective.
• Remove the medication from the refrigerator 30 minutes before you inject it to allow it to reach room temperature.
• Inject this medication under the skin (subcutaneously) usually once during each chemotherapy cycle, or as directed by your doctor.
• The dosage is usually one 6 milligram injection, but it may be adjusted for small adults (weighing less than 100 pounds or 45 kilograms).
• Do not give this drug during the period 14 days before to 1 day after your chemotherapy. Giving this drug during this time may increase your risk of certain side effects. Consult your doctor for details.
• If you are giving this medication to yourself at home, learn all preparation and usage instructions from your health care professional. Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid. Learn how to store and discard medical supplies safely.
• Choose a new injection site each time you give yourself a dose. This will help prevent soreness. Never inject Neulasta into skin that is tender, red, bruised, and hard, or has scars or stretch marks.
Joel T. Nowak, M.A., M.S.W.
