Contact:
Lisa Jacobs
Michael Fagan
212/880-5300
Annual Meeting News Room:
303/446-4472
EMBARGOED FOR RELEASE UNTIL TIME OF EACH PRESENTATION: (See times indicated below)
RESEARCH CHALLENGES STANDARD PROSTATE CANCER THERAPIES AND EXPLORES INNOVATIVE BIOLOGICAL STRATEGIES
-- Press Briefing Monday May 19, 12:00 PM (MDT) --
Denver, CO -- May 19, 1997 -- In the continuing search for more effective treatments and better insight into the causes of prostate cancer, leading investigators challenged current thinking about prostate cancer treatment at a press conference held at the Thirty-third Annual Meeting of the American Society of Clinical Oncology.
Several studies were reported, including research that has resettled the concept of ìtotal androgen blockade,î a study that has questioned the correlation between lowered PSA levels and disease prognosis in some settings, research showing that palliative care can be cost-effective for advanced prostate cancer, and data demonstrating that a unique compound that may inhibit the process of metastasis.
Prostate cancer is the most common malignancy in the United States, with 334,500 new cases diagnosed each year, and the second leading cause of cancer death among men, claiming 41,800 lives annually. Although important progress has been made in the diagnosis and treatment of early stage disease -- where the cancer remains limited to the prostate gland itself -- metastatic prostate cancer remains a major ongoing challenge facing patients and their treatment teams.
ìThis is an important time of consolidation in the battle against prostate cancer,î said Derek Raghavan, MD, PhD, of the Roswell Park Cancer Institute, the moderator of the press conference. ìAlthough there are many exciting new concepts that have been presented at this meeting, we also have a responsibility to test our hypotheses and theories carefully, to ensure that we are truly improving the outlook for our patients.î
Total Androgen Blockade - An Invalid Concept? Correlation between PSA Levels and Disease Response Also Questioned
M. Eisenberger, et al, The Johns Hopkins Oncology Center, ìA Comparison of Bilateral Orchiectomy with or without Flutamide in Stage D2 Prostate Cancerî (Plenary, Monday, May 19, 3:00 p.m. [MDT], Hall A, Abstract #3)
Prostate cancer relies heavily on androgens -- male hormones produced primarily in the testicles, but also in the adrenal glands -- for continued growth and metastasis. The major source of androgens can be inhibited by surgical castration or through the use of a chemical which blocks the production of testosterone by the testicles (medical castration). In addition, androgen blockers, such as flutamide, which inhibit uptake of androgens by prostate cells, have been used to try to block the effect of non-testicular androgens. The combined application of medical or surgical castration and antiandrogens constitutes the concept of ìtotal androgen blockade.î
Previous research by the Southwest Oncology Group has shown that the combination of flutamide plus medical castration significantly improved survival in patients with advanced prostate cancer, when compared to medical castration alone. Some concerns about this concept were raised by other studies which failed to show a consistent difference in outcome between the combination of surgical or medical castration plus flutamide or other antiandrogens compared to surgical or medical castration alone.
A new study, which has re-tested this theory, was presented at the Plenary Session of the ASCO Annual Meeting by Mario Eisenberger, MD of The Johns Hopkins Oncology Center on behalf of the Southwest Oncology Group and collaborating centers. This study shows that the androgen blocker flutamide offers no additional survival or progression-free survival benefits when used in combination with surgical castration. The research also casts doubt on the correlation between the reduction of PSA (prostate specific antigen) levels and disease response in some patients.
The randomized, double-blind study involving 1,387 patients with late-stage prostate cancer showed that flutamide in combination with surgical castration -- orchiectomy -- did not result in statistically significant improvement in progression free survival or overall survival when compared with patients given a placebo with orchiectomy. Overall progression free survival was 20 months for the study group, and 19 months for the control, while overall survival was 32 months for the study group and 30 months for the control.
In addition, despite no significant difference in survival rates, there was a significant difference in the reduction of PSA blood levels between the group receiving flutamide (80% reduction) and those who did not receive this drug (68% reduction). A major fall in PSA levels has traditionally been regarded as an indication of successful treatment, and this new discrepancy suggests that this may not always be true. Future studies will need to reassess changes in PSA levels in the light of this observation.
Unique Therapeutic Approach Targets the Process of Metastasis Itself
P. Boasberg, et al, John Wayne Cancer Center, ìMarimastat in Patients with Hormone-Refractory Prostate Cancer: A Dose-Finding Study,î (Oral Session, Monday, May 19, 9:45 a.m. [MDT], Currigan B, Abstract #1126)
Encouraging clinical data from an early trial of Marimastat -- the first orally-administered agent designed to inhibit the formation of blood vessels that feed tumors -- were presented by Peter Boasberg, MD, of the John Wayne Cancer Center. Marimastat, a matrix metalloproteinases inhibitor, targets enzymes that researchers believe are instrumental in tumor growth and spread. The targeted enzymes are the metalloproteinases (MMP), proteins associated with the formation of the blood vessels that accelerate tumor growth and migration through tissue. The study shows that Marimastat can be tolerated at high doses and reduces the rate of rise of prostate-specific antigen (PSA) levels, a possible indicator of tumor activity.
The study enrolled 88 patients with aggressive stage III/IV prostate cancer, who had not responded to earlier treatment, as evidenced by a rise in PSA levels of 25% or more over a four week period preceding study entry. The mean age of study participants was seventy-one. Pooling all dose levels together, the median rate of rise PSA after a four week regimen decreased from 53% to 29%. At higher doses of the drug, significantly more patients demonstrated a reduced rate of PSA rise that at lower doses: within the higher dose range, 50-70% of the patients demonstrated a reduced rate of rise in PSA levels to less than 25%. In a promising sign, survival was prolonged in patients who demonstrated a PSA response. Joint pain and stiffness were the only side effects mentioned by some patients, alleviated by adjusting the regimen and dose level. * * * ìHerein lies a problem. We have heard from Dr. Eisenberger that we may not be able to rely on PSA decreases in the usual way. On the other hand, we have some tremendously exciting translational research from Dr. Boasberg and his colleagues in which a major clue of anticancer activity comes from that very measure, the decline in PSA,î said Dr. Raghavan. ìThe way we resolve this is that we use the PSA change as an index, but not the sole index, of anticancer effect -- that is, it acts as a screen for effectiveness, which is then tested by other means.î
* * *
Palliative Treatment Can Be Cost-Effective for Terminally Ill
D.J. Bloomfield, et al, Princess Margaret Hospital, ìEconomic Evaluation of Chemotherapy with Mitoxantrone plus Prednisone for Symptomatic Hormone Resistant Prostate Cancer Based on a Canadian Randomized Trial with Palliative Endpointsî (Oral Session, Monday, May 19, 10:45 a.m. [MDT], Currigan B, Abstract #1130)
New research challenges the assumption that active treatment for incurable disease must prolong life if it is to be cost-effective, and goes further to demonstrate that a palliative treatment which is effective at reducing cancer symptoms may actually offset part or all of the cost of the treatment.
An economic analysis of palliative treatment for prostate cancer patients conducted by David Bloomfield, MD, of the Princess Margaret Hospital in Toronto, examined the cost-effectiveness of symptom relief in determining the benefits of chemotherapy for hormone-resistant prostate cancer patients.
While chemotherapy has not traditionally been considered clinically beneficial among patients with metastatic prostate cancer who do not respond to hormone therapy, a 1996 study that forms the basis of the economic analysis found that patients treated with chemotherapy plus prednisone enjoy a significantly higher quality of life, and that the palliative effects of chemotherapy reduced patientsà symptoms.
The current study found that not only is this treatment better for patients, the economic evaluation suggests it is cheaper overall due to a reduction in hospital admissions. The evaluation was undertaken by chart review of 114 patients enrolled at three sites contributing patients to the study. The mean total cost of health care from the start of the trial until death for patients allocated to the chemotherapy arm was CDN $27,300 vs. $29,000 for those allocated to prednisone alone. A cost saving was consistently found whichever time period was taken to compare the groups.
In the original trial, 161 patients with symptomatic hormone-resistant prostate cancer were randomized to receive chemotherapy with mitoxantrone plus prednisone or prednisone alone. Response was measured by a reduction in pain without an increase in analgesic intake, as assessed by patients and not doctors, or a reduction of analgesic use by 50% or more without an increase in pain. The overall palliative response rates were significantly higher -- 38% for the patients receiving chemotherapy plus prednisone versus 21% for the patients receiving prednisone alone -- and the duration of relief of symptoms was significantly longer in patients receiving chemotherapy. Response was also associated with improvement in various indices of health-related quality of life such as reduction in fatigue, increased physical activity and a reduction in the constipation associated with strong painkillers.
Beta-Carotene Supplementation May Reduce Prostate Cancer Risk in Patients with Low Levels
M.J. Stampfer, et al, Brigham and WomenÃs Hospital, Harvard Medical School, ìEffects of Beta-Carotene Supplementation on Total and Prostate Cancer Incidence Among Randomized Participants with Low Baseline Plasma Levels: The Physiciansà Health Studyî (Oral Session, Monday, May 19, 8:15 a.m. [MDT], A101-103, Abstract #1467)
Many studies have linked foods rich in beta-carotene -- but not supplements -- with a decreased risk of lung cancer and cancer at other sites, though not prostate cancer. New findings from the Physicians Health Study, the largest ongoing study of US male physicians, show that beta-carotene supplements may decrease the risk of prostate cancer among men with the lowest baseline blood levels. The data were presented by Meir Stampfer, MD of Brigham and WomenÃs Hospital and Harvard Medical School.
22,071 U.S. physicians were randomly assigned to take either a beta-carotene supplement or a placebo. Before randomization, blood samples had been collected from 14,916 of the participants. The trial randomized half to receive beta-carotene supplementation and the other half to placebo. After 12 years, blood samples were assayed from 1,318 men subsequently diagnosed with cancer, and 2,038 controls. The data show that, among men in the lowest 25% of baseline beta-carotene levels, those who had received beta-carotene supplements had a possible decrease in cancer risk over men who had not received the supplement. No such effect was seen among men with higher baseline levels of beta-carotene.
These results should be viewed cautiously, and further study is warranted, especially among those with low levels of beta-carotene.
# # #
RSS