Longer Hormone Treatment May Improve Prostate Cancer Outlook

European and U.S. studies find similar results


WEDNESDAY, June 10 (HealthDay News) -- Men with moderately advanced prostate cancer who get hormone-blocking drugs after radiation therapy do better when the drug treatment is continued for two or more years after an initial six-month regimen, a European study has found.

The results pretty much mirror those of a similar American trial reported in May, said Dr. Eric M. Horwitz, acting chairman of radiation oncology at Fox Chase Cancer Center in Philadelphia, who led the group that did the U.S. study.

"We have long believed that longer-term hormone therapy is the standard of care," Horwitz said. "These studies support that belief."

The results apply to men whose cancer shows signs of growth but has not spread beyond the prostate gland -- perhaps a quarter of all cases of prostate cancer, Horwitz said.

Earlier studies in the United States and Europe established the value of radiation therapy followed by six months of hormone-blocking treatment in such cases, he said. The new studies were designed to determine whether continuation of drug therapy that blocks the cancer-promoting activity of the male hormone testosterone could improve those results.

Though the studies differed in size and length, their results were similar in most respects.

The European trial, reported in the New England Journal of Medicine, included 970 men who were assigned to radiation therapy followed by either six months or three years of hormone-suppressing treatment. The five-year death rate of men in the longer-treatment group was 15.2 percent, compared with 19 percent for those in the shorter-term treatment group.

The U.S. study, published in the Journal of Clinical Oncology, included 1,554 men who were followed for 10 years. The study found no significant difference in overall survival -- 51.6 percent for the short-term group, given four months of treatment, and 53.9 percent for the long-term group, treated for two years.

But it did find a difference among men who were alive and cancer-free after 10 years. The disease-free survival rate for the short-term group was 13.2 percent, compared with 22.5 percent for those treated longer.

Other measures, such as the spread of cancer to other parts of the body and greater growth of the malignancy within the prostate gland, were consistently better for men in the U.S. study who'd had the longer-term therapy.

Horwitz said that differences between the American and European results were not unexpected. Similar differences had been found in the studies that established the value of the radiation-plus-hormone therapy, he said. One possible explanation, he said, is that prostate cancers tend to be diagnosed at an earlier stage in the United States because of extensive screening programs.

Both studies reported the expected side effects of hormone-blocking therapy, including hot flashes, weight gain, osteoporosis and loss of sexual function.

"Some men get them and some do not," Horwitz said. "Over the last few years, there has been a lot of attention paid to these side effects, in the medical literature and in public awareness, and there has been more reluctance to use this therapy. These studies clearly identify a group of men who benefit from this therapy."

But Dr. Peter C. Albertsen, chairman of urology at the University of Connecticut Health Center, said that it's those side effects that should limit the use of longer hormone-blocking therapy to a specific group of men with prostate cancer -- those with "disease that is clinically evident on palpation [by touching] but with no evidence that it has spread outside the prostate," Albertsen wrote in an accompanying editorial in the journal.

He agreed that earlier forms of the cancer are more often detected in the United States than in Europe because of extensive screening programs. The side effects that balance the benefits of hormone-blocking therapy rule against extended therapy for those men, Albertsen said.

"For men with localized disease that is screening-detected, the equation is quite different," he said.

More information:

The U.S. National Cancer Institute has more on prostate cancer.

New Approach For Treating Recurrent Prostate Cancer On The Horizon

ScienceDaily (June 15, 2009) — A new study shows that an alpha-particle emitting radiopeptide—radioactive material bound to a synthetic peptide, a component of protein—is effective for treating prostate cancer in mice, according to researchers at SNM's 56th Annual Meeting in Toronto. The results could eventually result in a significant breakthrough in prostate cancer treatment, especially for patients whose cancer recurs after the prostate is removed.

"Our study shows that this novel form of treatment has the potential to target and destroy cancer cells with minimal damage to surrounding healthy tissue," said Damian Wild, University Hospital Basel, Basel, Switzerland, lead author of the study. "Eventually, this therapy could give hope to some of the hardest-to-treat prostate cancer patients and also could be applied to other types of cancer."

Every year, more than 186,000 men in the United States are newly diagnosed with prostate cancer. The most common types of treatment include surgical removal of some, or all, of the prostate, followed by radiation therapy. More than 30,000 men each year who have had their prostates removed experience recurrence of the cancer. In most of these cases, the disease cannot be localized and treated adequately with conventional treatments; therefore, a systemic treatment that efficiently kills small tumors is needed.

Because tumor cells readily bind with certain peptides, researchers have been able to develop highly specific radiopeptides that bind with tumor cells and treat them using specific therapeutic radioactive substances attached to the radiopeptide. Prostate cancer cells—and many other types of cancer cells—have an overabundance of gastrin-releasing peptide receptors, making the cancer a strong candidate for treatment with radiopeptides.

The study compared two different types of radiopeptides. One group of mice was injected with 213 Bi-DOTA-PESIN, which emits alpha particles that are effective at killing cancer cells. The other group was injected with beta-emitting 177 Lu-DOTA-PESIN, which are also effective in tumor cell-killing, but can also cause damage to nearby healthy cells. Alpha particles are able to kill cancer cells without damaging surrounding healthy tissue. A third group of mice received no treatment.

However, at the maximum tolerated dose, the alpha-emitting 213 Bi-DOTA PESIN was significantly more effective, tripling the survival rate of the mice that received the therapy. The results indicate that the alpha-emitting radiopeptide could provide a new approach for treating prostate cancer and eventually other types of cancer.


Adapted from materials provided by Society of Nuclear Medicine.

Dramatic Outcomes In Prostate Cancer Study

ScienceDaily (June 19, 2009) — Two Mayo Clinic patients whose prostate cancer had been considered inoperable are now cancer free thanks in part to an experimental drug therapy that was used in combination with standardized hormone treatment and radiation therapy. The men were participating in a clinical trial of an immunotherapeutic agent called MDX-010 or ipilimumab.

In these two cases, physicians say the approach initiated the death of a majority of cancer cells and caused the tumors to shrink dramatically, allowing surgery. In both cases, the aggressive tumors had grown well beyond the prostate into the abdominal areas.

"The goal of the study was to see if we could modestly improve upon current treatments for advanced prostate cancer," says Eugene Kwon, M.D., Mayo Clinic urologist and leader of the clinical trial. "The candidates for this study were people who didn't have a lot of other options. However, we were startled to see responses that far exceeded any of our expectations."

The patients first received a type of hormone therapy called androgen ablation, which removes testosterone and usually causes some initial reduction in tumor size. Researchers then introduced a single dose of ipilimumab, an antibody, which builds on the anti-tumor action of the hormone and causes a much larger immune response, resulting in massive death of the tumor cells.

Both men experienced consistent drops in their prostate specific antigen (PSA) counts over the following weeks until both were deemed eligible for surgery. Then, during surgery, came a greater surprise.

"The tumors had shrunk dramatically," says Michael Blute, M.D., Mayo urologist, co-investigator and surgeon, who operated on both men. "I had never seen anything like this before. I had a hard time finding the cancer. At one point the pathologist (who was working during surgery) asked if we were sending him samples from the same patient."

One patient underwent radiation therapy after surgery; both have resumed their regular lives. Further research is being planned to understand more about the mechanisms of the antibody and how best to use the approach in practice. The researchers, however, note the significance of their findings.

"This is one of the holy grails of prostate cancer research," says Dr. Kwon. "We've been looking for this for years."

The research was supported by the Department of Defense, The Richard M. Schulze Family Foundation, the Mayo Clinic Cancer Center and the Mayo Clinic Center for Translational Science Activities. Medarex, Inc. provided the study drug free of charge and supported safety monitoring during the protocol.

Source: Mayo Clinic (2009, June 19). Dramatic Outcomes In Prostate Cancer Study.

Hormone Therapy May Confer More Aggressive Properties To Prostate Tumors

ScienceDaily (June 10, 2009) — Hormone therapy is often given to patients with advanced prostate cancer. While it is true that the treatment prevents growth of the tumour, it also changes its properties. Some of these changes may result in the tumour becoming more aggressive and more liable to form metastases.

This is one of the conclusion of a thesis presented at the Sahlgrenska Academy, University of Gothenburg, Sweden.

Hormone therapy has serious side effects and is therefore used only when the tumour has grown too large to be treated in any other way, or when the tumour has spread and formed metastases. The hormone that is given causes the natural production of male sex hormone to fall, and the tumour stops growing. Pain also usually decreases.

"Our results suggest that the tumour properties change following hormone therapy such that the tumours at a later stage can continue to grow and spread in the body. For this reason, it is probably necessary to supplement the hormone therapy in order to compensate for these changes", says pharmacist Karin Jennbacken, author of the thesis.

The results show that patients who have been given hormone therapy have higher levels of the proteins that enable the cancer cells to move through the body and attach to other organs. One of these proteins is known as "N-cadherin", and this protein is present in higher levels in patients who have been given hormone therapy.

"We don't have any good treatment alternatives in cases where the tumour returns after hormone therapy, and this means that it is particularly important to study how such tumours are controlled and how they behave. The properties that we have identified may become targets for new anti-metastatic drugs in advanced prostate cancer", says Karin Jennbacken.


Prostate Cancer

Approximately 9,000 new cases of prostate cancer are diagnosed each year in Sweden, making it the most common of all cancer forms. Many of the tumours grow very slowly and give no symptoms, but prostate cancer can also display a more aggressive course, spreading metastases to lymph nodes, the skeleton and other locations. The complete prostate is often surgically removed if the cancer is diagnosed early. Other treatments available are radiation therapy and hormone therapy.

Title of the thesis: Invasive and metastatic properties of advanced prostate cancer.

Adapted from materials provided by University of Gothenburg.

From Prostate Imaging to Prostate Cancer Imaging

DENVER—Magnetic resonance imaging (MRI) is customarily used for prostate imaging. However, by modifying a chemotherapy drug with a radioactive component, scientists should be able to image prostate cancer specifically while simultaneously providing therapy for the disease.

John P. Michael Sedelaar, PhD, MD, a postdoctoral research fellow at Johns Hopkins University, presented these findings at the American Association for Cancer Research 100th Annual Meeting 2009, noting that “By adding a radioactive imaging probe in these compounds, we can combine therapeutics with diagnostic imaging.”

The study, conducted in mice, employed the drug thapsigargin, a nonspecific, highly cytotoxic agent. The researchers added a tyrosine ring to this agent for the coupling of imaging probes. Once in the body, this prodrug is made active by proteins—either prostate-specific membrane antigen (PSMA) or prostate-specific antigen (PSA)—which are more prominently present in prostate cancer, and even more prevalent in highgrade prostate cancer and metastasis.

“This inactivated compound has an amino acid tail specifically chosen so that it can only be ‘clipped' by PSA or PSMA,” Dr Sedelaar explained in an interview with Oncology Nursing News. “When this tail is clipped off, the chemical compound is released and activated and can be taken up into the cell and be therapeutically active.”

“It's like a smart bomb, to use a military analogy,” he continued. “By retooling chemotherapy agents, we may be able to get more accurate treatment monitoring and follow-up.”

Unlike other targeted therapies, this treatment is based upon the general principles of prostate cancer, not the individual patient's genetic makeup. “These smart bombs we're developing are not `tailor-made,'” noted Dr Sedelaar; rather, they are based on “the fact that prostate cancers have elevated amounts of PSA and PSMA.”

The need for targeted approaches to prostate cancer is essential, according to Dr Sedelaar. “An increasing number of patients have minimal prostate cancer, and opt for either very focused treatment or the watchful waiting approach,” he noted. “In this environment, the need for an accurate imaging tool is paramount.”

In terms of the study results, singlephoton emission computed tomography imaging of the tumor-bearing mice showed uptake by tumors together with uptake by thyroid, liver, and spleen. The PSMA imaging drug was also detectable in the kidneys and bladder. No toxicity was noted; and even more importantly, there was a measurable reduction in prostate cancer cells.

When asked whether this approach might be transferable to other cancers and other drugs, Dr Sedelaar would say only that “there could be possibilities to retool the compounds for other chemotherapeutic agents, but we haven't reached that stage yet.”

Dr Sedelaar told Oncology Nursing News that a small multicenter trial of these PSMA therapies will start this year, but in terms of the imaging compounds, “We're still in the animal experiments. The compounds are not yet as specific as we want them to be.” He could provide no details about future human trials.

ASCO: Gene Test Predicts Prostate Cancer

ORLANDO, June 2 -- A set of six genes, measured in a blood test, can be used to tell whether a man has prostate cancer, a researcher said here.

In a case-control study, the six-gene panel outperformed a standard test -- age-adjusted prostate specific antigen -- in distinguishing between men with cancer and those without, according to Robert Ross, M.D., of Dana-Farber Cancer Institute in Boston.

When prostate specific antigen (PSA) levels were added to the group of genes, the performance of the test improved even more, Dr. Ross told attendees at the annual meeting of the American Society of Clinical Oncology.

The gold standard for diagnosing prostate cancer is a biopsy, he said, but 60% of biopsies in men thought to be at risk for the disease turn out to be negative.

The goal of this test is to avoid the "pain, discomfort, and anxiety" associated with biopsies, Dr. Ross said, by winnowing out the 60% of men who don't need the procedure.

Dr. Ross and his colleagues started with a set of 392 genes associated with inflammation, cancer, and the epidermal growth factor receptor, as well as some identified in other genetic studies of cancer.

In a training set of 76 healthy men and 76 with prostate cancer, six genes were significantly associated with disease. Of the six, five are less active in those with the disease and one has greater activity, the researchers found.

The finding was validated in a second cohort of 128 men with cancer and 94 without, he said.

In the second group, the six-gene test correctly detected 85.9% of the men with disease, compared with 69.5% detected by age-adjusted PSA, Dr. Ross said.

The six-gene test had a specificity of 83%, compared with 93.6% for PSA, he said.

When the researchers did both the six-gene test and measured PSA levels, the sensitivity and specificity improved -- to 87.5% and 92.6%, respectively.

The results are a "significant improvement" over the predictive value of PSA alone, Dr. Ross said.

"From a clinical hypothesis standpoint, this is great data," Dr. Ross said. But, he cautioned, "this is a case-control study (and) you'd like to see it validated prospectively."

He said his institution and several others are collaborating on a 1,000-patient prospective study -- dubbed PRECISE -- among men who meet the criteria for a biopsy, but have not yet had the test.

The goal will be to see if the test can predict the results of biopsy, he said.

Although the test is still in development, it will not be expensive, especially compared with the $2,000 it costs for a biopsy, said Karl Wassman, of Source MDx, the Boulder, Colo. company that has developed the test.

He said the blood test can be read by standard equipment, using a kit of primers and probes developed by Source MDx, so that the cost will be in the range of "a couple of hundred" dollars.

The various forms of PSA testing are "extremely valuable" in screening for prostate cancer, said Howard Sandler, M.D., of Cedars-Sinai Medical Center in Los Angeles, who was not involved in the study.
But the jury is out on whether screening and early detection have any benefit for patients, he said.

"If screening is beneficial, then better screening is important," he said, but there's no high-quality evidence that early detection is useful.

Dr. Sandler said the "weakness of this test" is that it doesn't answer the most important question about prostate cancer.

"The question is do you have clinically relevant prostate cancer or not?" he said. "Do you have potentially lethal cancer or do you have the cancer that will never kill you?"

Dr. Ross agreed that that question is important and said he and his colleagues have preliminary data that suggests it may be possible to use such a test to distinguish between types of cancer.

The study was supported by Source MDx, Dana Farber and the Harvard Cancer Center, the Gelb Center, and the Bing Sound Wong Fund.
Several researchers reported financial links with Source MDx.

Dr. Sandler reported financial links with sanofi-aventis, Genentech, Amgen, and AstraZeneca.

Primary source: Journal of Clinical Oncology
Source reference:
Ross RW, et al "Sensitivity and specificity of a whole-blood RNA transcript-based diagnostic test for the diagnosis of prostate cancer (CaP) compared with prostate-specific antigen (PSA) alone" J Clin Oncol 2009; 27(15S): Abstract 5052.