Short-Course ADT Passes Test in High-Risk Prostate Cancer

ORLANDO -- Men with node-negative high-risk prostate cancer lived just as long with a 50% shorter duration of androgen deprivation therapy (ADT) compared with standard duration therapy, results of a randomized clinical trial showed.

 

After a median follow-up of 6.5 years, 76.2% of patients who were treated with pelvic radiotherapy and androgen blockade remained alive after 18 months of ADT versus 77% of the men whose hormonal treatment continued twice as long, reported Abdenour Nabid, MD, of Sherbrooke University Hospital in Quebec.

 

The treatment groups also did not differ with respect to 5- and 10-year overall and disease-specific survival (DSS), said Nabid during a press briefing prior to the Genitourinary Cancers Symposium.
 

"In localized high-risk prostate cancer treated with radiotherapy and androgen blockade, androgen blockade duration can be safely reduced from 36 to 18 months." he explained. "Eighteen months of androgen blockade could represent the threshold effect, with no further benefit for our patients. For these patients, side-effect duration and treatment costs of androgen blockade are significantly reduced."

 

"My hope is that the shorter duration can become the standard," he added.

 

Noting that physicians will be eager to see the published results, press briefing moderator Bruce Roth, MD, of Washington University in St. Louis, agreed that 18 months of ADT could become a new standard.

 

The addition of ADT to radiation therapy has been shown to improve survival in men with high-risk prostate cancer. However, the optimal duration of ADT has yet to be determined.

 

The current standard of 24 to 36 months demonstrated superiority over 6 months of ADT. Treatment duration beyond 6 months, but less than 24 months, had not been compared with standard-duration ADT in a large randomized trial, Roth pointed out.

 

The issue of ADT duration has both medical and quality-of-life implications. The longer that patients are exposed to ADT, the more likely they are to encounter treatment-related adverse effects, Nabid said. Potential effects of ADT include bone pain, nausea and vomiting, acute renal insufficiency, back pain, mental confusion, bronchopulmonary complications, sweating, fever, cardiac arrhythmias, and swings in blood glucose levels.

 

Perhaps the most common effects of ADT are a constellation of symptoms and conditions known as "castration syndrome," which includes loss of libido and sexual interest, erectile dysfunction, and impotence, as well as fatigue and weakness, cognitive dysfunction, mood swings, and decreased muscle mass and increased abdominal fat. Decreased physical activity and vitality and osteoporosis may also occur.

 

Nabid and colleagues conducted a phase III trial to compare 18 months versus 36 months of combined androgen blockade with bicalutamide (50 mg for 1 month) and goserelin (10.8 mg every 3 months). They enrolled 630 patients with newly diagnosed prostate cancer associated with one or more high-risk features: PSA level >20 ng/mL, Gleason score >7, or stage T3-4 disease.

Randomized therapy began 4 months before definitive radiation therapy, continued during radiation therapy and for the specified duration of the treatment group. The primary endpoint was overall survival (OS).

 

In addition to the lack of statistical difference in OS, the treatment groups did not differ significantly with respect to biochemical failure rate, need for a second course of ADT, pelvic node metastasis, bone metastasis, or cause of death. The most common causes of death were second cancers (7.3%), prostate cancer (4.9%), and cardiovascular disease (4.4%).

 

The 5-year OS and DSS were 92.1% and 97.6%, respectively, with 36 months of ADT versus 86.8% and 96.4% with short-course ADT. Results at 10 years also did not differ significantly between treatment groups. OS was 63.6% with standard-course ADT and 63.2% with 18 months. DSS was 87.2% in both groups.

 

By multivariate analysis, only patient age predicted the risk of death.

 

On the basis of the results, Roth said he would be willing to change his own practice and adopt 18 months of ADT as a standard. The results add to an accumulation of evidence pointing to a higher risk of diabetes and cardiovascular disease with increasing duration of ADT.

 

"If anything over the last couple of years, the information we have gotten about the long-term consequences of androgen deprivation is more striking than the positive aspects of prolonging therapy," Roth said. "I think probably the most important thing is the chance of getting testosterone back at end of therapy."

 

"I think you can imagine if you are cured of high-risk prostate cancer and have several decades more to live, but have lowered your testosterone essentially to castrate levels permanently, I think there is a price to pay for that and not something we can answer in a couple of years of follow-up," he said.

Whether ADT duration can be shortened even more remains to be seen, he added.

 

The Genitourinary Cancers Symposium is co-sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

 

The study was supported by AstraZeneca.

Nabid and colleagues, as well as Roth, reported no conflicts of interest.

Treatment of Hormone Resistant Prostate Cancer

The following are treatment options for castrate-resistant prostate cancer (also called hormone-refractory prostate cancer). The types of treatments given are based on the unique needs of the person with cancer.

Hormonal therapy

 

Some form of hormonal therapy must always be continued even if the cancer is growing despite the hormonal therapy. If all hormonal therapy is stopped, the cancer is likely to grow very rapidly.

If a man is only taking an LHRH agonist, an anti-androgen (usually bicalutamide) will be added when there are signs of hormone-refractory growth (usually a rising PSA). The LHRH is not stopped. The PSA will often come down for a period of weeks or months before rising again. When it rises, the anti-androgen is stopped but the LHRH is continued.

Chemotherapy

 

Chemotherapy has an important role in the treatment of castrate-resistant or hormone-refractory prostate cancer.

The most common chemotherapy drugs used to treat prostate cancer are:

• docetaxel (Taxotere)
• mitoxantrone (Novantrone)
• cabazitaxel (Jevtana)

The most common chemotherapy combinations used are:

• docetaxel and prednisone – This combination reduces pain, improves quality of life and increases survival.
• mitoxantrone (Novantrone) and prednisone (Deltasone) – This combination reduces pain and improves quality of life.
• cabazitaxel (Jevtana) and prednisone – This combination prolongs survival in castrate-resistant prostate cancer.

Radiation therapy

 

Radiation therapy may be offered for hormone-refractory prostate cancer, either to relieve the urinary symptoms caused by the prostate tumour or to relieve the pain of bone metastases. The types of radiation therapy used is external beam radiation therapy:

• short course of treatment (1–10 treatments) to relieve bone pain
• not given for 4–6 weeks after a transurethral resection of the prostate (TURP), to reduce the risk of scarring in the urethra (urethral stricture)

Bisphosphonates

 

Bisphosphonates are drugs that strengthen bone. A bisphosphonate is used in combination with other standard treatments for hormone-refractory prostate cancer.

The type of bisphosphonate used with hormone-refractory prostate cancer is zoledronic acid (Zometa). It decreases bone-related complications in men with prostate cancer.

Biological therapy

 

A RANK ligand inhibitor is biological therapy in which a monoclonal antibody blocks the action of RANK ligand (a protein that promotes bone resorption). This helps to strengthen bone. The RANK ligand inhibitor denosumab is better than zoledronic acid in decreasing time to bone-related events in prostate cancer. It has recently been approved for use in men with prostate cancer in Canada.

 

 

Surgery

Transurethral resection of the prostate (TURP) may be offered for hormone-refractory prostate cancer. This type of surgery is used to relieve urinary symptoms caused by the prostate tumour (palliative surgery).

Clinical trials

 

Men with prostate cancer may be offered the opportunity to participate in clinical trials.

References

Cancer information / Cancer type / Prostate / Treatment / Castrate-resistant prostate cancer

American Cancer Society. Prostate cancer overview. (2011, May 4). Detailed Guide: Prostate Cancer. Atlanta, GA: American Cancer Society. Retrieved from: http://www.cancer.org/.

---

de Bono,J.S., Oudard,S., Ozguroglu, M., et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. (2010, October 2). Lancet. New York, NY: Elsevier, Inc. Retrieved from: http://www.thelancet.com/journals/lancet/issue/current.

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Fizazi K, Carducci M, Smith M,et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. (2011, March 5). Lancet. New York, NY: Elsevier, Inc. Retrieved from: http://www.thelancet.com/journals/lancet/issue/current.

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Prostate Cancer Treatment (PDQ®). National Cancer Institute. (2010, August). National Cancer Institute (NCI). Bethesda, MD: National Cancer Institute. Retrieved from: http://www.cancer.gov.

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Prostate cancer. National Comprehensive Cancer Network. (2010). NCCN Clinical Practice Guidelines in Oncology. National Comprehensive Cancer Network (NCCN).

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Ross, P. L., Carroll, P. R., Small, E. J., et al. Prostate. Ko, A. H., Dollinger, M., & Rosenbaum, E. (2008). Everyone's Guide to Cancer Therapy: How Cancer is Diagnosed, Treated and Managed Day to Day. (5th Edition). Kansas City: Andrews McMeel Publishing. pp. 789-806.

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Zelefsky MJ., Eastham JA, Sartor OA, et al. Cancers of the genitourinary system: cancer of the prostate. Devita, V. T., Jr., Lawrence, T. S., & Rosenberg, S. A. (2008). Cancer: Principles & Practice of Oncology. (8th Edition). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. 40.6: 1392-1451.

---

Source - Canadian Cancer Society:

http://www.cancer.ca/en/cancer-information/cancer-type/prostate/treatment/castrate-resistant-prostate-cancer/?region=on

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.

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.

Science Makes Inroads Against Prostate, Other Cancers

In studies, an immune boost fights prostate tumors, and better drugs outwit brain, pancreatic malignancies


SUNDAY, April 19 (HealthDay News) -- Harnessing cutting-edge techniques, a variety of human, animal and laboratory studies are suggesting innovative new ways to beat cancer.

Brain, prostate, and pancreatic cancer are some of the specific targets of the new research described Sunday in Denver at the annual meeting of the American Association for Cancer Research.

"This is an extremely exciting time in cancer research," observed Dr. David Carbone, director of the thoracic oncology center at the Vanderbilt-Ingram Cancer Center in Nashville. "Even in the kinds of cancers that traditionally have been very resistant to therapy, we're starting to see clues of amazing responses and clinical benefits for patients."

Carbone, himself a cancer survivor, was not engaged in any of the investigations under discussion in Denver.

One of the studies involved a clinical trial into a new therapy for prostate cancer. That study's lead author, Dr. Richard Junghans, described his team's effort as an attempt "to find a cure for patients who will ultimately die, because standard therapies don't really work".

"Prostate cancer kills about 3,000 [men] every month," observed Junghans, an associate professor in the department of surgery and medicine at Boston University School of Medicine, as well as chief of the division of surgical research at Roger Williams Medical Center in Providence, R.I.

"Chemotherapy doesn't work, and hormone treatment can keep the prostate under control for one to two and maybe even three years. But after that, there's very little left. So almost all patients who've had their cancer spread to the bones will die, and it can be a miserable way to go."

"So, what we've done is to go in a radical new direction to develop a therapy that is not a chemical, not an inert drug, not a hormone," he explained. "It's almost a living organism. It's actually the patient's own T-cells -- white blood cells that exist in everyone's body -- that have been modified and engineered to be 'fooled' into attacking the cancer."

Junghans said that the first two patients to receive a single infusion with the new treatment experienced a 50 percent to 75 percent reduction in their blood level of prostate-specific antigen (PSA), a measure of prostate cancer activity, over the following two months.

"So, I'm very excited, because this achievement was with the lowest dose of the therapy, which we now plan to try out at a level ten times as high," he noted. Junghans said he and his team hope to "achieve a 100 percent reduction (in PSA)."

Another of the four studies included work led by Florence Hofman, a professor of pathology at the University of Southern California, Keck School of Medicine, in Los Angeles. Her team targeted brain cancer with an inhibitor called "dimethyl-celecoxib".

Celecoxib may sound familiar: It's the more scientific name for the cox-2 inhibitor drug, Celebrex, which has been used as a pain reliever and cancer-fighter but also has some cardiovascular side effects. The new drug is "similar to a cox-2, but not quite the same," Hofman noted. "It's like a key in a lock. You just change one of the little teeth in the key -- a molecule for example -- and it does one thing but not another, even if it looks very much the same. So then, we get the very great advantage of avoiding some known and dangerous side effects."

The therapy appears to inhibit new blood vessel growth as part of its strong anti-tumor effect, Hofman said. Specifically, in animal studies, this cox-2-like agent achieved a 35 percent to 45 percent reduction in the density of tumor blood vessels without the development of any potentially damaging long-term side effects.

Hofman and her colleagues noted that though their current focus was on brain cancer, the therapy could have applications for other types of cancer, including breast cancer.

However, "this is not a wonder-drug," Hofman cautioned. "We don't have a cure for cancer here. But the approach we've taken and tested in lab and with rodent models looks very promising for future therapy with brain tumors."

Another study, led by researchers at the Mayo Clinic in Rochester, Minn., looked at inhibiting pancreatic cancer at the cellular level with a combination of two new agents: a histone deacetylase inhibitor called LBH589 and a mTOR inhibitor called rapamycin.

When used together, the two drugs appeared to provide more anti-cancer punch than they would have singly, the team said. While treatment with rapamycin alone only resulted in a tumor cell death rate of about 10 percent, the two drugs in combination elicited a 60 percent to 70 percent death rate. Any improvement in outcomes is welcome for patients battling pancreatic cancer, a malignancy that, because it is often detected late, has a very high mortality.

A fourth study was conducted by the biotech company Genentech. Researchers there honed in on specific proteins generated by a key player in cancer development, known as the "ras" oncogene.

In lab work, the study authors found evidence that by interrupting the pathways by which these proteins signal and trigger tumor growth, they were able to produce "significant" tumor cell death.

At this point in cancer research, "we obviously have a long way to go," remarked Vanderbilt's Carbone. "But this is all about more than just hope. I've been practicing for 18 years now, and I can say that we now are developing a new reality, as we learn more and more about cancer. And this will translate into real people having real responses and real improvements in their quality of life as they battle cancer. And that is what's so exciting."

More information

There's more on the effort to beat cancer at the American Association for Cancer Research.

ASCO: Estrogen Patch Looks Promising as Androgen Deprivation Therapy

This presentation from American Society of Clinical Oncology in Medpage Today reports outcome from a study exploring ability of estrogen therapy to replace androgen lowering treatments without some of the side effects.


ORLANDO, March 3 -- Estrogen could make a comeback as hormonal therapy for advanced prostate cancer if interim results from an ongoing clinical trial hold up in further testing.

Transdermal estrogen drove down testosterone and PSA levels to a similar extent as an LHRH analog, Ruth E. Langley, M.D., of the Medical Research Council in London, reported at the Genitourinary Cancers Symposium.

No worrisome adverse events have occurred with the estrogen patches, which could help preserve bone mineral density, unlike conventional androgen deprivation therapy.

"These data demonstrate that estrogen patches produce a similar fall in testosterone to LHRH analogs and concomitant falls in PSA in patients with metastatic and locally advanced prostate cancer," said Dr. Langley. "The patches have been generally well tolerated."

Cardiovascular safety data have yet to be released, pending accrual of the 200-patient total for the study.

Nonetheless, on the basis of the results, the data monitoring committee recommended that investigators "focus their plans towards developing a larger, phase III trial," said Dr. Langley.

Oral estrogen won support as hormonal therapy for prostate cancer in the 1960s. However, the treatment fell out of favor because it was associated with increased cardiovascular morbidity, said Dr. Langley.

"The [cardiovascular] toxicity has been attributed to first-pass hepatic metabolism, which affects lipids and coagulation proteins," she said. "Since transcutaneous administration of estrogen avoids the enterohepatic circulation, it should not be associated with the same high levels of cardiovascular toxicity."

In a preliminary trial involving 20 patients with prostate cancer, estrogen patches lowered testosterone to castrate levels and caused no cardiovascular events, aside from one case of edema.

On the basis of those results, investigators organized a multicenter, randomized study that included 172 patients as of mid-February.

The trial involved patients with newly diagnosed T3/4 prostate cancer or with cancer in PSA relapse following definitive surgery or radiation therapy. Castrate-level testosterone was defined as 50 ng/dL.

The patients were randomized 1:2 to an LHRH analog or to transdermal patches that released 100 µg of estradiol per hour. After a planned review of data, investigators increased the patch dosage.

As a result, the first 33 patients randomized to transdermal patches received three patches, which were changed twice weekly. The remaining patients assigned to the estrogen group received four patches that were changed twice weekly.

Estradiol, testosterone, and PSA levels were measured at four weeks and three months and then every six months. In addition, investigators measured PSA levels at nine, 15, and 21 months.

At week four, 20 of 33 patients (60.6%) in the LHRH analog group had castrate levels of testosterone, as did 20 of 30 (66.6%) who received three estradiol patches, and 30 of 33 (90.9%)who received four patches.

Four LHRH analog patients had testosterone levels between 50 and 100 ng/dL, compared with five in the three-patch group and three in the four-patch group.

By week 12, 26 of 28 evaluable patients (92.8%) assigned to the LHRH analog had castrate levels of testosterone, and none had levels between 50 and 100 ng/dL.

Among patients treated with three estradiol patches, 21 of 29 (72.4%) had castrate levels of testosterone and six had levels of 50 to 100 ng/dL.

In the four-patch group, 27 of 31 patients (87%) had castrate testosterone levels and the other four had levels of 50 to 100 ng/dL.

At six months, the median testosterone levels were 14.3 ng/dL in the LHRH analog group, 28.6 ng/dL in the three-patch group, and 22.9 ng/dL in the four-patch group.

Median PSA values were 0.9 ng/mL, 3.2 ng/mL, and 1.3 ng/mL, respectively.

Dr. Langley and her coinvestigators reported no disclosures.


By Charles Bankhead, Staff Writer, MedPage Today

Published: March 03, 2009

Primary source: ASCO: Genitourinary Cancers Symposium

Source reference:

Langley RE, et al "PATCH, a randomized phase II trial of estrogen patches versus LHRH as first-line hormonal therapy for prostate cancer: planned interim analysis results" ASCO: GU 2009; Abstract 173.


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Locally advanced prostate cancer: hormone therapy and radiation therapy can double survival.

When prostate cancer extends beyond the prostate but is still contained within the prostate region, it is called ‘locally advanced’. Cancer at this stage is at high risk of progression, but is still potentially curable. This report from a US radiotherapy conference suggests that using two therapies can be better than one alone.

From Medscape Medical News, News Author: Zosia Chustecka

September 23, 2008 — Adding radiation to androgen deprivation therapy in older men with locally advanced prostate cancer reduces the risk of dying from the disease by half. These results, from a randomized clinical trial, suggest that men should be offered this additional option, says lead researcher Anders Widmark, MD, professor in radiation oncology at Umea University in Umea, Sweden.

Dr. Widmark presented the results at a plenary session during the American Society for Therapeutic Radiology and Oncology (ASTRO) 50th Annual Meeting in Boston, Massachusetts.

"This trial will change clinical practice," predicted Anthony Zietman from Massachusetts General Hospital in Boston, who was moderating a press briefing at which the results were highlighted. Dr. Zietman is also president-elect of the ASTRO, taking on the role of president effective September 23, 2008.

"At present, there is a bit of a fatalistic attitude towards locally advanced prostate cancer, as it generally considered to have already quietly spread elsewhere," Dr. Zietman commented. "Often the only treatment often offered to older men with this stage of disease is hormonal therapy," he continued. "This attitude is maybe more common in Europe, but it's also prevalent in the United States."

"The thinking is that the cat is already out of the bag," Dr. Zietman commented, but "the results from this trial prove that this is not the case."

"This randomised trial is the first to show that men with locally advanced prostate cancer will survive substantially longer when radiation is added to their treatment plan," Dr. Widmark told journalists. .

American Society for Therapeutic Radiology and Oncology 50th Annual Meeting: Plenary session. Presented on September 22, 2008.


See: Medscape article

Hormone Therapy applicable for Prostate Cancer

Researchers made a new study which suggests hormone suppression therapy could increase substantially an advanced prostate cancer patient's chances of living free of the disease.

Michel Bolla, a professor at Grenoble University Hospital, examined the potential benefits of suppressing the male hormone androgen, similar to the more commonly known male hormone testosterone, among 400 patients in advanced stages// of their prostate cancer, meaning their chances of survival were deteriorating. The international study involved patients throughout Europe as well as in Canada and Israel.

In the study, the men were randomly assigned to receive either radiation therapy alone or androgen suppression given during and after radiotherapy for three years. The average follow-up period was five and a half years.

Study results revealed almost three-quarters of the men who received the combination therapy, or 70 percent, had an increased five-year, disease-free survival rate compared to only 30 percent of patients who received only radiotherapy. Overall, survival rates were 80 percent within the hormone-suppression group and 62 percent for the radiotherapy group.

Bolla felt that at the present time a long-term hormone therapy 2 or 3 years compared to short-term resulted in statistically significant improvements in overall survival, as shown by this trial. The long-term survival rate for men with aggressive prostate cancer is poor, so additional therapies are needed to improve their chances. He added the findings also indicate hormone suppression with radiotherapy or external irradiation could trigger apoptosis -- the cancer cells destroying themselves.

However, there were side effects, Bolla said, including hot flashes, loss of libido and impotency. Kenneth Koeneman, urology professor at University of Texas Southwestern Medical Center at Dallas, said the side effects go beyond sexual dysfunction. "It's systemic castration," Koeneman told UPI.

Hormone suppression also can cause breast enlargement, a drop in muscle mass and an increase in body fat, he said. Prostate cancer patients on this particular therapy also are vulnerable to osteoporosis.

Hormone suppression is used in the United States, "but not necessarily for three years," he said. The reason it is used cautiously is "taking away the male hormone actually affects the marker we use" to detect cancer levels, Koeneman explained. That marker is called prostate-specific antigen or PSA, which is hormone-dependent. Hormone suppression may lower PSA levels suggesting the prostate cancer has been cut back, which might be an incorrect assumption.

"We may just be fooling ourselves that the cancer is not there," Koeneman said. He also questioned Bolla's assertion androgen suppression could contribute to cancer cell death. "Androgen suppression in the history of man has never cured anybody that we know of." Dr. Rowan Chlebowski, chief of medical oncology at the Harbor-UCLA Research Education Institute in Los Angeles, said doctors sometimes walk a tightrope between the potential benefits and downsides of hormone therapy.

Fatigue in People with Cancer

What is fatigue?

Fatigue is feeling tired -- physically, mentally, and emotionally. It means having less energy to do the things you normally do or want to do. It can be caused by cancer, cancer treatment, and other factors. Fatigue can last a long time and can affect your day to day activities.

The fatigue that comes with cancer is different from the fatigue of everyday life. Everyday, normal fatigue is most often a short-term problem that gets better with rest. Cancer-related fatigue is worse and it causes more distress. Rest does not make it go away. And even a small amount of activity may make you feel exhausted. For some people, this kind of fatigue can cause even more distress than pain, nausea, vomiting, or depression. Cancer-related fatigue can:

* Differ from one day to the next in how bad it is and how much it bothers you
* Be overwhelming and make it hard for you to feel well
* Make it hard for you to be with your friends and family
* Make it hard for you to do your normal activities, including going to work
* Make it harder for you to follow your cancer treatment plan
* Last different lengths of time, which makes it hard to guess how long yours will go on

Cancer patients say fatigue is the most distressing side effect of cancer and its treatment -- it can have a major affect on a person's quality of life.


Fatigue is very common in people with cancer

Cancer-related fatigue is the most common side effect of cancer and cancer treatment. Research suggests that anywhere between 70% to 100% of cancer patients getting treatment have fatigue. And about 30% to 50% of cancer survivors have reported fatigue that lasts for months or even years after they finish treatment.

Even though fatigue is a very distressing symptom, doctors and nurses seldom focus on it, and patients and caregivers rarely report it. It may be hard to talk about, but fatigue is normal and common for people with cancer. There are things that can be done to help if your health care team knows you are having this problem.


Talk about your fatigue

Treating fatigue is an important part of care for you and your family. But before anything can be done to help you, your health care team must know about your level of fatigue, or how bad your fatigue is.

People with fatigue describe it in many ways. They may say they feel tired, weak, exhausted, weary, worn-out, or slow; have no energy; and cannot concentrate. They also talk about having heavy arms and legs; little drive to do anything; being unable to sleep or sleeping too much; or feeling moody, sad, irritable, or frustrated. Patients rarely describe their symptom as "fatigue" unless their health care team suggests it.

Only you know if you have fatigue and how bad it is. No laboratory tests or x-rays can diagnose or show your level of fatigue. The best measure of fatigue comes from your own report of your fatigue level to your health care team. But fatigue can be hard to describe.

You can describe your level of fatigue as none, mild, moderate, or severe. Or you can use a scale of 0 to 10, where a 0 means no fatigue at all, and a 10 means the worst fatigue you can imagine. Talk to your doctor or nurse about how to describe your fatigue so they can understand how it is affecting your everyday life.


How bad is your fatigue?

If you have moderate (4 to 6) to severe (7 to 10) fatigue, your doctor may ask you to give as much information as you can about your fatigue. You may be asked questions like:


When did the fatigue first start?

* When did you first notice that this fatigue is different than usual for you?
* How long has it lasted?
* Has it changed over time? How so?
* Does anything make it better? Worse?
* Do you have any other problems or concerns?
* How has the fatigue affected the things you do every day or the activities that give meaning and enjoyment to your life?

In planning how to treat your fatigue, your doctor may take into account your cancer, the type and length of treatment, how likely the treatment is to cause fatigue, and your response to treatment.


What causes fatigue in people with cancer?

Cancer itself can cause fatigue directly by spreading to the bone marrow, causing anemia (low red blood cell count), or indirectly, by forming toxic substances in the body that change the way normal cells work.

Fatigue is also very common with many cancer treatments, such as chemotherapy, radiation therapy, bone marrow transplant, and immunotherapy. Cancer treatments often kill fast-growing healthy cells, especially the blood-making cells in the bone marrow. This causes fatigue because red blood cells carry oxygen to fuel all the cells in the body.

Too few red blood cells (anemia) means too little energy to meet the body's needs. Treatments can kill normal cells and cancer cells, which leads to a build-up of cell waste. The body needs extra energy to clean up this waste and repair damaged tissue.


Here are some questions about fatigue and your cancer treatment that you may want to ask:

* Will the cancer treatment that I am getting cause fatigue?
* How bad will my fatigue likely get?
* Are there ways to control my fatigue or make it better?
* If my fatigue gets bad, how will you decide how to treat it?
* What can be done if the treatment does not make my fatigue better?
* What are the likely side effects of the treatments for fatigue?
* What other health care professionals can help manage my fatigue?
* Is my fatigue caused by anemia? If so, how will it be treated?

Other things that can affect fatigue

Fatigue is different for every cancer patient. Many treatment-related and disease-related factors have been linked to fatigue, but doctors still don't know exactly what causes cancer-related fatigue.

There are some other factors that often worsen fatigue, and you should be checked for them. Managing these factors can greatly help reduce the fatigue.

* Anemia
* Pain
* Emotional distress (including depression and anxiety)
* Sleep problems
* Medicines you are taking that could worsen your symptoms
* Other medical problems (such as infection; low thyroid function; and heart, lung, liver, kidney, or nervous system disease)
* Nutrition problems
* Low level of physical activity

Anemia

A low red blood cell count is called anemia (uh-nee-me-uh). Your red blood cell count will be measured with a blood test called a CBC. (CBC stands for complete blood count.) Doctors often define anemia as a blood hemoglobin (Hb) level of less than 12 g/dL (grams per deciliter). But many people do not feel much different until the hemoglobin level falls below 11 g/dL. Symptoms of anemia get worse as the hemoglobin gets lower. These symptoms can include:

* Rapid heart beat
* Shortness of breath
* Trouble breathing on exertion (such as when walking or climbing stairs)
* Dizziness
* Pale skin
* Fatigue

There are many different causes of anemia. Your health care team will try to find out the cause of your anemia so they can give you treatment that makes it better.


Pain

Cancer pain can make you less active, decrease your appetite, cause sleep problems, and cause depression -- all of which can lead to fatigue. Cancer pain should not be accepted as part of cancer treatment. There is always something that can be done to make pain better.

For more information about treating cancer pain, talk to your doctor or nurse. You can also learn more in our document, Pain Control: A Guide for People With Cancer and Their Families.


Emotional distress

People diagnosed with cancer go through many unpleasant emotions. There are many different types of feelings, from anger to depression, but their overall effect is distress. Distress can include a feeling of sadness about the loss of good health or fear of what will happen in the future. These are normal feelings. But sometimes the distress becomes so great that it causes physical problems like fatigue. Depression and anxiety are common types of distress that can cause the physical symptom of fatigue.


Sleep problems

If you wake up often during the night, have trouble falling asleep, or wake up early in the morning and cannot go back to sleep, you are most likely not getting the rest you need. This change in your sleep can lead to fatigue. Tell your doctor or nurse about your sleeping problems. They will try to find out why you are having trouble sleeping so they can help plan the best treatment for this problem.


Medicines

Many medicines can cause symptoms of fatigue and problems with thinking. This includes over-the-counter drugs, vitamins, herbs, and other supplements, as well as prescription medicines. The drugs most likely to cause fatigue are pain medicines; sleep medicines; anti-depressants; and anti-nausea and anti-seizure medicines. Some heart medicines can also cause fatigue. The degree of sleepiness varies from patient to patient. Taking many drugs with many side effects may make fatigue worse, too. It is important to tell your health care team about all vitamins, herbs, supplements, and medicines you are taking. Keeping a journal may help you keep track of your medicines and symptoms.


Other medical problems

Many people have other medical problems or illnesses that are not related to cancer, but may add to fatigue. These illnesses should be identified and treated. Examples of other medical problems that may be part of fatigue are:

* Heart problems, such as congestive heart failure
* Lung problems, such as emphysema or shortness of breath
* Kidney problems, such as kidney failure
* Brain problems, such as seizures or dementia
* Infections, such as pneumonia or viral illnesses
* Low thyroid function

Low thyroid gland function is very common in people in the United States. Anyone with fatigue should be tested for this. Blood tests are done to find out how much thyroid hormone is present in the blood. If the level of thyroid hormone is low, treatment can be given to replace the thyroid hormone so that the body gets what it needs.


Poor nutrition

The body needs protein, carbohydrates, fats, vitamins, minerals, and water to do its work. In people with cancer, changes in nutrition can affect fatigue. These changes include how well the body can process nutrients; the need for more energy than usual; and poor intake of food, fluids, and certain minerals. The changes can be caused by:

* Changes in metabolism (the body's ability to break down and use food)
* The need to repair damaged cells
* Uncontrolled tumor growth competing for nutrients
* Poor appetite
* Nausea and vomiting
* Diarrhea

You may have blood tests to measure things like sodium, potassium, calcium, and magnesium -- these are important minerals that your body needs. You may ask to be referred to a registered dietitian who can help you learn how to best meet your nutrition during this time.

You can find more information on nutrition in our document, Nutrition for the Person With Cancer During Treatment: A Guide for Patients and Families.


Inactivity

Cancer treatment along with less physical activity can make you less able to do the things you used to do. And you may find that it takes much more effort and more energy to do the things you need to do. This can worsen fatigue. Physical exercise can help you build up your energy level. If you have more energy, it can help you do your usual activities and have less fatigue. Talk to your doctor before you start any exercises. A careful work-up by a physical therapist can help plan the right exercise program for you.

You can find more information in Nutrition and Physical Activity During and After Cancer Treatment: Answers to Common Questions.


Treating fatigue

Many health professionals may be part of fatigue treatment. Treatment may involve doctors, nurses, social workers, physical therapists, nutritionists, and a number of others. Education and counseling are part of the treatment and help you learn how to save energy, reduce stress, and use distraction to think about things other than the fatigue.

Fatigue is often caused by more than one problem. Treating a certain problem, like anemia, may make you feel better, but other things may still need to be done. For this reason your health care team may have you try many different things to ease your fatigue. These may or may not include medicines.

If the cause of fatigue is known, treatment will focus on the cause. For example, if anemia is adding to your fatigue, the anemia can be treated. In another patient, treatment may include correcting fluid and mineral imbalances. A program of regular exercise, managing your stress, and finding ways to deal with anxiety and depression seem to work the best in dealing with fatigue. Still, treating sleep problems and correcting nutrition problems can help decrease fatigue, too.


Tips for managing fatigue

* Save your energy

Saving or conserving energy is one way to make sure you have enough energy to do what needs to be done on a daily basis. You may need to accept the fact that you can't do everything you want to do at your current level of energy. Each day, decide which things are the most important to do and focus on those tasks. Do things slowly, so that you will not use too much energy as you go. Let others help you. This can help them feel useful and get your tasks done, too.

* Distraction

Sometimes feeling tired can become so discouraging and frustrating that it's easy to let it become the focus of your thoughts. Try to distract yourself with other things, like listening to music, having relaxing visits with friends or family, or reading a book. These things can give you an escape from your fatigue without using up too much energy.

* Attention-restoring activities

Certain activities can help you relax, focus better, and direct your attention under stress. These activities include things like walking on a beach, sitting in a peaceful setting, gardening, doing volunteer activities not related to your illness, or bird watching.

* Reduce stress

Having cancer is stressful and cancer treatment can cause even more stress. Talk with a social worker or nurse on your health care team about your level of stress. This can help you know if it is "normal" stress or more worrisome anxiety or depression. Feeling tired may be related to feeling depressed and anxious. Support groups, mental health counseling, stress management training, and relaxation exercises are some ways you can improve the feelings related to fatigue and help you overcome the tiredness you feel.

* Exercise

Research has shown that there are some ways to improve your energy and activity level that do not involve medicine. An aerobic exercise program -- started only with your doctor's OK -- can lead to better heart and lung function, as well as more positive feelings about your life and well-being. You may need to see a physical therapist to learn the best exercise routine for you to follow at this time. You must be careful about any form of exercise if you have any of these:

* Bone metastasis (cancer that has spread to your bones)
* A low white blood cell count
* A low platelet count
* A fever
* Anemia

These factors can lead to more physical problems if they are not taken into account when planning an exercise program.

Not only can the right amount and type of exercise help fatigue, it can also help you sleep better. Another benefit of exercise is that it may make your mood better, too.


Nutritional counseling

Many cancer patients have changes in the way they eat, swallow, and taste during treatment. Talking with a registered dietician may help you learn ways to manage problems like loss of appetite, diarrhea, nausea, or vomiting. A nutritionist also can make sure you are getting enough fluids and nutrients so that your blood chemistry is balanced.


Sleep improvement

Sleep problems are common during cancer treatment. You may have trouble falling asleep or sleep too much. Sleep experts tell us that having a regular time to go to bed and get up helps us keep a healthy sleep routine. Avoiding caffeine in fluids (like coffee or soda), or even in foods (like chocolate) can help, too. Do not exercise too late in the evening; this may cause sleep problems. Naps may be needed, but try to keep them short (less than 45 minutes long) and early in the day so they don't interfere with nighttime sleep.


Medicines

There is no magic pill that can make you less tired and give you more energy. But there are some medicines that may help you with your fatigue. In some cases, fatigue may be bad enough that your doctor or nurse may recommend a stimulant medicine for a short period of time. Examples of this type of medicine are methylphenidate hydrochloride (Ritalin®) or modafanil (Provigil®). Anti-depressant drugs and steroids have also been used to ease fatigue. If you are having problems sleeping, your doctor or nurse may suggest a medicine to help you sleep.

More research is needed and is being done in this area, but there are drugs available that may give you relief if your fatigue gets bad.


Coping with fatigue

Learning about fatigue patterns, how bad it might be, and how long it may last are key parts of dealing with fatigue. Many times, a family member who learns with you can help you talk to your health care team about your fatigue.

Here is a recap of things you can do to manage and reduce your fatigue:

* List your activities in order of how important they are to you, so you can do the more important ones when you have the most energy.

* Ask for help and have other people do tasks for you when possible.

* Put things that you often use within easy reach.

* Set up and follow a structured daily routine, keeping as normal a level of activity as possible.

* Balance rest and activity. Too much time in bed can make you weak. Try to avoid it. Schedule activities so that you have time for plenty of rest that does not interfere with nighttime sleep. Shorter rest periods are reported to be better than one long one.

* Learn ways to deal with your stress. Try to reduce it using things like deep breathing, imagery, meditation, prayer, talking with others, reading, listening to music, painting, or any other things you like to do.

* Keep a record of how you feel each day. Take it with you when you see your doctor.

* Talk to your doctor about how to manage any pain, nausea, or depression you may have.

* Talk to your doctor about physical exercise before you start an exercise program.

* Get fresh air, if possible.

* Unless you are given other instructions, eat a balanced diet that includes protein (meat, milk, eggs, and beans) and drink about 8 to 10 glasses of water a day.

The best thing you can do for fatigue is talk to your doctor or nurse about it. Let them know how bad it is so you can get the help you need to deal with it.


Watch for signs of fatigue

Here is a list of some signs of fatigue that you and your family can watch for. Talk to your doctor if you have any symptoms of fatigue.

* You feel tired and it does not get better, it keeps coming back, or it becomes severe.

* You are more tired than usual during or after an activity.

* You are feeling tired and it is not related to an activity.

* Your tiredness does not get better with rest or sleep.

* You sleep more.

* You become confused or cannot concentrate or focus your thoughts.

* You have no energy.

* You are unable to get out of bed for more than 24 hours.

* Your tiredness disrupts your work, social life, or daily routine.

* You have no desire to do the things you normally do.

* You feel negative, sad, or irritable.

Fatigue can lead to distress. It can interfere with your daily activities and keep you from doing the things you need and want to do. Fatigue can make you unable to take care of yourself, affect your will to do things, and sometimes make you feel like you cannot continue your cancer treatment. Work with your health care team to find and treat the causes of your fatigue.

Remember: There is no one way to diagnose or treat fatigue. The best treatment for you is most likely to be found through open discussions with your doctor and your nurse.

Hormone (Androgen Deprivation) Therapy

Hormone therapy is also called androgen deprivation therapy (ADT) or androgen suppression therapy. The goal is to reduce levels of the male hormones, called androgens, in the body. The main androgens are testosterone and dihydrotestosterone (DHT). Androgens, produced mainly in the testicles, stimulate prostate cancer cells to grow. Lowering androgen levels often makes prostate cancers shrink or grow more slowly. However, hormone therapy does not cure prostate cancer.


Hormone therapy may be used in several situations:

* If you are not able to have surgery or radiation or can't be cured by these treatments because the cancer has already spread beyond the prostate gland
* If your cancer remains or comes back after treatment with surgery or radiation therapy
* As an addition to radiation therapy as initial treatment if you are at high risk for cancer recurrence
* Before surgery or radiation to try and shrink the cancer to make other treatments more effective

Types of Hormone Therapy

There are several types of hormone therapy used to treat prostate cancer.

Orchiectomy (surgical castration): Even though this is a type of surgery, its main effect is as a form of hormone therapy. In this operation, the surgeon removes the testicles, where more than 90% of the androgens, mostly testosterone, are made. With this source removed, most prostate cancers stop growing or shrink for a time.

This is done as a simple outpatient procedure. It is probably the least expensive and simplest way to reduce androgen levels in the body. But unlike some of the other methods of lowering androgen levels, it is permanent, and many men have trouble accepting the removal of their testicles. Some men having the procedure are concerned about how it will look. If wanted, artificial silicone sacs filled with saline (salt water) can be inserted into the scrotum. These look and feel like testicles.

Possible side effects of orchiectomy are generally related to changing levels of hormones in the body. About 90% of men who have had this operation have reduced or absent libido (sexual desire) and impotence. Some men also experience:

* Hot flashes (these may go away with time)
* Breast tenderness and growth of breast tissue
* Osteoporosis (bone thinning) which can lead to broken bones
* Anemia (low red blood cell counts)
* Decreased mental acuity (sharpness)
* Loss of muscle mass
* Weight gain
* Fatigue
* Decrease in HDL ("good") cholesterol
* Depression

Many of these side effects can be prevented or treated. For example, sometimes the hot flashes will be helped by treatment with antidepressants. Brief radiation treatment to the breasts before surgery can help prevent their enlargement.

Men getting this treatment should be watched and treated for osteoporosis to help prevent broken bones. There are several different drugs available. Exercise is a good way to reduce fatigue, weight gain, and the chance of loss of bone and muscle mass. If anemia occurs, it is often very mild and usually doesn't cause symptoms. Depression can be treated by antidepressants and/or counseling.

Luteinizing hormone-releasing hormone (LHRH) analogs: Even though LHRH analogs (also called LHRH agonists) cost more and require more frequent doctor visits, most men choose this method over orchiectomy. These drugs lower testosterone levels just as well as orchiectomy by lowering the levels of androgens (mainly testosterone) made by your testicles.

LHRH analogs are injected or placed as small implants under the skin. They are given either monthly or every 3, 4, 6, or 12 months. The LHRH analogs available in the United States include leuprolide (Lupron, Viadur, Eligard), goserelin (Zoladex), and triptorelin (Trelstar).

Possible side effects of LHRH analogs such as hot flashes, osteoporosis, and others are similar to those of orchiectomy (see above), and are largely due to low testosterone levels.

When LHRH analogs are first given, testosterone production increases briefly before falling to very low levels. This effect is called flare and results from the complex way in which LHRH analogs work. Men whose cancer has spread to the bones may experience bone pain. If the cancer has spread to the spine, even a short-term increase in growth could compress the spinal cord and cause pain or paralysis. Flare can be avoided by giving drugs called anti-androgens for a few weeks when starting treatment with LHRH analogs. (For more on anti-androgens, see below.)

Luteinizing hormone-releasing hormone (LHRH) antagonists: A newer drug, abarelix (Plenaxis), is an LHRH antagonist. It is thought to work like LHRH agonists, but it appears to reduce testosterone levels more quickly and does not cause tumor flare like the LHRH agonists do.

A small percentage of men (fewer than 5%) have serious allergic reactions to the drug. Because of this, it is only approved for use in men who have serious symptoms from advanced prostate cancer and who cannot or refuse to take other forms of hormone therapy.

The possible side effects are similar to those with orchiectomy (see above) or LHRH agonists.

Abarelix is given only in qualified doctors' offices. It is injected into the buttocks every 2 weeks for the first month, then every 4 weeks. You will be asked to remain in the office for 30 minutes after the injection to make sure you are not having an allergic reaction.

Anti-androgens: Anti-androgens block the body's ability to use any androgens. Even after orchiectomy or during treatment with LHRH analogs, a small amount of androgens is still made by the adrenal glands.

Drugs of this type, such as flutamide (Eulexin), bicalutamide (Casodex), and nilutamide (Nilandron), are taken daily as pills.

Anti-androgens are not often used by themselves (see below). An anti-androgen may be added if treatment with orchiectomy or an LHRH analog is no longer working by itself.

Anti-androgen treatment may be combined with orchiectomy or LHRH analogs as first-line hormone therapy. This is called combined androgen blockade (CAB). There is still some debate as to whether CAB is more effective in this setting than using orchiectomy or an LHRH analog alone. If there is a benefit, it appears to be small.

Some doctors are testing the use of anti-androgens instead of orchiectomy or LHRH analogs. Several recent studies have compared the effectiveness of anti-androgens alone with that of LHRH agonists. Most found no difference in survival rates, but a few found anti-androgens to be slightly less effective.

If hormone therapy including an anti-androgen stops working, some men seem to benefit for a short time from simply stopping the anti-androgen. Doctors call this the "anti-androgen withdrawal" effect, although they are not sure why it happens.

Side effects of anti-androgens in patients already being treated by orchiectomy or with LHRH agonists are usually not serious. Diarrhea is the major side effect, although nausea, liver problems, and tiredness can also occur.

The major difference from LHRH agonists and orchiectomy is that anti-androgens may have fewer sexual side effects. When these drugs are used alone libido and potency can often be maintained.

Other androgen-suppressing drugs: Estrogens were once the main alternative to orchiectomy for men with advanced prostate cancer. Because of their possible side effects (including blood clots and breast enlargement), estrogens have been largely replaced by LHRH analogs and anti-androgens. Still, estrogens may be tried if androgen deprivation is no longer working.

Ketoconazole (Nizoral), first used for treating fungal infections, blocks production of androgens and is sometimes used.


Current Controversies in Hormone Therapy

There are many issues around hormone therapy that not all doctors agree on, such as the best time to start and stop it and the best way to give it. Studies looking at these issues are now under way. A few of the issues are discussed here.

Early vs. delayed treatment: Some doctors think that hormone therapy works better if it is started as soon as possible if the cancer has reached an advanced stage (for example, when it has spread to lymph nodes), if it is large (T3) or has a high Gleason score, or if the PSA starts rising after initial therapy, even though the patient feels well. Some studies have shown that hormone treatment may slow down the disease and perhaps even lengthen patient survival. But not all doctors agree with this approach. Some are waiting for more evidence of benefit. They feel that because of the likely side effects and the chance that the cancer could become resistant to therapy sooner, treatment should not be started until symptoms from the disease appear. Studies addressing these questions are now under way.

Intermittent vs. continuous hormone therapy: Nearly all prostate cancers treated with hormone therapy become resistant to this treatment over a period of months or years. Some doctors believe that constant androgen suppression may not be needed, so they advise intermittent (on-again, off-again) treatment.

In one form of intermittent therapy, androgen suppression is stopped once the blood PSA level drops to a very low level. If the PSA level begins to rise, the drugs are started again. Another form of intermittent therapy involves using androgen suppression for fixed periods of time -- for example, 6 months on followed by 6 months off.

Clinical trials of intermittent hormonal therapy are still in progress. It is too early to say whether this new approach is better or worse than continuous hormonal therapy. However, one advantage of intermittent treatment is that for a while some men are able to avoid the side effects of hormonal therapy such as impotence, hot flashes, and loss of sex drive.

Combined androgen blockade (CAB): Some doctors treat patients with both androgen deprivation (orchiectomy or an LHRH agonist) and an anti-androgen. But most doctors are not convinced there's enough evidence that this combined therapy is better than one drug alone.

Triple androgen blockade (TAB): Some doctors have suggested taking combined therapy one step further, by adding a drug called a 5-alpha reductase inhibitor -- either finasteride (Proscar, Propecia) or dutasteride (Avodart) -- to the combined androgen blockade. There is very little evidence to support the use of this "triple androgen blockade" at this time.

Last Revised: 08/25/2008

PSA Test

Well the results are in!

I received the results of my PSA and Testosterone levels a couple of weeks ago, but have been too busy/pre-occupied to post them! Just this morning, I had a gentle nudge from my niece Kathy and decided that it was time to post the results.


Firstly to recap; we were hoping for a PSA result that was very close to zero. Such a result would mean that I could discontinue the anti-androgen (and therefore reduce the number of side affects) but still continue the Zoladex implant for a further period - two to three years is recommended.

The Testosterone level too, it was hoped, would be very close to zero. This would confirm that the Zoladex was suppressing the testosterone nicely and therefore starving any cancer that may still be present.


Testosterone

A 'normal' reading for adult males in regard to Testoterone is: 2.8 to 8.0ng/ml. For an adult FEMALE, the range is: 0.06 to 0.82ng/ml.

My result ... 0.51ng/ml!!

That means, I fit neatly into the 'normal' range for an adult female! Which explains a few things!! (Long term readers would be aware of the 'feminising affects of my meds).

But all is not lost, my result also puts me squarely in the range of a pre-pubescent male (7 to 12 years)!!

I've managed to turn back the clock!

Now before you scoff, such a proposition is not as fanciful as you might think - consider.

1) I no longer have any hair under my armpits!
2) My skin complexion is that of a pre-teen!
3) The hair ALL over my body (except on my head) is falling out!
4) The hair on my head is thickening and growing back!
5) My testicles are 'shrinking'!

I think you get the picture...


PSA level

The normal range of PSA (Prostate Specific Antigen) in an adult male aged 50-60 years, is 0 to 3.5ng/ml. Remember, I started this battle against cancer with a PSA of 84.8ng/ml just 11 months ago!!!

Well my test showed a level of 0.66ng/ml, a negligible amount of PSA and an excellent result!

Coupled together, these results are a 'shot in the arm' in regard to my quest for a complete cure!! These tests will be repeated in early November and I expect a similar result.

Side Effects

When is enough ... enough? In my case, when the Oncologist says so!

Reviewing my diary over the past couple of weeks, I had noticed that the number of side effects and the impact that they were having was increasing to the point of concern.

And so, a phone to my Oncologist soon confirmed what I had suspected. The Anandron was not a good option for me!

The past week in particular revealed that the side effects had resulted in:

• Dry mouth
• Increased hot flushes
• Increased fatigue
• Photo-sensitivity, and
• Nausea

The solution ... to immediately stop the Anandron and to commence Androcur (Cyproterone).

Unlike Anandron, Androcur is a steroidal antiandrogen. Cyproterone is available as an oral (by mouth) tablet and as a long-acting injectable. The recommended dose for cyproterone tablets is 200 mg to 300 mg (4 to 6 tablets) daily, divided into 2 to 3 doses and taken after meals. In my case, the recommended dose was 300 mg per day.

Imagine my delight when I read the list of possible side effects associated with Androcur ...

The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.


More common:

• impotence
• reduced (or increased) sexual interest
  swelling of the breasts or breast soreness

Less common or rare (0% to 10%)

• changes in walking and balance
• clumsiness or unsteadiness
• hair loss
• inability to move legs or arms
• increased sensitivity of skin to sunlight
• increase in bowel movements and loose stools
• loss of strength or energy
• skin bleeding, blistering, coldness, or discoloration
• unusual increase in hair growth
• weight gain

Although most of the side effects listed below don't happen very often, they could lead to serious problems if you do not seek medical attention. Check with your doctor as soon as possible if any of the following side effects occur:


Less common or rare (0% to 10%)

• abdominal pain or tenderness
• back pain
• blisters
• blurred vision
• chest pain
• chills
• clay colored stools
• confusion
• cough
• depression
• dizziness
• drowsiness
• dry mouth
• fainting or light-headedness when getting up
• fast heartbeat
• hallucinations
• hives
• increase in blood pressure
• increase in hunger and/or thirst
• lower back or side pain
• nausea and vomiting
• painful or difficult urination
• red, thickened or scaly skin
• shortness of breath
• skin rash
• sores, ulcers or white spots on lips or in mouth
• sore throat
• stiff neck
• stomach ache
• swollen and painful glands
• tightness in chest
• unexplained weight loss
• unusual bleeding or bruising
• vision changes
• wheezing
• yellow eyes or skin

Get immediate medical attention if any of the following side effects occur:


Less common or rare (0% to 10%)

• bloody or black, tarry stools or blood in urine
• irregular breathing
• pains in chest, groin, or legs, especially calves of legs
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• seizures
• sudden and severe weakness in arm and/or leg on one side of the body
• sudden loss of coordination
• sudden slurred speech
• temporary blindness

Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.

The 'saving grace' ... in all of this for me ... I was on this medication for 4 weeks at the commencement of my Hormone Therapy, and survived quite well!

Locally Advanced Disease (Stage T3–T4)

Locally advanced disease refers to prostate cancer that is no longer confined to the prostate and has started to invade nearby organs such as the seminal vesicles, but where there is no evidence of spread to distant sites such as the bone (T3–T4). This may also include those patients with biochemical failure following curative treatment, patients with N+ disease and those who are surgical margin positive after radical prostatectomy.

The aim of treatment for locally advanced disease is to reduce the risk of metastatic spread and tissue invasion and thereby prolong survival (Table 3.3). There are several possible treatment alternatives for patients with this early stage of prostate cancer. Some patients may be cured.


Radiotherapy + Hormonal Therapy

Neoadjuvant hormonal treatment prior to radiation therapy

Neoadjuvant hormonal therapy, used in combination with radiotherapy, is generally administered to reduce prostatic size/symptoms. The term neoadjuvant is used to describe a treatment is given before the primary treatment. Examples of neoadjuvant therapy may include hormone therapy commenced prior to radiation therapy.

EBRT (External beam radiotherapy) is often sufficient to suppress PSA levels to within normal ranges and delay disease progression. However, EBRT following neo-adjuvant hormonal therapy has been shown to produce better local control of disease and effect greater reductions in the risk of clinical or PSA relapse than EBRT alone.

The RTOG 86-10 trial investigated the use of MAB (goserelin – ZOLADEX plus flutamide) given for 4 months, starting 2 months before and continuing for 2 months during radiation therapy in T2–T4 disease. Disease free survival at 8 years was significantly improved (33%) in patients receiving neoadjuvant therapy compared to 21% in patients receiving radiation therapy alone.

Overall survival was improved in patients with a Gleason score of 2-6, although survival in all patients was not improved. In addition such neoadjuvant therapy reduces the number of patients requiring salvage therapy (Pilepich MV et al. Int J Radiat Oncol Biol Phys 2001; 50: 1243–52).

Figure 3.10. RTOG – 86-10 - Disease-free survival, all patients

CAB – Combined Androgen Blockade

Since my therapy has entered a new phase, incorporating 'Combined Androgen Blockade' (CAB) and Radiation Therapy, I thought a review of Hormone Therapy (HT) was necessary. In what follows you will see how HT and Anti-Androgen Therapy combine to become CAB. In a further post, we will look at the combination of CAB and IMRT with 'gold seed markers'.

The male sex hormone testosterone feeds the growth of prostate cells and prostate cancer. Male hormones are called androgens. Prostate cancer hormone therapy works by ablating or depriving testosterone in the body. With no hormone to fuel their growth, the cells stop growing. Hormone therapy does not provide a cure; the prostate cancer does not “starve” to death, but for a time the spread of the disease can be slowed or even halted.

Hormone therapy is most versatile of the postate cancer treatments. the ablation and deprivation of testosterone can be used as adjuvant therapy, neoadjuvant therapy, or monotherapy for either primary or salavage treatment. Adjuvant and neoadjuvant hormone therapy is more common for primary treatment. Androgen ablation and deprivation monotherapy is more common during salvage treatment.

During primary therapy, hormone therapy is given to shrink the volume of the prostate gland and tumor. Eventually, the prostate cells become resistant to the androgen deprivation therapy and begin to grow again. When prostate cells become resistant, the next steps are either to stop hormone therapy to see if the reintroduction of testosterone can slow the growth, or chemotherapy.

The testicles produce 90 percent to 95 percent of the body’s testosterone. The adrenal glands produce the remaining 5 percent to 10 percent. The two types of hormone therapies used to combat prostate cancer are castration or anti – androgens. There are two types of castration: surgical castration, also called orchiectomy or orchidectomy, and chemical castration, caused by LHRH agonists and LHRH antagonists.

LHRH agonists and antagonists are usually taken through injections or analogs which continuously release the therapy over a period of time. Castration affects production of testosterone in the testicles, while LHRH antagonists and agonists interrupt the communication in the brain when the brain is ordering the production of more testosterone.

Anti – androgens affect the hormones that are produced in the adrenal glands. They are designed to block receptors in the prostate cells and prevent androgens from feeding cancer cell growth. Anti-androgens are taken orally as a pill or tablet. The female sex hormone, estrogen is also sometimes used for hormone therapy.

When several hormone therapies are used together, it is called Combined Androgen Blockade or CAB, but may also be called total androgen blockade, combined hormonal therapy, or complete hormonal blockade. Combined androgen blockade usually consists of castration and anti – androgens. All men who undergo hormone therapy will experience side effects, however, men who undergo CAB tend to experience more side effects due to the elimination of 100 percent of the body’s testosterone.

New Plan of Attack

After a lengthy discussion with my Oncologist, concerning the possible treatment options, the following regime was decided upon as representing the best possible outcomes:

1. We will continue the Hormone Therapy, with the LHRH implants (Zoladex 10.8mg) every three months. This appears to be working pretty well but there remains some concern as to whether it is as effective as expected? I am scheduled to have another PSA test tomorrow; only this time, we will also test the Testosterone levels.
   


2. Because the PSA level has not declined at a faster rate, it has been decided to introduce an anti-agonist (Anandron ie Nilutamide) as well. This will continue for some time concurrent with the LHRH Implant.


3. I have been scheduled for an outpatient procedure, in which the Radiologist will insert several 'gold seeds' into the prostate. More on this procedure in my next post.


4. Following this, there will be a recovery period of 24 hours and then a 'planning week' in which the Radiotherapy treatment is discussed and mapped out.


5. I will most likely continue on the Hormone Treatment for at least 2 to 3 years. This then gives rise to the possibility of 'bone thinning' and so I have commenced a daily regime of Calcium and Vitamin D supplements.
   


6. The Radiotherapy will consist of a precisely targetted (thanks to the gold seeds), high dosage of radiation being applied to the prostate. A lower dosage of radiation will also be applied to certain bones and organs within the pelvic region.

The Radiologist also pointed out: "we only get one shot at this and so we will plan to maximise our chances of a successful outcome". While the prognosis remains, 5 years; it is anticipated that I will enjoy many more years, given the (expected good) results.

Prostate 'Gold Seeds' Improve Radiation Treatment

Today I attended my first appointment with the newest member of my healthcare team - 'Dr T' - my Radiation Oncologist. The appointment lasted for over 90 minutes - I finally got to ask, and have answered, ALL of my questions!!

Firstly, I want to talk about the 'new' technique that I will be undergoing in terms of my radiotherapy - sometimes referred to as 'gold seed technology'.

Gold seed technology is a fairly recent innovation in Australia and is only available in a (very) limited number of places. Fortunately for me, my radiologist is one of the few 'experts' who not only possess such technology, but have become very conversant with it's usage.

Now, some history...


November 2005

A new treatment method for prostate cancer patients undergoing radiation therapy that more accurately and effectively targets the cancer while minimizing side effects is now available in Australia.

Fiducial markers, or "gold seeds," are non-radioactive markers that are placed in the prostate. Because it is natural for the prostate to move around in the pelvic cavity, depending on how much liquid a patient has consumed and other factors, it can be challenging to locate the prostate precisely during radiation therapy.

Unlike brachytherapy, which uses radioactive seeds to treat the cancer, gold seeds simply allow the prostate's location to be tracked on a daily basis using X-ray imaging to ensure treatment accuracy. Only a handful of health care organizations offer this treatment in Australia.

Previously, physicians had to leave a margin of error when locating the cancerous tissue because it was difficult to target the exact location of the prostate before the gold seed technology emerged. During this process, healthy tissue may have been exposed to radiation.

Gold seed technology allows the physician to know exactly where the prostate is at any given time. Therefore, a higher dose of radiation can be delivered to a more precise area, while minimizing exposure to nearby healthy tissues.


Gold Seeds Help Pinpoint Prostate Cancer

WCVB-TV 04.07.2006

BOSTON -- Prostate cancer is the most common cancer among American men. One in six men will be diagnosed with the disease in his lifetime.

NewsCenter 5's Heather Unruh reported Friday that treating it can be tricky -- even a slight movement of the prostate can alter the effectiveness of radiation and potentially damage healthy tissue.

Now, doctors at Mount Auburn Hospital are using new technology to pinpoint prostate cancer with the help of some very tiny but very precious metals.

A tiny gold seed is helping doctors treat Joe Crowley's prostate cancer.

"I feel good about the treatment," Crowley said.

The gold seeds are actual gold, but they are not radioactive. Instead, they serve as markers for radiologists attempting to locate and treat the often hard-to-target prostate.

"In the past, our solution was very simple. You simply enlarge the area you're treating to make sure the target is going to be fully covered by the radiation -- but in the process, we were exposing more normal tissue to the radiation and increasing the risk of injury," Mount Auburn Hospital's Dr. Anthony Abner said.

With Gold Seed technology, [a number of] seeds are placed around the prostate. Using X-ray imaging, doctors can then monitor the location of the seeds. If the seeds have moved, the prostate has moved, and they can alter the radiation accordingly.

"The benefit is that we can dramatically reduce the amount of normal tissue that's hit by the radiation. By doing so, we can actually use higher doses of radiation with better cure rates," Abner said.

The treatment is less painful and more accurate than other options, such as balloon dilation and ultrasound. But it does require almost daily monitoring, which means many trips to the radiologist -- a price Crowley said he is willing to pay.

"It's a little lengthy, but I think I have 34 treatments, but hopefully they'll go by fast and I'll pick up where I left off," Crowley said.

While it's too soon to know exactly how much Gold Seed technology is improving prostate cancer outcomes, doctors said that patients report feeling better during treatment, having fewer side effects and fewer long-term complications.


The implications for me are ...

• I can benefit from the higher doses of radiation , without the risk of 'other organ damage'!


• I can also receive a variation of the 'whole-pelvic' treatment described in an earlier post - safely.

We'll look at this in more details in my next post.