Advanced Prostate Cancer

The Importance of Early Detection and Screening

Prostate Cancer is the uncontrolled growth of abnormal cells in the prostate gland.  Prostate cancer usually grows slowly, and do not extend outside the prostate.   Some cancers can grow and spread to other organs outside the prostate gland.  Prostate cancer usually has no signs or symptoms, especially in its earliest stages.

Once the cancer has grown, it may cause discomfort and a variety of other symptoms and becomes progressively more difficult to treat.  Therefore prostate cancer screening and early detection is extremely important for a number of reasons, including the facts that:

• If caught early, survival rates for prostate cancer are nearly 100%.
• Early detection and treatment are the best protections against advanced prostate cancer.

For patients in whom prostate cancer is detected early, a variety of potentially curative treatment options are available.  These include surgical removal of the prostate (radical prostatectomy), radiation therapy, radioactive seed implantation, and cryosurgery.  

More advanced forms of prostate cancer require different types of treatment, and may incorporate the expertise of surgeons, radiation oncologist, and medical oncologists.  When prostate cancer has spread to the bone or other organs, reduction of the male sex hormore, testosterone, will retard the growth of prostate cancer cells, and cause some prostate cancer cells to die.  Unfortunately, after an initial remission of 18-24 months, most men will show signs of their prostate cancer worsening.  This is called Androgen Independent Prostate Cancer (AIPC). 

Currently, no treatments can cure AIPC. Doctors do have a few ways to help control or slow its spread and minimize related symptoms. These treatments can cause side effects, and some patients decide that the risks of side effects outweigh the benefits of treatment.

Landmark Studies Show Survival Benefit to Treatment in Advanced Patients

While patients with Advanced Prostate Cancer [AIPC] have limited treatment options, two landmark clinical studies presented at the American Society for Clinical Oncology (ASCO) scientific conference in 2004 and published in the New England Journal of Medicine later that year. demonstrated for the first time that chemotherapy treatment could extend the survival of patients with this advanced disease.  Taxotere (docetaxel) was approved in 2004 by the U.S. Food and Drug Administration (FDA) for the treatment of Advanced Prostate Cancer [AIPC] based upon data from these studies.  Currently, extensive scientific and clinical research is underway at several biopharmaceutical companies and academic research institutions to further improve the survival benefit for patients with advanced disease and to enhance the quality of life, efficacy and safety of these treatment regimens.

In the sections that follow, this informational package will provide additional background information and an overview of the:

• four classifications (categories) of Advanced Prostate Cancer
• currently approved treatment options for advanced patients
• experimental treatments in clinical testing
• information on accessing investigational products through clinical trials

Four Categories of Advanced Prostate Cancer [AIPC]

The four most commonly encountered disease categories of prostate cancer are summarized below.  They range from prostate cancer confined to the prostate glad to prostate cancer that has spread to lymph node and bone.  . 

• Locally Advanced Prostate Cancer
  Cancer that has grown to fill the prostate or has grown through the prostate and may extend into the glands that help produce semen (seminal vesicles), or the lymph nodes.

  Occurs in men who have been treated for early prostate cancer, but the prostate specific antigen is rising.  A bone scan and cat scan in these patients is usually shows no evidence of cancer

• Biochemically Recurrent Prostate Cancer (Rising PSA)
  Patients who have a rising PSA after treatment, but do not have any evidence of disease spread to bone or other organs.  This can occur after local treatment, or after hormone therapy. The management of such patients is controversial, and may include investigational treatments, radiation therapy, or chemotherapy.
  
  
• Metastatic Prostate Cancer (Hormone Sensitive)
  Cancer that has spread (metastasized) to the bone , lymph nodes or other parts of the body.. Depletion of the male sex hormone, testosterone, results in improvement of tumor related symptoms such as bone pain or inability to urinate. This can be achieved by either surgical removal of the testosterone, as well as with medications such as lupron and zoladex.

• Hormone Refractory Prostate Cancer
  Prostate cancer that continues to grow despite the suppression of male hormones that fuel the growth of prostate cancer cells.

A Team Approach to prostate cancer is very important.  Your Prostate Cancer Treatment Team may include a urologist, a radiation oncologist, a medical oncologist, your family and nurses, patient navigators and others.

Before a diagnosis of advanced androgen- independent prostate cancer:

Your doctor will ensure  your testosterone level is zero.

Ensure that there’s a consistent rise in PSA, tested several times over several months.

Perhaps offer a secondary hormonal therapy in addition to the hormone suppression therapy you may already be taking to possibly control you PSA for an additional amount of time

Secondary hormonal therapies could include:

• Antiandrogen withdrawl (AAW)
• Antiandrogen addition (Low vs. High)
• Estrogens (I.V., oral, transdermal…)
• Ketoconazole (Nizoral)
• Aminoglutethimide (Cytadren)
• Corticosteroids

Currently Approved Treatment Options for Advanced Patients

There is no single treatment for advanced prostate cancer. Yet, there are ways to slow the course of the disease. In addition to these new therapies, you are usually  advised to stay on hormone-lowering therapy, even though it no longer stops your PSA from rising. The reason for this is that some of your prostate cancer cells remain sensitive to testosterone, and stopping hormone therapy may make them grow again.
Hormonal therapy

• Treatments for cancer that has spread to the bones
• Salvage radiation therapy
• Chemotherapy
• Adjuvant Therapy

The correct treatment choices are different for each man and are based upon many factors which should be discussed in detail with medical experts.

Treating Metastases

Doctors today have many tools to treat metastases. The broad categories include:

• Chemotherapy. Anti-cancer chemicals that kill tumors
• Secondary Hormonal Treatment – compounds that change hormone levels, but are not the first testosterone-suppression treatment to be used.
• Radiopharmaceuticals. Drugs linked to radioactive compounds which can target cancer spreac to the bone as well as other specific targets. These radioactive elements are delivered to or near tumor cells.  This approach is effective in controlling bone pain. Bone seeking radioisotopes such as strontium and samarium are effective in treating patients who have multiple sites of bone pain.
• External Beam Radiation. Targeted beams of radiation. Most useful when a man has just one or two specific sites painful sites. .
• Surgery. Cutting the tumor out.
• Bisphosphonates. Drugs that help bones from breaking down.  These drugs can prevent the thinning of bone, otherwise know as osteoporosis, which can increase the risk of bone fractures.

Within each of these treatment areas, there are several options. Your doctors will help choose the right treatments for you.

Side effects. You are probably aware that cancer treatments may have unpleasant side effects, such as nausea, weakness, and hair loss. While that’s true, it’s less true than it used to be. Today, side effects of treatment are usually short term, and most can be managed. In many cases, you can take a medication before your radiation or chemotherapy treatment, to keep the side effect from affecting your daily routine.

Alternative and Complementary Therapies

In addition to the medical options your doctors prescribe, other therapies can help you fight prostate cancer. Sometimes these are called “alternative” or “complementary” treatments. The National Institutes of Health (NIH) has an entire division devoted to research in these areas, called the National Center for Complementary and Alternative Medicine (NCCAM).

The nation's leaders in treating advanced disease recommend patients keep a diary of their medications and supplements.

Pain Management

Men with advanced prostate cancer  may experience pain. The pain can have a lot of different sources, doctors have may different effective ways to releive pain, so that you can enjoy your life and fight the disease with energy

Treat the underlying cause
When pain is caused by a tumor, treatment to reduce the tumor can also reduce the pain. Radiation, chemotherapy and bone-building drugs that shrink tumors can all be effective in controlling pain. Sometimes they are even more effective than heavy pain drugs. (abstract J. Clin Oncology 2004: 22: 3587-3592).

Narcotics
These powerful drugs mimic the body’s own pain-killing chemicals. Narcotics may be given as a pill, a patch, or as an intravenous (IV) drip by health-care professionals, for severe pain.

Pain pills and patches
Doctors have a wide range of drugs to choose from in treating pain. Different drugs work in different ways. If one does not work for you, tell your doctor, and ask about others.

Alternative therapies
Acupuncture has been proven in clinical studies to help relieve pain. Meditation, prayer, and hypnosis also help some people.

Experimental Treatments in Clinical Testing

Currently Approved Chemotherapeutic Treatment Option Demonstrated Survival Benefit for Patients with Advanced Disease.

In 2004, data were presented from two landmark scientific studies demonstrating for the first time that chemotherapy treatment could extend the survival of patients with AIPC. 

In these Phase 3 clinical trials (designed to test the safety and effectiveness of new drugs in large-scale mulitcenter studies), data demonstrated that treatment regimens including docetaxel chemotherapy extended median survival more than two months in patients with advanced prostate cancer [AIPC] no longer responsive to hormone therapy. 

Based upon these data and other scientific studies, the U.S. FDA approved Taxotere (docetaxel) for use in combination with prednisone as the first registered treatment for patients with androgen-independent (hormone-refractory) metastatic prostate cancer [AIPC].

At the time of these studies, no effective therapy existed for advanced prostate cancer that was unresponsive to hormonal therapy.  Chemotherapy with the combination of drugs prednisone and mitoxantrone had been shown to reduce pain in men with advanced prostate cancer that had spread to the bones, but the regimen did not help patients live longer. Several previous studies of different chemotherapy regimens had failed to identify a drug or combination of drugs that extended patients’ survival, thus underscoring the importance of the docetaxel survival data.

Scientific Research Building Upon Recent Survival Data to Extend Life and Improve Options for Late-Stage Patients

After docetaxel became the first drug to demonstrate the ability to prolong survival in patients with AIPC, physicians began using it to treat late-stage patients, offering new hope to increase survival. 

To build upon these recent survival data, a number of biopharmaceutical products are in development, several of which are in late-stage (Phase 3) testing to improve the survival, efficacy, safety and quality of life for AIPC patients. 

The following review of compounds in development is based upon a scientific publication in the European Journal of Cancer [41 (2005) 954-964] written by John M. Strother and colleagues, as well as from information provided by the U.S. National Cancer Institute, which lists additional resources on cancer therapeutics and clinical trials on its websites at: www.cancer.gov and www.clinicaltrials.gov.

New Chemotherapeutic Treatment Options

A number of new chemotherapeutic treatment (cytotoxic) regimens designed to kill rapidly growing cancer cells within the body are currently in late-stage clinical testing for the potential treatment of advanced prostate cancer.   Cytotoxic compounds currently in development include:

Mitotic Inhibitors, such as the investigational compound SB-715992, inhibit cell growth by stopping cell division.  SB-715992 inhibits the mitotic kinesin spindle protein (KSP) and is the first KSP inhibitor to enter clinical trials.  The compound demonstrated broad-spectrum activity in pre-clinical trials, including in models that were refractory or resistant to chemotherapy and in prostate cancer models.  Mitotic Inhibitors are also called antimitotic or antimicrotubule agents and taxanes.  Chemotherapeutic agents docetaxel and paclitaxel are mitotic inhibitors.

Epothilones are drugs obtained from bacteria that interfere with cell division.  One of these compounds, EPO906, is currently being studied in previously treated AIPC patients and another, BMS-247550, is being studied in patients with metastatic AIPC.  

Satraplatin (also known as BMS-182751 and JM 216) is a novel oralsubstance that is being studied in the treatment of cancer and belongs to the family of drugs known as platinum analogs (where platinum metal is an important component of these anti-cancer compounds).  A Phase 3 trial of satraplatin plus prednisone is underway as a potential chemotherapeutic regimen for prostate cancer.

Amonafide is a substance that is being studied in the treatment of cancer and belongs to the families of drugs called topoisomerase inhibitors (which block topoisomerase enzymes involved in DNA structure and cell growth) and intercalating agents (which wedge themselves between the bases of DNA to prevent DNA synthesis).  This compound is in clinical testing in patients with metastatic AIPC treated with up to one prior systemic chemotherapy regimen. 

Nuclear Receptors

Nuclear receptors are proteins located inside a cell nucleus that interact with and receive specific protein-based small molecule hormones or ligands (similar to the how a specific key fits a specific lock). Once activated or blocked, nuclear receptors are capable of controlling cellular activity.  Nuclear receptor anti-cancer compounds attempt to interfere with or control the replication of cancerous cells.

PPARγ Ligands.  One example of nuclear receptor-based therapies in development targets the peroxisome proliferator-activated receptor gamma (PPARγ), which is expressed by prostate cancer cells.  The class of synthetic PPARγ agonists have been shown to inhibit prostate cancer growth in vitro.  Studies of these compounds, including troglitazone and rosiglitazone, are being tested in patients with asymptomatic advanced prostate cancer or with rising PSA after local therapy.  As the role of this receptor is better understood in prostate cancer, combination therapies that include PPARγ ligands may emerge.

DN-101.  Another nuclear receptor-based drug in development is DN-101, which targets the vitamin D nuclear receptor (VDR).  DN-101 is a highly potent proprietary form of calcitriol, the most active metabolite of vitamin D.  The compound has demonstrated anti-cancer activity in multiple tumor types and appears to enhance the effects of some chemotherapeutic agents, including enhancing the survival benefits of docetaxel chemotherapy when given as part of a combination regimen to patients with androgen-independent prostate cancer [AIPC].

Growth Factor Receptor Antagonists

Naturally occurring growth factors in the body can trigger cell division.  In other forms of cancer, compounds that inhibit growth factors have been developed as therapeutics to block tumor growth and metastasis. 

Epidermal Growth Factor Receptor (EGFR) is a tyrosine kinase that triggers cell division.  In prostate cancer models, EGFR is thought to be one of the factors that might drive the progression of AIPC.   Compounds in development that bind to and inhibit EGFR include:  cetuximab, a monoclonal antibody that binds to and inhibits EGFRs, and gefitinib, an anilinoquinazoline with antineoplastic activity.

Human Epidermal Growth Factor Receptor 2 (HER-2) is known to be overly expressed on the surface of breast cancer cells and can be detected in some patients with prostate cancer.  Trastuzumab, a monoclonal antibody that targets HER-2, has been shown to extend survival when given in combination with chemotherapy to patients with metastatic breast cancer.  Data from clinical trials of trastuzumab in patients with hormone refractory prostate cancer have reported mixed results.

Platelet Derived Growth Factor (PDGF) and its receptor PDGF-R have been implicated as mediators in prostate cancer progression.  Imatinib is an agent that inhibits BCR-ABL, c-kit and PDGF receptor tyrosine kinases and may inhibit proliferation and induce apoptosis in prostate cancer tumor cells that overexpress these proteins.  Clinical trials of imatinib have been conducted in patients with hormone-naïve PSA progression after local therapy and additional studies are testing this compound in conjunction with chemotherapeutic regimens.

Insulin-like Growth Factor (IGF) may be associated with prostate cancer risk and is thus a target for prostate cancer prevention and therapy.  Agents that target IGF are in pre-clinical development.

Anti-angiogenic Agents

As cancerous cells grow and replicate, tumors need a supply of oxygen and nutrients the same as other living cells.  This occurs inside the body through the development of a series of new blood vessels that feed the cancerous growth.  This has led to the application of a new class of anti-angiogenic compounds that block angiogenesis, the development of new blood vessels.  Researchers hope that by cutting off the tumor’s access to oxygen and nutrients, they might be able to control the growth and spread of cancerous cells. 

Thalidomide is a synthetic derivative of glutamic acid (alpha-phthalimido-glutarimide) with teratogenic, immunomodulatory, anti-inflammatory and anti-angiogenic properties. Thalidomide acts primarily by inhibiting both the production of tumor necrosis factor alpha (TNF-alpha) in stimulated peripheral monocytes and the activities of interleukins and interferons. This agent also inhibits polymorphonuclear chemotaxis and monocyte phagocytosis. In addition, thalidomide inhibits pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), thereby inhibiting angiogenesis.  Thalidomide is currently in clinical trials for the treatment of AIPC as a single agent and in combination with other chemotherapeutic regimens.

Lenalidomide is a thalidomide analog with potential antineoplastic activity. The compound inhibits TNF-alpha production, stimulates T cells, reduces serum levels of the cytokines vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), and inhibits angiogenesis. This agent also promotes G1 cell cycle arrest and apoptosis of malignant cells.  Lenalidomide is currently in early clinical studies for its potential to treat AIPC patients.

Bevacizumab is a recombinant humanized monoclonal antibody directed against the vascular endothelial growth factor (VEGF), a pro-angiogenic cytokine. Bevacizumab, also known as Avastin, binds to VEGF and inhibits VEGF receptor binding, thereby preventing the growth and maintenance of tumor blood vessels.  This product is currently being tested in clinical trials in combination with other agents for the treatment of AIPC and has shown initial activity. 

Other anti-angiogenic compounds in development include PTK787/ZK 222584, an orally bioavailable anilinophthalazine with potential antineoplastic activity. Vatalanib binds to and inhibits the protein kinase domain of vascular endothelial growth factor receptors 1 and 2; both receptor tyrosine kinases are involved in angiogenesis. This agent also binds to and inhibits related receptor tyrosine kinases, including platelet-derived growth factor (PDGF) receptor, c-Kit, and c-Fms.  BMS-275291 has also been tested in patients with AIPC, but showed no response. 

Proapoptotic Agents

Apoptosis (or programmed cell death) is a type of cell death in which a series of molecular steps in a cell leads to its death, sometimes thought of as cell suicide. This is the body’s normal way of getting rid of unneeded or abnormal cells. The process of apoptosis may be blocked in cancer cells.

G3139 (oblimersen sodium) is an antisense compound in clinical development in combination with chemotherapeutic treatments in patients with AIPC with the hope that it might block the expression of the Bcl-2 protein, which is overexpressed in patients with AIPC and confers resistance to apoptosis. 

Selective apoptotic anti-neoplastic drugs (SAANDs) in development have been found to inhibit growth and induce apoptosis in prostate cancer cell lines by inhibiting cyclic GMP phosphodiesterases but not cyclooxygenase-1 or 2.  Compounds in this category currently in clinical testing in patients with advanced prostate cancer include:  exisulind (sulindac sulphone) and CP-461 (an exisulind analogue with broad anti-tumor activity).

Clusterin antisense oligonucleotide targets the survival gene clusterin, which confers resistance to chemotherapy and whose expression is increased in response to androgen-deprivation.  Oligonucleotide antisense molecules to clusterin are now being tested in clinical trials in patients with prostate cancer and are expected to be tested in combination with chemotherapy in the future.

Other Novel Targeted Agents

Bortezomib (PS-341, Velcade) is a boronic acid dipeptide that inhibits 26S proteasome activity and has been shown to block the androgen receptor signaling pathway and stop the growth of and induce apoptosis in LNCaP prostate cancer cells.  Bortezomib is currently in clinical testing in patients with metastatic AIPC and has shown initial activity.

Atrasentan belongs to a class of compounds called selective endothelin-A receptor antagonists (SERA™). SERAs are being investigated for their potential to block the activity of a protein, endothelin, thought to be involved in the stimulation of the spread of cancer cells.  Astrasentan is an oral, non-hormonal, non-chemotherapy agent in late-stage clinical trials for advanced prostate cancer.

Immunotherapeutic Agents

Immunotherapeutic agents harness the power of the human immune system and include therapeutic cancer vaccines designed to stimulate a patient’s own immune system to seek out and destroy cancerous cells.

GM-CSF or granulocyte-macrophage colony stimulating factor is an immunostimulatory cytokine. GM-CSF modulates the proliferation and differentiation of a variety of hematopoietic progenitor cells with some specificity towards stimulation of immune system cells, including leukocyte production.  It may also reverse treatment-induced neutropenia.  GM-CSF has been given to patients with metastatic AIPC and has shown some evidence in the reduction of PSA levels.

GVAX cancer vaccines are comprised of tumor cells that have been genetically modified to secrete GM-CSF.  Late-stage studies of GVAX are currently planned based upon initial immune stimulating activity seen in previous studies.

Provenge is designed to stimulate the immune system to attack cells that express prostatic acid phosphatase (PAP), a protein expressed on approximately 95 percent of prostate cancer cells. The technology delivers small pieces of the PAP protein to a patient's antigen presenting cells (APCs), specialized immune cells that activate other cells of the immune system to seek out and destroy PAP-containing prostate cancer cells.  Provenge is now being studied in patients with AIPC and in patients with rising levels of PSA after prostatectomy.

Vaccinia virus/fowlpox virus.  Immunotherapy with viral vectors can mimic natural infection and thus produce potent immune responses.  Scientific researchers are now working with vaccinia virus and fowlpox virus designed to express PSA (the prostate-specific antigen that is found to increase in blood-levels of men with prostate cancer).  Trials have been conducted in patients with PSA progression after local therapy, and randomized trials of fowlpox-PSA with and without GM-CSF are now in development.

MVA-MUC1- IL2 is a vaccine containing a recombinant vaccinia virus that encodes the gene for human mucin-1, a tumor-associated antigen. Vaccinia-MUC-1 vaccine may elicit a MUC-1-specific cytotoxic T cell response in the host.  TG4010 is a recombinant MVA expressing MUC1 and IL-2 that is in clinical trials for prostate cancer patients with hormone-naïve biochemical failure.

J591 Monoclonal Antibody is designed to attach specifically to prostate cancer cells and deliver radiation. Radioimmunotherapies involve treatment with a radioactive substance linked to an antibody (protein) that will attach to cancer cells when injected into the body.  By delivering the radiation directly to the cancer, researchers hope that more normal tissue is spared from radiation with fewer side effects. Y-J591 is in early stages of clinical testing in patients with hormone-refractory prostate cancer.

Information on Accessing Investigational Products through Clinical Trials

Clinical trials are an essential part of the drug development process to develop new therapies for patients with all types of cancer, including those with late-stage, androgen-independent, prostate cancer [AIPC].  Participation in clinical trials allows late-stage patients, who might have exhausted other treatment options, to access additional treatment regimens and emerging products still in development. Clinical trials are exciting. Each new trial offers hope for a better way to treat diseases like prostate cancer. The clinical trial system is the safest and most effective way we know to produce drugs that truly benefit patients. Being part of a clinical trial is one way you can help create better ways of fighting prostate cancer.

When you participate in a clinical trial, there is always the hope that the drug can help you. But there are risks, too. You should be aware of both the benefits and the risks before you sign up for a clinical trial. For more information on product candidates mentioned in this brochure or for information on ongoing clinical trials and eligibility criteria, please speak with your physician or oncologist and visit the U.S. National Institutes of Health web sites at:  www.cancer.gov or www.clinicaltrials.gov.

To find support groups near you:

1. National prostate cancer support groups, including Us TOO! International; Man to Man; and others, may be found on the internet.
2. Ask your doctor, social worker, or nurse about local groups.
3. Ask members of one support group about other support groups that they belong to or have heard about.

The Physician’s Conversation Corner

Webcast Perspectives on Advanced Prostate Cancer
A Conversation with Daniel Petrylak, M.D.
Columbia-Presbyterian Medical Center
Council Member of the Prostate Cancer Education Council
A Program of the Prostate Cancer Education Council (PCEC)

What are the treatment options for advanced prostate cancer disease?

Chemotherapy is now one treatment option for advanced prostate cancer disease in patients who have rising PSA levels after initial treatment  after hormone therapy or in whom cancer has come back (recurred) or spread (metastasized) to other organs in the body. 

Unfortunately, we still don’t know the optimal time to administer chemotherapy.  Traditionally, chemotherapy had only been given to the most advanced patients.  Often, these patients were at death’s door with significant bone pain and weight loss. 

Now, because of PSA monitoring, we are detecting relapses earlier and have the opportunity to give drugs earlier in the most advanced states of prostate cancer.  This has a big advantage for patients because we are more likely to be able to give patients a full dose of chemotherapy because they can tolerate it better, and they might not get as sick from the medication as they would if the drug had been given later as the cancer progresses.

Currently, the U.S. Food and Drug Administration (FDA) standard of care for advanced prostate cancer is the combination of docetaxel and prednisone. This basically improves the overall survival close to 20 months.  In the past, patients lived an average of about 12 months after detection of recurrent disease.  Now, they seem to be living longer with this chemotherapy, but it is important that patients talk to their oncologist about the optimal time to administer chemotherapy in their course of disease.

When should prostate cancer patients be referred to an oncologist?

Basically, there are two situations when a prostate cancer patient should be referred to an oncologist.  The first case is for patients with metastatic disease who have failed hormone therapy.  Then the oncologist has a number of different therapeutic options he or she can offer.  These include secondary hormonal manipulations, chemotherapy, radiation therapy and isotope therapy. 

The standard of care for the treatment of hormone refractory prostate cancer is now the combination of docetaxel and prednisone.  This combination has been shown to improve survival in patients with metastatic disease -- in other words where the cancer has spread to the bone, lymph nodes or other organs or in patients who have failed hormone therapy (the initial standard of care for metastatic prostate cancer).

When a patient’s cancer has spread to bone, liver or other organs, the urologist is often the first person to prescribe treatment and this is typically androgen blockade or castration.  When you lower a patient’s testosterone, prostate cancer cells die.  Unfortunately, this approach only works for an average of about 18-24 months.  At this point, when a patient shows a progressive disease, which can occur with a rising PSA, worsening bone scan or new lesions in liver, lung or lymph nodes, there are other options that should be discussed with the patient, which include second line hormones and chemotherapy.

What are the advantages of providing advanced prostate cancer therapies for men who have had primary treatment for prostate cancer?  When should men start these therapies?

One of the important research areas in prostate cancer is trying to identify patients who have had their prostate removed (prostatectomy) and who are at high risk for having their prostate cancer come back. 

We have actually developed a number of different predictive models that will assess the risk of the patient’s PSA rising as well as the chance of the cancer coming back.  One of the things we are trying to evaluate is whether prostate cancer is just like breast cancer or lung cancer, where chemotherapy is given to patients at high risk for the cancer coming back.  We can actually prolong survival by giving chemotherapy in lung, breast, and colon cancer patients who are at high risk of relapse The cancer is potentially curable in these patients, whereas it is incurable once it spreads to the bone or other organs

We are now asking the same question in prostate cancer.  For example, the Southwest Oncology Group is conducting a study  that is randomizing high risk patients to either the combination of hormone therapy plus mitoxantrone and prednisone (a chemotherapeutic agent) versus hormone therapy alone. 

This is really the first large trial that is looking at the particular question of whether we can prolong survival in our patients with the earlier use of chemotherapy (when a patient is more likely to tolerate chemotherapy better and thus may be able to make more of an impact).

What are some other healthcare concerns for patients with advanced prostate cancer?

Because patients have seen family members or friends in the past not tolerate chemotherapy well, one of the things patients often ask me is: “Can they maintain their quality of life when they are on chemotherapy?” 

It is important to point out to patients that because a patient has cancer that does not mean that they are receiving the same treatment as their neighbor or their friend or their family member.  Chemotherapeutic treatments vary depending on the type of cancer, and thus the side effects experienced by a patient being treated with chemotherapy for colon cancer may be very different from those side effects observed in patients treated with chemotherapy for prostate cancer.    

In our experience, some patients have trouble tolerating medication, but other patients who have severe bone pain actually have improvements in bone pain.  Other patients who can’t get out of bed are able to walk.  In fact, we had one football coach a number of years ago, one of the first patients we treated with Taxotere (docetaxel), who was bedridden just before he started treatment.  He started treatment and within about six weeks he was mowing the lawn again. 

So patients can maintain a normal quality of life. They can see real improvements.  And it can work.  Questions are always asked about the importance of a couple of months difference in survival or small survival benefits.  In that time, a patient may be able to see their grandson or granddaughter graduate from college; they may be able to see a birthday or some other important facet of their retirement that they weren’t able to enjoy in the past.

Should prostate cancer patients continue to get prostate cancer screenings?

The mission of the Prostate Cancer Education Council (PCEC) is to educate patients and their spouses about taking charge of their healthcare needs.  Specifically, the PCEC has been a  pioneer in PSA screening.  But the PCEC would like to extend this further.  The PCEC would like to be sure that those patients who have a high risk of their prostate cancer coming back are checked regularly .  Getting checked is not as difficult as it was initially.  You don’t necessarily need a rectal exam like you did before, but you do need  PSA monitoring  after radiation therapy or a prostatectomy.  This way your doctor  can detect disease relapse earlier, if it does happen and appropriately treat you and help you.

Are there other investigations or studies that advanced prostate cancer patients should know about?

Clinical trials are the backbone of our current practice in oncology.  And it is important for patients to know about what clinical trials are available to them. The combination of Taxotere (docetaxel) plus prednisone is really the backbone of treatment, and we clearly would like to improve this combination and extend survival even further than the 20-24% improvement that we have seen with our particular studies.  

A number of investigators are targeting blood vessels that are formed with tumors.  This is called angiogenesis, and there are a lot of new drugs that are basically targeting these blood vessels with tumors because we know that these synergize with taxanes. 

We are also looking at different growth factors to see how these will improve taxane-based therapies.  Certainly there are a lot of new trials out there and you really should contact the National Cancer Institute database either through the web or by telephone and speak to your oncologist about what different trials are available for you and what best suits you.

How can spouses, family members and caregivers best support their loved ones as they face prostate cancer?

In taking care of prostate cancer patients now for nearly 14 years, I have found the relationship between the prostate cancer care giver and the prostate cancer patient is essential to the patient’s healthcare.  The caregiver is often the one who searches the web, calls physicians or just looks at newspaper articles to see if there is something available for their spouse.  At PCEC, we would like to help you and we are putting various web links to different clinical trials on our website so that the caregivers can have access to these new exciting treatments.