Prostate Cancer Vaccine Meets Goal

April 14, 2009 -- Provenge, an experimental treatment vaccine for advanced prostate cancer, met researchers' goal in a key trial needed for FDA approval.

That news comes from Dendreon, the company that makes Provenge.

"We believe this is truly a breakthrough for the prostate cancer community and a testament to the promise of the field of cancer immunotherapies," Dendreon's president and chief executive officer Mitchell Gold, MD, said in a conference call today.

Provenge is a biologic drug given by infusion to spur the immune system to fight advanced prostate cancer that doesn't respond to anti-androgen treatment.

In 2007, an FDA advisory panel recommended that the FDA approve Provenge. But instead, the FDA requested more information about whether Provenge prolongs survival.

That request led to a new study of 512 men with advanced prostate cancer. Those men had metastatic, androgen-independent prostate cancer, meaning their cancer had spread and wasn't responding to anti-androgen treatment.

In that study, overall survival was significantly better for men taking Provenge than those taking a placebo.

The study's results were "unambiguous" and "very consistent" with previous Provenge trials, Gold says.

Dendreon plans to submit the study's results to the FDA in the fourth quarter of 2009; after that, the FDA will have six months to review the material, Gold says.

"This data supports Provenge being used as front-line treatment in men with metastatic, androgen-independent prostate cancer," says Gold, who notes that no new side effects from Provenge stood out in the study. In previous trials, the most common side effects in men taking Provenge were chills, fever, headache, fatigue, shortness of breath, vomiting, and tremor, mainly at a low level and for one to two days following infusion.

Gold says that those men would first have surgery or some form of local therapy, then anti-androgen therapy if their cancer recurred, and if their PSA levels rose after that, "Provenge would come into play as a potential treatment option for them."

In men with prostate cancer, PSA (prostate-specific androgen) levels are used to gauge the success of prostate cancer treatment.

Dendreon isn't releasing any further details of the study until April 28, when the findings will be presented at the American Urological Association's annual meeting in Chicago.

The technology used to make Provenge may also prove useful against other forms of cancer, Gold says.

American Cancer Society Responds

The American Cancer Society released a statement about today's Provenge news. The statement comes from Otis W. Brawley, MD, chief medical officer at the American Cancer Society.

Dendreon's announcement about the new Provenge study "is reason for optimism about a vaccine that has generated controversy for several years," Brawley says. "We have to respect the scientific process, an important part of which is a full disclosure and careful review and discussion of the data, which the company says will not be released until an upcoming medical meeting."

"One of the most important questions we'll be looking at will be the magnitude of the survival advantage; how much longer the men taking the vaccine lived compared to those on standard therapy," Brawley continues. "As with any new therapy, it will take a detailed analysis to fully understand the impact of this potential new treatment for patients with advanced prostate cancer. We look forward to the presentation of the study at the upcoming meeting."

Dendreon's Prostate Vaccine Boosts Survival

Dendreon's controversial Provenge cancer vaccine may get another chance two years after the FDA rejected it. The drugmaker's stock soared on the news

By Catherine Arnst

Dendreon's stock price soared, tripling at one point on Tuesday from the previous day's close of 7.30 to a high of 22.10 in morning trading. The stock closed at 16.99.

Provenge has divided cancer specialists and industry analysts ever since the Food & Drug Administration unexpectedly rejected the drug in May 2007, ignoring the recommendation of its own panel of outside experts. Although the panel said then that the drug was safe and potentially effective, based on the mixed results of a 127-patient trial, the FDA wanted more proof.

Larger Clinical Trial

That rejection set off a storm of demonstrations and lawsuits against the agency from cancer patients who wanted access to the drug, and from Dendreon investors angry about the nosedive in the company's stock.

But Seattle-based Dendreon was willing to try again and mounted a larger, more rigorous clinical trial in an effort to meet the agency's burden of proof—namely, that the drug could extend survival. Details of that later, 512-patient trial will not be released until a medical meeting on Apr. 28. But Gold said the trial met its goal, which was to reduce the risk of death in patients with advanced prostate cancer by at least 22%.

"They said some words that I really like: unambiguous, overall survival, and prespecified" end points, said Mark Monane, analyst with Needham & Co. "I think this is very encouraging news for the drug."

Dendreon plans to refile for approval with the FDA towards the end of this year. If Provenge wins U.S. approval, it will be the first new drug for advanced prostate cancer since 2004, and only the second in more than a decade. There are only three drugs available for advanced prostate cancer, a disease that kills some 29,000 men a year in the U.S. The few treatments for prostate cancer are extremely toxic, and often leave patients incontinent and impotent.

"results are quite exciting,"

If approved, analysts predict that Provenge could have initial annual sales of $200 million a year, and that sales could eventually exceed $1 billion. The drug, which is administered only once, is also likely to be costly, although the company has yet to release any pricing details.

Dendreon could also wind up with the first anticancer vaccine to win FDA approval. Provenge is one of a number of so-called immunotherapies in development that try to stimulate the body's immune system to attack cancer cells and prevent the disease from recurring. It is a controversial approach that scientists have been pursuing for decades, with little to show for their efforts. Only one such vaccine has won approval anywhere in the world, Antigenic's Oncophage, approved in Russia a year ago. Just a few months ago Cell Genesys shut down development of a prostate cancer vaccine, GVAX, which was once thought to be among the most promising of the group, after it failed to show a survival benefit.

This time, "the results are quite exciting," said Dr. William Oh, director or genital urinary oncology at Dana Farber Cancer Institute in Boston, "I do think this may offer a new strategy." And the size should make the results reliable, he said.

The stocks of a number of other companies developing cancer vaccines shot up Tuesday as well, riding Dendreon's coattails. That included Antigenics (AGEN), whose vaccine for kidney cancer, Oncophage, has been approved in Russia and is waiting a decision from the European Union. Antigenics CEO Garo Armen said the Dendreon data is "a small step in a giant wave of things to come" in the cancer-vaccine field. The Dendreon results "are a major milestone," he said.

Proving Survival

Provenge did show a survival benefit in the trial presented to the FDA two years ago, with 34% of the men who received the drug still alive after three years. That compared with 11% of those in the control arm. The drug also showed very few side effects, so an expert panel voted 13 to 4 that there was "substantial evidence" that Provenge worked. But because that trial enrolled only 127 patients and did not shrink the tumor, the end point of that trial, the FDA rejected the drug.

The new trial was only designed to prove survival, which is what the agency requested. It was not designed to show tumor shrinkage. Thus Dendreon CEO Gold said he believes the company will give the FDA what it wants.

"It meets the protocols set forth by the FDA," he said. As for the roller-coaster he and his company has been on the last two years—the stock was down to 2.55 in March—Gold waxed philosophical: "I think innovative meaningful science is often the most controversial."

Arnst is a senior writer for BusinessWeek based in New York.

Men and Prostate Health

If you had persistent symptoms such as trouble urinating, going to the bathroom more frequently or decreased force in your urine joins us at our seminar.  1 in 6 men will be diagnosed with prostate cancer in his lifetime.

Not sure what to do to reduce your risk of prostate cancer?

Presented By:

Elie Benaim, MD

Urologist on the Baylor Regional Medical Center at Plano Medical Staff

Introduction

You may be one of millions of people who suffer from frustrating and embarrassing bladder control problems such as retention and overactive bladder. Effects of bladder control problems can be devastating. These conditions prevent you from controlling when and how much you urinate and can make simple everyday activities a challenge and social lives very difficult. You may have to cut back on your hobbies or stop working. You may feel trapped by a fear of leaking accidents, the need to be close to a bathroom at all times, and an overall, preoccupation with your bladder. You can be any age to have bladder control problems. You have probably found that treatments such as drugs, behavior modification, diet changes, pelvic floor exercises or the use of a catheter to empty your bladder did not effectively treat your symptoms. In the past there were few options for patient who did not respond to these therapies. Now, however your doctor would like you to consider a therapy called sacral nerve stimulation (SNS). SNS involves the use of a device that can be thought of as a pacemaker for the bladder.

SNS therapy is not experimental. InterStim^® Therapy (InterStim^® is a registered trademark of Medtronic, Inc.), is a sacral nerve stimulation therapy made by Medtronic. It was approved by the U.S. Food and Drug Administration (FDA) in 1997 and has been used successfully to treat thousands of patients worldwide.

The intent of this handout is to help you understand the therapy. After you have read about the therapy, your doctor will help you make an informed decision about whether to proceed with a test to see if sacral nerve stimulation will work for you. If you want more information and/or plan to move forward with the therapy ask your doctor for a more detailed manual available from Medtronic.

Vasectomy reversal surgery restores fertility in most men. Find out what to expect and how to prepare.

Of the half a million men who have a vasectomy each year, 2 percent to 6 percent of them — 10,000 to 30,000 men — later decide to have the vasectomy reversed. This surgery reconnects the ducts that carry sperm from the testicles into the semen. After successful vasectomy reversal, sperm are present in your semen again and you may be able to get your partner pregnant.

Who is it for?

Men decide to have the surgery to restore fertility for a number of reasons, including loss of a child, remarriage or improved finances. A small number of men have a vasectomy reversal to treat testicular pain.

Before having vasectomy reversal surgery to restore fertility, your doctor will want to make sure you can produce healthy sperm. For most men, having gotten a woman pregnant before is proof enough. If your doctor is unsure whether you are producing enough healthy sperm, you may need a testicular biopsy. Your female partner also needs to be tested to make sure she doesn't have fertility problems.

Vasectomy reversal can be effective regardless of how long it's been since the original vasectomy. However, if more than 15 years have passed since the original vasectomy, you may have a lower chance of having enough healthy sperm in your semen to father a child.

Vasectomy is a straightforward surgery and an effective form of birth control — but surgery to undo a vasectomy is more involved and doesn't always work. The cost for a vasectomy reversal can range from $5,000 to $12,000 or more, and this procedure isn't usually covered by insurance.

How do you prepare?

Doctors usually perform vasectomy reversals at a surgery center or at a hospital. It's a delicate, microsurgical procedure that can be done using a few different surgical techniques.

• Before you choose a doctor, ask how many vasectomy reversals he or she has performed, and how many men have successfully fathered children after the reversal surgery.
• After choosing a doctor, meet with him or her to discuss the procedure, risks and potential complications. Include your partner in this initial consultation, if appropriate.
• Two weeks before and after your vasectomy, don't take aspirin, ibuprofen (Advil and Motrin, others) because they affect the platelets in your blood and can cause bleeding. Instead, use acetaminophen (Tylenol, others) if you need to relieve pain.
• Your doctor may ask you to clean and shave your scrotum before surgery and bring a clean jockstrap (athletic supporter) to wear after surgery.
• The surgery usually takes two to four hours. You'll also need time to recover from anesthesia. Arrange for someone to drive you home after surgery.

How is it done?

The surgery is more difficult than the original vasectomy because the tube that carries sperm from each testicle to your semen (vas deferens) must be sewn back together or attached to the epididymis. The surgery usually is done on an outpatient basis — without an overnight stay at the surgery center or hospital. Doctors can perform this surgery in one of two ways:

• Vasovasostomy (vas-o-va-ZOS-tah-me). With this procedure, the surgeon sews the severed ends of the vas deferens back together. However, sometimes this isn't possible and a more complex surgery is needed to restore the flow of sperm.
• Vasoepididymostomy (vas-o-ep-ih-did-ih-MOS-tah-me). This surgery attaches the vas deferens directly to the epididymis, the coiled tube on the back of each testicle where sperm matures. A vasectomy can cause blockages or a break in the vas deferens or the epididymis. This surgery is used when a vasovasostomy won't work because sperm flow is blocked. The vas deferens is connected to the epididymis above the point of blockage.

You probably won't know ahead of time which technique is needed. The surgeon will make the decision during the operation. You may need a combination of the two surgical techniques — a vasovasostomy on one side and a vasoepididymostomy on the other.

What can you expect during the procedure?

You may have general anesthesia to make you unconscious during the surgery. Or, your surgeon may use an epidural, spinal or local anesthetic. In any case, your anesthesia will need to keep you completely still because the surgery is so delicate. It's done using a microscope that magnifies the surgery area five to 20 times, and any movements are magnified by the operating microscope.

The surgeon will make a cut on the underside of your scrotum, expose the testicle, and release it from surrounding tissues. Next, he or she will cut open the vas deferens and examine the fluid inside.

Fluid assessment
Once the vas deferens has been opened, the surgeon will do a naked-eye inspection of the fluid that comes out as well as examine a drop of the fluid under a microscope. This is an important part of the operation because it helps your doctor determine what type of surgery you need to restore the flow of sperm.

• If the fluid contains sperm and plenty of clear fluid, surgery to reconnect the ends of the vas deferens — a vasovasostomy — is likely to work.
• Fluid below the vasectomy site that is thick or pasty, or that contains no sperm or partial sperm, can be a sign that there is scar tissue blocking the flow of sperm. In this case, attaching the vas deferens directly to the epididymis — a vasoepididymostomy — may be the best option.

Freezing sperm
If your doctor finds sperm during the surgery, you may choose to have some frozen in case your vasectomy reversal doesn't work. If after vasectomy reversal you're not able to father a child through sexual intercourse, your frozen sperm may be injected directly into an egg. This is a type of in vitro fertilization called intracytoplasmic sperm injection (ICSI).

After surgery
Immediately after surgery, your doctor may cover the incisions with bandages. You'll put on your jockstrap to hold any bandages in place and apply some pressure to reduce swelling and movement. You'll need to rest with an ice pack placed on your scrotum to reduce swelling. As the anesthetic wears off, you may have some pain and cramping that can be relieved with acetaminophen. For most men, the pain isn't severe and gets better after a few days to a week.

After you return home, take it easy. You may be sore for several days, which you can treat with acetaminophen or, if your doctor prescribes it, acetaminophen plus codeine. You may also have bruising, but the discoloration should lighten and disappear after about two weeks. Any stitches should dissolve in seven to 10 days.

• For the first two days after surgery, avoid bathing and swimming.
• Refrain from sports and heavy lifting for at least three weeks.
• If you have a desk job, you'll probably be able to return to work three days after surgery. If you perform physical labor or have a job that requires much walking or driving, talk to your doctor about when it's appropriate to resume working.
• You shouldn't have sexual intercourse or ejaculate for about four weeks. At that point, you may resume sexual activity.
• You'll need to wear a jockstrap for several weeks at all times, except when showering. After several weeks, you'll need to continue to wear a jockstrap during exercise.

Results

In successful vasovasostomy, sperm usually appear in the semen after a few months. After a vasoepididymostomy, it takes longer — from three to 15 months. Vasectomy reversal leads to pregnancy in about 52 percent of couples within two years. While some pregnancies occur within a few months after a vasectomy reversal, the average is about a year after the procedure.

Sometimes problems with conception are due to female infertility. When the female partner doesn't have fertility problems, couples are more likely to conceive a child after a vasectomy reversal.

Your surgeon will want to examine your semen after surgery to see if the operation was successful. Unless you achieve pregnancy, a sperm count is the only way to tell if your vasectomy reversal was a success.

If vasectomy reversal doesn't work
Vasectomy reversals sometimes fail if there is a sperm blockage that wasn't recognized during surgery, or if a blockage develops sometime after surgery. Some men have a second-attempt vasectomy reversal if the procedure doesn't work the first time.

Experts are investigating whether anti-sperm antibodies — proteins that develop after a vasectomy — might interfere with fertility after vasectomy reversal. Research shows anti-sperm antibodies can inhibit the function and movement of sperm, but experts are still not sure about their effect on fertility after a vasectomy reversal.

Risks

Risks of vasectomy reversal include:

• Bleeding within the scrotum. This may lead to a collection of blood (hematoma) that causes painful swelling. You can reduce this risk by avoiding aspirin before and after surgery and following your doctor's instructions to rest after surgery.
• Infection at the surgery site. This isn't common, but is a risk with any surgery.
• Inflammation. Sperm leakage into the scrotum can prompt your immune system to form an inflammatory mass called a sperm granuloma. Granulomas usually occur sometime after surgery and can be a sign that a vasectomy reversal wasn't successful.
• Damage to nerves and blood vessels. In some cases, this reduces fertility after a vasectomy reversal.

Call your doctor if you develop any of these signs and symptoms:

• Fever
• Swelling that worsens or won't go down
• Difficult urination
• A marble-sized lump in your scrotum
• Bleeding from an incision that continues after you've pinched the site between two gauze pads for 10 minutes

Please visit http://www.eliebenaim.com or http://www.dua.com for more information and to request an appointment.

In reality, the only truly (bad decision) you could make, is no decision.

Please visit http://www.eliebenaim.com or http://www.dua.com for more information and to request an appointment.

Past Positions:

Director of Urology Outpatient Services 2000-2002

Rural Medical Doctor 1984

Hospital Affiliations

Board Certification

Licensures

Honors and Awards

Surgery vs. Radiotherapy

The following table compares outcomes following prostate cancer treatment — specifically, surgery (radical prostatectomy), which is considered the gold standard treatment for localized prostate cancer — and radiation (brachytherapy and external beam radiation). Data is provided on survival, cancer recurrence, incidence of rectal and bladder cancer, bowel function, urinary issues and long-term erectile function.

In this table, radical prostatectomy includes all approaches to prostate surgery (open surgery through large incisions; conventional minimally invasive, or laparoscopic radical prostatectomy – also called LRP – as well as da Vinci Prostatectomy, or dVP). As you can see, surgery offers measurable advantages over radiation in terms of outcomes and survivability.

*Open surgery; comparable long-term data not yet available on da Vinci Prostatectomy.
**External Beam Radiation Therapy (EBRT) unless otherwise noted in the citation.

da Vinci vs. Open Surgery & Laparoscopy

The following table looks at patient outcomes following surgery for prostate cancer (radical prostatectomy), and compares "best in class" data from three types of surgery. As you can see, da Vinci Prostatectomy (dVP) shows measurable advantages as compared to both conventional open surgery (open), performed through large incisions, as well as conventional minimally invasive laparoscopic (lap) surgery.

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Please visit http://www.eliebenaim.com or http://www.dua.com for more information and to request an appointment.