As many as 30,000 U.S. women will be diagnosed with
ovarian cancer this year. In 2006, between 15,000 and
16,000 women are likely to die from this silent killer.
Ovarian cancer is the 5th leading cause of death among
women, and it is responsible for about five percent of all
cancer deaths. Chances are your doctor may have
misdiagnosed you. That is often the case. A recent British
study found 60 percent of all U.K. general practitioners
had misdiagnosed their patients.
Three-quarters of British doctors surveyed incorrectly
assumed that symptoms only occurred in the late stages of
ovarian cancer. Based upon that information, it should be
no surprise that Britain has one of the lowest survival
rates for ovarian cancer in the Western World – of 6,800
cases diagnosed each year, more than 4,600 die.
A similar discovery was made by University of California
researchers, who announced last year, “Four in 10 women
with ovarian cancer have symptoms that they tell their
doctors about at least four months — and as long as one
year — before they are diagnosed.” According to their study
of nearly 2,000 women with ovarian cancer, the researchers
discovered physicians:
• First ordered abdominal imaging or performed
gastrointestinal procedures instead of the more appropriate
pelvic imaging and/or CA-125 (a blood test that can detect
ovarian cancer).
• Only 25 percent of patients, who reported ovarian
cancer symptoms four or more months before diagnosis, were
given pelvic imaging or had CA-125 blood tests.
Patients with early symptoms are frequently
misdiagnosed. Abdominal imaging or diagnostic
gastrointestinal studies are less likely to detect ovarian
cancer. According to the American Cancer Society’s website,
“The most common symptom is back pain, followed by fatigue,
bloating, constipation, abdominal pain and urinary urgency.
These symptoms tend to occur very frequently and become
more severe with time. Most women with ovarian cancer have
at least two of these symptoms.”
By the time a woman reaches the fourth stage of ovarian
cancer, her first-line treatment is often Carboplatin,
Paclitaxel and Cisplatin as the specific chemotherapy for
ovarian cancer. In the first stage, cancer is contained
inside one or both ovaries. By stage two, the cancer has
spread into the fallopian tubes or other pelvic tissues,
such as the bladder or rectum. When the cancer has spread
outside the pelvis area into the abdominal cavity,
especially when tumor growths are larger than two
centimeters on the lining of the abdomen, then ovarian
cancer has reached stage three. The fourth and final stage
of ovarian cancer is reached when the cancer has spread
into other body organs, such as the liver or lungs.
If detected early, survival rates can be as high as 90
percent. Detected in the advanced stage, the survival rate
falls to between 30 and 40 percent. Various imaging tests
such as computed tomography (CT) scans, magnetic resonance
imaging (MRI) scans, and ultrasound studies can confirm
whether a pelvic mass is present. A laparoscopy can help a
doctor look at the ovaries and other pelvic tissue to in
order to plan out a surgical procedure, or to determine the
stage of the ovarian cancer. A biopsy, or tissue sampling,
would confirm if there is cancer in your pelvic region, and
would help determine how advanced it is. An elevated CA-125
blood test typically suggests the cancer has progressed to
the advanced stage.
About 50 percent of ovarian cancer patients are already
at an advanced stage by the time a correct diagnosis is
made. Only 10 to 14 percent of women with advanced cancer
are likely to survive more than five years.
Evaluation of Therapies
While research shows drinking black (or green) tea or
taking the herbal supplement gingko biloba may be useful,
as a preventative measure, or to reduce risk, a woman has
few choices when her cancer has moved to the advanced
stage. In the first stage, a woman faces surgical removal
of the tumor, and possibly one or both ovaries, to increase
her chances of survival. Beyond that, her choice is
chemotherapy.
One major problem with chemotherapy is the side effects.
The more advanced the cancer, the weaker one may be,
reducing the survival rate potential. Survival rates have
not changed very much over the past fifteen years.
Chemotherapy can increase survival time by as much as 50
percent. But, quality of life suffers. The side effects and
increased toxicity, accompanying chemotherapy, reduce how
one spends the prolonged survival time.
Some of Paclitaxel’s minor side effects, as reported by
Medline Plus, may include nausea, vomiting, loss of
appetite, change in taste, thinned or brittle hair, pain in
the joints of the arms or legs, changes in the color of
nails, and/or tingling in the hands or toes. More serious
side effects may include mouth blistering or fatigue. Some
alarming side effects could include unusual bleeding or
bruising, dizziness, shortness of breath, severe
exhaustion, chest pain, or difficulty swallowing. The most
common side effect of Paclitaxel is a decrease of blood
cells.
Carboplatin has its own list of side effects. It can
reduce platelet production, which can interfere with your
blood’s ability to clot. You may become anemic, feeling
tired or breathless. Nausea, vomiting, loss of appetite and
a general feeling of weakness are common with this
chemotherapeutic agent.
The latest breed of drugs, such as Eli Lilly’s Gemzar,
are hardly getting praise. On March 10th, the Food and Drug
Administration (FDA) said it was skeptical of the benefits
Eli Lilly’s Gemzar, which was being used with Carboplatin
to treat ovarian cancer patients. The FDA felt the 2.8
months increased survival time, provided by the
Gemzar/Carboplatin combination failed to offset the
treatment’s increased toxicity.
In January, the New England Journal of Medicine reported
on a remarkable new delivery system of chemotherapy, called
the “intra-abdominal, or intraperitoneal, chemotherapy.
Those who received the “belly bath” as it is now being
called by the media can survive 16 months longer than those
receiving intravenous chemotherapy. The major drawback is
that 60 percent of the women in the study were unable to
complete all six cycles of this chemotherapy. Those who did
survived longer, but only two in every five women were able
to advance to the end phase of the therapy.
One novel approach, now in Phase III trials at more than
60 research centers across the United States, is OvaRex ®
MAb, a murine monoclonal antibody, a type of biotech drug
derived from mouse cells. It is being tested by highly
regarded United Therapeutics, based in Silver Springs,
Maryland. Their lead drug Remodulin, an injection which
treats pulmonary arterial hypertension, is currently being
marketed inside and outside the United States. More than
$32 million has been spent researching, and on the
development of, OvaRex and may have it available on the
market by 2008.
OvaRex was developed in Canada by a company called
ViRexx Medical Corp, and first tested in that country.
According to Dr. Lorne Tyrrell, Chief Executive of ViRexx,
“The whole study has been set up with the FDA. This is a
study where the drug has been given fast track approval and
orphan drug status.” Dr. Tyrrell is also on leave (until
OvaRex become commercially available) as a Professor of
Medical Microbiology and Immunology at the University of
Alberta, and Director of the National Centre of Excellence
for Viral Hepatitis Research.
OvaRex was tested in Canada, prior to the current Phase
III trials in the U.S. “There have been a number of
patients that have received OvaRex,” said Dr. Tyrrell,
“We’ve had really no adverse effects from these patients.”
Dr. Tyrrell explained the procedure, “After being injected
intravenously, OvaRex binds to an antigen circulating in
the blood.” An antibody’s general purpose is to neutralize
an antigen. After an OvaRex injection, the murine
monoclonal antibody binds to the CA-125 antigen.
In a way the body is tricked. But, the body is tricked
in order to help “save” itself from the harmful antigen.
When the OvaRex antibody is bound to the CA-125 antigen,
the new combination is identified as a harmful unit. Before
then, the antigen wanders through the body, without
alerting the body’s defense systems, the dendritic cells,
to attack and destroy the harmful antigen. Because the body
is trained to identify and zero in on a foreign protein, in
this case a mouse protein, it alerts the dendritic cells.
Until then, the dendritic cells “tolerate” the cancerous
cells. The tolerance is what permits the cancer to spread
throughout the body.
OvaRex seeks to break that tolerance. The murine monoclonal
antibody is designed to target and bind exclusively to free
floating CA-125 antigen.
The dendritic cells refuse to tolerate the foreign
protein. When the antibody binds with the free-floating
antigen, the dendritic cells recognize the complex
(antibody plus antigen) as being foreign and engulf the new
unit. The dendritic cells break down the key proteins of
this unit, presenting all parts on the cells surface. At
the point, the body’s killer T-Cells are alerted to fight
the internal threat to the body. Once activated, the
T-Cells will replicate and create more killer T-Cells. Any
tumor cells expressing the CA-125 antigen is targeted for
destruction. The army of T-Cells move to attack the ovarian
cancer tumor.
The principle behind OvaRex is to re-program the immune
system to harness the body’s defenses to prevent the growth
and spread of the ovarian cancer. Will it cure ovarian
cancer? “In most cases, it will be a delay,” explained Dr.
Tyrrell. “However, I think that, and everyone hopes that,
often in some of these tumors, you’re making incremental
progress through careful clinical trials and adding new
therapy. Each thing we do that improves the outcome when
you start to look at the long term benefits of these, we
hope that one day we will be able to cure this disease. We
think this is a step. This has the potential to be an
important step at helping to stimulate immune response to
achieve a better outcome. Hopefully, one day we can improve
that to where it is a cure.”
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