It was announced today that the phase I/II trial of MDV3100 demonstrated positive results. MDV3100 is a novel triple-acting oral androgen receptor antagonist, the common antagonist most of us are familiar with today is Casodex. These results were published in the online April 15 version of The Lancet.
The trial used MDV3100 in men with progressive, metastatic castration-resistant prostate cancer (mCRPC). According to the Lancet, MDV3100 demonstrated anti-tumor activity in men with late-stage prostate cancer. The evaluative criteria were reductions in prostate specific antigen (PSA) levels, radiographic findings and circulating tumor cell (CTC) counts. It was also reported that anti-tumor effects were observed in men who were resistant to standard anti-androgen treatments, as well as in men who had progressed following chemotherapy. MDV3100 is currently in Phase 3 trial development for the treatment of advanced prostate cancer.
According to Howard Scher, M.D., lead author of The Lancet article and chief of the Genitourinary Oncology Service at Memorial Sloan-Kettering Cancer Center in New York, “MDV3100, with its unique mechanism of action, could offer an important new treatment option to men with prostate cancer that is resistant to currently available anti-androgens. It is particularly encouraging that antitumor activity was seen on all outcomes assessed in patients who had failed chemotherapy because their survival times are one year or less, on average, and their treatment options are limited.”
All of the men participating in the phase I/II trial had very progressed disease when they were enrolled. They were also very heavily pretreated, with 77 percent having failed at least two lines of prior hormonal therapy and 54 percent having failed one or more chemotherapy regimens. A total of 140 men were enrolled in the trial, which evaluated MDV3100 doses between 30 and 600 mg/day. During the trial the men were permitted to remain on treatment for as long as they continued to tolerate the drug and their disease did not progress. Efficacy endpoints included CTC counts, serum PSA levels, soft tissue and bony metastases, and time on treatment.
The Results of the Trial
MDV3100 was successfully associated with anti-tumor activity in men who were already resistant to bicalutamide (Casodex) as well as other standard anti-androgen treatments. This also included men who had failed prior chemotherapy (n=75) as well as those men who were chemotherapy-naïve (n=65). Anti-tumor activity was demonstrated by:
• Substantial reductions in PSA levels, including declines in serum PSA of 50 percent or more in 56 percent of patients.
o The PSA responses lasted for a median of 41 weeks for chemotherapy-naïve patients, 32 weeks for all patients and 21 weeks for post-chemotherapy patients.
• Improvement or stabilization in tumors that had spread to soft tissue or bone. Treatment with MDV3100 was associated with tumor regressions (22 percent of all patients — both chemotherapy-naïve and post-chemotherapy patients) and stable disease in soft tissue (49 percent of all patients) and stable disease in bone (56 percent of all patients).
o The median time to radiographic progression was not reached for chemotherapy- naïve patients; it was 47 weeks in all patients combined and 29 weeks for post-chemotherapy patients.
• A conversion from unfavorable to favorable CTCs in 49 percent of patients (75 percent of the chemotherapy-naïve and 37 percent of the post-chemotherapy groups). Of patients who initiated therapy with favorable counts, 91 percent retained favorable counts during treatment.
The morbidity problems were limited with most men able tolerate doses up to and including 240 mg/day. Fatigue was the most frequently reported adverse event. (Don’t forget the role of a phase I/II trial includes determining dosing levels).
“Based on the favorable benefit-risk ratio for MDV3100 observed in the Phase 1-2 trial, we initiated the randomized, placebo-controlled Phase 3 AFFIRM trial in men with progressive advanced prostate cancer following chemotherapy, as new treatments are urgently needed for this patient group,” said Lynn Seely, M.D., chief medical officer of Medivation. “We also plan to evaluate MDV3100 in earlier stages of prostate cancer, as those patients also are in need of new treatment options.”
Currently there is a phase III trial actively enrolling men in a clinical trial of MDV3100. This trial is designed for men with progressive disease following failed docetaxel treatment (chemotherapy). This phase III trial is known as AFFIRM, the randomized, placebo-controlled, double-blind, multi-national trial which is evaluating MDV3100 at a dose of 160 mg taken orally once daily in men with metastatic prostate cancer who were previously treated with docetaxel-based chemotherapy. The primary endpoint of the trial is overall survival; secondary endpoints include progression-free survival, safety and tolerability. The AFFIRM study is being conducted internationally with sites in Argentina, Austria, Australia, Belgium, Canada, Chile, France, Germany, Italy, Netherlands, Poland, South Africa, Spain, UK and U.S.
If you are interested in additional information about the trial, eligibility and enrollment you should go to: www.affirmtrial.com or call the AFFIRM study hot line, toll-free in the U.S. and Canada at 1-888-782-3256.
Information for this post was obtained from a press release from the pharmaceutical company.
Joel T Nowak, MA, MSW
OUR INTENT HERE IS NOT TO BELITTLE ANYONE OR ANY GROUP THAT HAS HAD OR THINKING ABOUT MEDICAL OPTIONS THEY HAD OR THINKING ABOUT PURSUING SUCH AS -SURGERY-RADIATION,CHEMO,HIFU, SEED IMPLANTS,HORMONE
THERAPY AND LAST BUT NOT LEAST CYRO- IF WANT TO HELP YOUR FELLOW MAN–(PLEASE)-EMAIL THIS TO AS MANY PEOPLE AS
YOU CAN AND ASK THEM TO EMAIL AS MANY PEOPLE (AS THEY
CAN)-AS WE HAVE THOUSANDS OF PROSTATE CANCER CLIENTS/PATIENTS—AND HAVE BEEN TELLING PEOPLE THIS OVER 20
YRS-PEOPLE THOUGHT I WAS CRAZY—AND I WANT YOU TO UNDERSTAND THAT THIS IS
WHY I HAVE SEEN THOUSANDS OF CANCER PATIENTS THAT HAVE CANCER (PROSTATE CANCER FOR SURE) THAT THE CANCER WILL RETURN WITHIN 17-36 MONTHS IN OVER 90% OF
THESE PEOPLE/MEN–I ALSO SEE THIS SAME PATTERN WITH WITH ANY OTHER TYPE OF
CONVENTIONAL TREATMENTS, SUCH AS RADIATION,CHEMO,HIFU, SEED IMPLANTS,HORMONE
THERAPYAND LAST BUT NOT LEAST CYRO-IT APREARS THAT IT DOES NOT MATTER–(BUT YET PEOPLE KEEP LISTING TO
THESE CLOWNS)–IT IS ALL ABOUT?
$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$———————————————————————————————————————————–
The article you are about to read is earth-shattering. It provides
overwhelming and compelling data that surgery itself is a significant cause
of metastasis.
The good news is that a wide variety of methods have been identified to
protect against surgically-induced recurrence and metastasis. Armed with
this knowledge, a cancer patient can follow simple steps ahead of time to
dramatically improve their odds of a cure. There is so much convincing data
provided in the following article that it could be expanded into an entire
book!
You would think that cancer surgeons would figure this out themselves. After
all, everything discussed in the following chapter is based on what is
published in the peer-reviewed scientific literature. Sadly, the
assembly-line mentality of conventional doctors too often results in these
important decisions being overlooked. As you will read, it is critical that
the right choices be made before surgery in order to derive optimal
benefits.
It is our sincere desire that the following chapter will educate not only
patients, but also their surgeons in a way that will revolutionize the way
cancer surgeries are planned and carried out in the future. If you are a
newly diagnosed cancer patient, the suggestions made in this article are
available right now to reduce painful and life-threatening complications,
while simultaneously protecting against surgically-induced metastasis and
recurrence of the primary tumor.
Cancer Surgery: What You Need to Know Ahead of Time
The surgical removal of the primary tumor has been the cornerstone of
treatment for the great majority of cancers. The rationale for this approach
is straightforward: if you can get rid of the cancer by simply removing it
from the body, then a cure can likely be achieved. Unfortunately, this
approach does not take into account that after surgery the cancer will
frequently metastasize (spread to different organs). Quite often the
metastatic recurrence is far more serious than the original tumor. In fact,
for many cancers it is the metastatic recurrence-and not the primary
tumor-that ultimately proves to be fatal.1
In a shocking irony, a growing body of scientific evidence has revealed that
cancer surgery can increase the risk of metastasis.2 This would fly in the
face of conventional medical thinking, but the facts are undeniable.
To gain a better understanding of how surgery can increase the risk of
metastasis, let’s first discuss the actual process of cancer metastasis. A
complicated sequence of events must occur in order for cancer to spread to
another part of the body.2 Isolated cancer cells that break away from the
primary tumor must first breach the connective tissue immediately
surrounding the cancer. Once the cancer cell has broken free of the
surrounding connective tissue, the next step is to enter a blood or
lymphatic vessel. This is easier said than done, as entry into a blood
vessel requires the cancer cell to secrete enzymes that degrade the basement
membrane of the blood vessel.3 Entry into a blood vessel is vitally
important for the aspiring metastatic cancer cell, since it uses the
bloodstream as a highway for transportation to other vital organs of the
body-such as the liver, brain, or lungs-where it can form a new deadly
tumor.
Cancer cells circulating in capillary (blood vessel) surrounded by red blood
cells.
Now that the lone cancer cell has finally entered the bloodstream, its
problems have only just begun. Traveling within the bloodstream can be a
hazardous journey for cancer cells. Turbulence from the fast moving blood
can damage and destroy the cancer cell. Furthermore, cancer cells must avoid
detection and destruction from white blood cells circulating in the blood
stream.
To complete its voyage, the rogue cancer cell must adhere to the lining of
the blood vessel, where it degrades through and exits the basement membrane
of the blood vessel. Its final task is to burrow through the surrounding
connective tissue to arrive at the organ that is its final destination. Now
the cancer cell can multiply and form a growing colony that serves as the
foundation for a new metastatic cancer. Time is working against these
solitary cancer cells. This entire sequence of events must happen quickly,
since these cells have a limited life span.1
We now see that cancer metastasis is a complicated and difficult process.
Fraught with peril, very few free-standing cancer cells survive this arduous
journey.2 The probability of cancer cells surviving this journey and forming
new metastases can be increased by anything that serves to make this process
easier.
In a groundbreaking study published in the medical journal Annals of Surgery
in 2009, researchers reported that cancer surgery itself can create an
environment in the body that greatly lessens the obstacles to metastasis
that cancers cells must normally face.2
Just as concerning is the revelation that cancer surgery can produce an
alternate route of metastasis that bypasses natural barriers. During cancer
surgery, the removal of the tumor almost always disrupts the structural
integrity of the tumor and/or the blood vessels feeding the tumor. This can
lead to an unobstructed dispersal of cancer cells into the bloodstream, or
seeding of these cancer cells directly into the chest or abdomen.4-7 This
surgery-induced “alternate route” can greatly simplify the path to
metastasis.
To illustrate, a study published in the British Journal of Cancer in 2001
compared the survival of women with breast cancer who had their tumors
removed surgically, to the survival of women with breast cancer who did not
have surgery. As expected, the findings established that surgery
substantially improved survival in the early years.
However, further analysis of the data determined that women who had surgery
had a spike in their risk of death at eight years that was not evident in
the group who did not have surgery.8 In their interpretation of the results,
the authors of the study stated: “A reasonable hypothesis to explain the
observed patterns of the hazard functions [risk of cancer death] is to
assume that.primary tumor removal may result in sudden acceleration of
metastatic process.”
Another group of researchers commenting on a study examining the surgical
treatment of colon cancer were far bolder in their conclusions: “This
finding strongly supports that surgery alters the natural course of the
disease by elongating life expectancy in the greater part of the patient
population, but also by simultaneously shortening survival in a smaller
subset of patients. Thus, both experimental and clinical evidence support
that surgery, although greatly reducing tumor mass and potentially curative,
paradoxically can also augment metastasis development.”2
Given these disturbing findings, what can individuals undergoing surgery for
their cancers do to protect themselves against an increased risk of
metastasis? A worthwhile strategy would be to examine all of the mechanisms
by which surgery promotes metastasis, and then create a comprehensive plan
that counteracts each and every one of these mechanisms. LARRY POPE-DR.
SPENCER .urologist-asst to-MR POPE–