http://www.medicalnewstoday.com/articles/151733.php
Prostate Cancer Drug Abiraterone Shows Impressive New Research Results
Article Date: 28 May 2009 - 6:00 PDT

New UK research confirms the groundbreaking cancer drug abiraterone
provides significant benefit for up to two-thirds of men with advanced and
aggressive prostate cancer, according to a study published online in the
Journal of Clinical Oncology.

The drug, discovered at The Institute of Cancer Research (ICR) in the
Cancer Research UK Centre for Cancer Therapeutics, made headlines in July
2008 when the first UK phase I clinical trial reported significant
shrinkage of patients' tumours and reduction in pain. Scientists hailed it
as one of the most significant developments in prostate cancer in 60
years.

This second publication of a phase I/II study, reporting on 54 patients,
confirms the Phase I results. In addition, ICR scientists have worked out
how to delay drug resistance and developed a test to identify the men most
likely to benefit from abiraterone.

These phase I/II studies were undertaken by the ICR and The Royal Marsden
Hospital and were funded by Cougar Biotechnology Inc. The lead researchers
on the study were funded by Cancer Research UK.

Lead researcher Dr Gert Attard says:

"Phase I/II results showed that up to 70 per cent of men responded to the
drug, abiraterone. About two-thirds of men experienced significant
benefits for an average of eight months, with scans showing their tumours
decreased in size and their PSA levels dropped substantially.

"Our latest study also shows that by combining abiraterone with a steroid
treatment when abiraterone stops working, we can reverse resistance and
extend the response to this treatment by another 12 months."

"We have also noticed that the majority of patients who had very
significant shrinkage of their tumors had an abnormality of a gene called
ERG that was probably driving their cancer. We have developed a test for
this ERG gene so we can identify the men most likely to benefit from
abiraterone."

Chief investigator Dr Johann de Bono is extremely optimistic about these
results: "Almost all these men had cancer that had spread to the bones,
lymph glands and elsewhere. Many were in pain and not enjoying life. The
patients involved in this trial remained pain-free for an average of about
eight months, a brilliant result for those with aggressive prostate cancer
and their families. For about a third of men - those who carried the ERG
gene - the benefit lasted for more than 18 months.

"In addition, this drug has changed the way the science community looks at
prostate cancer. It can block the production of male hormones, including
hormones produced by the tumour itself. The more we learn about how this
drug works the more we will be able to find further ways of counteracting
a patient's potential genetic resistance to it."

Mike Torr, 70, from Sheffield, was involved in the phase II abiraterone
clinical trial. He says: "Two years ago, I was in severe pain as my
prostate cancer had spread to my bones. I was involved in the earlier
trials and received the additional steroid treatment to combat resistance.
This drug has given me over two years of life, symptom-free. I have been
able to go back to fully enjoying my retirement and travelling with my
wife to places such as India."

Abiraterone is currently in Phase III prostate cancer trials at more than
150 hospitals across the world, in one of the largest ever trials for
end-state prostate cancer. More than 1300 men have been treated with the
drug and it is hoped that, should the trials continue to show a benefit,
abiraterone may be available for general use as a prostate cancer
treatment by 2011.

Professor Peter Johnson, chief clinician at Cancer Research UK, which
helped fund the lead investigators on the study, said: "These early
results hold great promise for treating a problem which affects many men
with prostate cancer and give us real hope for the future. We are keen to
see the results of the larger trials now underway, to find out whether
abiraterone should be made generally available. This drug is an excellent
example of how research which leads to better understanding of the biology
of a cancer can give us new opportunities for its treatment."

The Phase III abiraterone trial in prostate cancer patients has reached
full recruitment.

Abiraterone was discovered and developed in the Cancer Research UK Cancer
for Cancer Therapeutics at The Institute of Cancer Research and is
licensed to Cougar Biotechnology, Inc.

This study was funded by Cougar Biotechnology, Inc. the Medical Research
Council (MRC), Prostate Cancer Foundation (USA), Cancer Research UK, the
ICR and the Royal Marsden Hospital.

Notes

- Selective inhibition of CYP17 with abiraterone acetate is highly active
in the treatment of castration-resistant prostate cancer was published
online in the Journal of Clinical Oncology on 26 May 2009

- Phase I Clinical Trial of a Selective Inhibitor of CYP17, Abiraterone
Acetate, Confirms That Castration-Resistant Prostate Cancer Commonly
Remains Hormone Driven was published online in the Journal of Clinical
Oncology on 22 July 2008.

- Molecular Characterization of Circulating Tumor Cells from Patients with
Castration-Resistant Prostate Cancer (ERG gene paper) was published in
Cancer Research on 1 April 2009

This trial is a phase I/II study with a phase II expansion.
Abiraterone is also in an early clinical trial for women with advanced
breast cancer, who have exhausted all other treatments. This trial is
being run and funded by Cancer Research UK.

For patient information about the breast cancer study involving
abiraterone and other treatments, please visit CancerHelp UK
(www.cancerhelp.org.uk) or call the Cancer Research UK team of specialist
nurses on 0808 800 40 40. Lines are open Monday to Friday, between 9am and
5pm.

Prostate Cancer

- Prostate cancer has overtaken lung cancer to become the most common
cancer in men affecting more than 35,000 men every year in the UK. One man
dies of prostate cancer in the UK every hour.

- For the majority the majority of men, prostate cancer is not a
life-threatening disease, however about 10,000 men die of the aggressive
form of the disease each year.

Source
Institute of Cancer Research

http://en.wikipedia.org/wiki/Abiraterone
he first study run at the Royal Marsden Hospital, London, in patients who
had not received chemotherapy reported that abiraterone acetate induced
decline in prostate specific antigen in up to 70% of patients as well as
radiological shrinkage of tumors, symptom improvement, normalization of
lactate dehydrogenase.[4] However others have cautioned that it is too
early to know whether abiraterone treatment will have long term
benefit.[5][6]

Results of two Phase II trials indicate that abiraterone may reduce
prostate specific antigen (PSA) levels, as well as shrink tumors.[7] Many
of the 21 men in the Phase II trial reported significant improvements in
their quality of life and several were able to stop taking morphine, used
to control the pain caused after the cancer spread into their bones.[8]

http://www.icr.ac.uk/research/new_research_highlights/research_highlights/13503.shtml

Prostate Cancer Drug Abiraterone Shows Impressive New Research Results

26 May 2009 - The groundbreaking cancer drug abiraterone provides
significant benefit for up to two-thirds of men with advanced and
aggressive prostate cancer, according to a study published online in the
Journal of Clinical Oncology.

The drug, discovered at The Institute of Cancer Research, made headlines
in July 2008 when the first UK Phase I clinical trial reported significant
shrinkage of patients’ tumours and reduction in pain. The Phase I/II
study, reporting on 54 patients, confirmed the Phase I results. In
addition, ICR scientists have worked out how to delay drug resistance and
developed a test to identify the men most likely to benefit from
abiraterone.

“Our latest study also shows that by combining abiraterone with a steroid
treatment when abiraterone stops working, we can reverse resistance and
extend the response to this treatment by another 12 months,” lead
researcher Dr Gert Attard says. “We have also noticed that the majority of
patients who had very significant shrinkage of their tumours had an
abnormality of a gene called ERG that was probably driving their cancer.
We have developed a test for this ERG gene so we can identify the men most
likely to benefit from abiraterone.”

Abiraterone has now moved into Phase III prostate cancer trials at more
than 150 hospitals across the world, in one of the largest ever trials for
end-stage prostate cancer.

Back to other research highlights

http://www.mskcc.org/mskcc/html/2270.cfm?IRBNO=09-032
Phase III Study of Abiraterone Acetate Plus Prednisone in Men with
Metastatic Castration-Resistant Prostate Cancer
[Protocol 09-032]

Full Title :
   A PHASE 3 RANDOMIZED, DOUBLE BLIND, PLACEBO-CONTROLLED STUDY OF
ABIRATERONE ACETATE (CB7630) PLUS PREDNISONE IN ASYMPTOMATIC OR MILDLY
SYMPTOMATIC PATIENTS WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER

Purpose :

   Prostate cancers are initially dependent on the male hormone
testosterone for growth. Hormonal therapies that lower the level of
testosterone are among the most effective treatments for prostate cancers
that have spread to distant organs (metastasized). The effectiveness of
hormonal treatments, however, is not permanent, and over time many
prostate cancers progress in spite of hormones.

   The purpose of this study is to evaluate the effectiveness of an
investigational drug called abiraterone acetate for men with metastatic
castration-resistant prostate cancer. Abiraterone acetate works by
inhibiting an enzyme called CYP17, which plays an important role in the
production of hormones such as testosterone. Previous clinical studies
have shown that men with metastatic prostate cancer who received
abiraterone acetate experienced a reduction in PSA levels, a marker of
prostate cancer growth.

   Patients in this study will be randomly assigned to receive
abiraterone acetate plus prednisone or a placebo plus prednisone.
Prednisone is a standard steroid medicine commonly used in the treatment
of advanced prostate cancer.

Eligibility :

   To be eligible for this study, patients must meet several criteria,
including but not limited to the following:

       * Patients must have a confirmed diagnosis of metastatic prostate
cancer that has continued to grow despite hormonal therapy.
       * Patients' testosterone levels must be less than 50 ng/dL.
       * At least 6 weeks must have passed since completion of radiation
therapy, bicalutamide, or nilutamide and 4 weeks since receiving flutamide
and entry into the study. Patients may not have had prior chemotherapy or
biologic therapy for metastatic castration-resistant prostate cancer.
       * Patients must be physically well enough that they are fully
ambulatory, capable of all self care, and are capable of all but
physically strenuous activities. As an example, patients must be well
enough that they would be able to carry out office work or light
housework.
       * Patients must be age 18 or older.