New Research(1) Calls for Reclassification of Zoladex as Curative

New Research(1) Calls for Reclassification of Zoladex as Curative

November 13, 2006

-- Findings Challenge Historical Assumptions & Current Guidelines for Treating Non-Metastatic Poor Prognosis Prostate Cancer With Adjuvant LHRHas

    MACCLESFIELD, England, Nov. 13 /Xinhua-PRNewswire/ --
New research presented today at the 28th Congress of the
Societe Internationale d'Urologie (SIU), Cape Town, South
Africa demonstrates that adjuvant androgen-deprivation
therapy with ZOLADEX (goserelin) can consistently control
prostate cancer, allowing men to out-live their disease(1).
The researchers conclude that adjuvant goserelin should be
reclassified as a treatment of 'curative' intent for men
with poor prognosis, non-metastatic prostate cancer and
call for current clinical guidelines to reflect this.

    The research highlights other cancer treatments that
have been reclassified as 'curative,' including
cisplatinum-based chemotherapies that revolutionized
testicular cancer treatment so that the disease is
eradicated in a substantial proportion of men, and
long-term results with tamoxifen used after surgery in
women with breast cancer, which led to the drug being
reclassified as a treatment of curative intent.

    Dr. Neil Fleshner, Division of Urology, Princess
Margaret Hospital, Toronto, Canada, who presented the
research, commented: "Our analysis of four long-term
studies clearly shows that treatment with adjuvant
goserelin provides long-term control of non-metastatic,
poor prognosis prostate cancer such that a significant
number of men are out-living their disease. Historically,
LHRHas were a treatment for palliation of metastatic
prostate cancer, and physicians today still consider
adjuvant hormonal therapy as a palliative treatment option,
despite the number of trials showing positive survival
results for men with non-metastatic, poor prognosis cancer.
The findings fundamentally challenge this notion, which is
an important message for clinicians and men alike as it
means the current way we view and use this drug is
outmoded, meaning some men may not be receiving the best
chance of cure."

    Concept of 'cure' in cancer

    The concept of 'cure' in oncology is emotive and
fraught with complications: currently the diagnostic
technology that allows physicians to determine whether all
cancer cells are eradicated does not exist. Because of
this, oncologists are reluctant to use the term 'cure.' A
definition of cure for cancer was first established in the
1970s, which proposed that cure exists for disease-free
survivors whose overall survival rate is similar to that of
an age- and sex-related matched population(2). This concept
first led to the five-year survival rates becoming widely
accepted as an indication of the success of a cancer
treatment.

    However, advances in treatments, earlier detection, and
increasing international collaboration and data sharing have
made the five-year survival concept obsolete for many
cancers. A review of other genitourinary cancers (bladder
cancer, testicular cancer, and renal cancer) by the
researchers indicates that cure varies with tumour type and
disease stage. They found, for example, a five-year
follow-up of patients with transitional cell
muscle-invasive bladder cancer treated with a combination
of chemotherapy and radiation or surgery was insufficient
as the survival curve has not yet flattened, and a
follow-up period greater than five years to evaluate cure
was needed due to the progression of invasive bladder
cancer(3).

    Is it possible to 'cure' patients with poor-prognosis
non-metastatic prostate cancer?

    The researchers reviewed survival data from four
long-term, randomized, controlled clinical studies in men
with non-metastatic, poor prognosis prostate cancer who
received adjuvant hormonal therapy with goserelin following
their primary treatment (radical prostatectomy or radiation
therapy)(4),(5),(6),(7) . The researchers reviewed
goserelin as it is the most widely researched LHRHa and is
unique amongst LHRHas as it has been studied as an adjuvant
therapy in a number of randomized, controlled survival
studies with a follow-up of more than five years. From
these findings, the researchers assessed whether the
potential for cure was achieved using an amended definition
of cure specific to prostate cancer, defined as 1) when the
disease-free survival curve flattens out after 10-15 years
following treatment and 2) when the overall survival rate
approaches that of an age-related healthy male
population(1). Their findings showed that:

    -- Across all four trials, long-term disease control
was achieved in a
       sizeable proportion of men with non metastatic
prostate cancer and a 
       poor prognosis (poor prognosis is defined as having
PSA level >20ng/mL 
       and high Gleason scores >8 amongst other
criteria) who received 
       adjuvant goserelin

    -- The disease-free survival (Kaplan-Meier) curves
flattened during
       long-term follow up, indicating that many men are
not relapsing

    -- Importantly, the overall survival curves indicate
that patients were
       not experiencing significant additional mortality
associated with the
       side-effects of long-term goserelin use

    Guidelines outmoded

    In moving forward, Dr. Fleshner commented: "The
European Association of Urology and the American Society of
Clinical Oncology treatment guidelines do not currently
classify adjuvant hormonal therapy as being a potentially
curative treatment. It is worth noting that generally
similar long-term results with tamoxifen adjuvant to
surgery in women with breast cancer led to this drug being
classified as a treatment of curative intent. We believe
that adjuvant goserelin should be reclassified as a
treatment of curative intent for patients with poor
prognosis, non metastatic prostate cancer."

    Notes to Editors

    About AstraZeneca:

    AstraZeneca is a major international healthcare
business engaged in the research, development, manufacture
and marketing of prescription pharmaceuticals and the
supply of healthcare services. It is one of the world's
leading pharmaceutical companies with leading positions in
gastrointestinal, oncology, cardiovascular, neuroscience
and respiratory products. AstraZeneca is listed in the Dow
Jones Sustainability Index (Global) as well as the
FTSE4Good Index.
    'ZOLADEX' is a trademark of the AstraZeneca group of
companies.

    For more information visit:

     http://www.astrazenecapressoffice.com
     http://www.astrazeneca.com
     http://www.zoladex.com
     http://www.prostateline.com

    References:

    (1) N. Fleshner et al. Adjuvant androgen deprivation
therapy augments
        cure and long-term cancer control in men with poor
prognosis, 
        nonmetastatic prostate cancer. Presented at SIU,
Cape Town, November 
        2006

    (2) Frei III E, Gehan EA. Definition of cure for
Hodgkin's disease.
        Cancer Res 1971; 31: 1828-33

    (3) Fellin G, Graffer U, Bolner A, Ambrosini G, Caffo
O, Luciani L.
        Combined chemotherapy and radiation with selective
organ preservation 
        for muscle-invasive bladder carcinoma. A
single-institution phase II 
        study. Br J Urol 1997; 80: 44-9

    (4) Messing EM et al. Immediate versus deferred
androgen deprivation
        treatment in patients with node-positive prostate
cancer after radical
        prostatectomy and pelvic lymphadenectomy. Lancet
Oncol 2006: 7; 472-79

    (5) Pilepich MV, Winter K, Lawton CA et al. Androgen
suppression adjuvant
        to definitive radiotherapy in carcinomas of the
prostate - long term 
        results of phase III RTOG 85-31. Int J Radiat Oncol
Biol Phys 2005; 
        61: 1285-90

    (6) Bolla M, Collette L, Blank L et al. Long-term
results with immediate
        androgen suppression and external irradiation in
patients with locally
        advanced prostate cancer (an EORTC study): a phase
III randomized  
        trial. Lancet 2002; 360: 103-8

    (7) Hanks GE, Pajak TF, Porter A et al. Phase III trial
of long-term
        adjuvant androgen deprivation after neoadjuvant
hormonal cytoreduction 
        and radiotherapy in locally advanced carcinoma of
the prostate: the 
        Radiation Therapy Oncology Group Protocol 92-02. J
Clin Oncol 2003; 
        21: 3972-8

    For more information, please contact:
 
     Peter Edwards, 
     Prostate Franchise Global Brand PR Manager, 
     AstraZeneca, [phone]
     Mobile: [phone]

     Rebecca Hibble, 
     Cohn & Wolfe
     Tel:    [phone]
     Mobile: [phone]
     Email:  [e-mail]

SOURCE  AstraZeneca