MACCLESFIELD--13 Nov--PRNewswire-AsiaNet/InfoQuest Findings Challenge Historical Assumptions & Current Guidelines forTreating Non-Metastatic Poor Prognosis Prostate Cancer With Adjuvant LHRHas New research presented today at the 28th Congress of the SocieteInternationale d'Urologie (SIU), Cape Town, South Africa demonstrates thatadjuvant androgen-deprivation therapy with ZOLADEX (goserelin) can consistentlycontrol prostate cancer, allowing men to out-live their disease(1). Theresearchers conclude that adjuvant goserelin should be reclassified as atreatment of 'curative' intent for men with poor prognosis, non-metastaticprostate cancer and call for current clinical guidelines to reflect this. The research highlights other cancer treatments that have been reclassifiedas 'curative,' including cisplatinum-based chemotherapies that revolutionizedtesticular cancer treatment so that the disease is eradicated in a substantialproportion of men, and long-term results with tamoxifen used after surgery inwomen with breast cancer, which led to the drug being reclassified as atreatment of curative intent. Dr. Neil Fleshner, Division of Urology, Princess Margaret Hospital,Toronto, Canada, who presented the research, commented: "Our analysis of fourlong-term studies clearly shows that treatment with adjuvant goserelin provideslong-term control of non-metastatic, poor prognosis prostate cancer such that asignificant number of men are out-living their disease. Historically, LHRHaswere a treatment for palliation of metastatic prostate cancer, and physicianstoday still consider adjuvant hormonal therapy as a palliative treatmentoption, despite the number of trials showing positive survival results for menwith non-metastatic, poor prognosis cancer. The findings fundamentallychallenge this notion, which is an important message for clinicians and menalike 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 withcomplications: currently the diagnostic technology that allows physicians todetermine whether all cancer cells are eradicated does not exist. Because ofthis, oncologists are reluctant to use the term 'cure.' A definition of curefor cancer was first established in the 1970s, which proposed that cure existsfor disease-free survivors whose overall survival rate is similar to that of anage- and sex-related matched population(2). This concept first led to thefive-year survival rates becoming widely accepted as an indication of thesuccess of a cancer treatment. However, advances in treatments, earlier detection, and increasinginternational collaboration and data sharing have made the five-year survivalconcept obsolete for many cancers. A review of other genitourinary cancers(bladder cancer, testicular cancer, and renal cancer) by the researchersindicates that cure varies with tumour type and disease stage. They found, forexample, a five-year follow-up of patients with transitional cellmuscle-invasive bladder cancer treated with a combination of chemotherapy andradiation or surgery was insufficient as the survival curve has not yetflattened, and a follow-up period greater than five years to evaluate cure wasneeded due to the progression of invasive bladder cancer(3). Is it possible to 'cure' patients with poor-prognosis non-metastaticprostate cancer? The researchers reviewed survival data from four long-term, randomized,controlled clinical studies in men with non-metastatic, poor prognosis prostatecancer who received adjuvant hormonal therapy with goserelin following theirprimary treatment (radical prostatectomy or radiation therapy)(4),(5),(6),(7) .The researchers reviewed goserelin as it is the most widely researched LHRHaand is unique amongst LHRHas as it has been studied as an adjuvant therapy in anumber of randomized, controlled survival studies with a follow-up of more thanfive years. From these findings, the researchers assessed whether the potentialfor cure was achieved using an amended definition of cure specific to prostatecancer, defined as 1) when the disease-free survival curve flattens out after10-15 years following treatment and 2) when the overall survival rateapproaches that of an age-related healthy male population(1). Their findingsshowed 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 ofUrology and the American Society of Clinical Oncology treatment guidelines donot currently classify adjuvant hormonal therapy as being a potentiallycurative treatment. It is worth noting that generally similar long-term resultswith tamoxifen adjuvant to surgery in women with breast cancer led to this drugbeing classified as a treatment of curative intent. We believe that adjuvantgoserelin should be reclassified as a treatment of curative intent for patientswith poor prognosis, non metastatic prostate cancer." Notes to Editors About AstraZeneca: AstraZeneca is a major international healthcare business engaged in theresearch, development, manufacture and marketing of prescriptionpharmaceuticals and the supply of healthcare services. It is one of the world'sleading pharmaceutical companies with leading positions in gastrointestinal,oncology, cardiovascular, neuroscience and respiratory products. AstraZeneca islisted in the Dow Jones Sustainability Index (Global) as well as the FTSE4GoodIndex. 'ZOLADEX' is a trademark of the AstraZeneca group of companies. For more information visit: www.astrazenecapressoffice.com www.astrazeneca.com www.zoladex.com 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 SOURCE: AstraZeneca CONTACT: Peter Edwards, Prostate Franchise Global Brand PR Manager, AstraZeneca, +44-1625-232-685, Mobile: +44-7747-118-498; Rebecca Hibble, Cohn & Wolfe, Telephone: +44 207 331 5336, Mobile: +44 7813 096 161, [email protected] Web site: http://www.astrazeneca.com http://www.astrazenecapressoffice.com http://www.zoladex.com http://www.prostateline.com