183 The use of validated scoring systems to improve objective assessment of comorbid risk in men with localised prostate cancer

181

182

BICALUTAMIDE (‘CASODEX’) 150 MG AS ADJUVANT TO RADICAL PROSTATECTOMY SIGNIFICANTLY INCREASES PROGRESSIONFREE SURVIVAL IN PATIENTS WITH EARLY NON-METASTATIC PROSTATE CANCER: ANALYSIS AT A MEDIAN FOLLOW-UP OF 5.4 YEARS

BICALUTAMIDE (‘CASODEX’1 150 MG AS ADJUVANT TO RADIOTHERAPY SiGNIF1CANTi.Y IMPROVES PROGRESSION-FREE SURVIVAL IN EARLY NON-METASTATIC PROSTATE CANCER: RESULTS FROM THE BICALUTAMIDE EARLY PROSTATE CANCER PROGRAMME AFTER A MEDIAN 5.4 YEARS’ FOLLOW-UP

Wirth M.‘, Iversen P.2, McLeod D.3, See W.4, Morris C5, Morris T.5, Carroll K.5

McLeod

‘Technical University of Dresden, Department of Urology; Dresden, Germany, ‘University of Copenhagen, Department of Urology, Copenhagen. Denmark, 3Walter Reed Army Medical Centre, Department of Urology, Washington, United States, 4Medical College of Wisconsin, Department of Urology. Milwaukee, United States, 5Astrareneca, Department of Oncology, Global Clinical Development, Macclestield, United Kingdom

‘Walter Reed Army Medical Centre. Department of Urology, Washington, United States, ‘University of Copenhagen, Department of Urology, Copenhagen, Denmark, 3Medical College of Wisconsin, Department of Urology, Milwaukee, United States, 4Technical University of Dresden, Department of Urology, Dresden, Germany, 5AstraZeneca, Department of Oncology, Global Clinical Development, Macclesfield, Umted Kingdom

INTRODUCTION & OBJECTIVES: We report the results from the second protocolled analysis of the bicalutamide (‘Casodex’) Early Prostate Cancer (EPC) programme for patients (pts) who received radical prostatectomy (RP) as p rimary therapy. This subgroup includes pts with chnically localised disease, who were pathologically restaged as having locally advanced disease, as well as those with organ-confined disease at RF’.

INTRODUCTION & OBJECTIVES: The bicalutamide (‘Casodex’) Early Prostate Cancer (EPC) programme is evaluating bicalutamide 150 @day as adjuvant to standard care in patients cots) with localised or locallv advanced orostate cancer (Tl-4. MO. anv Ni. Protocolled analvsis at a mkdian 3 years’ (minimum 2 years) follow-up showed a s&&&t >2Oi reduction in the ;isk of objective disease progression for bicalutamide 150 mg compared with standard care alone (J Ural 2002; 168:429-35). Progression-free survival (PFS) was improved in the bicalutamide 150 mg group irrespective of primary therapy. A significant 37% reduction in the risk of progression occurred in pts who had received radiotherapy (RT) as primary therapy. Here we describe results of the second scheduled analysis for this pt group, after a median 5.4 years’ (minimum 4.5) follow-up.

MATERIAL & METHODS: The EPC programme consists of 3 prospective, double-bhnd, placebo-controlled clinical trials, and includes Xl 13 men with Tl-4, MO, any N prostate cancer. A total of 4454 pts received RP as standard care (bicalutamide, n=2236; placebo, “=221X). Primary endpoints are objective progression-free survival (PFS) and overall survival. The PFS endpoint includes objectively c&irmed progression (determined by ultrasound, MRI, CT or bone scan) or death from any cause. The hazard ratio (HR). the event-time ratio (ETR) (Carroll et al; Control Clin Trials [in press]) and the respective 95% confidence intervals (CI) were calculated. RESULTS: At a median 5.4 years’ follow-up, objective PFS was 19% longer in the bicalutamide 150 mg group compared with the placebo group (ETR 1.19,95% CI 1.04, 1.37). The reduction in risk of objective progression with bicalutamide 150 mg as adjuvant to RP was 20% (HR 0.80; 95% CI 0.68,0.95; p=O.O099). Overall, 251 RPpts (11.2%) randomised to bicalutamide 150 mg and291 RP pts random&d to placebo (13.1%) had objective disease progressloo. Exploratory subgroup analyses by disease stage showed that bicalutamide 150 mg significantly improved objective PFS specifically in RP pts with locally advanced disease, with a reduction in risk of objective progression of 29% (HR 0.71; 95% CI 0.57,0.89). There was no significant difference between the bicalutamide 150 mg and placebo groups with respect to objective PFS in pts with localised disease at this time (HR 0.93; 95% CI 0.72, 1.20). Survival data for the RP population are currently immature, with only 8% deaths. The tolerability profile of bicalutamide 150 mg was consistent with that reported at 3 years’ median follow-up in the first analysis; the most common adverse events in the overall trial population were gynaecomastia (68.3%) and breast pain (73.6%). CONCLUSIONS: At a median 5.4 years’ follow-up, lxcalutamide 150 mgiday significantly increases objective PFS in early non-metastatic prostate cancer pts who have received primaly RP, with those at higher risk of disease progression gaining most benefit. Bicalutamide 150 mg as adjuvant to RP offers pts wth clinically localised disease who are pathologically restaged with locally advanced disease a significant improvement in objective PFS. ‘Casodex’ is a trademark of the AstraZeneca group of companies.

OF VALIDATED SCORING SYSTEMS ASSESSMENT OF COMORBID RISK PROSTATE CANCER

Singh R.‘, Cahill D.‘; Pop&R.‘,

Beaney R.2, Wierzbicki

A.3, O’Brien

Strasser H. I, Marksteiner Bartsch G.‘, Hering S.2

MATERIAL & METHODS: A prospective study was started in May 200 1. All men 175 years of age diagnosed with localised prostate cancer at a single university hospital underwent a detailed comorbidity risk assessment, This included a comprehensive medical consultation, physical examination, blood pressure assessment, lipid profile (Total-cholesterol, LDLcholesterol, HDL-cholesterol, Triglycerides, Apolipoproteins); Lipoprotein A, high-sensitivity CRP and a 12.lead ECG. Cardiac specific indexes (Framingham, PROCAM) and general comorbid indexes (Charlsons combined ageicomorbidity score, Kaplain-Feinstein score) were then used to assess lo-year risk of major cardiac events and death from all cause respectively. RESULTS: 170 men < 75 years of age with localised prostate cancer were assessed. Median age was 65.5 years (range 40.75 years) and median PSAwas 8.3 “g/ml (range 0.7-55.0 “g/ml). 55% had abnormal DRE, 95% were diagnosed following biopsy and 5% following TURP 2%, 4%. 59%, 30%, 4% and 1% had Gleason grade 4, 5, 6, 7, 8, 9 respectively. Using Framingham 13%, 34%, 33% and 20% had a 30% lo-year risk of a major adverse cardiac event respectively. More than 50% of those with a Gleason score of 6 and 7 l&d a >20% risk of a major ahverse cardiac event over 10.years. Using PROCAM 41%. 39%. 13% and 7% of men less than or eaual to 65 wars of see had a <10°~, IO-20% 20-30& and’>30% IO-year risk of a major ad&e cardiac kvent respkctively. 16% of those v&h a Gleason score of 6 and 20% of those with a Gleason score of 7 had a >20% risk of a major adverse cardiac event over IO-year. Using Charlsons score 2%, 15%, 41%, 29%, 11% and 2% had a score of 0, 1, 2, 3, 4 and 5 respectively representing a low (Score 0), moderate (score l-2), high (score 3-4) and very high (score >4) lo-year risk Using KFI 28%, 59%, 12% and 1% had a score Of 0, 1, 2 and 3 respectively representing a low (score 0), moderate (score l), high (score 2), and very high (score 3) IO-year risk. CONCLUSIONS: Significant comorbid disease is very common in men with localised prostate cancer being considered for radical treatment. Using the Framingham index over 50% of men had a cardiac risk of >20% and using Charlsons score over 40% had a high risk of death from competing comorbid disease at IO-years.

Supplements

3 (2004)

No. 2, pp. 48

CONCLUSIONS: Bicalutamide 150 mg/day increases PFS in pts with early non-metastatic prostate cancer who have received primary RT, the greater benefit at this time is apparent in pts at higher risk of progression. ‘Casodex’ is a trademark of the AstraZeneca group of companies.

T.’

INTRODUCTION & OBJECTIVES: Development of Partins tables has allowed Urologists to make accurate predictions about the behaviour of localised prostate cancers. However predicting overall outcome and survival is not solely dependent on turnour characteristics. Comorbidity is also a vital determinant of outcome. Numerous -validated tools for accurate comorbidity assessment exist but have yet to be incomorated into routine uroloeical clinical uractice. We have exammed the role of these tools in the &sessment of men with lo&&d pros&e cancer under consideration for radical treatment.

Urology

RESULTS: Bicalutamide 150 mg adjuvant to RT significantly increased PFS by 26% (ETR 1.26; 95% CI 1.09, I .45) compared with placebo. The risk of disease progression with bicalutamide 150 mg as adjuvant to RT was significantly reduced by 28% (HR 0.72; 95% CI 0.59, 0.89; p=O.OOZ). Objective disease progression occurred in 1681699 (24%) pts randomised to bxalutamide 150 mg, compared with 19X/671 (29.5%) pts random&d to placebo. The benefits were particularly evident for RT pts with locally advanced disease, in whom bicalutarmde 150 mg significantly increased PFS by 53% (ETR 1.53; 95% CI 1.16, 2.02) compared with placebo. In this group, the risk of disease progression was reduced by 42% (HR 0.58; 95% CI 0.41, 0.84). In RT pts with localised disease, a 20% reduction in the risk of progression was obserwd with bicalutamide 150 mg compared with placebo (not significant: HR 0.80; 95% CI 0.62, 1.03). Analysis of overall sumival in RT pts showed no difference between treatment groups at 19% mortality (HR 0.95; 95% CI 0.74, 1.21). The most frequently reported side effects for bicalutamide 150 mg overall were gynaecomastia (68.3%) and breast pain (73.6%), consistent with the analysis carried out at 3 years.

TO IMPROVE IN MEN WITH

IGuys Hospital, Urolom, London, Umted Kmgdom, 2St Thomas Hospital, Oncology. London, United Kingdom, 3St Thomas Hospital, Chemical Pathology, London, United Kingdom

European

MATERIAL & METHODS: Primary endpoints include survival and PFS (progression confirmed by ultrasound, MRI. CT or bone scan; or death from any cause). Hazard ratio (HR) and event-time ratio (ETR) (Carroll et al; Control Clin Trials [m press]) were calculated with 95% confidence intervals (CI). A total of 8113 pts were recruited, of whom 1370 received RT as primaly therapy.

SUI: TREATMENT TOMORROW AND TODAY Thursday, 25 March, 13.45-15.15, Hall I-W Blue level STEM CELL THERAPY IN TREATMENT OF NENCE: FIRST CLINICAL RESULTS

183 THE USE OBJECTIVE LOCALISED

D.l, Iversen P.2, See W.3, Wirth M.4, Carroll K.5, Morris C.5, Morris T.5

Pll

‘University Innsbruck, Innsbruck,

R.2,

Margreiter

E.Z,

of Irmsbtuck, Department of Urology, Institute for Biochemical Pharmacology, Department of Radiology II, Innsbruck,

INTRODUCTION

& OBJECTIVES:

of urinary incontinence by means preclinical studies. In a first clinical were treated with sonographically myoblasts and fibroblasts.

184 URINARY

Frauscher

Innsbruck, Innsbruck; Austria

INCONTI-

F.3, Pinggera

Austria, Austria,

G-M.l,

2University 3University

of of

In the last years the prerequisites for treatment of autologous stem cells have been gathered in study patients suffering from urinary incontinence guided transurethral injections of autologous

MATERIAL & METHODS: Between September 2002 and September 2003 10 patients (7 women, 3 men after radical prostatectomy) suffering from urinary stress incontinence were treated (age: 36-78 years). Before and after therapy a defined incontinence score, changes in quality of life as well as morphology and function of urethra and rhabdosphincter were evaluated. Transurethral ultrasound and threedimensional ultrasound were used to investigate the lower urinary tract. Furthermore, urodynamic and laboratory tests were performed pre- and postoperatively. The myoblasts and fibroblasts were cultured under GMP (“good manufacturing practice”) conditions. Quality of cells was evaluated and documented prior to injection. The fibroblasts were mixed with collagen and injected into the urethral submucosa to treat atrophies of the mucosa. The myoblasts were directly injected into the rhabdosphincter to treat morphological and functional defects and to reconstruct the muscle. RESULTS: In 8 patients (all 7 women, 1 man) urinary incontinence was completely cured after injection of stem cells. None of these patients needed to wear pads. Quality of life was dramatically improved postoperatively. Thickness of urethra and rhabdosphincter as well as contractility of the rhabdosphincter was increased significantly after therapy. In ultrasound it could be shown that the injected myoblasts were completely integrated into the rhabdosphincter. In 2 male patients who had to undergo radiotherapy and internal urethrotomy after radical prostatectomy symptoms were markedly improved in 1 and improved in the second patient. CONCLUSIONS: The first clinical data clearly demonstrate that urinary incontinence can be treated effectively by means of autologous stem cells. The present data support the conclusion that this new therapeutic concept may represent a very promising treatment modality to cure urinary incontinence.