Re: Effect of dutasteride on the risk of prostate cancer

[Guest guest]

Sammy

I would agree that the stats are not wholly convincing, but it looks worth more investigation to me, after all the drug is better than without

B

Effect of dutasteride on the risk of prostate cancer

I don't think I have ever seen so many writers and collaboratros listed in a single study before. Beneath all the verbiage is a single statement that stands out:-During years 3 and 4, there were 12 tumors with a Gleason score of 8 to 10 in thedutasteride group, as compared with only 1 in the placebo group (P=0.003).Can someone please tell me why this snake-oil is being flogged by so many people who should know better ? My understanding is that the 'square' androgen causes - castration cures

paradigm is being mindlessly pounded into a 'round' evidence base that is saying androgen is good for you.It is the finasteride story being repeated even louder. Right from 1998 the signs were that 5-alpha reductase inhibitors would cause some precancerous states to progress to prostate cancer much more quickly than 'doing nothing'. The stand I have taken on this issue in PC21 is thoroughly exonerated.I just wish that research would take the right turn now. Give us a sign that prostate cancer science is above boardroom bullying.Sam.http://fitcare.org.uk/P.S. The book is now selling for $21N Engl J Med. 2010 Apr 1;362(13):1192-202.Effect of dutasteride on the risk of prostate cancer.Andriole GL, Bostwick DG, Brawley OW, Gomella LG, Marberger M, Montorsi F,Pettaway CA, Tammela TL, Teloken C, Tindall DJ, Somerville

MC, TH, Fowler IL, Rittmaster RS; REDUCE Study Group.Collaborators: Bogado H, Borghi M, Casabé A, eda R, Kobelinsky M, Mazza O,Metrebián S, Villaronga A, Costello A, Gardiner RF, Love C, Lynch WJ, Millard R, Nicol D, Stricker P, Sutherland P, Woo H, Wood S, Yaxley J, Bartsch G, Marberger M, Schmidbauer C, Studler G, Gres A, Strockyi A, Ackaert K, Boeckx G, Naudin M,Oosterlinck W, Roumeguère T, Schulman C, Tombal B, Van Erps P, Van Poppel H, Van Velthoven R, Vossaert P, Abdo JA, Atta G, Chaves O, Damião R, Koff W, Saber G,Telöken C, androv E, Mladenov D, Neykov K, Panchev P, Petkova L, Saltirov I, L, Abara E, Abramovitch A, Andreou C, Barkin J, Bell D, Bryniak S, Casey R,Chetner M, Cronje D, Dagenais L, Di Costanzo G, Egerdie RB, Eiley D, Flax S,Fleshner N, Gleave M, Goldfarb B, Jansz GK, Kinahan T, Klotz L, Kuzmarov I,Lacombe L, Lee J, Liquornik M, Love W, Maillete A,

B, Nickel JC, Okafo B, Paradis JB, A, Pliamm L, Pommerville P, Saad F, Simard J, Steinhoff G,Tanguay S, Tessier J, Valiquette L, Velji A, Zadra J, Huidobro Alvarado C, LiraLueje M, Orellana N, Salazar A, Kraus O, Kjaer TB, Mommsen S, Nordling J, ArpoHE, Zirel U, Hellstrom P, Isotalo T, Kauppinen R, Laato M, Leppilahti M,Lukkarinen O, Permi J, Petas A, Rauvala M, Salo J, Taari K, Tammela T, TuhkanenK, Al Youssef J, Allard P, Alno L, Ayed M, Baron JC, Benraid N, Billebaud T,Bittard H, Bladou F, Boccon-Gibod L, Bocquillon V, Bothorel P, Botto H, BoutinJM, Brunet P, Cadi PO, Chebil M, Colombel M, Colomes G, Defourmestraux N,Descamps F, Desgrandchamps F, Devonec M, Dufeuil P, Horchani A, Hurel JP, Iborra F, Ibrahim H, Lamotte F, Lan O, Le Portz B, Lepelley M, Lesur P, Levigne F,Loulidi S, Marc B, Masson J, Mege JL, Mhiri MN, Monod P, Mosbah AT, Mottet N,Pagès A, G, Rabut B, Rischmann P, Soton G,

Teillac P, Tremeaux JC, Turblin JM, Valton M, Villamizar J, Villena P, Villers A, Younes E, Bakir S, Bauer HW,Bauer L, Behrendt U, Benedic M, Benush T, Berberich H, Berse M, Binder M,Bischoff W, Bluemlein HM, Boehle A, Boergmann H, Bohnenkamp A, Boness J, BrandsF, Braun HC, Bruns T, Bruske T, Buecherl R, Decker M, Degen S, Demmler I,Dierkopf W, Dubiel J, Eckert R, Eichler U, Farahmandi R, Fehsel F, enau P,Fuhrberg J, Girke C, Glass M, Gleissner J, Graf C, Gratzke P, Groeschel P, HaasW, Hagel WC, Hamann M, Hechelmann W, Heidrich A, Heisler M, Helmbrecht J, HenkeG, Henschel T, Hentschke T, Herrmann B, Herrmann K, Herzig J, Himstedt HW, Hofer J, Hoffmann M, Hollberg H, Hübner A, Hudemann B, i G, Jansen H, Johann KU,Karras R, Karstedt H, Keipert D, Kellner T, Kennerknecht M, Kern J, Klammert R,Köferl F, Konert J, Köttig T, Kriegmair M, Kube U, Kublanck A, Kuehne A, KuetgensP, Kühn SH, Kühne F,

Kunz J, Kutscher KR, Kwela M, Laag R, Langer KC, LanghorstW, Laval KU, Leonhard W, Lock UC, Lunz C, Malsy-Mink P, Marin J, Markow M, MassekF, Matz U, Meisel J, Mertins B, Michel W, Miersch WD, Mohr S, Müller B, Müller D,Müller H, Mumperow E, Münch A, Nette U, Netzer M, Neubauer H, Nietzsch D, OstwaldR, Pauthner H, Petry A, Pielmeier T, Plate H, Ploss HJ, Quack T, Quast D,Radlmaier M, Radulescu M, Rehm B, Renner P, Rollenhagen AR, Romitan-Baum R, RompfM, Rothe P, Rotter C, Rüssel C, Rüth J, Sablotny J, Schachschneider H, SchäningM, Schaub W, Scheffler M, Scheunpflug K, Schewe J, Schlichter A, Schmidt JJ,Schmidt PS, Schneider B, Schneider J, Schneider T, Schreieer H, Schroeder A,Schrötter U, Schulz T, Schulze M, Schwegmann A, Simson G, Sippel F, Solga M,Speck T, Stahl HD, Surrey HW, Szymula S, Telle J, S, Uellendahl K, UmbreitO, Unger U, von Keitz A, von Kügelgen T, von Ostau C, Wächter S,

Walter T,Warnack W, Weck B, Weitz P, Weizert P, Wengler R, Willgerodt J, Winter M, WurschiM, Zellner M, Ziegner D, Ziemacki A, Zillmann R, Zürner T, Barbalias G,Hatzichristou D, Kalafatis P, Karanastasis D, Katsifotis H, Kokotas N, Liatsikos E, Malovrouvas D, Margaritopoulou A, Melekos M, Poulias I, Salpigidis G,Sofikitis N, Sofras F, Touloupidis S, Tsidavis A, Fehér J, Kisbenedek L, RomicsI, Fitzpatrick J, McDermott TE, Sweeney P, Bercovich E, Caggiano S, D'Armiento M,DiSilverio F, La P, Manieri C, Mensi M, Montrosi F, Motta M, Pagliarule A,Pecoraro G, Raciti G, Selli C, Usai E, Usai P, Akaza H, Nakatsu H, Sagiyama K,Sakai H, Sakamoto S, Tsukamoto T, Dale R, Gilis D, Gordins S, Hohlovs A, Karulis A, Vjaters E, Bekeris T, Cerniauskiene A, Gaizauskas S, Jankevicius F, Jievaltas M, Palaikiene Z, Stakenas A, Ulys A, Calderon Ferro F, Calvo-Domínguez D,Carvajal-García R, Feria-Bernal G, Lugo-Nevarez

MA, Manzanilla- HA,Martínez-Castro MA, Pacheco-Gahbler C, - JA, Barten EJ, Blitz W,Cornel EB, de Bruin MJ, de Lange DC, Kil PJ, Koldewijn EL, Kropman RF, Kupfer HW,Leenarts JA, Mulders PF, Schrier BP, Schröder FH, Timmer EC, van Andel G, VanAubel OG, van Balken MR, van Berkel JT, van Haarst EP, van Vierssen T, Oncko B,Vergunst H, Vijverberg PL, Bary P, son P, Gilling P, Meffan P, Nixon T,Tuckey J, Andersen M, Beisland HO, Bjerklung J, Truls E, Hoeg OM, Øgreid P,Omland H, Borkowski A, Duda W, Galezia M, Jarzemski P, Kwiatkowski S, Meller J,Mikszewica A, Niezabitowski J, Roslan M, Sikorski A, Sokolowski J, Szkarlat K,Tereszkiewicz J, Pinheiro JC, Pinheiro LC, de Oliveira AF, Días JR, Gomes C,Guimarães M, Ferreira AM, Monteiro H, Pires MB, Rolo F, Morales-Ramírez JO,Ambert V, Bina MN, Calomfirescu N, Aljaev Y, Al-Shukri S, Apolikhin O, GorilovskyL, Grigoriev M, Krupin V,

Lopatkin N, Mazo E, Petrov S, Shaplygin L, Breza J,Kliment J, Bizjak I, Kisner K, Sedmak B, Vodopija N, Bongers M, Glocer J,Haffejee M, Harden P, Heyns C, Mackenzie T, Reif S, Van der Walt JS, Webb G,Astobieta A, Azparren J, Benejam J, Cabezudo I, Castiñeiras J, Chéchile TonioloG, Cuya L, Díaz JL, Franco E, Gallego Sánchez JA, Galvis Palau F, MatresMJ, García Pérez M, Gelabert Mas A, Gimeno Collado A, Hevia Suarez M, KilaniElmasri S, Llorente C, López Alcina E, -Alda A, Lorente Garin JA, MoralesAM, ez Javaloyas J, ez-Sagarra Oceja JM, -Marquina Aspiunza A, Montesino M, Morales A, Morote J, Mouaffak N, Nogueras MA, Paños Lozano P, Pedro, Pastor Sempere F, P, Romero J, Saladie JM, Chapado M,Sanz Jaca JP, Serrallach Milá N, Silmi Moyano A, Solsona E, Tallada Buñuel M,Teba del Pino F, Unda Urzaiz M, Villavicencio H, Zaragoza J, Damber JE,

FolmerzP, Gedda S, Magnusson B, Norming U, Paradis A, Pileblad E, Sandin T, Schain M,Stattin P, Ströberg P, Wagrell L, Waldén M, Mauritz, Wang YH, Willén M, Eberle J,Eigenmann J, Gunst M, Gygi C, Heering F, is WE, Mottax A, Recker F, RochatCH, Trinkler F, Akdas A, Atan A, Ozcan F, Ozen H, Abdulhakim E, Akhtar M, C, D, P, Chinegwundoh F, Cole O, Cumming J, Donnachie H,Emberton M, Fraser J, Gillatt D, V, Govindraj S, Hamilton G, Hehir M,Jaganathan R, Jassel G, Javle PM, Kaisary A, Kanagasundaram S, Khursheed M, LeungH, Liu S, MacDermott J, Maroni J, R, Matanhelia SS, McClinton S, McFarlaneJ, McInerney P, McNeill SA, Mc T, Meddings R, Mellon J, P,O'Reilly P, A, Pavel I, Pawa R, Perrapato S, Persad R, Philp T, Pickard R,Pttman W, Pitts C, Pocock R, Puri R, Raja A, Rao P, J, J, SaeedI, Salman M, Sarmiento R, Schwaibold H,

Sethia K, Sharma N, Shaw H, Speakman M, S, H, Lesovoy V, G, Altman D, Andriole G, Apaydin A, Aronson W, Auerback S, Baier C, Bailen J, Baker W, Bannow J, Bardot S, Barham R, Barkley C, Barnswell C, Basler J, Bass J, Baum N, Baumann L, Beam T, Belkoff L, Benaim E,Benitez O, Bergner D, Bergreen P, Bernstein G, Bernstein M, Bidair M, Blath R,Bobrowski J, Bock D, Bondhus M, Bowling B, Bracken RB, Brawer M, Brodak P, BrokerR, S, Brosman S, Brown D, Brown G, Brown J, Bruno D, K, BundrickWS, Burke WR, Camps J Jr, Capo J Jr, Castellanos R, Chang S, Childs S, Ching V,Chinn S, Chiou R, Chiura A, Chodak G, Chu F, Chung S, R, W, CochranJ, Cohen J, Cohen S, Cole F, Concepcion R, Cook D, Corman J, Corral D, Costa F,Cowan B, Coyle C, Crawford D, Cudecki J, s M, B, DeFelippo JD,Deichmann R, Diener C, Diokno A, Drehobl M, Dula E, Edelman R, , Ellis D,Ellis W,

Eure G, Fay R, Fei R, Feldman R, Finkbeiner A, Fishman R, Fitch W,Forrest J, Freedberg P, Freedman S, Freeman J, Fromang D, Galdieri L, Gange S,Gardner T, Garvin D, Gassner L, Gaylis F, Gburek B, Gerber G, Gershman A,Ghavamian R, Gill H, Gittelman M, Gleason D, Gluckman G, Godschalk M, Goldberg K,Green B, Greene G, Greengold R, Grubb R 3rd, Grubman J, Guice S, Hagan M, Hagood P, Hamad M, Hamway S, Harkaway R, Harper W, R, Hatcher P, R,Hertzman B, Hey W, Hezmall H, Hollowell C, Hoppmann H, Houser E, Hudnall C,Husain A, Igel T, Iliades C, Immergut M, Isen J, Israeli R, Jablonski D, J, Kaempf M, Kaminetsky J, Kane R, Kaplan M, Kaplinsky R, Karlin G, Karsh L, KatzPG, Kauder D, Kaufman J, Kaufman R, Keanne T, Killorin W, Kistein S, King E,Kleer E, Klimbert I, Klorfein E, Kornitzer G, Koukol S, Kriteman L, Kronhaus R,Lasky R, Lawton S, Levine M, Liberman S, Libin M, Lieber M, Lieberman M,

LipkisD, Lipsitz D, Lochner J, Lubin B, Lugg J, Lynch D, Macaluso J Jr, Maggiacomo F,Mandel E, Manion S, Marks J, Marks L, Mason T, McLeod D, McMurray J, Mehlhaff B, Mellinger B, Menashe D, D, Mirelman S, Mitcheson H, Mobley D, Modarelli R,Mollen M, Monath JR, Monnig W, J, Morgenstern J, Moseley W, Murdock M, G, Myers R, Naslund M, J, Neustein P, Niku S, O'Leary M, O'ReillyK, Oselinksky D, Parham R, Parr G, Parries G, Parulkar B, Passarella M, Pathroff R, T, A, Pettaway C, Pinto A, Price V, Puopolo A, Rainwater L,Ralph L, Ramos C, Rapo S, Ray P, D, Reese C, Riff D, Ritter H Jr, B,Roehrborn C, Roper R, Saslawsky M, Sawczuk I, Schiff W, Schwartz E, Sharifi R,Shinohara K, Sidhorn A, Sieber P, Sigman D, Singh E, Sipio J, Slaski A, Slawin K,Slutsky J, Snyder J, Spigner D, Spirnak J, Stallings J, Steidle C, Stein B, StoutD, Streisand S, Teigland C,

D, Thrasher JB, Threatt C, P,Tomasic N, Tomera K, Torgerson E, Tortora F, Tremann J, Troia P, Tutrone R,Twidwell J, Usow B, Utz W, Van Cleef M, Wachs B, Walther P, Walton J, Wei D, WestJ Jr, White CF, Whiting J, Whitlock N, Wiatrak ML, Wieskopf B, Wurzel R, YavariM, Yeoman G, Young J, Young J, Zacharias A, Zagula JZ, Zinner N, Zusman E.Division of Urology, Washington University School of Medicine in St. Louis, St.Louis, MO 63110, USA. andriolegwustl (DOT) eduComment in: N Engl J Med. 2010 Apr 1;362(13):1237-8.BACKGROUND: We conducted a study to determine whether dutasteride reduces therisk of incident prostate cancer, as detected on biopsy, among men who are atincreased risk for the disease. METHODS: In this 4-year,

multicenter, randomized,double-blind, placebo-controlled, parallel-group study, we compared dutasteride, at a dose of 0.5 mg daily, with placebo. Men were eligible for inclusion in thestudy if they were 50 to 75 years of age, had a prostate-specific antigen (PSA)level of 2.5 to 10.0 ng per milliliter, and had had one negative prostate biopsy (6 to 12 cores) within 6 months before enrollment. Subjects underwent a 10-coretransrectal ultrasound-guided biopsy at 2 and 4 years. RESULTS: Among 6729 menwho underwent a biopsy or prostate surgery, cancer was detected in 659 of the3305 men in the dutasteride group, as compared with 858 of the 3424 men in theplacebo group, representing a relative risk reduction with dutasteride of 22.8%(95% confidence interval, 15.2 to 29.8) over the 4-year study period (P<0.001).Overall, in years 1 through 4, among the 6706 men who underwent a needle biopsy, there were 220 tumors with a Gleason score of 7 to 10 among 3299 men in thedutasteride group and 233

among 3407 men in the placebo group (P=0.81). Duringyears 3 and 4, there were 12 tumors with a Gleason score of 8 to 10 in thedutasteride group, as compared with only 1 in the placebo group (P=0.003).Dutasteride therapy, as compared with placebo, resulted in a reduction in therate of acute urinary retention (1.6% vs. 6.7%, a 77.3% relative reduction). The incidence of adverse events was similar to that in studies of dutasteride therapyfor benign prostatic hyperplasia, except that in our study, as compared withprevious studies, the relative incidence of the composite category of cardiacfailure was higher in the dutasteride group than in the placebo group (0.7% [30men] vs. 0.4% [16 men], P=0.03). CONCLUSIONS: Over the course of the 4-year studyperiod, dutasteride reduced the risk of incident prostate cancer detected onbiopsy and improved the outcomes related to benign prostatic hyperplasia.(ClinicalTrials.gov number, NCT00056407.) 2010 Massachusetts Medical SocietyPMID: 20357281

[Guest guest]

> Sammy I would agree that the stats are not wholly convincing,

> but it looks worth more investigation to me, after all the

> drug is better than without

Sammy sez that " it's the finasteride story all over again. "

So far as he goes, I agree.

The truth of the finasteride matter was that the increase of PCa

was " an artifact " of the reduction in size of the gland, and not

a true increase.

So I recall.

Regards,

Steve J