PMID- 20818862 OWN - NLM STAT- MEDLINE DCOM- 20100910 LR - 20231120 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 363 IP - 5 DP - 2010 Jul 29 TI - Sipuleucel-T immunotherapy for castration-resistant prostate cancer. PG - 411-22 LID - 10.1056/NEJMoa1001294 [doi] AB - BACKGROUND: Sipuleucel-T, an autologous active cellular immunotherapy, has shown evidence of efficacy in reducing the risk of death among men with metastatic castration-resistant prostate cancer. METHODS: In this double-blind, placebo-controlled, multicenter phase 3 trial, we randomly assigned 512 patients in a 2:1 ratio to receive either sipuleucel-T (341 patients) or placebo (171 patients) administered intravenously every 2 weeks, for a total of three infusions. The primary end point was overall survival, analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum prostate-specific antigen (PSA) and lactate dehydrogenase. RESULTS: In the sipuleucel-T group, there was a relative reduction of 22% in the risk of death as compared with the placebo group (hazard ratio, 0.78; 95% confidence interval [CI], 0.61 to 0.98; P=0.03). This reduction represented a 4.1-month improvement in median survival (25.8 months in the sipuleucel-T group vs. 21.7 months in the placebo group). The 36-month survival probability was 31.7% in the sipuleucel-T group versus 23.0% in the placebo group. The treatment effect was also observed with the use of an unadjusted Cox model and a log-rank test (hazard ratio, 0.77; 95% CI, 0.61 to 0.97; P=0.02) and after adjustment for use of docetaxel after the study therapy (hazard ratio, 0.78; 95% CI, 0.62 to 0.98; P=0.03). The time to objective disease progression was similar in the two study groups. Immune responses to the immunizing antigen were observed in patients who received sipuleucel-T. Adverse events that were more frequently reported in the sipuleucel-T group than in the placebo group included chills, fever, and headache. CONCLUSIONS: The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer. No effect on the time to disease progression was observed. (Funded by Dendreon; ClinicalTrials.gov number, NCT00065442.) FAU - Kantoff, Philip W AU - Kantoff PW AD - Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. philip_kantoff@dfci.harvard.edu FAU - Higano, Celestia S AU - Higano CS FAU - Shore, Neal D AU - Shore ND FAU - Berger, E Roy AU - Berger ER FAU - Small, Eric J AU - Small EJ FAU - Penson, David F AU - Penson DF FAU - Redfern, Charles H AU - Redfern CH FAU - Ferrari, Anna C AU - Ferrari AC FAU - Dreicer, Robert AU - Dreicer R FAU - Sims, Robert B AU - Sims RB FAU - Xu, Yi AU - Xu Y FAU - Frohlich, Mark W AU - Frohlich MW FAU - Schellhammer, Paul F AU - Schellhammer PF CN - IMPACT Study Investigators LA - eng SI - ClinicalTrials.gov/NCT00065442 GR - P30 CA008748/CA/NCI NIH HHS/United States PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 0 (Androgen Antagonists) RN - 0 (Antineoplastic Agents) RN - 0 (Cancer Vaccines) RN - 0 (Tissue Extracts) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - 8Q622VDR18 (sipuleucel-T) SB - IM CIN - N Engl J Med. 2010 Jul 29;363(5):479-81. PMID: 20818868 CIN - N Engl J Med. 2010 Nov 11;363(20):1966; author reply 1967-8. PMID: 21067392 CIN - Expert Rev Anticancer Ther. 2011 Jan;11(1):25-8. PMID: 21166508 CIN - Cancer Biol Ther. 2014 Oct;15(10):1299-300. PMID: 25046606 MH - Aged MH - Aged, 80 and over MH - Androgen Antagonists/therapeutic use MH - Antigen-Presenting Cells MH - Antineoplastic Agents/therapeutic use MH - Cancer Vaccines/adverse effects/*therapeutic use MH - Cell Culture Techniques MH - Combined Modality Therapy MH - Disease Progression MH - Double-Blind Method MH - Humans MH - *Immunotherapy/adverse effects MH - Infusions, Intravenous MH - Intercellular Adhesion Molecule-1/adverse effects/*therapeutic use MH - Kaplan-Meier Estimate MH - Male MH - Middle Aged MH - Proportional Hazards Models MH - Prostatic Neoplasms/drug therapy/mortality/*therapy MH - Tissue Extracts/adverse effects/*therapeutic use FIR - Ahmed, T IR - Ahmed T FIR - Amin, A IR - Amin A FIR - Arseneau, J IR - Arseneau J FIR - Barth, N IR - Barth N FIR - Bernstein, G IR - Bernstein G FIR - Bracken, B IR - Bracken B FIR - Burch, P IR - Burch P FIR - Caggiano, V IR - Caggiano V FIR - Chin, J IR - Chin J FIR - Chodak, G IR - Chodak G FIR - Chu, F IR - Chu F FIR - Corman, J IR - Corman J FIR - Curti, B IR - Curti B FIR - Dawson, N IR - Dawson N FIR - Deeken, J F IR - Deeken JF FIR - Dubernet, T IR - Dubernet T FIR - Fishman, M IR - Fishman M FIR - Flanigan, R IR - Flanigan R FIR - Gailani, F IR - Gailani F FIR - Garbo, L IR - Garbo L FIR - Gardner, T IR - Gardner T FIR - Gelmann, E IR - Gelmann E FIR - George, D IR - George D FIR - Godfrey, T IR - Godfrey T FIR - Gomella, L IR - Gomella L FIR - Guerra, M IR - Guerra M FIR - Hall, S IR - Hall S FIR - Hanson, J IR - Hanson J FIR - Israeli, R IR - Israeli R FIR - Jancis, E IR - Jancis E FIR - Jewett, M A S IR - Jewett MA FIR - Kassabian, V IR - Kassabian V FIR - Katz, J IR - Katz J FIR - Klotz, L IR - Klotz L FIR - Koeneman, K IR - Koeneman K FIR - Koh, H IR - Koh H FIR - Kratzke, R IR - Kratzke R FIR - Lance, R IR - Lance R FIR - Lech, J IR - Lech J FIR - Leichman, L IR - Leichman L FIR - Lemon, R IR - Lemon R FIR - Liang, J IR - Liang J FIR - Libertino, J IR - Libertino J FIR - Lilly, M IR - Lilly M FIR - Malik, I IR - Malik I FIR - Martin, S E IR - Martin SE FIR - McCaffrey, J IR - McCaffrey J FIR - McLeod, D IR - McLeod D FIR - McNeel, D IR - McNeel D FIR - Miles, B IR - Miles B FIR - Murdock, M IR - Murdock M FIR - Nabhan, C IR - Nabhan C FIR - Nemunaitis, J IR - Nemunaitis J FIR - Notter, D IR - Notter D FIR - Pantuck, A IR - Pantuck A FIR - Perrotte, P IR - Perrotte P FIR - Pessis, D IR - Pessis D FIR - Petrylak, D IR - Petrylak D FIR - Polikoff, J IR - Polikoff J FIR - Pommerville, P IR - Pommerville P FIR - Ramanathan, S IR - Ramanathan S FIR - Rarick, M IR - Rarick M FIR - Richards, J IR - Richards J FIR - Rifkin, R IR - Rifkin R FIR - Rohatgi, N IR - Rohatgi N FIR - Rosenbluth, R IR - Rosenbluth R FIR - Santucci, R IR - Santucci R FIR - Sayegh, A IR - Sayegh A FIR - Seigne, J IR - Seigne J FIR - Shapira, I IR - Shapira I FIR - Shedhadeh, N IR - Shedhadeh N FIR - Shepherd, D IR - Shepherd D FIR - Sridhar, S IR - Sridhar S FIR - Stephenson, R IR - Stephenson R FIR - Teigland, C IR - Teigland C FIR - Thaker, N IR - Thaker N FIR - Vacirca, J IR - Vacirca J FIR - Villa, L Jr IR - Villa L Jr FIR - Vogelzang, N IR - Vogelzang N FIR - Wertheim, M IR - Wertheim M FIR - Wolff, J H IR - Wolff JH FIR - Wurzel, R IR - Wurzel R FIR - Yang, C IR - Yang C FIR - Young, J IR - Young J EDAT- 2010/09/08 06:00 MHDA- 2010/09/11 06:00 CRDT- 2010/09/08 06:00 PHST- 2010/09/08 06:00 [entrez] PHST- 2010/09/08 06:00 [pubmed] PHST- 2010/09/11 06:00 [medline] AID - 10.1056/NEJMoa1001294 [doi] PST - ppublish SO - N Engl J Med. 2010 Jul 29;363(5):411-22. doi: 10.1056/NEJMoa1001294.