Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial

BACKGROUND: Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone.

METHODS: Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m(2)) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544).

FINDINGS: 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60-71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23-184). Median follow-up was 43 months (IQR 30-60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC + ZA (HR 0·94, 95% CI 0·79-1·11; p=0·450), 81 months (41 to not reached) for SOC + Doc (0·78, 0·66-0·93; p=0·006), and 76 months (39 to not reached) for SOC + ZA + Doc (0·82, 0·69-0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3-5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC + ZA, 288 (52%) receiving SOC + Doc, and 269 (52%) receiving SOC + ZA + Doc.

INTERPRETATION: Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy.

FUNDING: Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network, Swiss Group for Clinical Cancer Research.

A Concert of 17th and 18th Century Music, November 16, 1953

Concert Program for A Concert of 17th and 18th Century Music, November 16, 1953

Información estadística sobre embarcaciones utilizadas en la pesca industrial en el Perú 1953 -1962

Estadística del desarrollo de la flota pesquera en el Perú por un periodo de 10 años y a través del tipo de pesca, clases de eslora y puertos de inscripción. Los informes más detallados corresponden al año 1961 y 1962, donde la flota empleada para cada tipo de pesca industrial fue agrupada en clases de eslora y puertos de inscripción para la flota nacional y por puertos de desembarqué, para las embarcaciones de bandera extranjera. Solamente algunos cuadros se han hecho con indicadores analíticos para demostrar la estructura de la flota bolichera

Reporte de datos sobre índices de afloramiento y turbulencia diarios para Trujillo y Callao, Perú, 1953-1985

Se presentan los índices de afloramiento y turbulencia para Trujillo (08º06'S) y Callao (12°00'S) durante 1953-85. Estos están basados en el cálculo de transporte Ekman y la intensidad al cubo usando datos de dirección y velocidad de viento registrados en los aeropuertos de las mencionadas localidades.

Abundancia de aves guanera y su relación con la pesquería de anchoveta peruana de 1953 a 1999

Se actualizaron las series de tiempo sobre las poblaciones de guanay Leucocarbo bougainvillii, piquero peruano Sula variegata y pelícano peruano Pelecanus thagus entre 1953 y 1999. El desarrollo de la pesquería industrial de anchoveta a inicios de los años 50, significó un cambio en la dinámica poblacional de las aves guaneras. A partir de El Niño 1965, que causó una mortandad del 76%, reduciendo 17 millones de aves guaneras a sólo alrededor de 4, ellas no han recuperado sus más altos valores poblacionales, alcanzados antes del desarrollo de la pesquería industrial. Sin embargo, la tendencia a un paulatino crecimiento de la población de las aves guaneras, registrado a partir de 1983, fue afectado drásticamente por El Niño 1997-98. Hacia finales de 1999, se ha observado una progresiva recuperación de las colonias de estas especies en todas las islas y puntas, pero permanecen muy por debajo de los tamaños alcanzados antes de El Niño 1997-98. Se ha sugerido que el alimento es la principal causa de la regulación poblacional de las aves marinas, y estudios recientes muestran que la disponibilidad de presas actúa como un factor limitante en el tamaño de las poblaciones reproductoras. La reducción de áreas adecuadas para la reproducción de las aves guaneras, debido a una creciente perturbación humana, podría también restringir el crecimiento de sus poblaciones.

Algunos resultados de las anillaciones de Guanay (Phalacrocorax bougainvillii L.) efectuados durante 1939-1941 y 1949-1953

Proporciona información sobre el guanay, ave guanera, que es estudiado para determinar su proceso de anidación y la influencia que tiene en la producción del guano en todo el litoral peruano. Realizan una técnica de marcación de ejemplares para hacerles seguimiento en el periodo de los años 1939 a 1953.

Speech of Com. Jesse Duncan Elliott, U.S.N. delivered in Hagerstown, Md. on 14th November, 1843.-

Published by the Committee of Arrangement of Washington County, Maryland.

Speech of Com. Jesse Duncan Elliott, U.S.N. delivered in Hagerstown, Md. on 14th November, 1843

Published by the Committee of Arrangement of Washington County, Maryland Printed by G.B. Zeiber and Co.

Niagara Falls Bridge Commission Scrapbooks, 1941-1948, 1953-1963, 1965-1974

The Niagara Falls Bridge Commission was created by a joint resolution of the 1938 U.S. Congressional Third Session. The Extra Provincial Corporations Act of Ontario, Canada licenses the Niagara Falls Bridge Commission. Canada and the United States are equally represented on the Commission by an 8 member Board of Commissioners. Canadian commissioners are appointed by the Premier of Ontario. The three Niagara bridges are the Whirlpool Bridge, the Lewiston-Queenston Bridge and the Rainbow Bridge. Source:http://niagarafallsbridges.com/index.php3

Barnes Wines Fonds

4 Minute Books dated: 1880, 1892, 1901, 1934, 1948-1950, 1952-1953, 1955, 1958, 1962 – 1975, 1981, 1984, 1986; 3 Common stock books dated: 1934-1935, 1937-1941, 1946, 1948-1950, 1955-1956, 1958, 1961-1974, 1981 and 2 Class A stock books dated:1948 - 1951

Proceedings of the Grand Chapter of Royal Arch Masons of Canada at the annual convocation, 1953

Annual Convocation proceedings for the year 1953. The title varies slightly and convocation held at different cities or towns in Canada. Ninety-fifth annual convocation.

Invitation - Presentation Party in the Garden of Buckingham Palace, 1953

An invitation to an "Afternoon Presentation Party in the Garden of Buckingham Palace on Thursday 28th May 1953 from 4 to 6 o'clock". The invitation is to Mr. and Mrs. Arthur Schmon and lists dress attire for ladies and gentlemen.