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.)

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Sipuleucel-T immunotherapy for castration-resistant prostate cancer.

https://www.europeanurology.com/article/S0302-2838(07)01145-1/pdf/eau-guidelines-on-prostate-cancer

EAU guidelines on prostate cancer

INTRODUCTION The postmortem observations of Green, published in the Lancet in 1836, were the fi rst to describe the distinct pathological features of tuberculous meningitis and set it apart from the other recognised causes of ‘acute hydrocephalus’ (Green 1836). The challenge for the physician then lay in distinguishing the disease before death, and delivering the grave prognosis. Thomas Mann captures the full horror of this process in Dr Faustus as the helpless Dr Kurbis presides over the agonizing death of a small child from tuberculous meningitis: The whole thing lasted scarcely two weeks, including the earliest signs that all was not quite well with the child; from the beginnings no one – I believe no one at all – even dreamed of the horror to come ... Kurbis tested the child’s eyes, the pupils of which were tiny and showed a tendency to squint. The pulse raced. Muscular contractions developed, and an incipient rigidity of the neck. It was cerebrospinal meningitis, infl ammation of the meninges. The good man pronounced the name with a deprecating movement of the head shoulderwards, probably in the hope that they might not know the almost complete powerlessness of medical science in the face of this onslaught. Tuberculous meningitis was invariably fatal before the advent of anti-tuberculosis chemotherapy. Therefore, the need to diagnose the disorder became a priority after streptomycin was found to reduce mortality of tuberculous meningitis by one third in 1948 (MRC 1948). Progress was rapid over the next 5 years: adding para-aminosalicylic acid to streptomycin reduced mortality to 30%, and the addition of isoniazid to both of these compounds lowered the mortality still more to Robert Koch: photograph taken in the 1880s, around the time of his discovery of the tubercle bacillus (or ‘bacille Koch’, as it is still called in Vietnam).

The diagnosis and management of

Background The use of androgen-deprivation therapy for prostate cancer has increased substantially over the past 15 years. This treatment is associated with a loss of bone-mineral density, but the risk of fracture after androgen-deprivation therapy has not been well studied. Methods We studied the records of 50,613 men who were listed in the linked database of the Surveillance, Epidemiology, and End Results program and Medicare as having received a diagnosis of prostate cancer in the period from 1992 through 1997. The primary outcomes were the occurrence of any fracture and the occurrence of a fracture resulting in hospitalization. Cox proportional-hazards analyses were adjusted for characteristics of the patients and the cancer, other cancer treatment received, and the occurrence of a fracture or the diagnosis of osteoporosis during the 12 months preceding the diagnosis of cancer. Results Of men surviving at least five years after diagnosis, 19.4 percent of those who received androgen-deprivation therapy...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa041943

Risk of Fracture after Androgen Deprivation for Prostate Cancer

Guideline for the Management of Clinically Localized Prostate Cancer: 2007 Update

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(02)09408-4.pdf

Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial.

Metastatic prostate cancer treated by flutamide versus cyproterone acetate. Final analysis of the "European Organization for Research and Treatment of Cancer" (EORTC) Protocol 30892.

PSA evolution: a prognostic factor during treatment of advanced prostatic carcinoma with total androgen blockade.

La valeur pronostique de la reponse de l'antigene specifique de la prostate (PSA) et sa correlation avec d'autres facteurs pronostiques initiaux ont ete etudies dans le traitement du carcinome prostatique avance traite par blocage androgenique total. Cinq cent quarante-six patients presentant des metastases loco-regionales (MO) ou des metastases a distance (M1) ont ete traites avec du flutamide combine soit a une orchidectomie soit a un analogue de la LHRH. On a evalue la relation entre, d'une part les caracteristiques initiales et la reponse du PSA chez les patients M0 et M1, et, d'autre part la survie sans progression, dans une analyse univariee et multivariee (regression Cox). Les facteurs pronostiques suivants etaient indicatifs d'une diminution de la survie dans progression : absence de normalisation du PSA ( 1, presence de douleur et absence de dysurie. Chez les patients du groupe M1 la combinaison des facteurs de normalisation du PSA a 3 ou a 6 mois, grade G et statut de performance ECOG constitue la valeur predictive la plus importante. En conclusion, cette etude demontre que les facteurs de normalisation du PSA a 3 ou a 6 mois avec stade initial de tumeur, grade et statut de sante du patient sont les facteurs pronostiques les plus importants apparentes a la survie sans progression dans le traitement hormonal du carcinome prostatique avance.

PSA evolution: a prognostic factor during treatment of advanced prostatic carcinoma with total androgen blockade. Data from a Belgian multicentric study of 546 patients.

Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial

J Mattelaer

Papers

Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial.

Metastatic prostate cancer treated by flutamide versus cyproterone acetate. Final analysis of the "European Organization for Research and Treatment of Cancer" (EORTC) Protocol 30892.

PSA evolution: a prognostic factor during treatment of advanced prostatic carcinoma with total androgen blockade.

PSA evolution: a prognostic factor during treatment of advanced prostatic carcinoma with total androgen blockade. Data from a Belgian multicentric study of 546 patients.

Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial