José Lopez Torecilla

Bio: José Lopez Torecilla is an academic researcher. The author has contributed to research in topics: Goserelin & Androgen suppression. The author has an hindex of 2, co-authored 3 publications receiving 2392 citations.

External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study

Abstract: Summary Background We did a randomised phase 3 trial assessing the benefit of addition of long-term androgen suppression with a luteinising-hormone-releasing hormone (LHRH) agonist to external irradiation in patients with prostate cancer with high metastatic risk. In this report, we present the 10-year results. Methods For this open-label randomised trial, eligible patients were younger than 80 years and had newly diagnosed histologically proven T1–2 prostatic adenocarcinoma with WHO histological grade 3 or T3–4 prostatic adenocarcinoma of any histological grade, and a WHO performance status of 0–2. Patients were randomly assigned (1:1) to receive radiotherapy alone or radiotherapy plus immediate androgen suppression. Treatment allocation was open label and used a minimisation algorithm with institution, clinical stage of the disease, results of pelvic-lymph-node dissection, and irradiation fields extension as minimisation factors. Patients were irradiated externally, once a day, 5 days a week, for 7 weeks to a total dose of 50 Gy to the whole pelvis, with an additional 20 Gy to the prostate and seminal vesicles. The LHRH agonist, goserelin acetate (3·6 mg subcutaneously every 4 weeks), was started on the first day of irradiation and continued for 3 years; cyproterone acetate (50 mg orally three times a day) was given for 1 month starting a week before the first goserelin injection. The primary endpoint was clinical disease-free survival. Analysis was by intention to treat. The trial is registered at ClinicalTrials.gov, number NCT00849082. Findings Between May 22, 1987, and Oct 31, 1995, 415 patients were randomly assigned to treatment groups and were included in the analysis (208 radiotherapy alone, 207 combined treatment). Median follow-up was 9·1 years (IQR 5·1–12·6). 10-year clinical disease-free survival was 22·7% (95% CI 16·3–29·7) in the radiotherapy-alone group and 47·7% (39·0–56·0) in the combined treatment group (hazard ratio [HR] 0·42, 95% CI 0·33–0·55, p vs 11 of 63 in the radiotherapy group; p=0·60) and in those who did not (14 of 154 vs six of 145; p=0·25). Two fractures were reported in patients allocated combined treatment. Interpretation In patients with prostate cancer with high metastatic risk, immediate androgen suppression with an LHRH agonist given during and for 3 years after external irradiation improves 10-year disease-free and overall survival without increasing late cardiovascular toxicity. Funding AstraZeneca; Ligue Nationale Contre le Cancer (France), through the EORTC Charitable Trust.

Sipuleucel-T immunotherapy for castration-resistant prostate cancer.

Abstract: 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.)

The diagnosis and management of

Abstract: 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).

Clinical practice guidelines in oncology

Abstract: Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions in the breast ducts. The goal for management of DCIS is to prevent the development of invasive breast cancer. This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.