Nonsteroidal anti-inflammatory drugs (NSAIDs) and prostate cancer risk: results from the EPICAP study.

Chronic inflammation may play a role in prostate cancer carcinogenesis. In that context, our objective was to investigate the role of nonsteroidal anti-inflammatory drugs (NSAIDs) in prostate cancer risk based on the EPICAP data. EPICAP is a population-based case-control study carried out in 2012-2013 (département of Hérault, France) that enrolled 819 men aged less than 75 years old newly diagnosed for prostate cancer and 879 controls frequency matched to the cases on age. Face to face interviews gathered information on several potential risk factors including NSAIDs use. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated using unconditional logistic regression models. All-NSAIDs use was inversely associated with prostate cancer: OR 0.77, 95% CI 0.61-0.98, especially in men using NSAIDs that preferentially inhibit COX-2 activity (OR 0.48, 95% CI 0.28-0.79). Nonaspirin NSAIDs users had a decreased risk of prostate cancer (OR 0.72, 95% CI 0.53-0.99), particularly among men with an aggressive prostate cancer (OR 0.49, 95% CI 0.27-0.89) and in men with a personal history of prostatitis (OR 0.21, 95% CI 0.07-0.59). Our results are in favor of a decreased risk of prostate cancer in men using NSAIDs, particularly for men using preferential anti-COX-2 activity. The protective effect of NSAIDs seems to be more pronounced in aggressive prostate cancer and in men with a personal history of prostatitis, but this needs further investigations to be confirmed.

Epidemiological study of prostate cancer (EPICAP): a population-based case-control study in France.

BACKGROUND: Prostate cancer is the most common cancer in male in most Western countries, including France. Despite a significant morbidity and mortality to a lesser extent, the etiology of prostate cancer remains largely unknown. Indeed, the only well-established risk factors to date are age, ethnicity and a family history of prostate cancer. We present, here, the rationale and design of the EPIdemiological study of Prostate CAncer (EPICAP), a population-based case-control study specifically designed to investigate the role of environmental and genetic factors in prostate cancer. The EPICAP study will particularly focused on the role of circadian disruption, chronic inflammation, hormonal and metabolic factors in the occurrence of prostate cancer. METHODS/DESIGN: EPICAP is a population-based case-control study conducted in the département of Hérault in France. Eligible cases are all cases of prostate cancers newly diagnosed in 2012-2013 in men less than 75 years old and residing in the département of Hérault at the time of diagnosis. Controls are men of the same age as the cases and living in the département of Hérault, recruited in the general population.The sample will include a total of 1000 incident cases of prostate cancer and 1000 population-based controls over a 3-year period (2012-2014).The cases and controls are face-to-face interviewed using a standardized computed assisted questionnaire. The questions focus primarily on usual socio-demographic characteristics, personal and family medical history, lifestyle, leisure activities, residential and occupational history. Anthropometric measures and biological samples are also collected for cases and controls. DISCUSSION: The EPICAP study aims to answer key questions in prostate cancer etiology: (1) role of circadian disruption through the study of working hours, chronotype and duration/quality of sleep, (2) role of chronic inflammation and anti-inflammatory drugs, (3) role of hormonal and metabolic factors through a detailed questionnaire, (4) role of individual genetic susceptibility of genes involved in biological pathways of interest. The EPICAP study will also allow us to study prognostic factors and tumor aggressiveness.Taken together, the EPICAP study will provide a comprehensive framework to go further in the understanding of prostate cancer occurrence and its prognosis.

Subcutaneous interleukin-2 and interferon-alpha in metastatic renal cell carcinoma: results of a French regional experience in Languedoc.

OBJECTIVES: To assess the efficacy and toxicity of an immunotherapy regimen combining subcutaneous (SC) interleukin-2 (IL-2) and interferon-alpha (IFN) in patients with metastatic renal cell carcinoma (MRCC). METHODS: The present study included 86 patients with MRCC. Data on treatment toxicity and efficacy (responses rates and overall survival) were collected on a hospital database. Treatment consisted of 6-week cycles repeated every 2 months for a maximum of 3 cycles. Each cycle included SC IL-2 20 x 10 MIU/m2 3 times/wk on weeks 1 and 4; 5 x 10 MIU/m2 3 times/wk on weeks 2, 3, 5, and 6, in combination with IFN 6 x 10 MIU/m2 once weekly on weeks 1 and 4; and 3 times/wk on weeks 2, 3, 5, and 6. RESULTS: Seventy (82%) and 71 (83%) patients received more than 80% of the planned doses of IL-2 and IFN during the first cycle, respectively. Ten patients had to stop therapy before the end of the first cycle because of excessive toxicity (7 patients) or rapidly progressive disease (3 patients). Only 17 (28%) proceeded to the second cycle. Main toxicities included fever and asthenia in 86 (100%) patients, nausea/emesis in 83 (96%) patients, skin disorders in 69 (80%) patients, hypotension in 56 (65%) patients, and diarrhea in 50 (58%) patients. Sixty-seven (78%) patients developed at least one episode of grade 3 toxicity. Objective responses were observed in 13 patients, including 4 complete and 9 partial responses (15%; 95% confidence interval, 9.5-20.5%). After a median follow-up of 45 months, the median time to progression was 4 months (range, 1-41) and the median survival was 14 months (range, 1-89). CONCLUSIONS: Only a small subset of patients with MRCC is likely to benefit from treatment with IL-2 and IFN. As toxicity is significant, the refinement of predictive variables for sensitivity to immunotherapy is mandatory.