Tobacco smoking in urban neighborhoods: exploring social capital as a protective factor in Santiago, Chile.

INTRODUCTION: Research examining the relationship between social capital and health in Latin America has been limited. The aim of this study is to evaluate the association between social capital and tobacco use in four low-income neighborhoods in Santiago, Chile. METHODS: A multistage probability sample was used to select households in 4 of the 10 poorest neighborhoods in the district of Puente Alto, in Santiago, Chile. A cross-sectional survey of 781 participants (81.2% response rate for households) included sociodemographic variables, questions pertaining to neighborhood social capital, and questions pertaining to tobacco. Main analyses were carried out at the individual level by performing a multiple logistic regression of individual tobacco use on individual perceptions of community social capital. RESULTS: The prevalence of smoking was 43.9% of the surveyed population. A five-factor structure for social capital was identified, including "perceived trust in neighbors," "perceived trust in organizations," "reciprocity within the neighborhood," "neighborhood integration," and "social participation." An inverse relationship between trust in neighbors and tobacco smoking was statistically significantly with an adjusted odds ratio of 0.95 (95% CI: 0.91-0.99). Trust in neighbors was also significantly inversely associated with the number of cigarettes smoked. DISCUSSION: Tobacco control remains a significant challenge in global health, requiring innovative strategies that address changing social contexts as well as the changing epidemiological profile of developing regions.

Phase 1 trial of high-dose exogenous testosterone in patients with castration-resistant metastatic prostate cancer.

BACKGROUND: Growth of selected castration-resistant prostate cancer (CRPC) cell lines and animal models can be repressed by reexposure to androgens. Low doses of androgens, however, can stimulate tumor growth. OBJECTIVE: We performed a phase 1 clinical trial to determine the safety of high-dose exogenous testosterone in patients with castration-resistant metastatic prostate cancer (CRMPC). DESIGN, SETTING, AND PARTICIPANTS: Patients with progressive CRMPC who had been castrate for at least 1 yr received three times the standard replacement dose of transdermal testosterone. INTERVENTION: Cohorts of 3-6 patients received testosterone for 1 wk, 1 mo, or until disease progression. MEASUREMENTS: Toxicities, androgen levels, prostate-specific antigen (PSA) assays, computed tomography (CT) scans, bone scintigraphy, positron emission tomography (PET) scans, and metastatic tumor biopsy androgen receptor levels were assessed. RESULTS AND LIMITATIONS: Twelve patients were treated-three in cohorts 1 and 2 and six in cohort 3. No pain flares were noted. One patient came off study because of epidural disease, which was treated with radiation. Average testosterone levels were within normal limits, although dihydrotestosterone (DHT) levels on average were supraphysiologic in cohort 3. One patient achieved a PSA decline of >50% from baseline. No objective responses were seen. For cohort 3, median time on treatment was 84 d (range: 23-247 d). CONCLUSIONS: We have demonstrated that patients with CRMPC can be safely treated in clinical trials using high-dose exogenous testosterone. Patients did not, on average, achieve sustained supraphysiologic serum testosterone levels. Future studies should employ strategies to maximize testosterone serum levels, use contemporary methods of identifying patients with androgen receptor overexpression, and utilize PSA Working Group II Consensus Criteria clinical trial end points. TRIAL REGISTRATION: ClinicalTrials.gov; NCT00006044.

A phase II trial of bortezomib and prednisone for castration resistant metastatic prostate cancer.

PURPOSE: We defined the antitumor effects of bortezomib alone and in combination with prednisone in patients with progressive, castration resistant metastatic prostate cancer. MATERIALS AND METHODS: A total of 30 men with progressive castration resistant disease were treated in 2 groups. Cohort 1 received 1.5 mg/m2 bortezomib intravenously twice weekly for 2 cycles (2 weeks on and 1 week off), followed by 1.6 mg/m2 weekly (4 weeks on and 2 weeks off). Prednisone (10 mg) was given orally throughout. Cohort 2 comprised patients with limited chemotherapy exposure who received a decreased dose of bortezomib (1.3 mg/m2) during the induction period with prednisone added only at disease progression. The primary end point was no evidence of disease progression at 12 weeks, defined as no increase in prostate specific antigen from baseline and no radiographic progression. Interleukin-6 was assessed to correlate with antitumor effects. RESULTS: One of 24 evaluable patients (4%) achieved the primary end point. In cohort 1, 18 patients were treated, 13 were evaluable for response and 4 discontinued treatment due to toxicities, including 3 before attaining the point of being evaluable. No patient achieved the primary end point. In cohort 2, 12 patients were treated and 11 were evaluable for response. Toxicity was slightly mitigated compared with that in cohort 1. One patient achieved the primary end point. Interleukin-6 did not correlate with posttreatment prostate specific antigen changes in either cohort. CONCLUSIONS: Although interleukin-6 and other pathways regulated by nuclear factor-kappa B may be legitimate targets, treatment with bortezomib alone and with prednisone does not appear to have significant antitumor effects in patients with castration resistant metastatic prostate cancer.

Rapid androgen cycling as treatment for patients with prostate cancer.

PURPOSE: To investigate the safety and feasibility of rapid androgen cycling for men with progressive prostate cancer. EXPERIMENTAL DESIGN: Schedule 1 included a 4-week induction of androgen depletion, followed by 4-week treatment cycles of a monthly gonadotropin-releasing hormone agonist, testosterone on days 1 to 7, and an estrogen patch on days 8 to 21. Schedule 2 included a 12-week induction of androgen depletion followed by 4-week cycles of gonadotropin-releasing hormone agonist and testosterone, but no estrogens for patients with a prostate-specific antigen (PSA) nadir <1 ng/mL after induction. The primary end point was serially declining PSA trough values over six treatment cycles. RESULTS: Thirty-six patients were treated; 27 were evaluable after cycling, of whom 8 of 12 (67%) and 9 of 15 (60%) on schedules 1 and 2, respectively, reached the end point. Five patients with PSA >1 ng/mL following induction did not cycle. No patient progressed radiographically or clinically during cycling. Three posttherapy PSA patterns were observed: a decline followed by a rapid increase in trough levels, a sustained decline with a plateau at a detectable nadir, and a decline to an undetectable nadir. Mean testosterone levels were castrate at the time of trough and in the normal physiologic range following androgen repletion. Major toxicities included grades 1 and 2 fatigue, hepatitis, gynecomastia, and hot flashes. CONCLUSIONS: Rapid hormonal cycling is feasible and well tolerated, and successive declines in PSA troughs are achievable. Although the sample size was small, the proportion of patients achieving declining PSA at the end of six cycles was comparable with that reached with continuous androgen depletion therapy.