BACKGROUND Androgen-deprivation therapy (ADT) has been the backbone of treatment for metastatic prostate cancer since the 1940s. We assessed whether concomitant treatment with ADT plus docetaxel would result in longer overall survival than that with ADT alone. METHODS We assigned men with metastatic, hormone-sensitive prostate cancer to receive either ADT plus docetaxel (at a dose of 75 mg per square meter of body-surface area every 3 weeks for six cycles) or ADT alone. The primary objective was to test the hypothesis that the median overall survival would be 33.3% longer among patients receiving docetaxel added to ADT early during therapy than among patients receiving ADT alone. RESULTS A total of 790 patients (median age, 63 years) underwent randomization. After a median follow-up of 28.9 months, the median overall survival was 13.6 months longer with ADT plus docetaxel (combination therapy) than with ADT alone (57.6 months vs. 44.0 months; hazard ratio for death in the combination group, 0.61; 95% confidence interval [CI], 0.47 to 0.80; P<0.001). The median time to biochemical, symptomatic, or radiographic progression was 20.2 months in the combination group, as compared with 11.7 months in the ADT-alone group (hazard ratio, 0.61; 95% CI, 0.51 to 0.72; P<0.001). The rate of a prostate-specific antigen level of less than 0.2 ng per milliliter at 12 months was 27.7% in the combination group versus 16.8% in the ADT-alone group (P<0.001). In the combination group, the rate of grade 3 or 4 febrile neutropenia was 6.2%, the rate of grade 3 or 4 infection with neutropenia was 2.3%, and the rate of grade 3 sensory neuropathy and of grade 3 motor neuropathy was 0.5%. CONCLUSIONS Six cycles of docetaxel at the beginning of ADT for metastatic prostate cancer resulted in significantly longer overall survival than that with ADT alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00309985.)

Purpose Docetaxel added to androgen-deprivation therapy (ADT) significantly increases the longevity of some patients with metastatic hormone-sensitive prostate cancer. Herein, we present the outcomes of the CHAARTED (Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) trial with more mature follow-up and focus on tumor volume. Patients and Methods In this phase III study, 790 patients with metastatic hormone-sensitive prostate cancer were equally randomly assigned to receive either ADT in combination with docetaxel 75 mg/m for up to six cycles or ADT alone. The primary end point of the study was overall survival (OS). Additional analyses of the prospectively defined low- and high-volume disease subgroups were performed. High-volume disease was defined as presence of visceral metastases and/or ≥ four bone metastases with at least one outside of the vertebral column and pelvis. Results At a median follow-up of 53.7 months, the median OS was 57.6 months for the chemohormonal therapy arm versus 47.2 months for ADT alone (hazard ratio [HR], 0.72; 95% CI, 0.59 to 0.89; P = .0018). For patients with high-volume disease (n = 513), the median OS was 51.2 months with chemohormonal therapy versus 34.4 months with ADT alone (HR, 0.63; 95% CI, 0.50 to 0.79; P < .001). For those with low-volume disease (n = 277), no OS benefit was observed (HR, 1.04; 95% CI, 0.70 to 1.55; P = .86). Conclusion The clinical benefit from chemohormonal therapy in prolonging OS was confirmed for patients with high-volume disease; however, for patients with low-volume disease, no OS benefit was discerned.

BackgroundEnvironmental pollutants such as polycyclic aromatic hydrocarbons (PAHs), lead, and mercury are released by combustion of coal and other fossil fuels.ObjectivesIn the present study we evaluated the association between prenatal exposure to these pollutants and child development measured by the Gesell Developmental Schedules at 2 years of age.MethodsThe study was conducted in Tongliang, Chongqing, China, where a seasonally operated coal-fired power plant was the major source of ambient PAHs and also contributed lead and mercury to the air. In a cohort of nonsmoking women and their newborns enrolled between March 2002 and June 2002, we measured levels of PAH–DNA adducts, lead, and mercury in umbilical cord blood. PAH–DNA adducts (specifically benzo[a]pyrene adducts) provided a biologically relevant measure of PAH exposure. We also obtained developmental quotients (DQs) in motor, adaptive, language, and social areas.ResultsDecrements in one or more DQs were significantly associated with cord blood levels of PAH–DNA adducts and lead, but not mercury. Increased adduct levels were associated with decreased motor area DQ (p = 0.043), language area DQ (p = 0.059), and average DQ (p = 0.047) after adjusting for cord lead level, environmental tobacco smoke, sex, gestational age, and maternal education. In the same model, high cord blood lead level was significantly associated with decreased social area DQ (p = 0.009) and average DQ (p = 0.038).ConclusionThe findings indicate that exposure to pollutants from the power plant adversely affected the development of children living in Tongliang; these findings have implications for environmental health policy.

Patients with a higher burden of metastatic prostate cancer starting androgen deprivation therapy (ADT) have a poorer prognosis and are more likely to benefit from early docetaxel. Low-volume patients have longer overall survival with ADT alone, and the toxicity of docetaxel may outweigh its benefits.

BACKGROUND Predicting life expectancy (LE) in patients with metastatic cancer who are receiving palliative therapies is a difficult task. The purpose of the current study was to develop a LE prediction model among patients receiving palliative radiotherapy (RT) that identifies those patients with short (<3 months) and long (>1 year) LEs. METHODS The records of 862 patients with metastatic cancer receiving palliative RT at the Dana-Farber/Brigham and Women’s Cancer Center between June 2008 and July 2011 were retrospectively reviewed. Cox proportional hazards models were used to evaluate established and potential clinical predictors of LE to construct a model predicting LE of <3 months and >1 year. RESULTS The median survival was 5.6 months. On multivariate analysis, factors found to be significantly associated with a shorter LE were cancer type (lung and other vs breast and prostate), older age (>60 years vs ≤60 years), liver metastases, Eastern Cooperative Oncology Group performance status (2–4 vs 0–1), hospitalizations within 3 months before palliative RT (0 vs ≥1), and prior palliative chemotherapy courses (≥2 vs 0–1). Patients were divided into 3 groups with distinct median survivals: group A (those with 0–1 risk factors), 19.9 months (95% confidence interval [95% CI, 13.9 months–31.1 months]); group B (those with 2–4 risk factors), 5.0 months (95% CI, 4.3 months–5.6 months); and group C (those with 5–6 risk factors), 1.7 months (95% CI, 1.2 months–2.1 months). CONCLUSIONS The TEACHH model (type of cancer, Eastern Cooperative Oncology Group performance status, age, prior palliative chemotherapy, prior hospitalizations, and hepatic metastases) divides patients receiving palliative RT into 3 distinct LE groups at clinically informative extremes of the LE spectrum. It holds promise to assist radiation oncologists in tailoring palliative therapies to a patient’s LE.