Randomized phase III trial of gemcitabine-based chemotherapy with in situ RRM1 and ERCC1 protein levels for response prediction in non-small-cell lung cancer.

PURPOSE: We evaluated the efficacy of gemcitabine versus gemcitabine and carboplatin in patients with advanced non-small-cell lung cancer (NSCLC) and a performance status (PS) of 2 and assessed if tumoral RRM1 and ERCC1 protein levels are predictive of response to therapy. PATIENTS AND METHODS: A randomized phase III trial was conducted in community-based oncology practices. Tumor specimens were collected a priori and shipped to a single laboratory for blinded determination of in situ RRM1 and ERCC1 protein expression levels by an automated quantitative immunofluorescent-based technology. RESULTS: One hundred seventy patients were randomly assigned. Overall median survival was 5.1 months for gemcitabine and 6.7 months for gemcitabine and carboplatin (P = .24). RRM1 (range, 5.3 to 105.6; median, 34.1) and ERCC1 (range, 5.2 to 131.3; median, 34.7) values were significantly and inversely correlated with disease response (r = -0.41; P = .001 for RRM1; r = -0.39; P = .003 for ERCC1; ie, response was better for patients with low levels of expression). A model for response prediction that included RRM1, ERCC1, and treatment arm, was highly predictive of the treatment response observed (P = .0005). We did not find statistically significant associations between survival and RRM1 or ERCC1 levels. CONCLUSION: Single-agent chemotherapy remains the standard of care for patients with advanced NSCLC and poor PS. Quantitative analysis of RRM1 and ERCC1 protein expression in routinely collected tumor specimens in community oncology practices is predictive of response to gemcitabine and gemcitabine and carboplatin therapy. Oncologists should consider including in situ expression analysis for these proteins into their therapeutic decisions.

Selenium accumulation in prostate tissue during a randomized, controlled short-term trial of l-selenomethionine: a Southwest Oncology Group Study.

PURPOSE: Epidemiologic and clinical data suggest that selenium could prevent prostate cancer, but it has not been shown that supplemental selenium leads to an increased concentration of selenium in prostate tissue compared with adjacent tissue. EXPERIMENTAL DESIGN: We conducted a randomized, controlled, short-term trial of l-selenomethionine (SeMet) versus observation in men with organ-confined prostate cancer. The primary endpoint was the measurement of selenium concentration in prostate tissue and seminal vesicle (SV). We assessed baseline selenium levels in serum and in toenail specimens (reflecting long-term intake) and post-intervention selenium levels in serum, and in prostate and SV tissues using hydride generation atomic fluorescence spectroscopy. RESULTS: Sixty-six eligible patients were randomly assigned to the SeMet (n = 34) or observation (n = 32) arm; both arms had similar baseline patient characteristics. Baseline serum selenium was similar in the two groups (P = 0.64). Baseline toenail selenium levels were slightly higher in the SeMet group than in the control group (P = 0.07). After the intervention, the mean serum selenium level increased 15% in the SeMet arm and was higher than in the observation arm (P = 0.001). The selenium concentration in prostate tissue was 22% higher in the SeMet arm (n = 26) than in the observation arm (n = 25; 1.80 versus 1.47 ppm; P = 0.003, Wilcoxon rank sum test) and remained significantly higher after adjusting for chronic selenium intake (P = 0.021, ANCOVA). SV selenium concentration was similar in both groups (P = 0.384) and was lower than in prostate tissue. CONCLUSIONS: The present study is the first to show that selenium taken as oral supplementation accumulates preferentially in the human prostate gland as opposed to the SV. These findings support the hypothesis that oral selenium supplementation may contribute to the cancer preventive effects of selenium.

Research and commentary: Change in exercise tolerance, activity and sleep patterns, and quality of life in patients with cancer participating in a structured exercise program.

PURPOSE/OBJECTIVES: To investigate the feasibility of an exercise program patterned after a phase II cardiac rehabilitation program to improve selected physiologic and psychological parameters of health in patients with cancer. DESIGN: Prospective, repeated measures study. SETTING: Two major military medical centers in the southwestern United States. SAMPLE: 62 patients diagnosed with cancer within the previous two years. Ages ranged from 24-83 (meanX = 59). Half of the participants were male and half were female. Minorities made up 29% of the sample. Participants had a wide range of cancer diagnoses and all stages of cancer. Fifteen subjects were undergoing treatment when they enrolled in the study. More than half of the subjects exercised prior to their cancer diagnoses, but fewer than half were able to resume an exercise routine following their cancer diagnoses. METHODS: Subjects met two days each week for 12 weeks for exercise and education. MAIN RESEARCH VARIABLES: Exercise tolerance as measured with a graded exercise test, activity and sleep patterns as measured with a wrist actigraph, and quality of life (QOL) as measured with the Cancer Rehabilitation Evaluation System-Short Form. FINDINGS: Significant improvements were observed over time in exercise tolerance, selected activity and sleep patterns, and QOL among the 46 (74%) subjects who completed the program. CONCLUSIONS: Patients with various types and stages of cancer can safely exercise using a cardiac rehabilitation model and can realize significant improvements in exercise tolerance, selected activity and sleep patterns, and QOL. IMPLICATIONS FOR NURSING: Most people are aware that regular exercise is part of a healthy lifestyle. After cancer diagnosis and treatment, patients experience uncertainty regarding how to resume exercise or how to begin an exercise program as part of their rehabilitation. Participation in a structured exercise program can provide patients with a safe environment within which to exercise at an intensity appropriate to their individual needs.