Cisplatin-based therapy for elderly patients with advanced non-small-cell lung cancer: implications of Eastern Cooperative Oncology Group 5592, a randomized trial

BACKGROUND: Older patients, even if fit, are often considered incapable of tolerating platinum-based systemic therapy. We performed a retrospective analysis of Eastern Cooperative Oncology Group (ECOG) 5592, a phase III randomized trial of platinum-based chemotherapy regimens for non-small-cell lung cancer (NSCLC), and compared outcomes in enrollees 70 years of age and older with those in younger patients. METHODS: ECOG carried out a randomized phase III trial of cisplatin plus either etoposide or paclitaxel in chemotherapy-na?ve NSCLC patients with stages III(B) or IV disease. Toxic effects, response rates, and survival rates were compared between age groups. All P values were two-sided. RESULTS: A total of 574 patients enrolled from August 1993 through December 1994 were evaluable. Eighty-six (15%) were 70 years old or older. Older patients had a higher incidence of cardiovascular (P =.009) and respiratory (P =.04) comorbidities and nonanalgesic medication use (P =.02). Leukopenia (P<.001) and neuropsychiatric toxicity (P =.002) were more common in elderly men than in younger men. Elderly women lost more weight than younger women (P =.006). Other toxic effects were similar in older and younger patients. The proportions with clinical partial or complete response (21.5% versus 23.3%; Fisher's exact test, P =.66), median time to progression (4.37 versus 4.30 months; log-rank test, P =.29), and survival distribution (log-rank test, P =.29; median survival, 9.05 versus 8.53 months; 1-year survival, 38% versus 29%; and 2-year survival, 14% versus 12%) were similar in patients younger than 70 years and 70 years old or older. Baseline quality-of-life and treatment-outcome indices were similar. Equivalent declines over time in functional well-being occurred in both groups. CONCLUSION: Response rate, toxicity, and survival in fit, elderly NSCLC patients receiving platinum-based treatment appear to be similar to those in younger patients, although patients 70 years old or older have more comorbidities and can expect more leukopenia and neuropsychiatric toxicity. Advanced age alone should not preclude appropriate NSCLC treatment.     

Phase II trial of Paclitaxel and Dacarbazine with filgrastim administration in advanced malignant melanoma

A Phase II trial was conducted in patients with advanced malignant melanoma with intravenous Paclitaxel and Dacarbazine (DTIC). The initial starting dose for Paclitaxel was 135 mg/m² followed by DTIC 800 mg/m². Due to the lack of myelosuppression and other toxicities, the starting dose for Paclitaxel was escalated to 250 mg/m² and the dose for DTIC escalated to l000 mg/m². Twenty-five patients were enrolled in this study. Among the 25 patients assessable for response, three patients had a partial response with a response rate of 12% (CI 3-31%) and one patient had stable disease. Three additional patients showed evidence of anti-tumor activity with minor responses. For patients who had no prior chemotherapy or biochemotherapy, the response rate was 20%. Toxicity was generally tolerable and included mainly neurotoxicity from Paclitaxel. At the doses and schedule used, the combination of Paclitaxel and DTIC did not appear to increase the response rate compared to each agent used singly.     

Employment histories of homeless persons with mental illness

This study examined the work histories of 7,228 homeless persons with mental illness who were enrolled into the multi-site Access to Community Care and Effective Services and Supports (ACCESS) research demonstration program. Multiple logistic regression analyses suggest that use of vocational services is significantly associated with increased likelihood of paid employment. The role of vocational rehabilitation services in removing persons from homelessness and improving their quality of life is discussed.     

Childhood adversities associated with risk for eating disorders or weight problems during adolescence or early adulthood

OBJECTIVE: A community-based prospective longitudinal study was conducted to investigate the association between childhood adversities and problems with eating or weight during adolescence and early adulthood. METHOD: A community-based sample of 782 mothers and their offspring were interviewed during the childhood, adolescence, and early adulthood of the offspring. Childhood maltreatment, eating problems, environmental risk factors, temperament, maladaptive parental behavior, and parental psychopathology were assessed during childhood and adolescence. Eating disorders and problems with eating or weight in the offspring were assessed during adolescence and early adulthood. RESULTS: A wide range of childhood adversities were associated with elevated risk for eating disorders and problems with eating or weight during adolescence and early adulthood after the effects of age, childhood eating problems, difficult childhood temperament, parental psychopathology, and co-occurring childhood adversities were controlled statistically. Numerous unique associations were found between specific childhood adversities and specific types of problems with eating or weight, and different patterns of association were obtained among the male and female subjects. Maladaptive paternal behavior was uniquely associated with risk for eating disorders in offspring after the effects of maladaptive maternal behavior, childhood maltreatment, and other co-occurring childhood adversities were controlled statistically. CONCLUSIONS: Childhood adversities may contribute to greater risk for the development of eating disorders and problems with eating and weight that persist into early adulthood. Maladaptive paternal behavior may play a particularly important role in the development of eating disorders in offspring.     

Drug use and the risk of major depressive disorder,alcohol dependence,and substance use disorders

BACKGROUND: The Children in the Community Study is a prospective longitudinal study investigating the association between early drug use (childhood, adolescence, and early 20s) and later psychiatric disorders (in the late 20s). METHODS: Using data from a community-based sample of 736 adults (50% female) from upstate New York, the subjects were interviewed at the mean ages of 14, 16, 22, and 27 years. Psychiatric disorders, measured by age-appropriate versions of the University of Michigan Composite International Diagnostic Interview, and participant's drug use were assessed. RESULTS: Adolescent and young adult tobacco use was significantly associated with an increased risk of alcohol dependence and substance use disorders at a mean age of 27 years, but not with new episodes of major depressive disorder. Earlier alcohol use significantly predicted later major depressive disorder, alcohol dependence, and substance use disorders in the late 20s, as did early marijuana use and other illicit drug use. Except for the effect of tobacco use on major depressive disorder, early drug use was significantly related to later psychiatric disorders, even after statistically controlling for age, sex, parental educational level, family income, and prior episodes of major depressive disorder and substance use disorders. CONCLUSIONS: Our results suggest that early drug use is associated with and predicts later psychiatric disorders. Preventive implications stem from the importance of studying a range of psychiatric disorders in the context of substance use assessed over a wide age range.     

Reversible posterior encephalopathy syndrome: case report

The posterior reversible leukoencephalopathy syndrome (PRES) is a recently proposed cliniconeuroradiologic entity.The most common causes of PRES are hypertensive encephalopathy, eclampsia, cyclosporin A neurotoxicity and the uremic encephalopathies.Most patients are markedly hypertensive at presentation, although some have only mildly elevated or even normal blood pressure. Symptoms may include headache, nausea, vomiting, altered mental status, seizures,stupor, and visual disturbances. On CT and MR studies, edema has been reported in a relatively symmetrical pattern, typically in the subcortical white matter and occasionally in the cortex of the occipital and parietal lobes. These often striking imaging findings usually are resolved on follow-up studies obtained after appropriate therapy. Diffusion-weighted images would not show hyperintense signal because of the presence of interstitial rather than cytotoxic edema. We report a case of PRES due to hypertensive encephalopathy studied by CT and MRI.