William H. Fisher

Phase III Study of Cisplatin, Etoposide, and Concurrent Chest Radiation With or Without Consolidation Docetaxel in Patients With Inoperable Stage III Non–Small-Cell Lung Cancer: The Hoosier Oncology Group and U.S. Oncology

PURPOSE Concurrent chemoradiotherapy is standard treatment for patients with inoperable stage III non-small-cell lung cancer (NSCLC). A phase II study by the Southwest Oncology Group using consolidation docetaxel after cisplatin (P), etoposide (E), and radiation (XRT) resulted in a median survival time (MST) of 26 months. This randomized phase III trial evaluated whether consolidation docetaxel was responsible for this improved survival. PATIENTS AND METHODS Eligible patients had stage IIIA or IIIB NSCLC, baseline performance status of 0 to 1, forced expiratory volume in 1 second >or= 1 L, and less than 5% weight loss. Patients received P 50 mg/m(2) intravenously (IV) on days 1, 8, 29, and 36 and E 50 mg/m(2) IV on days 1-5 and 29-33 concurrently with chest XRT to 59.40 Gy. Patients who did not experience progression were randomly assigned to docetaxel 75 mg/m(2) IV every 21 days for three cycles versus observation. The primary end point was to compare overall survival (Kaplan-Meier analysis). RESULTS On the basis of evidence of futility, a data and safety monitoring board recommended early termination after an analysis of the initial 203 patients. Patient characteristics (n = 203) were as follows: 34% female; median age, 63 years; 39.4% stage IIIA; and 60.6% stage IIIB. One hundred forty-seven (72.4%) of 203 patients were randomly assigned to docetaxel (n = 73) or observation (n = 74). Grade 3 to 5 toxicities during docetaxel included febrile neutropenia (10.9%) and pneumonitis (9.6%); 28.8% of patients were hospitalized during docetaxel (v 8.1% in observation arm), and 5.5% died as a result of docetaxel. The MST for all patients (n = 203) was 21.7 months; MST was 21.2 months for docetaxel arm compared with 23.2 months for observation arm (P = .883). CONCLUSION Consolidation docetaxel after PE/XRT results in increased toxicities but does not further improve survival compared with PE/XRT alone in patients with stage III inoperable NSCLC.

Semuloparin for Thromboprophylaxis in Patients Receiving Chemotherapy for Cancer

BACKGROUND Patients receiving chemotherapy for cancer are at increased risk for venous thromboembolism. Limited data support the clinical benefit of antithrombotic prophylaxis. METHODS In this double-blind, multicenter trial, we evaluated the efficacy and safety of the ultra-low-molecular-weight heparin semuloparin for prevention of venous thromboembolism in patients receiving chemotherapy for cancer. Patients with metastatic or locally advanced solid tumors who were beginning to receive a course of chemotherapy were randomly assigned to receive subcutaneous semuloparin, 20 mg once daily, or placebo until there was a change of chemotherapy regimen. The primary efficacy outcome was the composite of any symptomatic deep-vein thrombosis, any nonfatal pulmonary embolism, and death related to venous thromboembolism. Clinically relevant bleeding (major and nonmajor) was the main safety outcome. RESULTS The median treatment duration was 3.5 months. Venous thromboembolism occurred in 20 of 1608 patients (1.2%) receiving semuloparin, as compared with 55 of 1604 (3.4%) receiving placebo (hazard ratio, 0.36; 95% confidence interval [CI], 0.21 to 0.60; P<0.001), with consistent efficacy among subgroups defined according to the origin and stage of cancer and the baseline risk of venous thromboembolism. The incidence of clinically relevant bleeding was 2.8% and 2.0% in the semuloparin and placebo groups, respectively (hazard ratio, 1.40; 95% CI, 0.89 to 2.21). Major bleeding occurred in 19 of 1589 patients (1.2%) receiving semuloparin and 18 of 1583 (1.1%) receiving placebo (hazard ratio, 1.05; 95% CI, 0.55 to 1.99). Incidences of all other adverse events were similar in the two study groups. CONCLUSIONS Semuloparin reduces the incidence of thromboembolic events in patients receiving chemotherapy for cancer, with no apparent increase in major bleeding. (Funded by Sanofi; ClinicalTrials.gov number, NCT00694382.).

Cisplatin plus etoposide with and without ifosfamide in extensive small-cell lung cancer: a Hoosier Oncology Group study.

PURPOSE To determine whether the addition of ifosfamide to cisplatin plus etoposide improves the response rate, time to disease progression, or overall survival in previously untreated patients with extensive-stage small-cell carcinoma of the lung (SCLC). PATIENTS AND METHODS Patients with extensive SCLC with a Karnofsky performance score (KPS) > or = 50 and adequate renal function and bone marrow reserve were eligible. Patients with CNS metastases were eligible and received concurrent whole-brain radiotherapy. Patients were randomized to receive cisplatin (20 mg/m2) plus etoposide (100 mg/m2) (VP) both given intravenously (i.v.) on days 1 to 4 or cisplatin (20 mg/m2), ifosfamide (1.2 g/m2), and etoposide (75 mg/m2) (VIP) all given i.v. on days 1 to 4. Cycles were repeated every 3 weeks for four cycles. RESULTS From May 1989 through March 1993, 171 patients were randomized (84 to VP and 87 to VIP). The median follow-up duration is 26 months. All patients were assessable for survival; 163 were fully assessable for response and 162 for toxicity. Myelosuppression was greater with VIP. Objective responses were observed in 55 of 82 (67%) and 59 of 81 (73%) assessable patients treated with VP and VIP, respectively (difference not significant). The difference in the median time to progression was statistically different (P = .039). The median survival times on VP and VIP were 7.3 months and 9.0 months, respectively (P = .045 for survival curves by stratified log-rank test) with 2-year survival rates of 5% versus 13%, respectively. CONCLUSION VIP combination chemotherapy is associated with an improved time to progression and overall survival over VP therapy in patients with extensive SCLC.

Beyond Criminalization: Toward a Criminologically Informed Framework for Mental Health Policy and Services Research

The problems posed by persons with mental illness involved with the criminal justice system are vexing ones that have received attention at the local, state and national levels. The conceptual model currently guiding research and social action around these problems is shaped by the “criminalization” perspective and the associated belief that reconnecting individuals with mental health services will by itself reduce risk for arrest. This paper argues that such efforts are necessary but possibly not sufficient to achieve that reduction. Arguing for the need to develop a services research framework that identifies a broader range of risk factors for arrest, we describe three potentially useful criminological frameworks—the “life course,” “local life circumstances” and “routine activities” perspectives. Their utility as platforms for research in a population of persons with mental illness is discussed and suggestions are provided with regard to how services research guided by these perspectives might inform the development of community-based services aimed at reducing risk of arrest.

Longitudinal patterns of offending during the transition to adulthood in youth from the mental health system

Arrest rates among the population of youth who have been served in child mental health systems are known to be high during adolescence and young adulthood, but individual longitudinal patterns have not been examined. The present study used developmental trajectory modeling, a contemporary method used widely in criminology, to examine clusters of individual criminal justice involvement patterns at ages 8 through 25, from database records of 131 individuals in public adolescent mental health services. Three groups of particular concern emerged: one with increasingly high offense rates and two with moderate to high violent offense rates that did not desist. Offense patterns in these groups indicate that early intervention should occur before age 15. Some risk factors were identified. Peak offending for most groups occurred between ages 18 and 20. Implications of these findings for mental health services during the transition to adulthood are offered.

The efficacy of involuntary outpatient treatment in Massachusetts

One means to address some of the unintended consequences of the shift of treatment for individuals with serious mental illness from hospitals to communities has been involuntary outpatient treatment (IOT). Using Massachusetts data, 19 patients with court orders for IOT were matched to all and to best fits on demographic and clinical variables, and then to individuals with the closest fit on utilization before the IOT date. Outcomes indicated the IOT group had significantly fewer admissions and hospital days after the court order. The full impact of IOT requires more study, particularly directed toward IOTs effects on insight and quality of life.

Mothers with severe mental illness caring for children

This research identifies and describes the Massachusetts population of Department of Mental Health (DMH) case-managed women with severe mental illness who are caretakers of their minor children (N = 314), and compares their demographic and clinical characteristics and service utilization with those of a matched, randomly selected group of DMH case-managed noncaretaking women (N = 328) using the Client Tracking System database. Caretakers were significantly younger, had less formal education, and had higher rates of marriage than did noncaretakers. They are diagnosed more often with major affective disorders and less often with psychotic disorders. Caretakers demonstrate higher levels of functioning and are less likely to have a representative payee. Although caretakers function better, the groups do not differ significantly in their use of DMH services. This is the first systematic, statewide effort to specify the unique characteristics of this substantial group of women with severe mental illness who are caring for their children.

The Changing Role Of The State Psychiatric Hospital

State hospitals were once the most prominent components of U.S. public mental health systems. But a major focus of mental health policy over the past fifty years has been to close these facilities. These efforts led to a 95 percent reduction in the countrys state hospital population. However, more than 200 state hospitals remain open, serving a declining but challenging patient population. Using national and state-level data, this paper discusses the contemporary public mental hospital, the forces shaping its use, the challenges it faces, and its possible future role in the larger mental health system.

Community mental health services and the prevalence of severe mental illness in local jails: are they related?

The excessive prevalence of severe mental illness noted in correctional settings has sometimes been attributed to the inadequacy of community based mental health services. This study examines the prevalence of severe mental illness in two jails situated within catchment areas featuring markedly different levels of community mental health services. We use these settings to test the hypothesis that greater levels of services in a community are associated with lower prevalence of severe mental illness in the communitys jail. An epidemiologic approach, using standardized field instruments, was used to estimate the prevalence of major mental illness in detainees arriving at the two sites over a 6-month period. The hypothesis that greater levels of mental health resources in a community would be associated with lower prevalence of mental illness in the communitys jail was not supported. These findings suggest that community-based mental health services by themselves do not affect the prevalence of mental illness in jail.

Envisioning the next generation of behavioral health and criminal justice interventions.

The purpose of this paper is to cast a vision for the next generation of behavioral health and criminal justice interventions for persons with serious mental illnesses in the criminal justice system. The limitations of first generation interventions, including their primary focus on mental health treatment connection, are discussed. A person-place framework for understanding the complex factors that contribute to criminal justice involvement for this population is presented. We discuss practice and research recommendations for building more effective interventions to address both criminal justice and mental health outcomes.