Phase II Trial of Dolastatin-10, a Novel Anti-Tubulin Agent, in Metastatic Soft Tissue Sarcomas.

PATIENTS: Soft tissue sarcomas are uncommon malignancies with few therapeutic options for recurrent or metastatic disease. Dolastatin-10 (Dol-10) is a pentapeptide anti-microtubule agent that binds to tubulin sites distinct from vinca alkaloids. Based on the novel mechanism of action, limited activity of other anti-microtubular agents, and anti-neoplastic activity in pre-clinical screening of Dol-10, this multi-institutional phase II study was conducted to determine the objective response rate of Dol-10 in recurrent or metastatic soft tissue sarcomas that had not been treated with chemotherapy outside of the adjuvant setting. METHODS: Dol-10 was given intravenously at a dose of 400 mug/m(2) and repeated every 21 days. Toxicities were assessed using the Common Toxicity Criteria (version 2.0). Radiographic studies and tumor measurements were repeated every two cycles to assess response [Miller AB, et al. Cancer 1981; 47(1): 207]. RESULTS: Dol-10 was associated with hematological toxicity and with some vascular toxicities. There was no significant gastrointestinal, hepatic or renal toxicity. There was one death on study due to respiratory failure. There were no objective responses in 12 patients treated with Dol-10. DISCUSSION: Based on this phase II trial, further study of Dol-10 on this schedule is not recommended in advanced or metastatic soft tissue sarcomas.

The influence of granulocyte macrophage colony-stimulating factor and prior chemotherapy on the immunological response to a vaccine (ALVAC-CEA B7.1) in patients with metastatic carcinoma.

Granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to be an effective vaccine adjuvant because it enhances antigen processing and presentation by dendritic cells. ALVAC-CEA B7.1 is a canarypox virus encoding the gene for the tumor-associated antigen carcinoembryonic antigen (CEA) and for a T-cell costimulatory molecule, B7.1. After an initial dose escalation phase, this study evaluated vaccination with 4.5 x 10(8) plaque-forming units ALVAC-CEA B7.1 alone (n = 30) or with GM-CSF (n = 30) in patients with advanced CEA-expressing tumors to determine whether the addition of the adjuvant GM-CSF enhances induction of CEA-specific T-cells. Patients were vaccinated with vaccine intradermally every other week for 8 weeks. GM-CSF was given s.c. for 5 days beginning 2 days before vaccination. Patients with stable or responding disease after four immunizations received monthly boost injections alone or with GM-CSF. Biopsies of vaccine sites were obtained 48 h after vaccination to evaluate leukocytic infiltration and CEA expression. Induction of peripheral blood CEA-specific T-cell precursors was assessed in HLA-A2 positive patients by an ELISPOT assay looking for the production of IFN-gamma. Therapy was well tolerated. All of the patients had evidence of leukocytic infiltration and CEA expression in vaccine biopsy sites. In the patients receiving GM-CSF, leukocytic infiltrates were greater in cell number but were less likely to have a predominant lymphocytic infiltrate compared with patients receiving vaccine in the absence of the cytokine adjuvant. After four vaccinations, CEA-specific T-cell precursors were statistically increased in HLA-A2 positive patients who received vaccine alone. However, the GM-CSF plus vaccine cohort of HLA-A2 positive did not demonstrate a statistically significant increase in their CEA-specific T-cell precursor frequencies compared with baseline results. The number of prior chemotherapy regimens was negatively correlated with the generation of a T-cell response, whereas there was a positive correlation between the number of months from the last chemotherapy regimen and the T-cell response. ALVAC-CEA B7.1 is safe in patients with advanced, recurrent adenocarcinomas that express CEA, is associated with the induction of a CEA-specific T-cell response in patients treated with vaccine alone but not with vaccine and GM-CSF, and can lead to disease stabilization for up to 13 months.

Testing a life-style risk model in an Afro-American population.

This article discusses the results of a research study investigating the possible relationship between life-style risk factors, e.g., weight, dietary patterns, stress, activity and smoking in the development of diseases. The author concludes that there is a need for individuals to improve weight, dietary patterns, reduce stress and increase recreational activity to reduce life-style risk.

The grief of parents of murdered children: a suggested model for intervention.

The grief of parents who have lost children to murder is extreme, prolonged, and unique. The authors, themselves bereaved by homicide, suggest a model to facilitate understanding such grief and to guide intervention. The model postulates that homicide survivor grief occurs in three arenas: the private, personal world; the public world of the media; and the world of the criminal justice system. Each arena contains features unique to homicide survivor bereavement. These features are described for the reader.

Advances in meta-analysis as a research method.

Meta-analysis is a method of data analysis applied to summarizing research findings, both quantitative and qualitative summaries of individual studies. Rooted in the fundamental values of the scientific enterprise of replicability, causal and correlational analysis, it is useful for answering three general questions: What is the central tendency or typical study outcome? How much variability exists among study outcomes? What is the explanation of the variability? Advanced statistical and mathematical techniques are being used in counting studies with significant and non-significant findings; in combining effect size estimates based on fixed- or random-effects models; in the use of general linear models; and, Bayesian procedures. The methodology of meta-analysis and suggestions for publications are presented as well as appropriate software programs available for use in the meta-analytic process are explored. The benefits of meta-analysis as a research method in effecting health policy development is offered as a pragmatic perspective for future consideration. Conclusions have implications for the use of meta-analysis as a teaching strategy and as a methodology in nursing research and other applied sciences. In view of the rapid pace of knowledge development and increased public demand for accountability, meta-analysis offers an opportunity for organizing phenomena which gives direction for provision of quality health care.

Research methodology. Part IV: Understanding canonical correlation analysis.

Canonical correlation is presented as a technique to determine how sets of dependent variables are related with sets of independent variables. Canonical correlation reveals the strength of the relationship between the clusters using case data as illustration, three pairs of clusters (factors or profiles) emerged. Interpretation of the clusters are presented. As indicated in the case presentation, Canonical Correlation (CA) is the fourth in a series of methodologies selected for illustration as precursors to advanced statistics and modeling. In this paper, background will be given, a schematic example presented, sample size and CA, SPSS procedure to perform CA, and interpretation of CA and possible uses of CA in nursing research.

Research methodology. Part III: understanding multiple correlation analysis and multiple regression.

This is part III of a case series on research methodology with additional case demographic information. The relationship of a dependent variable with two or more independent variables is explained and used to illustrate multiple correlation and multiple regression.

Research methodology: Part II, Essentials of factor analysis.

This article is part two of our four part series on basic statistical analytical methods. Using a case method presentation, the basic essentials of factor analysis is described.

Research methodology. Part I: Understanding correlational analysis.

This paper is part one of a four part series on basic statistical analytical methods. Using a case method presentation, the basic essentials of correlational analysis is described.

Norplant: nursing's responsibility in procreative rights.

PIP: Trained nurse practitioners can insert the contraceptive implant system Norplant. Courts may call on nurse practitioners to insert Norplant in poor women. Legislative and prosecutorial initiatives to coerce low-income women and female parolees to use contraceptives should not become law. Offering incentives to poor women is another form of involuntary fertility control. Eugenics and the sterilization campaign of the past form the basis for judicial and legislative initiatives to coerce women to accept Norplant. Providers have inserted Norplant in women from other countries without the women knowing the side effects. Often medical personnel do not remove Norplant when women request its removal. Nurses have historically played a public policy role in reproductive rights. They have promoted procreative rights through their roles as educators/counselors, advocators, empowerers, and practitioners. Nursing's power and expertise help protect against punitive government intrusion in reproductive rights and make sure that contraceptive breakthroughs (e.g., Norplant) strengthen procreative choices. They can guide the development of sound public policy. Norplant is not the answer to poverty, child abuse, or drug abuse. Nursing research can help policymakers become more responsive to the contraceptive and reproductive rights of everyone.^ieng

The efficacy of group therapy by nurses for hospitalized patients.

To investigate the effect of group therapy by nurses on chronic psychiatric patients, 100 chronic psychiatric patients between the ages of 30 and 59, hospitalized on two regressed, continued care wards and one community care preparation ward at the Veterans Administration Hospital, Augusta, Georgia, were paired, using the variables of age, diagnosis, and number and duration of hospitalizations, and assigned to five control and five experimental groups (ten patients per group). Experimental subjects attended group therapy sessions, led by two nurses, twice a week; control subjects did not. All subjects were evaluated by two nursing assistants on the NOSIE-30 scale prior to group therapy, after ten sessions, and at the end of 20 sessions. Paired t-tests were computed on pre- and postdata for six factors. Data from an evaluation scale of the most regressed ward indicated leader-patient interaction. Sociogram evaluation revealed 79 percent positive interactions. Topics most frequently mentioned were nature in regard to delusional systems and interpersonal relations in the hospital and home. Findings supported the use of group therapy with chronic regressed psychiatric patients.