Chemoradiation for locally advanced squamous cell carcinoma of the head and neck for organ preservation and palliation.

OBJECTIVES: To measure the efficacy and toxic effects of our chemoradiotherapy regimen by means of response and survival in patients with advanced squamous cell carcinoma of the head and neck (HNSCC) for organ preservation in resectable disease or palliation in unresectable disease. DESIGN: All patients underwent evaluation by the multidisciplinary head and neck cancer team, with pathological diagnosis and staging. All patients underwent assessment for response to therapy using results of physical examination and radiologic imaging. Patients were followed up at 3-month intervals for a planned period of 5 years. SETTING: Academic center. PATIENTS: Thirty-eight previously untreated patients with newly diagnosed HNSCC were treated from June 1, 1996, through December 31, 1998, of whom 20 had resectable and 18 had unresectable tumors. INTERVENTION: Patients received intravenous cisplatin, 100 mg/m(2) for 1 hour on days 1 and 29; a 24-hour continuous infusion of fluorouracil, 1000 mg/m(2) on days 1 through 4 and 29 through 32; and radiation therapy, 150 rad twice daily for 12 days. The patients were given a 7- to 10-day break, and radiation therapy was restarted on day 29 for 12 additional days (total dose, 7200 rad). MAIN OUTCOME MEASURES: Complete, partial, and total response rates; disease-free survival; overall survival; and toxic effects. RESULTS: Toxic effects of treatment were moderately severe, including grades III to IV mucositis (89%), neutropenia (71%), and renal toxic effects (8%). In the 18 patients in the unresectable group, complete response in the 17 primary tumors and 15 cervical nodal metastases was achieved in 12 (71%) and 9 (60%), respectively; in the 20 patients undergoing organ preservation, complete response rates were 100% in the 23 primary tumors and 15 cervical nodal metastases. Complete response for all 38 patients was achieved in 31 (82%). In the unresectable group, the Kaplan-Meier relapse-free survival estimate is 56%, with follow-up from 29 to 45 months. In the organ preservation group, 75% of patients are alive without disease, and 8 have been followed up for 36 to 48 months. Of the 5 patients who have died, only 2 died of disease, with recurrences at 13.0 and 16.5 months. CONCLUSIONS: Chemoradiotherapy consisting of cisplatin, fluorouracil, and twice-daily external beam radiation is highly effective in achieving durable complete responses in patients with resectable HNSCC undergoing organ preservation and patients with unresectable HNSCC undergoing palliation. Toxic effects of this regimen were moderate to severe.

Phase I trial of twice-weekly gemcitabine and concurrent radiation in patients with advanced pancreatic cancer.

PURPOSE: To determine the maximum-tolerated dose, dose-limiting toxicities, and potential antitumor activity of twice-weekly gemcitabine and concurrent radiation in patients with locally advanced pancreatic cancer. PATIENTS AND METHODS: Nineteen patients with histologically confirmed adenocarcinoma of the pancreas were studied at the Wake Forest University Baptist Medical Center and the University of North Carolina at Chapel Hill. The initial dose of gemcitabine was 20 mg/m(2) by 30-minute intravenous infusion each Monday and Thursday for 5 weeks concurrent with 50.4 Gy of radiation to the pancreas. Gemcitabine doses were escalated in 20-mg/m(2) increments in successive cohorts of three to six additional patients until dose-limiting toxicity was observed. RESULTS: The dose-limiting toxicities at 60 mg/m(2) given twice-weekly were nausea/vomiting, neutropenia, and thrombocytopenia. Twice-weekly gemcitabine at a 40-mg/m(2) dose was well tolerated. Of the eight patients eligible for a minimum follow-up of 12 months, three remain alive, one of whom has no evidence of disease progression. CONCLUSION: A dose of twice-weekly gemcitabine at 40 mg/m(2) produced mild thrombocytopenia, neutropenia, nausea, and vomiting when delivered with concurrent radiation to the upper abdomen in patients with advanced pancreatic cancer. These data suggest this regimen is well tolerated and may possess significant activity. These data and other observations have resulted in a phase II Cancer and Leukemia Group B study to ascertain the efficacy of this treatment regimen in patients with locally advanced pancreatic cancer.

Role reward and role stress in managerial and professional women.

The importance of balancing personal and work demands has become increasingly relevant in recent years as large numbers of women move into the labour market full time. The present study was designed to examine differences in role rewards and stress amongst a group of 163 managerial and professional women. Subjects completed a questionnaire about the stress and rewards associated with their work and family roles. Although no significant differences were found between managerial and professional women, the mean scores indicated the role of employee is both the most rewarding and the most stressful. Findings are discussed in terms of sample occupation and changing home-work patterns.

Phase I-II study of advanced head and neck squamous cell carcinoma patients treated with recombinant human interferon gamma.

The association of immunodeficiency with head and neck squamous cell carcinoma has generated the concept of supplying immunologically active agents as a means of treating these cancers. One of the most active immunologic messengers is interferon gamma, which has been observed in our laboratories to also have a direct cytotoxic effect on cultures of squamous cell carcinoma derived from the head and neck. To test the feasibility of treating patients with advanced but resectable head and neck cancer with this agent, we designed a phase I-II trial of recombinant human interferon gamma using a 24-hour infusion repeated weekly for four times. In this study, both tumor and immunologic parameters were studied before and after treatment. Eight patients were entered into the study with the highest recombinant human interferon gamma dose attempted being 0.25 mg/m2 per 24 hours. Minimal side effects were observed. Three patients had clinically measurable responses, four had stabilization of disease, and one had progression while receiving treatment. Histopathologic results of treatment were similar to in vitro observations. Necrosis, as well as differentiation of tumor cells, was observed. In some tumors there was a marked decrease in cellularity without a change in tumor volume due to increased extracellular keratin deposition. Our study indicates that evaluation of adoptive immunotherapy trials in head and neck cancer needs to include parameters other than simple tumor regression as an end point, otherwise therapeutically important lymphokine-induced changes may be missed. Further evaluation of recombinant human interferon gamma and agents that induce human interferon gamma are warranted.

Adolescents' self-perceptions of competence in life skill areas.

The perceptions of a sample of 1061 adolescents of their own competence in a number of life-skill areas were assessed. Three sets of scales were used-those concerned with competence viewed as efficacy in various life areas and situations, those concerned with competence as the satisfaction of goals based on Maslow's hierarchy of needs, and assessments of the structural complexity of performance on a short essay task. In addition to comparisons among self-perceptions for different areas, a number of major comtextual and personal variables was studied for differences in self-perceptions-course type, school type, state, career aspirations and expectations, major life concerns, age, and gender. There were strong gender differences that suggested that females generally underrated their own competence. The major educational or work contexts reflected important differences in patterns of self perceptions of skill. Differences between those with different major life concerns and career hopes and expectations aligned with course type differences. Finally, there were strong indications that the self-perceptions of competence that were reported formed a strong general factor, favoring the notion of generic over domain specific self-perceptions.

Orientations to the future: A comparison of adolescents in Australia and Singapore.

Using an event-listing approach, this study examined the personal and societal future orientations of 15-year-old males and females in Singapore and Sydney. Three aspects were examined: content, affect, and time span. Overall, the study found that adolescents perceived their personal and societal features in separate noninterlocking planes, seeing more pleasant, proximal, personal futures, and more unpleasant, distal, societal futures, especially in relation to nuclear war and political problems. Demographic and personal construct variables influenced this general pattern of future orientation.

Work and leisure relationships: An exploration of life possibilities during adolescence.

This study explored the relationship between leisure preferences and work/occupational aspiration for adolescents in Singapore and Australia. Three hypothesized relationships between the domains of "spillover", "compensation", and "segmentation" were investigated. Except for females in the Australian sample, it appeared that adolescents saw leisure preferences and occupational aspirations as two independent spheres of their personal futures, supporting the segmentation hypothesis.

Decade differences in rural adolescents' views of life possibilities.

In a small-town high school ninth-graders were administered the same research instrument in 1967 and 1979. They listed events they thought would happen to them in the future, occupations, free-time activities, and people known, and answered questions related to perceptions of autonomy and family decision making. Except for the time span of future events, which remained between four and five years ahead, the later group showed many significant increases in cognitive possibilities, especially for occupations and free-time activities. Boys in 1979 perceived less family cohesiveness and girls more autonomy than their 1967 counterparts. Content analyses showed expansion of the girls' possibilities into formerly male-stereotyped occupations and an increase in perceptions of sexual and possibly antisocial activities, particularly among boys.

Who stays? who leaves? an examination of sex differences in staying and leaving.

This article examines some of the major variables associated with the "staying" and "leaving" process, particularly as it operates similarly or differentially for male and female adolescents. Sixty attitude statements about aspects of school, parents, peers, teachers, and value orientations were obtained from 796 adolescents and factor analyzed. This subset of independent variables, together with a set of personality and ability measures, was then used to predict "staying" or "leaving" status. The discriminant analysis was undertaken using "leaving" status and sex (LVSEX) as the dependent variable. Using a stepwise solution method of discriminant analysis, two significant functions were identified-the first suggesting a sex dimension, the second a stayer-leaver dimension.