Chemoradiotherapy with or without granulocyte-macrophage colony-stimulating factor in the treatment of limited-stage small-cell lung cancer: a prospective phase III randomized study of the Southwest Oncology Group.

PURPOSE: This phase III randomized trial was designed to determine if granulocyte-macrophage colony-stimulating factor (GM-CSF) reduces the hematologic toxicity and morbidity induced by chemoradiotherapy in limited-stage small-cell lung cancer (SCLC). METHODS: This multicenter prospective trial randomized 230 patients to receive chemotherapy and radiotherapy (RT) with or without GM-CSF given on days 4 to 18 of each of six cycles. The primary end point was hematologic toxicity. Secondary end points included the following: nonhematologic toxicities; days of (1) fever, (2) antibiotics, (3) hospitalization, and (4) infection; number of transfusions; drug doses delivered; and response rates and survival. RESULTS: There was a statistically significant increase in the frequency and duration of life-threatening thrombocytopenia (P < .001) in patients randomized to GM-CSF. GM-CSF patients had significantly more toxic deaths (P < .01), more nonhematologic toxicities, more days in hospital, a higher incidence of intravenous (IV) antibiotic usage, and more transfusions. Patients randomized to GM-CSF had higher WBC and neutrophil nadirs (P < .01), but no significant difference in the frequency of grade 4 leukopenia or neutropenia. Patients randomized to GM-CSF had a lower complete response rate (36% v 44%), but the differences were not significant (P = .29). There were no significant differences in survival (median, 14 months on GM-CSF and 17 months on no GM-CSF; P = .15). CONCLUSION: GM-CSF, as delivered in this study, should not be included with concurrent chemoradiotherapy treatment programs for limited-stage SCLC. The simultaneous use of hematopoietic colony-stimulating factors (CSFs) and chemoradiotherapy should be performed only in experimental settings. Chemoradiotherapy programs with cisplatin and etoposide ([VP-16] PE) and simultaneous chest RT produce grade 4 neutropenia and thrombocytopenia in a small-enough proportion of patients that prophylactic hematopoietic growth factors are clinically unnecessary.

Role of recombinant interferon alfa-2a maintenance in patients with limited-stage small-cell lung cancer responding to concurrent chemoradiation: a Southwest Oncology Group study.

PURPOSE: This study was designed to determine if recombinant interferon alfa-2a (rIFN alpha-2a) could prolong remission duration and/or survival in patients with limited-stage small-cell lung cancer (SCLC) who achieved an objective response to chemoradiotherapy. A secondary end point was to assess the toxicity of chronic IFN administration. PATIENTS AND METHODS: One hundred seventy-one of 215 eligible patients achieved an objective response and were eligible to receive rIFN alpha-2a (3 million units [MU]/m2 subcutaneously three times per week escalated to 9 MU/m2 as tolerated) or observation for 2 years. RESULTS: One hundred thirty-two of 140 registered patients were eligible. Sixty-four patients were randomized to receive IFN and 68 to observation alone. The median time from randomization to progression was 9 months on the IFN arm and 10 months on the observation arm (P = .72). The overall median survival time was 16 months on the observation arm versus 13 months on the IFN arm (P = .77). Significant toxicities occurred in the rIFN alpha-2a arm. Grade 3 or higher toxicities included malaise, fatigue, and/or lethargy (30%), leukopenia (14%), neutropenia (13%), dyspnea (13%), nausea (11%), and respiratory infection (6%). Forty-three patients discontinued treatment due to intolerable side effects. CONCLUSION: rIFN alpha-2a in the dose and schedule used in this study failed to prolong response duration or survival in patients with limited-stage SCLC who had previously responded to an induction chemoradiotherapy program. Failure may have been partly related to poor tolerance and inability to complete therapy.

Walking the en-abling/dis-abling symbolic tightrope: toward a constitutive, dialectical view of disability symbolism.

In his essay, 'From handicap to disability: language use and cultural meaning in the United States', Patrick J. Devlieger raises some important and intriguing claims about the symbolic nature of the terms 'handicap' and 'disability'. As communication scholars, we applaud the attention Devlieger devotes to issues that fit comfortably under the general heading of the symbolic construction of health. In this response, we wish to highlight some contributions Devlieger makes and, hopefully, advance this conversation by offering some important extensions of the issues raised in his essay.

"Typical Clinton: brazen it out".

Ten excerpts of both President Clinton's Grand Jury Testimony of August 17, 1998 and of each of two interviews with Hillary Rodham Clinton (Today Show, January 27, 1998; Good Morning America, January 28, 1998) were analyzed. In all of them, the topic under discussion was the President's insistence on his innocence in the Lewinsky case. Comparisons between the President and First Lady revealed long and short within-speaker pauses, respectively. His replies to questions average more than twice the length of hers. Comparisons were also made with other speech genres, including modern presidential inaugural rhetoric. In particular, President Clinton's statement of his innocence at the conclusion of an educational press conference on January 26, 1998 and his prepared statement at the beginning of his Grand Jury Testimony were found to vary notably from all the other corpora. Both are characterized by several of Ekman's (1985, p. 286) behavioral cues for the detection of deception.

Challenges posed by non-random missing quality of life data in an advanced-stage colorectal cancer clinical trial.

Effects of variations in agent, dose, and route of treatment administration on patient reported quality of life (QOL) were examined for 279 patients enrolled on a seven-arm randomized clinical trial (S8905) of 5-FU and its modulation for advanced colorectal cancer. Patients completed QOL questionnaires at randomization and weeks 6, 11, and 21 post-randomization with five QOL endpoints considered primary: three treatment-specific symptoms (stomatitis, diarrhea, and hand/foot sensitivity); physical functioning; and emotional functioning. Patient compliance with the QOL assessment schedule was good, supporting the feasibility of including QOL measures in cooperative group trials. However, death and deteriorating health produced substantial missing data. Cross-sectional analyses indicated that the seven therapeutic arms did not differ in their impact on QOL. Unfortunately, longitudinal analyses of the QOL data were inappropriate given non-random missing data. Graphical presentation of non-random missing data identified the seriousness of this problem and its effect on potential conclusions about QOL during treatment. This problem appears to be particularly challenging in the context of advanced-stage disease. Failure to recognize the presence of non-random missing data can lead to serious overestimates of patient QOL over time.

Improving breast self-examination compliance: a Southwest Oncology Group randomized trial of three interventions.

BACKGROUND: Only 20-40% of U.S. women conduct breast self-examination (BSE). This Southwest Oncology Group experimental study compared the impact of three interventions on BSE compliance. METHODS: Subjects were randomly assigned to one of three arms: (1) physician message; (2) physician message and BSE class; or (3) physician message, BSE class, and reinforcement (phone and postcard). Compliance (frequency and accuracy) was measured by interview at intake and at 6 months and by phone contact at 1 year. Logistic and multiple regression were employed. RESULTS: This analysis included 2,233 subjects from six institutions. At 1 year the percentages of women doing BSE were 59, 62, and 78% for Arms 1-3, respectively; gains over intake frequency (27% average) were significant within each arm (P < or = 0.0001). At both 6 months and 1 year the differences between Arm 1 and Arm 2 average accuracy scores and the differences between Arm 2 and Arm 3 in the percentage of women doing BSE were significant (P < or = 0.0001). Findings within institutions were consistent with the overall findings. CONCLUSIONS: The addition of a BSE class increased accuracy over physician message alone; physician message, BSE class, and reinforcement gave the highest percentage of women doing BSE.