Benefit of continuous positive airway pressure on work quality in patients with severe obstructive sleep apnea.

BACKGROUND: The objective of this prospective study was to assess the effect of CPAP therapy on job productivity and work quality for patients with severe obstructive sleep apnea (OSA). METHODS: A convenience sample of patients diagnosed with severe OSA using polysomnography or polygraphy and with a therapeutic indication for CPAP was enrolled in our study. Patients completed two self-administered questionnaires: the first before CPAP therapy and the second during the first 6 months after CPAP treatment. OSA symptoms were evaluated through self-administered questionnaires assessing potential effects on occupational activity: excessive daytime sleepiness was rated by the Epworth Sleepiness Scale (ESS), emotional status was rated by the Hospital Anxiety and Depression (HAD) scale, work quality was rated by the Work Role Functioning Questionnaire (WRFQ). RESULTS: Forty patients (30 men, mean age 47.3 ± 8.3, mean BMI 31.6 ± 7.4, mean apnea-hypopnea index 51.8 ± 16.3) showed a beneficial effect of CPAP therapy on ESS score (mean 11.6 to 8.2, p < 0.0001), the anxiety dimension (mean 57.5% to 20%, p = 0.0002), and the overall anxiety-depressive score (mean 50% to 22.5%, p = 0.0006). Mean WRFQ scores were significantly improved in the second questionnaire for the dimensions of timetable requirements (69.3% to 83.5%, p < 0.0001), productivity requirements (71.4% to 82.2%, p < 0.0001), mental requirements (72.0% to 84.3%, p < 0.0001), and social requirements (82.6% to 91.4%, p < 0.003). CONCLUSIONS: We observed that adherence to CPAP therapy for patients with severe OSA mitigates the impact of symptoms on work including excessive daytime sleepiness, impairment of work ability, and anxiety and depressive disorders.

Subcutaneous interleukin-2, interferon alfa-2a, and continuous infusion of fluorouracil in metastatic renal cell carcinoma: a multicenter phase II trial. Groupe Français d'Immunothérapie.

PURPOSE: A phase II trial was designed to determine the efficacy and the tolerance of interleukin-2 (IL-2), interferon alfa-2a (IFNalpha), and fluorouracil (5-FU) in patients with metastatic renal cell carcinoma. PATIENTS AND METHODS: One hundred eleven patients were included. Patients received subcutaneous IL-2 9 x 10(6) IU daily for 6 days and IFNalpha 6 x 10(6) IU on days 1, 3, and 5 every other week for 8 weeks. 5-FU was administered through a continuous infusion at 600 mg/m2 for 5 consecutive days for 1 week every 4 weeks. RESULTS: The response rate was 1.8% (95% confidence interval [CI], 0% to 4.3%) with only two partial responses (PRs). Toxicity was moderate with 3.6% grade 4 events and two deaths related to treatment. CONCLUSION: This regimen of IL-2, IFNalpha, and 5-FU in patients with metastatic renal cell carcinoma was ineffective. The results raise the question of the dose and schedule of subcutaneous cytokines that must be used in metastatic renal carcinoma.

Long-term follow-up of patients with metastatic renal cell carcinoma treated with intravenous recombinant interleukin-2 in Europe.

PURPOSE: The median survival for patients with metastatic renal cell carcinoma (mRCC) is generally < 1 year. Immunotherapy with high-dose recombinant interleukin (IL)-2 has been reported to produce objective responses in approximately 15% of treated patients and is associated with durable complete responses and prolonged survival in responding patients. The impact of IL-2 therapy on survival of metastatic renal cell carcinoma patients has begun to emerge, based on long-term follow-up data from large databases. Combinations of IL-2 and interferon alfa (IFN-alpha) have also been intensively investigated in mRCC. PATIENTS AND METHODS: Between 1987 and 1990, 281 mRCC patients were treated with continuous infusion IL-2 in three European multinational, single-arm phase II trials. Long-term treatment outcomes for these patients were analyzed, and the results are presented here. The results of a large, randomized French cooperative group trial (the Cancer Renal Cytokine [CRECY] study) that enrolled 425 patients between 1991 and 1995 are also summarized. Patients on this trial were randomized to treatment with IL-2 alone, IFN-alpha alone, or the combination. RESULTS: Among patients included in the 281-patient database, the objective response rate was 15%. Median survival was 10 months; 41% of patients were alive at 1 year, 22% were alive at 2 years, and 8% were alive at 5 years. Among patients with a complete or partial response, 60% and 18% were alive at 5 years, respectively. No clinical factors were predictive for response or survival; however, no patient with a high endogenous IL-6 level at diagnosis responded to IL-2 therapy. The CRECY trial demonstrated that the combination of IL-2 and IFN-alpha induced a significantly higher response rate (P < 0.01) and significantly improved 1-year event-free survival (P = 0.01) compared with either agent alone, but overall survival was not significantly different between the three treatment groups. CONCLUSION: The European experience suggests that the 5-year survival rate for metastatic renal cell carcinoma patients treated with high-dose continuous infusion IL-2 therapy is approximately 8% and that the majority of the therapeutic benefit is restricted to patients achieving a complete response. Therefore, given the toxicity, candidates for IL-2 therapy should be carefully selected. The combination of IL-2 and IFN-alpha does not appear to provide additional survival benefit. Efforts to further improve therapeutic outcome for patients with metastatic renal cell carcinoma should focus on understanding the underlying mechanisms of cytokine-induced tumor regression.