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Purpose: Intergroupe Francophone de Cancérologie Thoracique-0401 phase II trial aimed to evaluate the efficacy and safety of gefitinib as a first-line treatment for patients with adenocarcinoma with bronchioloalveolar carcinoma subtype (ADC-BAC)., Methods: Chemotherapy-naive patients (n = 88) with advanced ADC-BAC were treated with 250 mg/d of gefitinib. The primary objective was assessment of disease control rate (DCR [objective response + stable disease]) at 3 months using World Health Organization criteria. A disease control rate of 25% or greater would be of interest in this patient population. Progression-free survival (PFS), overall survival (OS), and toxicity were the secondary criteria. Clinical and disease characteristics that conferred a favorable prognosis under gefitinib were also analyzed., Results: Disease control was achieved in 25 patients (29.4%); 11 patients (12.9%) had partial response and 14 (16.4%) had stable disease. Median PFS was 2.9 months (95% confidence interval [CI], 2.3-3.2) and median OS was 13.2 months (95% CI, 10.2-17.3). Never smokers, patients with low respiratory symptoms score, occurrence of cutaneous rash, and nonmucinous ADC-BAC subtype were associated with increased probability of disease control. Nonmucinous ADC-BAC was associated with increased PFS and OS at 3 years. Patients with nonmucinous BAC had longer OS and PFS compared with patients with other ADC-BAC variants; median PFS for nonmucinous BAC was 11.3 months (95% CI, 3.2-14.7), whereas it was 2.6 months (95% CI, 2.1-3) for mucinous BAC. As expected, toxicity was low, with dermatological problems, diarrhea, and nausea being the most common adverse events., Conclusion: Results from the Intergroupe Francophone de Cancérologie Thoracique-0401 trial demonstrate that gefitinib combines efficacy with low toxicity and is, therefore, suitable as a first-line treatment of advanced ADC-BAC, particularly in patients with nonmucinous BAC subtype.

The aim of this animal study was to test the hypothesis that low and high doses of 17beta-estradiol (E2) may differentially influence airway responsiveness. Ovariectomized female rats received either placebo or E2 (10 or 100 microg/kg per day) for 21 days. The concentration of inhaled acetylcholine (ACh) required to double pulmonary resistance (EC200 RL) was calculated as the in vivo index of airway responsiveness. Ex vivo airway responsiveness was evaluated by the cumulative concentration-response curve (CCRC) of isolated tracheal segments. Rats treated with low-dose E2 were less responsive to ACh than rats given either placebo or high-dose E2 (P=0.003). Ex vivo, low-dose E2 treatment decreased (P=0.01) and high-dose E2 increased the potency of ACh (P<0.001) compared to placebo. E2 treatment did not alter smooth muscle cross-sectional area or epithelium thickness. Accumulation of liquid within the tracheal mucosa was moderately enhanced by high-dose E2 treatment compared with animals given either placebo or low-dose E2 (P=0.03). We conclude that E2 treatment has differential, dose-dependent effects on airway responsiveness to acetylcholine.

Pulmonary hypertension (PH) is a classic complication associated with intravenous drug addiction. Various pathogenic mechanisms may be involved but HIV infection now appears to be the main etiologic factor. We report herein 10 case of PH occurred in HIV+ intravenous drug abusers. Each patient had several pathogenic factors: HIV infection, pills crushed and intravenously injected (6 cases), heavy and repeated consumption of amphetamines and cocaine (6 cases), cirrhosis with portal hypertension (2 cases), anticardiolipid antibodies (2 cases). The clinical findings were similar to those reported for PH in HIV seronegative patients; however, in 5 cases, opiates could have alleviated dyspnea, which became perceptible only at the time of drug withdrawal. Because drug addicts usually exhibit a weak support for medical prescriptions, long term therapy needing regular follow-up such as anticoagulation appears to be hazardous and even dangerous. The prognosis remains poor, since the progression of PH led to the death of one third patients within the year following the diagnosis.