Maintenance therapy with gefitinib after first-line chemotherapy in patients affected by advanced non-small cell lung cancer.

BACKGROUND: Chemotherapy extends life for patients with advanced non-small cell lung cancer (NSCLC). Second-line treatment of NSCLC includes the use of cytotoxic drugs; however, toxicity is of concern. One molecular target for lung cancer is the epidermal growth factor receptor (EGFR). Gefitinib (Iressa) is an EGFR inhibitor. The aim of our study was to evaluate time to progression (TTP), overall survival (OS) and toxicities in a population affected by NSCLC using Iressa as maintenance therapy after first-line chemotherapy. PATIENTS AND METHODS: Thirty patients were enrolled with stable disease or partial response. Six cycles of a platinum-based first-line chemotherapy were administered. Iressa was administered at the dose of 250 mg/d. RESULTS: Median TTP was 5 months; median overall survival was 8 months. TTP for adenocarcinoma and non-adenocarcinoma patients was 10 months and 3.2 months, respectively. No toxic effects were seen in 80% of the patients; 17% of the patients had grade 1 follicolitis. OS for adenocarcinoma and non-adenocarcinoma patients were 15 and 5.9 months, respectively. CONCLUSION: Gefitinib could be an ideal second-line therapy for adenocarcinoma patients responding to first-line chemotherapy.

Evaluation of the impact of guidelines on tuberculosis control in Italy. National AIPO "Tuberculosis" Study Group. Associazione Italiana Pneumologi Ospedalieri.

This study was performed in Italy, where a central tuberculosis (TB) unit and national guidelines on TB control are lacking. The objectives of the study were: 1) to design comprehensive guidelines on TB control; 2) to discuss them within the scientific community and to present them to administrators and politicians: and 3) to evaluate their impact from a public health perspective. The ultimate goal was to improve TB control nationwide through a consensus-based initiative. The steps taken in planning were as follows: 1) an assessment of control activities operating in the country was made by means of three surveys: 2) guidelines on TB control were designed, presented, discussed and approved during three Consensus Conferences involving representatives of organizations operating in TB control and services; and 3) their impact was evaluated by means of objectively verifiable indicators (availability of TB case definition, regional control programmes, surveillance reports, guidelines on treatment, staff training). Regional TB control programmes were implemented in three major regions (30% of the national population), and are in advanced process in other four regions (29% of the national population). The protocol approved during the three Consensus Conferences benefited from the co-ordinated action of governmental and nongovernmental organizations. Its impact on tuberculosis control was positive, particularly at the regional level.

Malignant pleural mesothelioma. Multivariate analysis of prognostic factors on 113 patients.

We report on clinical features of 113 cases of pathologically confirmed Malignant Pleural Mesothelioma, observed in Genoa (Italy) between 1979 and 1985. Overall median survival was 10 months. Among the pretreatment variables studied (age, sex, asbestos exposure, pathological type, chest pain and dyspnea at the time of diagnosis), the only one of prognostic value in the univariate analysis was the histological subtype: median survivals were 12, 7 and 4 months for the patients in the epithelial, mixed, and fibrosarcomatous groups, respectively (p = 0.0012). A multivariate analysis confirmed the independent predictive power of the histotype (p = 0.0022). A review of literature data concerning prognostic factors in Malignant Pleural Mesothelioma is presented.

Tissue polypeptide antigen (TPA) in pleural effusions.

The usefulness of tumor marker assay in pleural effusions for differential diagnosis is still debated. From the observation of common antigens on tissue polypeptide antigen (TPA) and keratins 8, 18 and 19 and vimentin, all substances contained in normal and neoplastic mesothelium, we felt it opportune to evaluate the use of TPA assay in 105 pleural effusions (46 benign and 59 malignant). The values were much higher than those found in blood. In hydrothorax the median value was 454 U/l (range, 59-1923), in exudative effusions 846 U/l (range, 258-4485), in metastatic pleural effusions 1277 U/l (range, 58-32352) and in mesotheliomas 7705 (range, 759-16000). The maximum value found in nonmalignant effusions was 4485 U/l; this value was taken as a cutoff level, so only 29.9% of the tumors were positive to the test. Our results showed this assay to be not very important for a differential diagnosis of malignant and nonmalignant pleural effusions. Nevertheless, the different TPA patterns in mesotheliomas (66.6% positive) and metastatic pleural effusions (15.9%) suggest that further studies are warranted.

Adriamycin, cyclophosphamide and etoposide (ACE) in the treatment of small cell lung cancer.

Thirty-five small cell lung cancer (SCLC) patients were treated with combination chemotherapy including adriamycin, cyclophosphamide, etoposide (ACE). Out of 32 evaluable patients there were 21.9% complete responses and 53.1% partial responses with an overall median survival of 37 weeks (50 weeks for patients with limited disease and 34 weeks for patients with extended disease). Toxicity was generally well tolerated. In conclusion the ACE regimen results in being active and safe in the treatment of SCLC.

Etoposide and high-dose cisplatin in good-risk patients with advanced squamous cell carcinoma and adenocarcinoma of the lung.

Fifty patients with advanced squamous cell carcinoma and adenocarcinoma of the lung having good prognostic features (performance status less than or equal to 2; weight loss less than or equal to 10%; age less than or equal to 70 years; absence of brain metastases; and no prior treatment) were treated on an outpatient basis with etoposide (120 mg/m2 on Days 1, 3, and 5) and cisplatin (60 mg/m2 on Days 1 and 2) every 21-28 days. One complete response and 14 partial responses were observed, with a median duration of response of 170 days and an overall median survival of 230 days. Toxicity was generally mild. Despite the high-dose cisplatin employed and the choice of patients with favorable prognostic factors in this study, results of this therapy remain disappointing.

The role of concurrent determinations of pleural fluid and tissue carcinoembryonic antigen in the distinction of malignant mesothelioma from metastatic pleural malignancies.

A combined determination of pleural fluid and tissue carcinoembryonic antigen (PF-CEA and T-CEA) by radioimmunoassay and immunoperoxidase staining technique respectively was performed in patients with malignant mesotheliomas (12), metastatic pleural carcinomas (17) and benign pleural diseases (seven). All PF-CEA-positive (greater than 39 ng/ml) cases were T-CEA-positive metastatic carcinomas. In contrast, 4/30 PF-CEA-negative (less than 39 ng/ml) cases were T-CEA-positive metastatic carcinomas (three cases) and idiopathic pleuritis (one case). These results suggest that CEA, though present in the tumour, is not always released in measurable amounts in effusions. Hence T-CEA content should be determined in the PF-CEA-negative cases when an early and definite diagnosis of tumour type is required to enable correct management of these patients. These ancillary tests aim at enhancing the level of confidence of the routine morphological diagnosis of serous surface malignancies in living patients using minimal intervention instead of resorting to open chest surgery.

Carcinoembryonic antigen in pleural effusions. Diagnostic value in malignant mesothelioma.

The usefulness of the determination of carcinoembryonic antigen (CEA) in pleural effusion was assessed as an aid to the diagnosis of malignant mesothelioma. The concentration of CEA was determined by radioimmunoassay (RIA) in pleural fluid of 213 adult patients, of which 140 had malignant pleural disease and 73 had nonmalignant pleural disease. Pleural fluid CEA (PF CEA) was lower than 12 ng/ml in all 15 mesotheliomas. The statistical probability of a mesothelioma associated with PF CEA greater than 15 ng/ml was found to be zero. The CEA assay in pleural effusion proved to be a valuable adjunct to other diagnostic procedures in differentiating the malignant mesothelioma from metastatic serosal spread.