Gemcitabine and cisplatin versus mitomycin, ifosfamide, and cisplatin in advanced non-small-cell lung cancer: A randomized phase III study of the Italian Lung Cancer Project.

PURPOSE: To compare gemcitabine and cisplatin (GC) with mitomycin, ifosfamide, and cisplatin (MIC) chemotherapy in patients with stage IIIB (limited to T4 for pleural effusion and N3 for supraclavicular lymph nodes) or stage IV non-small-cell lung cancer (NSCLC). The end points were the evaluation of quality of life (QoL), response rates, survival, and toxicity. PATIENTS AND METHODS: Three hundred seven patients were randomized to receive either gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 plus cisplatin 100 mg/m(2) on day 2, every 28 days, or mitomycin 6 mg/m(2), ifosfamide 3,000 mg/m(2), and mesna on day 1 plus cisplatin 100 mg/m(2) on day 2, every 28 days. The whole-blood cell count was repeated on day 1 in both arms and weekly in the GC arm before each gemcitabine administration. RESULTS: No major differences in changes in QoL were observed between the two treatment arms. The objective response rate was 38% in the GC arm compared with 26% in the MIC arm (P =.029). The median survival time was 8.6 months in the GC arm and 9.6 months in the MIC arm (P =.877, log-rank test). Grade 3 and 4 thrombocytopenia was significantly worse in the GC arm (64% v 28%, P <.001), whereas grade 3 and 4 alopecia was reported more commonly in the MIC arm (39% v 12%, P <. 001). CONCLUSION: We report an increased response rate without changes in QoL and a similar overall survival, time to progression, and time to treatment failure for the GC when compared with the MIC regimen in the treatment of advanced NSCLC.

Standard versus alternating non-cross-resistant chemotherapy in extensive small cell lung cancer: an EORTC Phase III trial.

Alternating chemotherapy for small cell lung cancer has been tested in several studies. Some have shown positive results that have not been confirmed in other studies. In all of the studies, however, the degree of non-cross-resistance in the regimens was questionable. The EORTC Lung Cancer Study Group developed two equipotent regimens: (i) standard (CDE)-cyclophosphamide, doxorubicin, etoposide; (ii) (VIMP)-vincristine, carboplatin, ifosfamide, mesna, both non-cross-resistance. These two combinations were alternated and compared with the standard chemotherapy regimen in a group of 143 patients with extensive small cell lung cancer. Median survival was 7.6 months in the standard arm and 8.7 in the alternating arm (P = 0.243). Median time to progression was 5.8 and 6.4 months, respectively (P = 0.166). Median response duration was 7.0 and 6.8 months (P = 0.221). The use of two alternating regimens with a proven degree of non-cross-resistance did not result in any improvement in survival in patients with extensive small cell lung cancer.

Phase II study of vinorelbine (Navelbine) in previously treated small cell lung cancer patients. EORTC Lung Cancer Cooperative Group.

26 previously treated patients with progressive recurrent small cell lung cancer (SCLC) were given vinorelbine (Navelbine), 30 mg/m2 weekly. All patients had responded to first-line chemotherapy and were off therapy for at least 3 months. Partial response was observed in 4 out of 25 eligible patients (16%; 95% confidence interval 4-36%), stable disease in 7 patients and progression in 12 patients. The limiting toxicity was a non-cumulative leucopenia (80%, 32% WHO grade 3-4). Reaction at the site of injection was observed in 5 patients, causing treatment discontinuation in 2 cases. Other non-haematological toxicities were moderate. These results suggest acceptable toxicity and some antitumour activity of vinorelbine in pretreated SCLC patients.

Combined measurements of neuron specific enolase and bombesin/gastrin releasing peptide in lung cancer.

Pretreatment serum neuron specific enolase (NSE) and plasma bombesin/gastrin releasing peptide (BN/GRP) were measured in 92 lung cancer patients and 17 controls. The mean level of NSE (p less than 0.001) and BN/GRP (p less than 0.05) was significantly raised in patients with small cell lung cancer (SCLC, n = 62) compared to non-SCLC (n = 30) and controls. The mean concentration of NSE in extensive SCLC was significantly greater (p less than 0.005) than in limited stage but with a substantial overlap of values. Forty-seven out of 62 SCLC patients had at least one of the two markers raised (sensitivity 76%, specificity 83%), 44 had raised NSE (sensitivity 71%, specificity 89%) but only 24 had BN/GRP raised (sensitivity 42%, specificity 91%). At restaging, 16 of 19 patients with SCLC responsive to chemotherapy showed a significant fall of NSE; on the other hand, BN/GRP fell significantly in only 3 patients, remaining unchanged in the majority of responding patients. In conclusion, the combined determination of NSE and BN/GRP in SCLC, at diagnosis and during the follow-up, was not found to be superior to NSE determination alone.

Chronic administration of lonidamine in untreated non-small cell lung cancer of stage III M0-1.

Lonidamine (LND) interferes with the energy mechanisms of neoplastic cells and decreases the oxygen consumption in human and experimental tumors. The present study was performed in advanced non-small cell lung cancer patients, previously untreated, to confirm the preliminary data of activity against this kind of tumor. LND was given orally in three divided doses increasing to 250 mg/m2 over 4 days. Thirty-six patients were evaluable for toxicity and 33 for response. Partial responses were 3 (9%) and stabilization of disease 15 (45,5%). Recorded side effects (testicular pain, nausea and vomiting, skin hyperesthesia) were mostly mild to moderate with the exclusion of myalgias. Chronic treatment was devoid of haematological, renal, cardiac and pulmonary toxicities. LND as single agent seems to be marginally active in advanced non-small cell lung cancer.

Combination chemotherapy for non small cell lung cancer stage III M0-1 with cisplatin and vinblastine in a divided-dose schedule.

Twenty-nine patients with advanced non small cell lung cancer (NSCLC) were treated with a combination of high-dose cisplatin and divided-dose vinblastine. In 27 evaluable patients 15% reached partial response and 59% stable disease. Extension of disease, histological type, performance status and weight loss had no relationship to response. Median duration of response was 10.2 months with a median survival time of 15.4 months in responding patients compared with 14 months of stable disease (p:n.s.) and 4.8 months of progressive disease (p less than 0.001). Gastrointestinal, neurological side effects and the development of a severe debilitation syndrome were the most troublesome toxicities of this treatment. The regimen is not generally suitable for treatment of advanced NSCLC.

Unresectable non-small cell lung cancer chemotherapy with high-dose cisplatin and etoposide.

69 patients with unresectable non-small cell lung cancer, previously untreated, received cisplatin 100 mg/m2 on day 1 and etoposide 120 mg/m2 on days 4, 6, 8 at 4-week intervals. 66 patients were evaluable for tumor response and toxicity. Overall objective response was 25.7% (3 complete responses and 14 partial responses). Response rate in limited disease was 41% and in patients with performance score 0 it was 40%. Squamous cell carcinoma and adenocarcinoma responded in 31 and 24% of evaluable patients. Complete response was associated with a long duration of remission. Median survival time of responding patients was significantly superior to the median of nonresponding patients (p less than 0.001) but compared to stable disease no statistical significance was demonstrable (p greater than 0.05). Hematological and renal toxicity of proposed regimen was generally mild. Nausea and vomiting were the most noxious side effects.

Etoposide by oral route in the treatment of unresectable non-small cell lung cancer.

Twenty patients with unresectable non-small cell lung cancer (10 squamous cell carcinoma, 7 adenocarcinoma, 3 large cell carcinoma), previously untreated, received etoposide 300 mg/m2 by oral route days 1-3-5 every three weeks. No complete or partial remissions were observed but only two minor responses. There were 7 stable diseases and 11 progressive diseases. Myelosuppression activity was usually mild and gastro-intestinal side effects were the most prominent. In this trial etoposide by oral route has shown only marginal activity against non-small cell lung cancer.

[Clinical aspects of viral respiratory infections]. / Aspetti clinici delle infezioni virali respiratorie.

The Authors deal with some clinical aspect of the commonest types of respiratory tract viral infections. After a description of the characteristics of the most important diseases (common cold, ARD, influenza, viral pneumonia) they deal with some particular problem difficult in resolution, both from a pathogenetic and clinical viewpoint and quite constant bacterial over infection, the cardiac complications, th possible evolution to fibrosis and the relationship between viral infections and asthma. The nowadays problem of immunological and chemotherapeutic prevention of viral infections, particularly of type A influenza, is also discussed.

[Ultrastructure of the pulmonary alveolus. Correlations with the endoalveolar tensioactive system]. / Ultrastruttura dell'alveolo polmonare. Correlazioni con il sistema tensioattivo endoalveolare.

The knowledge of chemical structure and physiologic role of endoalveolar tensioactive system are a progress of the last ten years. The authors deal with the origin, fate and relationships with pulmonary surfactant metabolism of alveolar cells. Morphology and functions of alveolar-capillary membrane, type I and II cells, bronchiolar non-ciliated Clara cells and alveolar macrophages have been outlined. Lamellar bodies, alveolar type II cells intracitoplasmatic inclusions were particularly considered, as well as tubular myeline structures.

Radioisotopic labelling of endoalveolar surface-active phospholipidic fractions from rabbit pulmonary lavage.

A simple method of detecting endoalveolar tensioactive system fractions employing intravenously injected 131I-triolein has been devised. The tracer has been administered to 7 adult rabbit groups then sacrificed at different time intervals after the injection. Endoalveolar tensioactive system lipidic fractions collected by pulmonary lavage have been separated with thin-layer chromatography and their radioactivity evaluated by scanning plates. Endoalveolar tensioactive system fractions containing considerable amounts of C 18 fatty acids have been selectively labelled.