Can simvastatin reduce COPD exacerbations? A randomised double-blind controlled study.

BACKGROUND: Several studies have shown that statins have beneficial effects in COPD regarding lung function decline, rates and severity of exacerbation, hospitalisation and need for mechanical ventilation. METHODS: We performed a randomised double-blind placebo-controlled single-centre trial of simvastatin at a daily dose of 40 mg versus placebo in patients with Global Initiative for Chronic Obstructive Lung Disease criteria grades 2-4 at a tertiary care pulmonology department in Austria. Scheduled treatment duration was 12 months and the main outcome parameter was time to first exacerbation. RESULTS: Overall, 209 patients were enrolled. In the 105 patients taking simvastatin, time to first exacerbation was significantly longer compared to the 104 patients taking placebo: median 341 versus 140 days (log-rank test p<0.001). Hazard ratio for risk of first exacerbation for the simvastatin group was 0.51 (95% CI 0.34-0.75; p=0.001). Rate of exacerbations was significantly lower with simvastatin: 103 (41%) versus 147 (59%) (p=0.003). The annualised exacerbation rate was 1.45 events per patient-year in the simvastatin group and 1.9 events per patient-year in the placebo group (incidence rate ratio 0.77, 95% CI 0.60-0.99). We found no effect on quality of life, lung function, 6-min walk test and high-sensitivity C-reactive protein. More patients dropped out in the simvastatin group compared to the placebo group (39 versus 29). CONCLUSION: In our single-centre RCT, simvastatin at a dose of 40 mg daily significantly prolonged time to first COPD exacerbation and reduced exacerbation rate.

Induction chemotherapy with the TIP regimen (paclitaxel/ifosfamide/cisplatin) in stage III non-small cell lung cancer.

Induction chemotherapy may improve clinical outcome of locally advanced non-small cell lung cancer (NSCLC). To further pursue this, the Austrian Association for the Study of Lung Cancer (AASLC) performed a multi-center phase II trial with TIP induction chemotherapy (Taxol 175 mg/m2 over 3h on day 1, ifosfamide 1000 mg/m2 daily on days 1-3, cisplatin 60 mg/m2 on day 1, and prophylactic filgrastim 5 microg/kg daily on days 4-13). Treatment cycles were repeated every 3 weeks for 3 cycles. Then patients were re-staged and selected for local treatment. Forty-seven patients (33 male, 14 female; median age 58 years, range 36-78; 22 cIIIA, 25 cIIIB; 26 adenocarcinomas, 14 squamous cell carcinomas, 4 large cell carcinomas, 3 undifferentiated carcinomas) were included in this trial. Forty-five patients were evaluable for response and toxicity. An overall response rate of 43% (complete remission 4.5% and partial remission 38%) was achieved. Stable disease and progressive disease were seen in 38 and 15% of the patients, respectively. Down-staging occurred in 36% of the patients. The toxicities of the chemotherapy were mild and, in particular, no severe hematotoxicity was observed. Surgery was performed in 24 (51%) patients and resulted in complete tumor resection in 19 patients. Twenty-four patients received thoracic radiotherapy, 10 patients after surgery. Median survival was 10.3 months for the total population, 13.5 months for patients with cIIIA and 10 months for patients with clinical cIIIB. Survival was longer for patients with down-staging as compared to those without (median not reached versus 10 months, p=0.005) and for patients with complete tumor resection as compared to the remaining patients (27 months versus 10 months, p=0.05). In conclusion, the TIP regimen shows activity and good tolerance as induction chemotherapy in patients with locally advanced NSCLC.