Topotecan for Relapsed Small-cell Lung Cancer: Systematic Review and Meta-Analysis of 1347 Patients.

Topotecan is the most reliable chemotherapy regimen for relapsed small-cell lung carcinoma (SCLC). The efficacy and adverse effects of topotecan as reported by previous studies varied greatly. The inclusion criterion was a prospective study that was able to provide data for 6-month over-all survival (OS) rate, 1-year OS rate, objective responses, and/or adverse effects of single agent topotecan as a second line chemotherapy for SCLC, written in English language as a full article. Any topotecan regimen were allowed. Binary data were meta-analyzed with the random-model generic inverse variance method. We included 14 articles consisted of 1347 patients. Pooled values were estimated as follows. Six-month OS rate: 37% (95% CI: 28-46%). One-year OS rate: 9% (95% CI: 5-13%). Response rate: 5% (95% CI: 1-8%). Six-month OS rate: 57% (95% CI: 50-64%). One-year OS rate: 27% (95% CI: 22-32%). Response rate: 17% (95% CI: 11-23%). Grade III/IV neutropenia 69% (95% CI: 58-80%). Grade III/IV thrombopenia 41% (95% CI: 34-48%). Grade III/IV anemia 24% (95% CI: 17-30%). Non-hematorogical events were rare. Chemotherapy-related death 2% (95% CI: 1-3%). In conclusion, Topotecan provided a possibly promising outcome for sensitive-relapse SCLC and poor outcome for refractory relapse SCLC. Adverse events were mainly hematological.

Minimum clinically important difference in diffusing capacity of the lungs for carbon monoxide among patients with severe and very severe chronic obstructive pulmonary disease.

BACKGROUND: The minimum clinically important difference (MCID) for diffusing capacity of the lungs for carbon monoxide (DLCO) has not yet been solidly established. METHODS: We used the dataset of surgical cohort of National Emphysema Treatment Trial. Briefly, severe and very severe chronic obstructive pulmonary disease (COPD) patients who were candidate for volume reduction surgery and who could provide sufficient data at 12-month follow-up were included. We used two anchor methods using 6-minute walk distance (6MWD. MCID = 40 m) and forced expiratory volume in 1 sec (FEV1. MCID = 100 ml) as anchors, and two distribution methods. We proposed MCID with a median of estimated values. We estimated MCID for DLCO in raw value and % change from the baseline independently. RESULTS: The surgical cohort included 356 patients, whose average age was 66.6 ± 5.5 years, and the average % predicted FEV1 was 27.8 ± 7.3%. The estimated MCID for DLCO in raw value and % change from the baseline were as follows: anchor method (average, 6MWD) 1.2 ml/min/mmHg, 17%; anchor method (average, FEV1) 0.7 ml/min/mmHg, 11%; anchor method (receiver operating characteristic, 6MWD) 1.1 ml/min/mmHg, 10%; anchor method (receiver operating characteristic, FEV1) 1.2 ml/min/mmHg, 3%; distribution method (0.3 units of standard deviation), 0.9 ml/min/mmHg, 11%; distribution method (standard error of measurement), 1.1 ml/min/mmHg. The median of these values was 1.1 ml/min/mmHg and 11%. CONCLUSION: We estimated the group-level MCID for DLCO for patients with severe and very severe COPD patients as 1.1 ml/min/mmHg and 11% of baseline DLCO.

Statins reduce all-cause mortality in chronic obstructive pulmonary disease: a systematic review and meta-analysis of observational studies.

BACKGROUND: Recent observational studies have suggested that use of statins reduces mortality in patients suffering from chronic obstructive pulmonary disease. However, no meta-analysis has reported the pooled hazard ratio of statins to all-cause mortality. METHODS: We searched for eligible articles using five databases. We included randomized controlled trials and cohort studies written in English using original data reporting the hazard ratio of statins to all-cause, cardiovascular-related, cancer-related, or respiratory-related mortality. A fixed model with the confidence interval method was used. Publication bias was evaluated by funnel plot and Begg's test, and was corrected using Duval's trim and fill method. Sensitivity analyses were also conducted. RESULTS: We included 10 out of 128 articles. The pooled hazard ratio of statins to all-cause mortality involving 16269 patients was 0.81 (95% CI: 0.75-0.86, P < 0.001) with moderate heterogeneity (I2 = 52%, P = 0.032). The sensitivity analysis and funnel plot suggested the existence of publication bias. After three possibly unpublished cohorts were imputed, the pooled hazard ratio of 0.83 (95% CI: 0.78-0.88, P < 0.001) still suggested a favorable prognosis in statin-treated patients. The pooled hazard ratio of statins to cardiovascular-related, cancer-related, and respiratory-related mortality were 0.52 (95% CI: 0.27-1.01, P = 0.052), 0.57 (95% CI: 0.32-1.01, P = 0.056), and 0.55 (95% CI: 0.43-0.78, P < 0.001), respectively, although these results were not conclusive as we could not find a sufficient number of original studies dealing with those forms of mortality. CONCLUSIONS: The use of statins for patients suffering from chronic obstructive pulmonary disease may reduce all-cause mortality. This conclusion should be re-evaluated by a registered large-scale randomized controlled trial.

Evidence suggesting that oral corticosteroids increase mortality in stable chronic obstructive pulmonary disease.

BACKGROUND: Oral corticosteroids were used to control stable chronic obstructive pulmonary disease (COPD) decades ago. However, recent guidelines do not recommend long-term oral corticosteroids (LTOC) use for stable COPD patients, partly because it causes side-effects such as respiratory muscle deterioration and immunosuppression. Nonetheless, the impact of LTOC on life prognosis for stable COPD patients has not been clarified. METHODS: We used the data of patients randomized to non-surgery treatment in the National Emphysema Treatment Trial. Severe and very severe stable COPD patients who were eligible for volume reduction surgery were recruited at 17 clinical centers in the United States and randomized during 1998-2002. Patients were followed-up for at least five years. Hazard ratios for death by LTOC were estimated by three models using Cox proportional hazard analysis and propensity score matching. RESULTS: The pre-matching cohort comprised 444 patients (prescription of LTOC: 23.0%. Age: 66.6 ± 5.4 year old. Female: 35.6%. Percent predicted forced expiratory volume in one second: 27.0 ± 7.1%. Mortality during follow-up: 67.1%). Hazard ratio using a multiple-variable Cox model in the pre-matching cohort was 1.54 (P = 0.001). Propensity score matching was conducted with 26 parameters (C-statics: 0.73). The propensity-matched cohort comprised of 65 LTOC(+) cases and 195 LTOC(-) cases (prescription of LTOC: 25.0%. Age: 66.5 ± 5.3 year old. Female: 35.4%. Percent predicted forced expiratory volume in one second: 26.1 ± 6.8%. Mortality during follow-up: 71.3%). No parameters differed between cohorts. The hazard ratio using a single-variable Cox model in the propensity-score-matched cohort was 1.50 (P = 0.013). The hazard ratio using a multiple-variable Cox model in the propensity-score-matched cohort was 1.73 (P = 0.001). CONCLUSIONS: LTOC may increase the mortality of stable severe and very severe COPD patients.