Simultaneous chemoradiotherapy compared with radiotherapy alone after induction chemotherapy in inoperable stage IIIA or IIIB non-small-cell lung cancer: study CTRT99/97 by the Bronchial Carcinoma Therapy Group.

PURPOSE: The aim of this study was to examine whether, after preceding induction chemotherapy, simultaneous chemoradiotherapy is superior to radiotherapy alone. PATIENTS AND METHODS: Patients with non-small-cell lung cancer in inoperable stage IIIA or IIIB received induction chemotherapy with two cycles of paclitaxel 200 mg/m2 and carboplatin area under the curve 6 every 3 weeks. Patients without progression at restaging after induction chemotherapy were randomly assigned to radiotherapy (60 Gy) or chemoradiotherapy (paclitaxel 60 mg/m2 weekly). The primary end point was overall survival; secondary end points were time to progression, response, and toxicity. RESULTS: Three hundred three patients entered the study, and 276 completed induction chemotherapy. Two hundred fourteen patients were randomly assigned (radiotherapy alone: n = 113; simultaneous chemoradiotherapy: n = 101). Median follow-up time of all randomly assigned patients was 13.6 months (interquartile range [IQR], 6.4 to 29.0 months), and median follow-up time of the subgroup of censored patients (n = 52) was 37.4 months (IQR, 5.9 to 57.0 months; maximum, 76.1 months). Toxicities during the induction phase were mild. During radiotherapy, overall toxicity rates were not significantly different between the two arms. Median survival times in the radiotherapy group and chemoradiotherapy group were 14.1 months (95% CI, 11.8 to 16.3 months) and 18.7 months (95% CI, 14.1 to 23.3 months; difference not statistically significant, P = .091). Median time to progression significantly favored simultaneous chemoradiotherapy (11.5 months; 95% CI, 8.3 to 14.7 months) versus radiotherapy alone (6.3 months; 95% CI, 5.0 to 7.6 months; P < .001, log-rank test). CONCLUSION: Induction chemotherapy followed by chemoradiotherapy with weekly paclitaxel is feasible. Response, time to progression, and survival favor chemoradiotherapy compared with radiotherapy alone.

Randomized multicenter phase II study of gemcitabine versus docetaxel as first-line therapy with second-line crossover in advanced-stage non-small-cell lung cancer.

BACKGROUND: A randomized phase II study was performed to determine whether single-agent gemcitabine or docetaxel with the introduction of the opposite agent in case of disease progression (ie, in the second-line setting) is feasible and effective in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: The doses were 1,000 mg/m2 for gemcitabine and 35 mg/m2 for docetaxel, each given on days 1, 8, and 15 every 4 weeks. After a planned interim analysis, the docetaxel/gemcitabine arm (ie, docetaxel followed by gemcitabine) was closed after enrollment of 49 patients because of poor predefined feasibility. A total of 98 patients were recruited to the gemcitabine/docetaxel arm (ie, gemcitabine followed by docetaxel). RESULTS: Quality of life remained near baseline levels during the administration of 6 cycles of gemcitabine/docetaxel chemotherapy, whereas it deteriorated after 2 cycles of docetaxel/gemcitabine. Toxicity was comparable between arms. Median times to progression were 4.3 months and 2.2 months with gemcitabine/docetaxel and docetaxel/gemcitabine, respectively, and median overall survival times were 9 months (gemcitabine/docetaxel) and 5 months (docetaxel/gemcitabine; P=0.029, Wilcoxon rank-sum test). CONCLUSION: These results indicate that first-line gemcitabine followed by second-line weekly docetaxel is feasible, with promising survival in patients with advanced NSCLC.

Differential diagnosis of pleural effusions by fuzzy-logic-based analysis of cytokines.

Pleural effusions can be caused by highly different underlying diseases and are characterized by complex interactions of various local and circulating cells as well as numerous soluble parameters like interleukins (IL). Knowledge about this complex network could help to indicate underlying disease. Therefore, we have investigated immunoreactive concentrations of IL-4, IL-6, IL-11, IL-15, IL-17, IL-18, and tumor necrosis factor-alpha (TNF-alpha) in pleural effusions and peripheral blood from patients with tuberculosis, bronchial carcinoma and other carcinomas as well as congestive heart failure (CHF) and pneumonias. To determine the value of cytokine measurement for differential diagnosis, statistical and fuzzy-logic methods were applied. Quantitative analysis showed high concentrations of IL-6 and IL-11 only in pleural effusions. IL-15, IL-17, IL-18 and TNF-alpha could be detected also in blood plasma. Lowest amounts were detected in CHF indicating the non-inflammatory origin of effusions. Statistical analysis did not provide evidence for diagnostic relevance of singular cytokines. Fuzzy-logic analysis was able to assign patients to the correct diseases with 80% accuracy using IL-6 and IL-15 measurement. Our results confirm the pathogenetic role of these cytokines in pleural effusions. Fuzzy-logic-based procedures may help to characterize and distinguish effusions of unknown origin even in small patient groups.