Naive Non-small Cell Lung Cancer Research Articles

Triplet chemotherapy combination with gemcitabine, cisplatin, and docetaxel in patients with chemotherapy-naive advanced non-small cell lung cancer.

e18064 Background: The synergistics effects of new generation chemotherapeutics when combined with cisplatin have encouraged the development of new triplet combination in treatment of advanced non-small cell lung cancer (NSCLC). We conducted the feasibility of triplet chemotherapy using weekly cisplatin-docetaxel-gemcitabine for patients with chemotherapy naive NSCLC. Methods: Twenty seven patients with stage IIIB/IV disease and performance status of 0 to 2 were included. Combination of gemcitabine 750 mg/m2, cisplatin 25 mg/m2 and docetaxel 25 mg/m2 was administered on days 1, 8 and 15, with cycles repeated every 3 weeks. Results: Leucopenia and/or neutropenia and to a lesser extent thrombocytopenia were the main dose-limiting toxicities. Grade 3-4 neutropenia and thrombocytopenia occurred in 26% and 7% of the patients, respectively. Only one patient developed febrile neutropenia. Dose reductions were required in 26% of patients, delays in 44% patients and early treatment discontinuation in 15% of patients. The overall response rate was 52%, and all of them were partial response. Median progression free and overall survival survivals were 6 months and 13 months, respectively. One-year survival rate was 46%. Conclusions: Weekly administration of cisplatin-gemcitabine-docetaxel combination is an active first line therapy with acceptable toxicity in advanced NSCLC patients.

Gemcitabine, Vinorelbine, and Cisplatin in the Treatment of Advanced Nonsmall Cell Lung Cancer

Currently, cisplatin-based doublet combinations are accepted to be the first-line chemotherapy for advanced nonsmall cell lung cancer (NSCLC). Although triplet chemotherapeutics have been shown to be more effective and active than doublets, their toxicity was higher as expected. Therefore, we conducted this phase II trial using the combination of gemcitabine-cisplatin-vinorelbine with lower than usual but acceptable doses of gemcitabine and cisplatin to obtain higher response rate than doublet but less toxicity than triplet combinations. In this trial, stage IIIB and IV chemotherapy naive NSCLC patients with measurable disease and performance status of 0 to 2 were included. Gemcitabine and vinorelbine at the doses of 900 mg/m and 25 mg/m, respectively were administered on days 1 and 8, and cisplatin at a dose of 50 mg/m on day 1, every 21 days. Three of the 39 patients included in the trial were complete responders (7.7%). The overall response rate was 56.4%, median time to the progression was 6 months, median overall survival time was 12 months, and 1-year survival rate was 49.6%. Grade II to III neutropenia and thrombocytopenia occurred in 24% and 30% of the patients, respectively. Febrile neutropenia was observed in 13.5% of the patients and only these patients received G-CSF. Platelet and erythrocyte transfusions were required in 12 (32.4%) patients. No toxic or early death was observed. This combination of gemcitabine-cisplatin-vinorelbine with lower doses of cisplatin and gemcitabine was effective and active in advanced NSCLC. The overall response rate, 1-year survival and median survival time were nearly similar to previous trials in which higher doses of these 3 drugs were used. The toxicities were more acceptable and manageable than the regimes with higher doses; therefore, we may suggest a treatment option for advanced stage NSCLC.

MET Gene Copy Number in Non-small Cell Lung Cancer: Molecular Analysis in a Targeted Tyrosine Kinase Inhibitor Naïve Cohort

Recent clinical success of epidermal growth factor (EGFR)-tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) have raised hopes that targeting other deregulated growth factor signaling, such as the hepatocyte growth factor/MET pathway, will lead to new therapeutic options for NSCLC. Furthermore, NSCLC present secondary EGFR-TKIs resistance related to exons 20 and 19 EGFR mutations or more recently to MET amplification. The aim of this study was to determine MET copy number related to EGFR copy number and K-Ras mutations in a targeted TKI naive NSCLC cohort. We investigated 106 frozen tumors from surgically resected NSCLC patients. Genes copy number of MET and EGFR were assessed by quantitative relative real-time polymerase chain reaction and K-Ras mutations by sequencing. MET is amplified in 22 cases (21%) and deleted in nine cases (8.5%). EGFR is amplified in 31 cases (29%). K-Ras is mutated in 11 cases (10.5%). As observed for EGFR amplification, MET amplification is never associated with K-Ras mutation. MET amplification could be associated with EGFR amplification. MET amplification is not related to clinical and pathologic features. MET amplification and EGFR amplification showed a trend toward poor prognosis in adenocarcinomas. In EGFR-TKIs naive NSCLC patients, MET amplification is a frequent event, which could be associated with EGFR amplification, but not with K-Ras mutation. MET amplification may identify a subset of NSCLC for new targeted therapy. It will also be important to evaluate MET copy number to properly interpret future clinical trials.