bluuebunny/crossref_metadata_2025_split huggingface dataset:
KRAS mutation in the primary or acquired resistance of Chinese NSCLC to EGFR tyrosine kinase inhibitors
Authors: Chen H. , Wu Y. , Zhang X. , Chen Z. , Guo A. , Cheng H. 
Published: August 2020

e19071 Background: Prevalence of KRAS mutation in Asian NSCLC is different to population of white ethnicity. Data about KRAS mutation after development of resistance to EGFR tyrosine kinase inhibitors (TKIs) are rare. This study was to investigate the prevalence of KRAS mutation in Chinese NSCLC after primary or acquired resistance to EGFR TKIs. Methods: 155 EGFR TKI-naive NSCLC patients and corresponding tumor specimens were collected to establish baseline of KRAS mutation. 45 specimens from six patients with primary resistance to TKIs and twenty-nine patients with acquired resistance to TKIs were analyzed. Genomic DNA was prepared after purified cancer cells were isolated by laser microdissection. Mutations in codon 12 and 13 of the KRAS gene in TKI-naive patients were analyzed by direct sequencing. Mutations in TKI-resistant patients were meanwhile detected by DxS KRAS Mutation Test Kit and direct sequencing. Results: KRAS mutation (G12X) was detected in 7.1% (11/155) of the TKI- naive patients by direct sequencing. In 6 primary resistant patients (two paired specimens and four resistant specimens) and in 29 acquired resistant patients (eight paired specimens and twenty-one resistant specimens), absence of KRAS mutation was detected in all pre- treatment and post-treatment tissues by both methods. Conclusions: KRAS mutation exists in TKI-naive NSCLC patients instead of TKI-resistant setting. KRAS mutation couldn’t thoroughly explain the primary resistance to EGFR TKIs and it might not be the crucial consideration in the mechanisms of acquired resistance. No significant financial relationships to disclose.
Microarray study of gene expression profiles in peripheral blood samples from lung cancer patients before and after erlotinib treatment
Authors: Irigoyen A. , Olmedo C. , Valdivia J. , Comino A. , Cano C. , Luque R. , Conde V. , Delgado J. , Blanco A. , Bueno P. 
Published: August 2020

e19072 Background: The gene expression profile in peripheral blood samples from lung cancer patients is a potential predictor to treatment response. Methods: The study has been developed using 10 healthy volunteers as the control group and 10 lung cancer patients (stage IV). Written informed consent was obtained being the protocol approved by the local Clinical Research and Ethics Committee. Peripheral blood samples were obtained from lung cancer patients before (T0) and after treatment (T15d). RNA from peripheral blood samples was extracted and purified selecting 28S/18S ratios>1.5 to obtain cDNA and cRNA for hybridization of the 20,000 genes included in Human 20K CodeLink. An array from each participant was obtained in duplicate. For each array, 2 μg of cRNA was compared to 2 μg of healthy cRNA.. Significant genes were found using Significance Analysis of Microarrays which uses repeated permutations of the data. Results: The selected genes were expressed >3-fold with a false discovery rate =0.05. Before treatment (T0) when patients were compared to healthy volunteers there was an increase in the expression of: histone 1 H4c, transforming growth factor beta 2, endothelial cell growth factor 1 (platelet-derived), glucose-6-phosphatase catalytic 2, Relaxin 3 receptor 1, Insulin-like growth factor binding protein 2, RAS-like family 11 member B, and ELK4. After treatment (T15d), when each lung cancer patient's results were compared to their own before treatment results (T0), there was an increase in the expression of: Bcl2, myosin light polypeptide 4; interferon alpha-inducible protein 27; interferon gamma receptor 1; RASSF5, ARHGEF6, IGFBP5, tumor protein p53 inducible nuclear protein 1, peroxisome proliferative activated receptor gamma. Conclusions: The data presented identifies biologically relevant over-expressed genes in lung cancer. A validation of these results and the analysis of the genes that identify patients who will respond positively to erlotinib treatment is being carried out. No significant financial relationships to disclose.
Safety and effectiveness of malignant pleural mesothelioma patients treated with pemetrexed: A postmarketing drug registered study under performance linked access system
Authors: Watanabe M. , Yamamoto T. , Arakawa K. , Imai J. , Sekiguchi R. , Enatsu S. , Nambu Y. 
Published: August 2020

e19084 Background: Approximately 1000 patients are newly diagnosed as malignant pleural mesothelioma (MPM) each year in Japan, however MPM patient profile and their outcome are not well understood. Pemetrexed is the only approved chemotherapeutic agent for MPM. Limited safety information was available at launch of pemetrexed in Japan where drug induced interstitial pneumonitis are reported at higher rate than the rest of the world. Therefore postmarketing drug registered study (PDRS) for pemetrexed was conducted in Japan to investigate patient characteristics, adverse events and survival of MPM patients based on a regulatory requirement for approval. Methods: From February 2007 to May 2008, all of histologically proven MPM patients to be treated with pemetrexed were required to register the PDRS in Japan. The observation period was six-months. Supply of pemetrexed was restricted to institutes with experienced medical oncologists based on pre-determined criteria. Results: During the 15-months enrollment period, 948 MPM patients were registered. Until August 3th 2008, data for 437 patients were collected. Among these, 389 were male, 48 female, median of age 65 (35–86). 72.3% patients had a known history of being exposed to asbestos. The treatment regimen mainly consists of 500 mg/m2 of pemetrexed and 75 mg/m2 of cisplatin every 21 days. Median treatment cycle was 3.0. Hematological NCI-CTC Grade ¾ adverse events in laboratory data were hemoglobin decrease 19.9 %, neutropenia 20.1%, thrombocytopenia 7.6%. Serious non-hematological adverse events were nausea 3%, vomiting 3.2%, fatigue 0.2%, constipation 0.2%, diarrhea 0.9%. Pneumotoxicity was found in 1.4%. 152 deaths (34.8%) were observed and six-month survival rate estimated by Kaplan-Meier method was 70.9%. Conclusions: This large size PDRS shows that safety profile of pemetrexed appeared similar to the previous clinical trial without additional safety signal. The study has minimum selection bias and provides useful information to health care professionals on safety and effectiveness of pemetrexed in real clinical setting in Japan. [Table: see text]
Is hepcidin involved in anemia of advanced non-small cell lung carcinoma (NSCLC) patients treated with platin-based chemotherapy? An exploratory study
Authors: De Castro J. , Cejas P. , Belda-Iniesta C. , Ramirez-Merino N. , Barriuso J. , Hernandez-Agudo E. , Feliu J. , Moreno-Garcia V. , Martinez-Marin V. , Gonzalez-Baron M. 
Published: August 2020

e19086 Background: Anemia is a common complication in NSCLC patients. Hepcidin, a liver-produced peptide, acts to cause a block on cellular iron export by internalisation and degradation of ferroportin.This results in iron sequestration and interrupts iron delivery to erythroid precursor cells thus causing anemia. To date there are no studies addressing whether hepcidin expression contributes to the anemia in NSCLC. Methods: to investigate whether hepcidin is implicated in NSCLC anemia, hemoglobin (Hb), iron metabolism and serum hepcidin levels, were studied in newly diagnosed advanced NSCLC patients. Blood samples of each patients were collected before starting cisplatin based chemotherapy treatment. Serum was separate by centrifugation at 2,500 g for 10 min at 4ºC. Hepcidin was detected by a solid phase enzyme-linked immunosorbent assay (ELISA) on the serum of each patient. The ELISA test is based on the principle of competitive binding. The microtiter wells are coated with a polyclonal antibody directed towards an antigenic site on the hepcidin prohormone molecule. Endogenous hepcidin prohormone of patient sample competes with a hepcidin prohormone biotin conjugate for binding to the coated antibody. Hepcidin absolute quantitation was achieved using a standard curve. Hepcidin results were correlated with serum parameters related to iron metabolism. Results: In a exploratory analysis, 20 patients with advanced NSCLC were selected for hepcidin prohormone detection. Only 10% were anemic at the diagnosis but 70% developped anemia during the treatment. 50% of the patients had iron deficiency. 70% received treatment for anemia (40% erythropoetin and iron, 20% iron, 10% erythropoetin). Median serum hepcidin levels was 151 ng/ml (range 99–308). The serum hepcidin level correlated with serum ferritin but no correlation was found with other iron metabolism parameters. An inverse correlation was seen between serum hepcidin level and Hb evolution after 4 cycles of chemotherapy. Conclusions: These results support a potential relationship between hepcidin expression and anemia in NSCLC patients. Further confirmatory study is ongoing and final results will be presented in the meeting. No significant financial relationships to disclose.
A phase II study of docetaxel and carboplatin in patients with advanced non-small cell lung cancer after treatment with non-platinum regimens
Authors: Ikeda T. , Fukuda M. , Fukuda M. , Soejima Y. , Doi S. , Nagashima S. , Nakamura Y. , Soda H. , Oka M. , Kohno S. 
Published: August 2020

e19087 Background: Docetaxel and platinum is active in patients with non-small cell lung cancer (NSCLC) as first-line chemotherapy, and docetaxel is also effective in previously-treated patients. This study was designed to evaluate activity and toxicity of docetaxel and carboplatin as second-line chemotherapy in advanced NSCLC patients treated with non-platinum regimens. Methods: Patients with stage IIIB or IV NSCLC treated with non-platinum regimens, a performance status ≤ 2, and an adequate organ function were eligible. Patients were treated with docetaxel 50 mg/m2/day and carboplatin AUC 5 mg/ml/min on day 1 of each 21-day cycle. Primary endpoint was response rate. Results: Twenty-nine patients with a median age of 63 years were included. Median number of cycles for docetaxel and carboplatin was 3.2. Grade 3/4 neutropenia and anemia occurred in 21 (72.4%) and 2 patients (7.0%), respectively. Febrile neutropenia occurred in 2 patients (7.0%). Grade 3 non-hematological toxicity included diarrhea and peripheral neuropathy in each 1 patients (3.5%). Complete and partial response was observed in 1 and 4 patients, respectively. Overall response rate was 17.2% (95%CI: 5.9–35.8). Median survival time was 12.7 months (95%CI: 7.8–17.6) and 1- year survival rate was 52.5% (95%CI: 31.8–73.2). Conclusions: The combination of docetaxel and carboplatin as second-line chemotherapy may be promising in advanced NSCLC patients treated with non-platinum regimens. No significant financial relationships to disclose.
Bevacizumab (B), cisplatin, and vinorelbine in chemotherapy-naive patients (p) with nonsquamous non-small cell lung cancer (NSCLC): A Galician Lung Cancer Group phase II study
Authors: Leon L. , Vázquez S. , Gracia J. M. , Lázaro M. , Fírvida J. L. , Casal J. , Amenedo M. , Santomé L. , Gallego R. , Anido U. 
Published: August 2020

e19089 Background: Bevacizumab, an anti-VEGF monoclonal antibody, improves response rates and prolongs survival in p with non squamous NSCLC when combined with carboplatin-paclitaxel or cisplatin-gemcitabine. This single-arm, open-labeled phase II trial aims to evaluate the efficacy and safety profile of B in combination with another widely used chemotherapy doublet for NSCLC: cisplatin and vinorelbine. Methods: Chemotherapy-naïve p diagnosed with stage IIIB or IV non squamous NSCLC received cisplatin (80 mg/m2), vinorelbine (25 mg/m2 IV days 1 and 8) and B (15 mg/kg IV) on day 1 every 3 weeks for up to 6 cycles followed by B 15 mg/kg alone every 3 weeks until disease progression. Main eligibility criteria were: PS 0–1, no brain metastases, no history of hemoptysis, stable cardiac condition and no full dose anticoagulation. Primary endpoint was progression-free survival and secondary endpoints were RR, duration of response, OS, 1-year survival and safety profile of the combination. Results: 38 p have been enrolled in the study and data of 27 p have been included in this analysis. P characteristics were: male 66.7%; median age 57 years (range 41–74); ECOG PS 0/1 (%) 33.3/66.7; adenocarcinoma/other (%) 74.1/25.9; stage IIIB/IV (%) 25.9/74.1. Median number of cycles for B/cisplatin/vinorelbine was 4.0 (range 1–6) and median number of cycles for B maintenance was 2 (range 1–4). 17 p were evaluable for response according to RECIST criteria: PR 29.4% and SD 41.2%. With a median follow-up of 3.9 months (range 0.7–11.1), median PFS was 4.6 months (95% CI: 2.6–6.6) and median OS has not been reached yet. Hematological toxicities were: 1 p gr. 3 anemia; 2 p gr. 3 and 2 p gr. 4 leucopenia; 10 p gr. 3, 1 p gr. 4 neutropenia and 3 p febrile neutropenia. Most common grade 3/4 non hematological toxicities were: vomiting (1p gr. 4), high blood pressure, asthenia and hyperglycemia. 1 p experienced gr. 4 abdominal pain, 1 p. gr. 4 constipation, 1 p. gr. 4 nausea and 1 p gr. 4 respiratory infection. No grade 3/4 hemoptysis were reported. Conclusions: This interim analysis shows that B in combination with cisplatin and vinorelbine is safe and well tolerated and has a promising activity in chemo-naïve p with non squamous NSCLC. Survival data will be updated. [Table: see text]
Randomized phase III trials of standard chemotherapy with or without targeted agents as first-line therapy in non-small cell lung cancer
Authors: Hoang T. 
Published: August 2020

e19092 Purpose: To characterize the pattern and outcome of randomized phase III trials involving standard chemotherapy with/without novel agents as first-line treatment in advanced NSCLC patients (pts). Methods: The trials included in this analysis were identified through a search of MEDLINE as well as websites (ASCO, IASLC) and meeting proceedings. Studies comparing novel agents alone to standard regimens were excluded. Results: Of 20 identified trials (16,050 pts), 11 (8,647 pts) were published between 2004–2008, and 9 (7,403 pts) were reported at scientific meetings (mostly between 2005–2008), but have not been published yet. All studies were conducted within the last 10 years. Majority were industry-sponsored studies; 4 (20%) were conducted by cooperative or non-profit groups. Chemotherapy chosen as the standard regimens involved cisplatin or carboplatin in combination with a third-generation drug with paclitaxel (10 trials) and gemcitabine (6 trials) being the most common drugs. The experimental drugs included agents with different molecular targets (EGFR, VEGF, MMP, PKC, FTI, TLR-9¼). Overall survival was primary endpoint in all 11 published studies. PFS was chosen as primary in 2 non-published studies. When comparing the standard arms (chemotherapy alone) across the 11 published trials, there was a large difference in term of response rate RR (15% to 47%), while survival endpoints showed a smaller difference (median overall survival OS 9–10.9 months; progression free survival PFS 4.5–5.5 months; and time to progression TTP 4.9–6 months). Among 11 published studies, only one showed positive result with a consistency in all endpoints (OS, PFS and RR). Of 9 non-published studies, 2 studies were reported as positive by the investigators, although preliminary results of primary and secondary endpoints were somewhat inconsistent. Conclusions: Within the last decade, 20 randomized phase III trials involving a large number of chemo-naïve NSCLC patients were conducted. There was a variation in eligibility and patient characteristics, study design (primary endpoints) as well as results among the studies. No significant financial relationships to disclose.
Treatment guided by ERCC1, RRM1, and BRCA1 protein expression in patients with advanced-stage NSCLC
Authors: Han B. , Shen J. , Gao Z. 
Published: August 2020

e19094 Purpose: We investigated whether Treatment Guided by ERCC1,RRM1 and BRCA1 protein expression levels could improve clinical outcomes in Patients With Advanced-Stage NSCLC. Experimental Design: Eligibility: Main inclusion criteria: Stage IV or stage IIIB NSCLC; Eastern Cooperative Oncology Group(ECOG) performance status (PS) 0–1; Measurable disease; Adequate bone marrow, kidney, liver function. Main exclusion criteria: previous NSCLC therapy; Central nervous system metastasis; Requiring immediate intervention or Untreated with radiation within 28 days of study regimen initiation. Previously untreated patients with Stage IV or stage IIIB NSCLC(N=180): Standard chemotherapy group(N=60): Cisplatin 75mg/m2 Day1+Vinorelbine 25mg/m2 Days 1,8 every 28 days; Individualized chemotherapy group (N=120) (ERCC1,RRM1 and BRCA1 protein expression assayed with IHC); Low ERCC1 protein expression subgroup: Cisplatin 75mg/m2 Day1+Vinorelbine 25mg/m2 Days 1,8 every 28 days; High ERCC1 protein subgroup: Vinorelbine 25mg/m2 Days 1,8+Gemcitabine 1250mg/m2 Days 1,8 every 28 days. Description of Current Analysis: ERCC1,RRM1 and BRCA1 protein expression assayed with IHC; Assigned treatment based on ERCC1 protein expression; Primary endpoint: overall response rate; Secondary endpoints: Overall survival (OS), Progression-free survival (PFS). Enrollment progress (As of time Dec-31–2008): See Table . [Table: see text] No significant financial relationships to disclose.
Effect of zoledronic acid combined with cisplatin and paclitaxel on inhibition of non-small cell lung cancer cell lines
Authors: Gao Z. , Han B. , Teng J. 
Published: August 2020

e19095 Backgrounds: Recent studies reported that zoledronic acid, a biphosphonate with proposed apoptotic activity, could cause a direct antitumor effect. Our prior study [J Clin Oncol 26: 2008 (May 20 suppl; abstr 19116)] reported that Zoledronic acid combined with Cisplatin shows significantly synergistic antitumor effects on lung cancer cell line A549 and subcutaneous implanted tumor on nude mice. Investigate whether zoledronic acid, augmented the cytotoxicity of cisplatin and/or paclitaxel in A549 lung cancer cell line. Methods: This cell line was subjected to different concentrations of the above chemotherapeutic agents and zoledronic acid. Cytotoxicity was assessed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide) assay. Flow cytometry was used to examine cell cycle,cell apoptosis rate. Results: Zoledronic acid in in 50 micromolar (mM) concentration augmented the cytotoxicity by cisplatin in 10μmol/L and paclitaxel in 5μmol/L. Zoledronic acid could inhibit the proliferation of lung cancer cells in vitro,which was associated with arresting of G1 phase and inducing apoptosis by a time-dependent and dose-dependentmanner. The apoptosis rate of cell increased after zoledronic acid combined with cisplatin and/or paclitaxel. Conclusions: Zoledronic acid can induce apoptosis and block cell cycle of lung cancer cells. Zoledronic acid has also shown synergistic antitumor effects when combined with cisplatin and/or paclitaxel. The clinical potential of this finding should be further studied. No significant financial relationships to disclose.
Cisplatin (CDDP) plus oral vinorelbine (NVBO) as first-line treatment for advanced non-small cell lung cancer (NSCLC): Prospective analysis to improve the patient's convenience on day 8 NVBO administration
Authors: Sanchez A. , Provencio M. , Artal A. , Constenla M. , Garcia-Gomez R. , Viñolas N. , Domine M. , Perez F. J. , Gayo J. 
Published: August 2020

e19096 Background: Severe neutropenia observed during chemotherapy (CT) is a clinical finding leading to treatment modification and, sometimes, life-threatening events. The results of a previous study with 180 p treated with IV vinorelbine plus CDDP as first-line treatment for advanced NSCLC could lead to consider not performing a blood count prior to day 8 vinorelbine administration for patients aged 70 years (y) or less who presented a good haematological tolerability profile during previous cycles (cy) in order to improve treatment convenience. The aim of this study is to prospectively validate these results with the combination of NVBO plus CDDP. Methods: Between October 2007 and September 2008, 31 chemo-naïve p with histologically confirmed stage IIIB/IV NSCLC were included. Treatment consisted of CDDP 75 mg/m2 day 1 plus NVBO 80 mg/m2 days 1 and 8, with a prior test of myelosensitivity at 60 mg/m2 for the first cycle, every 21 days. Patient's characteristics were: Median age, 62 years (range 32–73); males, 93.5%; smokers, 38.7%; all PS 0–1; adenocarcinoma, 33.3% / squamous, 36.7%; stage IIIB, 14.8% / IV, 85.2%. Results: We analyzed 129 cy. NVBO administration on day 8 was cancelled in 3 cycles due to haematological events (2.3% [95% CI: 0.4%-6.6%]. The reported events were: 1 grade-2 neutropenia, 1 grade-4 neutropenia and 1 grade- 2 thrombocytopenia. Among 22 p evaluable for response, 10 p achieved partial response (overall response rate, 45.5% [95% CI: 24.4- 67.8]). Toxicity was mild with neutropenia WHO grade 3–4 observed in 2.1% cy (9.7% p), leukopenia grade 3 in 1.4% cy (6.5% p); 1 case of febrile neutropenia was reported. Grade-3 fatigue was observed in 6 cy (6 p), grade-3 nausea in 2 cy (2 p) and grade-3 vomiting in 2 cy (2 p). Conclusions: The findings of this study could lead to consider not performing a blood count prior to day 8 NVBO administration for patients aged 70 y or less who presented a good haematological tolerability profile during previous cycles in first-line treatment for advanced NSCLC. [Table: see text]
Use of gemcitabine plus vinorelbine (GV) to treat advanced and metastatic non-small cell lung cancer (NSCLC) in second line after recurrent disease
Authors: Gamaz M. B. , Bouzid K. 
Published: August 2020

e19104 Background: Docetaxel is approved as second-line monotherapy in advanced NSCLC. In this study, we evaluate the efficacy, safety and survival of gemcitabine + vinorelbine in patients with advanced NSCLC previously treated with platine salts + taxane. Methods: From January 2007 to October 2008, twenty three patients with NSCLC stage IIIB or IV who received platine salts + taxane in first line were treated in second line with (GV) gemcitabine (G) 1,250 mg/m2 D1 and D8 + vinorelbine (V) 25 mg/m2 D1 and D8 every three weeks. Twenty one male and 2 female, median age was 59.3 (range 40 -71) years. Twelve (12) patients had IIIB stage and 11 patients had IV stage disease. Squamous cell cancer was found in 12 patients, adenocarcinoma in 11 patients. Results: No objective response were observed, stable disease was achieved in 7 (30.4 %) patients, and disease progression was observed in 16 (69.5 %) patients. Toxicities grade ¾ was 15 %, mainly hematological (leucopenia and anemia). Median follow up was 14 months, median TTP was 6 months and median survival was 7.1 months. Conclusions: Gemcitabine + Vinorelbine could be another alternative for treatment of NSCLC in second line after recurrent disease when first line chemotherapy is platine + docetaxel. No significant financial relationships to disclose.