bluuebunny/crossref_metadata_2025_split huggingface dataset:
ALK and EGFR mutation analysis in a phase II trial of cisplatin/pemetrexed in Japanese patients with advanced nonsquamous non-small cell lung cancer.
Authors: Kaburaki Kyohei , Ohyanagi Fumiyoshi , Tanimoto Azusa , Sakatani Toshio , Kawano Yuko , Saito Ryota , Yanagitani Noriko , Kudo Keita , Horiike Atsushi , Hagiwara Sachiko , Motoi Noriko , Takeuchi Kengo , Ishikawa Yuichi , Horai Takeshi , Nishio Makoto 
Published: March 2020

e18017 Background: Recently, ethnic differences and genotypes such as EGFR mutation (EGFRm) or fusion gene (ALK translocation: ALKt) are important factors in non-small cell lung cancer (NSCLC) treatment. Pemetrexed (P)/cisplatin (C) is one of the standard care for advanced non-squamous (Nsq) NSCLC. However, the efficacy of the CP regimen has not been well examined in Japanese Nsq NSCLC patients (pts); furthermore, the difference in efficacy between genotypes was not thoroughly examined. Therefore, the present study was conducted to evaluate the efficacy of the CP regimen in Japanese Nsq NSCLC pts, and to determine whether EGFRm and ALKt impacted the treatment. Methods: This study was conducted from May 2009 to December 2010. Pts were eligible for this study if they had histologically or cytologically confirmed recurrent or metastatic Nsq NSCLC previously untreated with chemotherapy, an ECOG performance status of 0 or 1, life expectancy of more than 12 weeks, and adequate organ function. Pts received C (75 mg/m2) plus P (500 mg/m2) on day 1 every 3 weeks. Of the 50 pts initially enrolled, 49 were evaluated, and 43 tumor samples were available for analysis. Most pts were male (80%), and 80% of the pts had adenocarcinoma. The primary endpoint was the response rate that was evaluated according to RECIST. EGFRm was examined using PCR-based methods, and the ALK fusion protein was examined using a highly sensitive IHC method in the available tumor specimens. Although the CP regimen demonstrates consistent efficacy in Japanese Nsq NSCLC pts, EGFRm and ALKt may have impacted this treatment. Results: The objective response rate and disease control rate in all pts were 44.9% and 79.6%, respectively. The median progression-free survival was 4.4 months, and the 1-year survival was 73.5%. Toxicities were mild; no new toxicity profile was identified. Among the 43 samples, the following mutations were identified: 9 EGFRm (21%), 5 ALKt (12%), and 29 wild-type (67%). Objective response was observed in 6 (66.7%) EGFRm, 2 (40%) ALKt, and 13 (44.8%) wild-type. Conclusions: Although the CP regimen demonstrates consistent efficacy in Japanese Nsq NSCLC pts, EGFRm and ALKt may have impacted this treatment.
Frequency and clinical correlations of epidermal growth factor receptor (EGFR) mutations in a large cohort of Italian non-small cell lung cancer (NSCLC) patients (pts) within the EGFR FASTnet program.
Authors: Normanno Nicola , Pinto Carmine , Taddei Gian Luigi , Troncone Giancarlo , Graziano Paolo , De Maglio Giovanna , Mottolese Marcella , Ludovini Vienna , Zupo Simonetta , Larocca Luigi Maria , Roz Elena , Russo Antonio , Palmieri Giuseppe , Perrone Giuseppe , Di Maio Massimo , Ardizzoni Andrea , Crino Lucio , Perrone Francesco , Clemente Claudio , Marchetti Antonio 
Published: March 2020

e18021 Background: Gefitinib was approved in Italy for treatment of pts with advanced NSCLC carrying mutant EGFR in May 2010. Methods: The EGFR FASTnet program was designed to facilitate the exchange of biological material, clinico-pathological data and reports between medical oncologists, primary pathologists and referral laboratories. EGFR mutational analysis was carried by Sanger sequencing, Real Time PCR, Pyrosequencing, Fragment Analysis and High resolution melting. The Italian Association of Medical Oncology (AIOM) and the Italian Society of Surgical Pathology and Cytopathology (SIAPEC-IAP) have full access to the anonymous EGFR FASTnet database. Results: As of December 31, 2011, 503 oncologists, 135 pathologists and 38 referral laboratories joined the EGFR FASTnet program. The enrolled cohort of 3819 pts with advanced NSCLC was significantly enriched for adenocarcinoma histology (3172 [83%]), female sex (1361 [36%]) and smoking history (never smoker 911 [24%], former smoker>15 yrs 880 [23%], light smoker 194 [5%]). Mutational analysis was feasible in 3567 pts (93%). At registration, 72% of the pts had not received yet treatment for advanced disease. Mutational analysis was carried by Sanger sequencing in 2021 cases (57%), Real Time PCR in 174 (5%), Pyrosequencing in 636 (18%) and other techniques in 736 (21%). EGFR mutations were found in 520 cases (14.6%): 334 in exon 19 (9.4%), 163 in exon 21 (4.6%), 7 in exon 18 (0.2%) and 16 in exon 20 (0.4%). Proportion of mutated cases was slightly higher with Real time PCR compared to other techniques: Sanger 14.8%, Real time PCR 21.3%, Pyrosequencing 13.5%, other 13.3% (p = 0.049). A higher mutation rate was found in never smokers (32.0%), light smokers (18.7%) and former smokers >15 yrs (12.4%), as well as in adenocarcinoma (15.7%) and females (25.2%). Conclusions: The pts for EGFR mutational screening are spontaneously selected by medical oncologists according to known predictive factors. The results of the mutational analysis from clinical practice in Italy are consistent with data from literature.
Failure pattern after response to reversible tyrosine kinase inhibitors in advanced non-small cell lung cancer.
Authors: Serra Olbia , Peralta Sergi , Heras Lucia , Garcia Alicia , Plana Maria , Villanueva Rafael , Martin Montse , Losa Ferran 
Published: March 2020

e18030 Background: Reversible tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) significantly increase survival for patients with previously treated advanced non-small cell lung cancer (NSCLC). Some studies have shown that most of responders to TKIs failed due to the appearance of new lesions without progression of the pre-existing target lesions. Methods: We retrospectively reviewed patients with advanced NSCLC diagnosed from 2005 to 2010 at two different hospitals in Catalonia (Spain) to identify those treated with TKIs. Patients with a clinical objective benefit as defined by Jackman were included. We analyzed both the clinical features of patients and their failure pattern. Results: There were 34 patients, 14 were women, with a median age of 64 years (range: 38 -81 years). Twenty-seven cases were adenocarcinoma while only 3 were squamous cell carcinoma. Eleven patients had never smoked. Previously to TKI, all patients received at least one line of chemotherapy except nine patients who received TKI as first-line treatment. Median time to progression after initiation of TKI was 8.7 months (1.9 - 38.9 months). Radiological TKI response was CR/PR/SD: 1/15/17 (1 not available). Rash and diarrhea were the most common toxic effects. No grade 3 or 4 toxicities were observed. TKI was discontinued in all patients after disease progression; 12 patients were unable to receive further therapy due to symptomatic deterioration. In 19 patients, PD was due to the appearance of new lesions and not to progression of the pre-existing lesions. Results of mutations of EGFR were available in 7 patients (ratio of mutant/wild status was 5/2). In all patients with known EGFR mutation, only new lesions leaded to progression. Conclusions: In spite of our series’ heterogeneity, results are consistent with previous data and suggest that a wide range of patients can benefit from TKIs. Furthermore, more than half of progressions were due to new lesions. Patients with known EGFR mutation strictly followed this failure pattern, though larger studies in EGFR mutated patients are needed to assess both failure patterns and benefits of continuing TKIs after progression when pre-existing lesions are stable.
Usefulness of serial measurement of serum N-telopeptides of type I collogen (NTx) in patients with lung cancer who developed bone metastasis: A prospective study.
Authors: Tamiya Motohiro , Okada Hideaki , Kobayashi Masashi , Suzuki Hidekazu , Okamoto Norio , Sasada Shinji , Morishita Naoko , Matsuura Yuka , Daga Haruko , Tokunaga Shinya , Taira Koichi , Hattori Michiyo , Miyamoto Natsuko , Takeda Koji , Hirashima Tomonori 
Published: March 2020

e18036 Background: The bone resorption biomarkers urinary NTx (uNTx) and serum NTx (sNTx) have been shown to aid in the diagnosis of bone metastasis in patients with lung cancer. Patients with metastatic bone disease from lung cancer (MBDLC) are often treated with zoledronic acid. Zoledronic acid reduces the levels of bone resorption biomarkers and also the risk of skeletal adverse events in patients with MBDLC. We studied the effects of treatments including zoledronic acid on levels of sNTx during disease progression. Methods: Patients with MBDLC at the initial diagnosis were entered to this study. sNTx was measured once a month using the sNTx assay OSTEOMARK serum NTx (Alere Medical). MBDLC was characterized by monthly physical examination and by bone scintigraphy every 3 months for 12 months. All patients were required to provide written informed consent. Results: Twenty patients were enrolled between June and December 2010. The mean +/- 1 SD of the sNTx concentrations was 19.8 +/- 5.8 nM BCE/L at baseline. In the 16 patients receiving zoledronic acid, the levels of sNTx showed a significant decrease in the first month of treatment (baseline: 21.3 +/- 5.5 nM BCE/L; one month later: 13.6 +/- 2.7 nM BCE/L; p<0.01). During follow-up period, 12 of the patients treated with zoledronic acid experienced worsening MBDLC or had died from lung cancer, and there were statistically significant differences in the levels of sNTx at baseline (19.7 +/- 4.47 nM BCE/L), at the lowest levels after the administration of zoledronic acid (11.5 +/- 2.73 nM BCE/L) and at the point of measurable disease progression or death (13.0 +/- 2.07 nM BCE/L). Conclusions: Serial measurements of sNTx in patients with MBDLC treated with zoledronic acid might predict disease progression of bone metastasis. Administration of zoledronic acid significantly decreased the level of sNTx from baseline within one month and maintained the level of sNTx lower than baseline during study periods.
Combination chemotherapy of intermittent erlotinib with pemetrexed for pretreated patients with advanced non-small cell lung cancer: A phase I dose-finding study.
Authors: Takahashi Ryo , Minami Seigo , Kijima Takashi , Kida Hiroshi , Nakatani Takeshi , Hamaguchi Masanari , Takeuchi Yoshiko , Nagatomo Izumi , Yamamoto Suguru , Tachibana Isao , Komuta Kiyoshi , Kawase Ichiro 
Published: March 2020

e18056 Background: Erlotinib and pemetrexed have been approved in second-line treatment for non-small cell lung cancer (NSCLC) and have different mechanisms of action. Their combination could potentially augment the antitumor activity brought by either agent alone. We investigated the safety in combination of erlotinib and pemetrexed in pretreated NSCLC patients. Methods: A phase I dose-finding study was performed in patients with stage III/IV nonsquamous NSCLC whose disease had progressed on or after receiving first-line chemotherapy. This study was registered as UMIN000002900. Patients received 500 mg/m2 of pemetrexed intravenously every 21 days and erlotinib (100 mg in Level 1, 150 mg in Level 2) orally on days 2-16. Results: Twelve patients were recruited. Patient characteristics included median age of 66 (range, 48-78), 9 males, 9 stage IV, 7 adenocarcinoma, and 2 activating mutation-positives in the gene of epidermal growth factor receptor. Treatment was well-tolerated and the recommended dose of erlotinib was fixed on 150 mg. Dose-limiting toxicities were experienced in 3 patients: grade 3 elevation of serum alanine aminotransferase, repetitive grade 4 neutropenia that required the second dose reduction of pemetrexed, and grade 3 diarrhea. None experienced drug-induced interstitial lung disease. Three patients achieved partial response and 5 kept stable disease. Conclusions: Combination chemotherapy of intermittent erlotinib with pemetrexed was well-tolerated with promising efficacy against pretreated advanced nonsquamous NSCLC.
Effect of germline polymorphisms of DNA repair genes on chemotherapy outcome in advanced non-small cell lung cancer (NSCLC) patients.
Authors: Sullivan Ivana , Majem Margarita , Páez David , Pallares Cinta , Paré Laia , Del Rio Elisabeth , Ramon Y Cajal Teresa , Barnadas Agust , Baiget Montserrat 
Published: March 2020

e18057 Background: The identification of predictors of efficacy of chemotherapy in NSCLC could help in the selection of patients who are more likely to benefit from a particular scheme and the avoidance of undue toxicity in poor responders. We examined the role of several polymorphisms in DNA repair and DNA synthesis genes as pharmacogenetic markers in the outcome of NSCLC patients. Methods: A blood sample was collected from 117 patients with NSCLC and genomic DNA was isolated from the peripheral blood nucleated cells. Polymorphisms were analyzed by polymerase chain reaction amplification and automated sequencing techniques or using a 48.48 dynamic array on the BioMark system. The germline polymorphisms studied were excision repair cross-complementing-1 (ERCC1 Asn118Asn), xeroderma pigmentosum group D (XPD Lys751Gln), thymidylate synthase (TS) (VNTR/5’UTR, 2R G>C SNP, 3R G>C SNP) and Methylenetetrahydrofolate reductase (MTHFR) (C677T, A1298C). Progression-free survival (PFS) and overall survival (OS) were evaluated according to each genotype. Results: 103 patients with stage III-IV NSCLC (47% adenocarcinoma, 41% squamous cell carcinoma, 12% NOS) receiving platinum-based chemotherapy were eligible (14 patients with stage I-II were excluded). The median PFS was significantly longer in patients with C/T or T/T genotypes in codon 118 in ERCC1: 13 months (m) and 10 m, respectively, as compared to 6 m for the C/C patients (p=0.034). Patients with ERCC1 C/T or T/T genotypes had a trend to longer median OS (20 m) than those C/C (10.5 m; p=0.1). Subgroup analysis revealed that ERCC1 C/T or T/T genotypes were associated with increased PFS in male (p=0.005), smokers (p=0.036) and age <70 years (p=0.012). Patients with A/A or A/C genotypes in codon 751 in XPD had a trend to longer median OS than those C/C (p=0.09). No differences in median PFS were observed. No association between TS and MTHFR polymorphisms and outcome was found in overall population. Conclusions: ERCC1 C/T or T/T genotype in codon 118 might be useful for predicting the outcome of NSCLC patients treated with platinum-based chemotherapy specially in male, smokers and age <70 subgroups.
Final result of phase II study of irinotecan (CPT-11) plus oral S-1 for previously treated advanced NSCLC patients.
Authors: Arai Daisuke , Soejima Kenzo , Naoki Katsuhiko , Ikemura Shinnosuke , Terai Hideki , Sato Takashi , Satomi Ryousuke , Nakayama Souhei , Yoda Satoshi , Ishioka Kouta , Ohgino Keiko , Miyata Jun , Kabata Hiroki , Miyazaki Masaki , Betsuyaku Tomoko 
Published: March 2020

e18058 Background: Both CPT-11 and S-1, which contains a prodrug of 5-FU, have moderate activity against NSCLC as a single agent and the combination of these agents have been reported to possess marked synergistic effects and tolerability in several gastrointestinal cancers. So the combination of CPT-11 and S-1 will be a promising alternative for the second line treatment of NSCLC patients. We have previously reported the phase I study of this combination and determined the recommended doses of these agents. This study was conducted as a phase II trial to evaluate the efficacy and safety of CPT-11 and S-1 for NSCLC patients who had previously treated. Methods: :This trial was open-label, multicenter study. NSCLC patients who had received one prior chemotherapy with performance status 0-1 were enrolled. Primary endopoint was response rate and secondary endpoints were progression free survival, overall survival, 1-year survival rate and adverse events. CPT-11 (60mg/m2 on days1, 8) and oral S-1 (80mg/m2/day on days1-14) was administered on every 21 days, maximally 6 cycles. Results: By October 2011, 31 patients were enrolled. Nineteen were adenocarcinoma and 12 were non-adenocarcinoma. The median age was 60 y/o (range 35-74) and the median number of treatment cycles was 4 (range 1-6). The objective response rates were PR 7.7%, SD 61.5% and PD 30.8%. Median PFS, median OS and 1-year survival rate were 2.8 month, 12.6 month and 55%, respectively. Grade 3-4 hematologic toxicities comprised neutropenia (15%), anemia (11%) and thrombocytopenia (3%). Other grade 3-4 non-hematologic toxicities comprised pneumonitis (7%), diarrhea (3%), anorexia (3%), liver dysfunction (3%) and mucosal disability (3%). No treatment related death was observed. Conclusions: Combination of CPT-11 and oral S-1 was moderately effective with acceptable toxicities as a second line treatment for advanced NSCLC patients.
The influence of gastric secretion inhibitors on gefitinib therapy in patients with non-small cell lung cancer harboring epidermal growth factor receptor activating mutations.
Authors: Saeki Sho , Sasaki Jiichiro , Morioka Junko , Sato Ryo , Sakata Shinya , Ichiyasu Hidenori , Fujii Kazuhiko , Saita Naoki , Kohrogi Hirotsugu 
Published: March 2020

e18059 Background: Gefitinib is orally available, selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor used in patients with non-small cell lung cancer (NSCLC), especially harboring EGFR activating mutations. Pharmacokinetic study revealed absorption of gefitinib was affected by the gastric pH. However, cancer patients in advanced stage are frequently administered gastric secretion inhibitors, such as proton pump inhibitors (PPIs) and H2 blockers (H2Bs) for various reasons. We hypothesized that gastric secretion inhibitors might suppress the efficacy of gefitinib therapy in NSCLC patients with EGFR activating mutations. The purpose of this study is to investigate the influence of PPIs/H2Bs on the efficacy of gefitinib therapy in the patients with NSCLC harboring EGFR activating mutations. Methods: From Apr 2004 to Aug 2011, we retrospectively analyzed the correlation between administration of PPIs/H2Bs and efficacy of gefitinib therapy in the patients with NSCLC harboring EGFR mutations. Results: Forty-three patients with EGFR mutations received gefitinib therapy in our hospital. 65.1% (28/43) patients administered PPIs/H2Bs simultaneously. Patients who received PPIs/H2Bs (PPIs/H2Bs group) had similar response rate compared with patients who didn’t receive PPIs/H2Bs (non-PPIs/H2Bs group) (77.8% vs 73.3%, p=1.00). Median progression free survival was 291 days in PPIs/H2Bs group and 353 days in non-PPIs/H2Bs group ( HR 1.23, Log-rank trest, p=0.578), respectively. Median overall survival was 718 days in PPIs/H2Bs group and not reached in non-PPIs/H2Bs group ( HR 1.53, Log-rank trest, p=0.403), respectively. Conclusions: Gastric secretion inhibitors didn’t affect the efficacy of gefitinib treatment in patients with NSCLC harboring EGFR activating mutations.
First-line cisplatin-fractionated doublet for unfit patients with advanced/metastatic non-small cell lung cancer.
Authors: Mansueto Giovanni , Narducci Filomena , Quadrini Silvia , Mancini Maria Laura , Sperduti Isabella , Gamucci Teresa 
Published: March 2020

e18072 Background: standard treatment for unfit patients (pts) with stage IIIB-IV non-small cell lung cancer (NSCLC) is single-agent chemotherapy. Such pts are usually not suitable for cisplatin (CDDP)-based chemotherapy due to poor performance status (PS) and/or significant comorbidity that could enhance toxicity of high-dose CDDP. They also are not able to tolerate hydric load that is recommended for CDDP at high doses. We investigated a schedule of fractionated CDDP as first-line treatment in unfit pts with stage IIIB/IV NSCLC. Methods: 42 consecutive unfit pts with advanced/metastatic NSCLC were treated. They all had ECOG PS 2 and/or significant comorbidity and were not eligible for a standard CDDP-based doublet. Median age was 65,6 years (range 46-77), stage IIIB/IV=15/27 pts. Histology: squamous 62,4%, adenocarcinoma 37,5%, other/NOS 0,1%. All pts received q3w CDDP 35 mg/mq d1-8 plus Gemcitabine 1000 mg/mq d1-8 or Pemetrexed 500 mg/mq d1 according to histology, for a maximum of 6 cycles. Maintenance Pemetrexed was allowed in pts with non-squamous histology. Progression-free survival (PFS), clinical benefit rate (CBR) and toxicity were evaluated. Results: 33 pts are evaluable for efficacy and 35 for toxicity. Mean number of cycles per patient was 5,03 (total 211). Maintenance with q3w Pemetrexed was performed in 10 pts (23,8%)(mean 4,3 cycles per patient). Five pts in response after CDDP received thoracic RT. A partial response was observed in 42,5% of pts and a stable disease in 35,4% of pts, for an overall CBR of 77,9%. Median PFS was 10,1 months (Kaplan-Meier); 31,9% of pts were progression-free at 1 year. Pts with adenocarcinoma had significantly better PFS than those with squamous histology (11 vs 8 months, p=0.03). G3-G4 haematological toxicity: neutropenia 48,4% (3% febrile), thrombocytopenia 27,2% and anaemia 9,0%. A 25% dose reduction was required in 39,3% of patients. One patient died for cardiac failure during treatment. Conclusions: fractionated CDDP seems to be effective in our patients population with advanced NSCLC. Adequate supportive care help to manage severe hematological toxicity. A randomized phase II trial of fractionated CDDP-doublet versus monotherapy has been planned.
Customized first-line chemotherapy according to ERCC1 and RRM1 SNPs in advanced NSCLC patients: A phase II study.
Authors: Mazzoni Francesca , Cecere Fabiana Letizia , Meoni Giulia , Giuliani Costanza , Camerini Andrea , Allegrini Giacomo , Amoroso Domenico , Boni Luca , Martella Francesca , Ranchicchio Prabha , Giommoni Elisa , Torricelli Francesca , Di Costanzo Francesco 
Published: March 2020

e18074 Background: Excision repair cross complementing group 1 (ERCC1) and ribonucleotide reductase1 (RRM1) expression levels are predictive of CT efficacy in some malignancies. “Customized” CT has several advantages: (1) pts are more likely to be treated with agents that they will respond to, (2) pts can be spared the toxicity of agents that they are resistant to, (3) effective treatment can be delivered early in the course of disease. Methods: We planned a phase II multicentric open label study in two steps (based on Simon design) to evaluate ERCC1 SNPs (T118C and C8092A) and RRM1 SNPs (-37C>A and -524T>C) in advanced NSCLC pts. Here we report the first step for futility. Pts received first line CT according to the assessed ERCC1 and RRM1 SNPs status and the correlated expression levels: treatment A (low ERCC1 and low RRM1) Cisplatin plus Gemcitabine; treatment B (low ERCC1 and high RRM1) Cisplatin plus Docetaxel; treatment C (high ERCC1 and low RRM1) Gemcitabine plus Docetaxel; treatment D (high ERCC1 and high RRM1) Docetaxel plus Vinorelbine. Results: 42 pts were enrolled from Jan. 2010 to Oct. 201, 40 pts received at least 1 cycle of CT; median age was 66 yrs (range 47-73); 33 pts were males; 23(55%) pts were ECOG PS 0, 19(45%) PS 1; all pts had stage IV; 23(55%) pts had adenoca, 13(31%) squamous, 6(14%) other types; 25(62%) pts received treatment A, 3(8%) treatment B, 11(27%) treatment C, 1(3%) treatment D. As primary end-point we assessed the overall best response: 18(45%) pts achieved PR, 12(30%) SD, 8(20%) PD, 2(5%) pts were not evaluable. Updated information on OS and PFS will be presented. CT was well tolerated, there were no treatment related deaths. Conclusions: We observed an improved RR in this setting of NSCLC pts treated with CT according to ERCC1 and RRM1 SNPs status. We are planning to continue the second step of this trial (total 110 pts).