bluuebunny/crossref_metadata_2025_split huggingface dataset:
Economic analysis of TORCH: Erlotinib versus cisplatin and gemcitabine as first-line therapy for advanced non-small cell lung cancer (NSCLC).
Authors: Chung Carmen , Isaranuwatchai Wanrudee , Di Maio Massimo , Jiang Haiyan , Lau Anthea , Hoch Jeffrey S. , Feld Ronald , Tsao Ming Sound , Gridelli Cesare , Ciardiello Fortunato , Butts Charles Andrew , Gallo Ciro , Perrone Francesco , Leighl Natasha B. 
Published: March 2020

e19031 Background: The TORCH (“Tarceva or Chemotherapy”) randomized phase III trial demonstrated that first-line erlotinib compared to cisplatin/gemcitabine in unselected advanced NSCLC patients yielded inferior survival, but no major differences in global quality of life. We determined the incremental costs and utility between arms, including in the EGFR mutation positive subgroup. Methods: Direct medical resource utilization data and EQ5D scores were collected prospectively during the trial. Costs for medications, outpatient visits, investigations and toxicity management including hospitalization were determined, and presented in 2012 Canadian dollars (CAD). The outcome of the analysis was the incremental cost per life year and quality-adjusted life-years (QALYs) gained. Results: The incremental mean cost per patient in the chemotherapy arm was $4,163CAD, largely related to drug and outpatient visit costs, while higher costs from hospitalization and adverse events were seen in the erlotinib arm. Mean overall and quality-adjusted survival times were longer in the chemotherapy arm. In the subset of patients with EGFR mutations (n=39), mean survival was not significantly different between arms (1.35 years for chemotherapy versus 1.29 years for erlotinib, p-value=0.86), but quality-adjusted survival favoured erlotinib treatment (i.e. mean QALYs were 1.04 for chemotherapy, and 1.40 for erlotinib). The incremental cost-effectiveness ratio for initial erlotinib in the EGFR mutation positive subgroup was $30,301 CAD per QALY. Conclusions: Initial chemotherapy in unselected advanced NSCLC yields better survival at minimal increased cost compared to erlotinib. In the EGFR mutation positive subgroup, first-line erlotinib is cost effective compared to first-line platinum doublet therapy, supporting routine EGFR genotyping to select first-line therapy in advanced NSCLC.
Reduced folate carrier (RFC) as a predictive marker for response to pemetrexed in advanced non-small cell lung cancer (NSCLC).
Authors: Alvarez Fernandez Carlos , Pérez Arnillas Quionia , Ruiz Ana Lucrecia , Rodriguez Rubi David Jose , Sánchez Lorenzo Luisa , Li Torres Walter Antonio , Izquierdo Manuel Marta , Berros Fombella Jose Pablo , Luque Cabal Maria , Jiménez Paula , Villanueva Palicio Noemi , Esteban Emilio 
Published: March 2020

e19034 Background: RFC is the major transport system in mammalian cells for folate cofactors and antifolate therapeutics. The aim of this study was to assess the predictive value of RFC expression in patients receiving pemetrexed for advanced NSCLC. Methods: The study was carried out in a population of 48 patients with advanced NSCLC which have received pemetrexed monotherapy in second and third line. RFC expression was assessed using a two-step model of immunohistochemical staining in paraffin-embedded tissue samples. Results: RFC expression was detected in 16 (33%) patients. In the global population, the median progression free survival (PFS) and the median overall survival (OS) were 3.3 and 6.5 months respectively. The subgroup of patients with expression of RFC had a tendency to better median PFS (4.5 vs 2.8 months; p=0.926) and median OS (11.7 vs 4.8; p=0.150). In patients with adenocarcinoma histology and RFC expression median OS after treatment with pemetrexed was 14.4 months versus 5.0 in those with adenocarcinoma but without RFC expression (p=0.039). Conclusions: These results suggest the possible relation between RFC expression and response to treatment with antifolates (pemetrexed) independently of the tumor histology. Further studies are required to confirm these results.
Benefits of a centralized cancer control program on outcomes: Evaluation of wait times for diagnosis and management of advanced non-small cell lung cancer (NSCLC).
Authors: Noonan Krista , Laskin Janessa J. , Tong King Mong , Ramsden Katherine , Zhai Yongliang , Ho Cheryl 
Published: March 2020

e19039 Background: Canada has a national cancer registry that tracks patterns across the population; British Columbia (BC) has the lowest lung cancer mortality in the country. The BC Cancer Agency (BCCA) operates five regional cancer centres and community outreach sites that deliver cancer care using evidence-based standards and guidelines established by the BCCA. The province is 945,000 km2; the population is distributed 85% urban and 15% rural. We hypothesize that adherence to provincial cancer control programs results in equitable services in all geographic locations. Methods: A retrospective population-based review of stage IIIb/IV NSCLC patients (pts) diagnosed from Jan 2008 to Dec 2010 referred to the BCCA was done. Pt characteristics and time intervals between diagnosis, referral, oncology consultation and palliative therapy were extracted. The Kruskal-Wallis test was used to compare wait times (WT). The Kaplan-Meier method and log rank test was used for OS. Results: 1,431 pts were identified. Median time from diagnosis (DX) to referral (RF) was similar across all geographic regions (11-13 days). Median time from RF to oncology consultation ranged from 7-16 d. Table 1 describes medical oncology (MO) WT to chemotherapy (CT) and radiation oncology (RO) WT to radiotherapy (RT). Conclusions: While WT varied between key events in the pts’ lung cancer trajectory by geographic location, the overall survival from diagnosis was similar in all groups. Provision of provincially mandated guidelines and care conferred equitable outcomes in advanced NSCLC across BC. [Table: see text]
Survival analysis of induction cisplatin (CDDP)-docetaxel (DOC)-bevacizumab (BEV) chemotherapy followed by maintenance BEV-pemetrexed (PEM) therapy in advanced nonsquamous non-small cell lung cancer (NonSq NSCLC): A phase II trial from Okayama Lung Cancer Study Group 0903.
Authors: Nogami Naoyuki , Hotta Katsuyuki , Kozuki Toshiyuki , Yoshioka Hiroshige , Nishiyama Akihiro , Fukuda Yasushi , Tabata Masahiro , Shinkai Tetsu , Tanimoto Mitsune , Kiura Katsuyuki ,   Okayama Lung Cancer Study Group
Published: March 2020

e19040 Background: BEV maintenance therapy and PEM maintenance therapy in platinum-based chemotherapy yield a significant survival advantage in CALGB and PARAMUNT trials, respectively, but each agent gave only modest impact on survival. We conducted a phase II trial of CDDP-DOC-BEV therapy followed by maintenance BEV-PEM therapy inchemo-naïve advanced NonSq NSCLC. Methods: Forty-one patients (pts) participated in the induction phase, specified as four cycles of induction CDDP (80 mg/m2), DOC (60 mg/m2) and BEV (15 mg/kg) on day 1 of a 21-day cycle. Pts who had not progressed during CDDP-DOC-BEV received maintenance BEV (15 mg/kg) and PEM (500 mg/m2) on day 1 of a 21-day cycle until disease progression. The primary endpoint was PFS, and the secondary endpoints included OS, toxicity, and response. Survival time was calculated from the date of registration. Results: Pt characteristics were as follows: median age: 62 yrs; 76% male; 32% PS 0; 73% stage IV; 93% Ad; 5% EGFR-mutant and 2% ALK-mutant. At the time of this analysis, 34 pts (83%) discontinued the treatment, mainly due to progressive disease (53%). The principal toxicity was myelosuppression (gr. 4 hematological: 21 pts [51%]), and grs. 3/4 febrile neutropenia was observed in 10 (24%) despite no treatment-related deaths. The objective response rate and disease control rate (DCR, % pts with CR/PR/SD) was 82.9% and 97.6%, respectively. Median follow-up time was 15.6 months, and 1-yr PFS rate was 34.2% with 95% confidence interval (CI) of 20.3-48.5%, which met the primary endpoint. Also, 1-yr OS rate was 75.6% (95%CI: 59.4-86.1%). Exploratory analysis for pts with both EGFR- and ALK-wild-typed NonSq NSCLC (n = 16) demonstrated 1-yr PFS and OS rates of 50.0% (24.5-71.1%) and 87.5% (58.6-96.7%), respectively. Also, pts with maintenance therapy (n = 34) had 1-yr PFS and OS rates of 41.2% (24.8-56.9%) and 82.4% (64.9-91.7%), respectively. Conclusions: CDDP-DOC-BEV followed by BEV-PEM maintenance seems highly effective despite moderately toxic profiles in chemo-naïve pts with advanced NonSq NSCLC. Clinical trial information: UMIN000004127.
Phase I study of the safety and pharmacokinetics of epitinib, an oral EGFR tyrosine kinase inhibitor, in patients with advanced solid tumors.
Authors: Zhou Qing , Wu Yi Long , Yu Xiyong , Yang Jinji , Wen Limin , Sai Yang , MU Hua 
Published: March 2020

e19042 Background: Epitinib is an oral small molecule compound selectively inhibits epidermal growth factor receptor (EGFR). It has demonstrated potent inhibitory effects on multiple human tumor xenografts with a large safety window and broad tissue distribution including high drug contribution in brain. This first-in-human study is being conducted to assess the safety and tolerability, pharmacokinetics (PK), and preliminary anti-tumor activity of Epitinib. Methods: This phase I study uses a 3+3 design for dose-escalation of Epitinib given once daily (QD) in 28-day treatment cycles in patients with solid tumors who failed or have no access to standard therapies. Safety and tumor response are assessed according to NCI CTCAE 4.0 and RECIST 1.1, respectively. Results: By Dec 31, 2012, 19 pts aged 40-66 yr old (ECOG PS 1) with NSCLC (n=16) or breast cancer (n=3) were enrolled in 5 dose cohorts of 20-160 mg. Six NSCLC pts had EGFR mutations (3 with T790M). All pts had ≥2 lines of prior systemic treatments (7 pts with gefitinib or elotinib). Most AEs were mild (Gr1). Treatment-related AEs included skin rash (36.8%), abnormal liver function tests (42.1%), diarrhea (10.5%), vomiting (5.3%), paronychia (5.3%), decreased neutrophil count (5.3%) and increased creatinine (5.3%). Three SAEs were reported as possibly unrelated to the study drug. No DLT was observed and MTD has not been reached yet. PK analysis showed that the mean elimination half-life of Epitinib was approximately 40 hours and Tmax was around 2 h. Both Cmaxand AUC exhibited good dose proportionality over the studied dose range with low inter-patient variability following single and multiple doses. Among 15 evaluable pts, 1 EGFR mutation+ NSCLC pt achieved confirmed partial response (66.7% tumor reduction) for more than 6 months and the treatment is ongoing; 8 pts had stable disease, including 1 with T790M for 6 months and 1 with brain metastasis for 12 months who is still on treatment. Conclusions: Epitinib was well tolerated at doses up to 160mg QD to date with manageable adverse events and excellent pharmacokinetic properties. Encouraging clinical activity was observed, including durable SD in NSCLC patients with T790M or brain mets.
Hydration with magnesium and mannitol without furosemide prevents the nephrotoxicity induced by cisplatin and pemetrexed in patients with advanced non-small cell lung cancer.
Authors: Muraki Keiko , Koyama Ryo , Suina Kentaro , Asao Tetsuhiko , Honma Yuichiro , Shukuya Takehito , Ohashi Rina , Shimada Naoko , Takahashi Fumiyuki , Takahashi Kazuhisa 
Published: March 2020

e19043 Background: The aim of this study was to examine the effect of hydration with magnesium and mannitol without furosemide on the nephrotoxocity accompanying combination chemotherapy using cisplatin and pemetrexed in patients with advanced non-small cell lung cancer (NSCLC). Methods: Fifty patients with NSCLC who received cisplatin plus pemetrexed, using either old hydration protocol including normal saline with mannitol and furosemide, or a new one including normal saline with magnesium and mannitol without furosemide were retrospectively analyzed. Nephrotoxicity was compared between patients treated using the old protocol and those treated with the new protocol. Univariate and multivariate analyses were performed to identify the independent factors associated with protection against nephrotoxicity in patients with NSCLC who received cisplatin plus pemetrexed. Results: Thirty patients received the old hydration protocol, while 20 patients were treated using the new hydration protocol. The patients treated using the new hydration protocol showed a significantly greater increase in creatinine clearance (p=0.0004) and a decrease in the serum creatinine level (p=0.0148) after one course of chemotherapy compared with those treated using the old hydration protocol. There were no differences in the chemotherapeutic response or overall survival between the groups (p=0.572). The new hydration protocol with supplemented magnesium with mannitol without furosemide was an independent factor for the protection against nephrotoxicity induced by cisplatin and pemetrexed in patients with advanced NSCLC (HR 0.232 (95% CI: 0.055-0.986), p=0.039). Conclusions: These results demonstrate that the new hydration protocol comprising supplementation with magnesium without furosemide could prevent the nephrotoxicity induced by cisplatin and pemetrexed without affecting the treatment outcome.
EGFR mutation rate in liquid-based cytology compared with biopsies from primary and metastatic lung cancer using real-time PCR.
Authors: Buglioni Simonetta , D'Alicandro Valerio , Melucci Elisa , Ercolani Cristiana , Visca Paolo , Fabi Alessandra , Filippetti Massimo , Milella Michele , Mottolese Marcella 
Published: March 2020

e19052 Background: Specific EGFR tyrosine kinase inhibitors (TKIs) are recommended as first-line therapy in patients with non-small cell lung cancer (NSCLC) that have active EGFR mutations. Although cytology and tumor biopsy are a very common approaches to evaluate patient eligibility to TKIs, the limited number of tumor cells present in these samples may often constitute a bias for molecular analysis. In this context, the use of sensitive methods to detect EGFR mutations may be of pivotal clinical importance. The aim of this study was two-fold: 1) to determine the accuracy and sensitivity in detecting EGFR mutations between liquid-based cytology (LBC) and bioptic specimens, 2) to compare the performance of direct DNA sequencing and real-time PCR (qPCR) in two different series of cytologic and histologic primary and metastatic NSCLC. Methods: DNA wasextracted from 537 specimens of NSCLC patients including 422 biopsies and 115 ThinPrep (TP) collected samples respectively. EGFR mutations were analyzed by direct sequencing (exons 19 and 21) in 284 biopsies and 68 TP samples and by qPCR (exons 18, 19, 20, 21) in 138 biopsies and 47 LBC samples. Results: The overall specimen insufficiency rate between LBC and biopsies was significantly higher by direct sequencing compared to qPCR (biopsies: 11.6% vs 7.2%) and (LBC: 14.7% vs 2.3%). In the series of 309 valuable cases analyzed by direct sequencing (251 bioptic and 58 LBC), we found 34 (11%) EGFR mutations (11.2% biopsies and 10.3% LBC ). Of interest, a higher percentage of EGFR mutant cases (18.1%) was observed in the 170 valuable cases analyzed by qPCR (11.1% biopsies and 21.4% LBC). Conclusions: Our data indicate that TP collected specimens seem to be more reliable than formalin fixed biopsies for molecular analysis, probably due to the better quality of the extracted DNA. Furthermore, qPCR enabled detection of EGFR mutations in samples with low tumor content for which conventional Sanger sequencing was not informative.
Clinical characterics of mixed neuroendocrine cancer of lung: Retrospective analysis of 20 cases from 2,501 lung cancer.
Authors: Li Dong-Hai , Zhou Lin , Ding Zhenyu 
Published: March 2020

e19055 Background: The mixed neuroendocirne cancer of the lung consists endocrine cancer and other pathological types of cancer, and is generally overlooked in daily practice. The current study to explore the clinical characteristics of mixed neuroendocirne cancer of the lung. Methods: Totally 2,501 cases with primary lung cancer were retrieved from the archive of the Cancer Center, West China Medical School. And the relevant medical records including diagnosis, histology, therapy, and outcome were collected. Results: Among the 2, 501 cases, 20 were found to have mixed neuroendocrine cancer with morbidity rate 0.01% (19 male, 1 female). The median age was 60 years. The surgery (13 cases, 65%) and chemotherapy (19 cases, 95%) were the mainstay of therapy. 2 cases (10%) received thoracic radiation, and 3 cases (15%) received whole brain radiation. Chemotherapy regimens included etoposide-based doublets (A) or the third-generation agent-based (B) regimens. The long-term follow-up data were available for 18 cases (90%) with the median follow-up duration of 20.5 months. The overall survival of the stage IV patients was 18.2 months, while that of the stage I-III was not reached (P=0.325). The chemotherapy regimens (A or B) did not exert impact on survival (P=0.535). Patients received operation (11 cases) had less mortality compared with those without operation (7 cases) (P<0.001). Conclusions: The mixed neuroendocrine cancer of lung is a rare disease. Male takes a predominant part. Stage and histology are important for the prognosis. The chemotherapy seems to have less impact on the prognosis, but the surgery is critical for the long survival.
Association of clinical and nutritional factors with treatment related toxicity of “fixed standard dose” of afatinib in patients with advanced NSCLC.
Authors: Arrieta Oscar , de la Torre Martha , Pérez Dana , Turcott Jenny , Juárez Eva , Sanchez-Lara Karla , López Diego 
Published: March 2020

e19068 Background: Afatinib, an irreversible tyrosine kinase inhibitor of ErbB-family, has shown clinical benefits and prolonged progression free survival in EGFR mutated patients. Adverse effects related to afatinib such as diarrhea, stomatitis and rash can negatively impact on QoL and survival by interrupting treatment. Dose of TKI´s of EGFR are fixed regardless of weight or body surface (BS), which could affect the severity of treatment related toxicity. Methods: We prospectively studied patients with advanced NSCLC treated with afatinib in order to determine if malnutrition and clinical factors are associated to higher incidence of severe toxicity. Prior treatments with afatinib 40mg, 78 patients were assessed. Nutritional status was assessed by Subjective Global Assessment (SGA), and toxicity was obtained during 2 cycles by CTCAE 4.0, severe toxicity is defined as grades 3 and 4. Results: Mean age was 59.2 years, 71.8% were women, 89.7% had adenocarcinoma, 76.9% had a good performance status (ECOG 0-1), and median weight and BS were 59.9kg and 1.58m2. Sixty percent of patients had some grade of malnutrition (SGA B+C). Factors associated to severe diarrhea, mucositis and other gastrointestinal toxicity are shown in Table 1, no factors were found to be associated with the development of severe rash. Conclusions: The performance status, malnutrition and body surface are independent factors related to severe gastrointestinal toxicity to Afatinib. This study suggests that for the initial dose selection of TKI´s of the EGFR these factors should be considered in order to reduce the risk of severe toxicity.
Epidermal growth factor +61 a/g polymorphisms as predictors for survival in advanced lung adenocarcinoma and squamous cell carcinoma.
Authors: De Mello Ramon Andrade , Ferreira Monica , Soares-Pires Filipa , Costa Sandra , Oliveira Pedro , Hespanhol Venceslau , Reis Rui M 
Published: March 2020

e19069 Background: Our purpose was to evaluate epidermal growth factor (EGF) +61 A/G polymorphisms as prognostic marker for progression free survival (PFS) and overall survival (OS) in advanced non-small cell lung cancer (NSCLC). Methods: 148 Portuguese Caucasian, medically treated for NSCLC between February 2010 and April 2011, were included in this study. DNA was extracted from peripheral blood leucocytes. Genotyping was performed by PCR-RFLP. Chi-square test, Kaplan-Meier estimator and cox regression hazard model were used to assess the prognostic value of selected polymorphisms. Results: Genotype frequency was A/A (25.3%), A/G (55.6%), G/G (19.2%). We found no differences in PFS among EGF+61 A/G polymorphisms and NSCLC (p = 0.339). However in G/G+A/G genotype patients group showed a trend to higher OS than A/A genotype (p = 0.055). Moreover, adenocarcinoma and squamous cell (SC) lung cancers patients harboring in A/G+G/G genotype group showed a trend to higher OS than those harboring A/A genotype (p = 0.074). Furthermore, patients in advanced stages carrying G/G genotype presented higher OS than those carrying A/A genotype: 13 months versus 3 months (adenocarcinoma); and 6 months versus 1 month (SC lung cancer), respectively, p = 0.043. Conclusions: We were able to observe the G/G genotype of EGF+61 A/G polymorphisms as a positive predictor for survival in medically treated advanced adenocarcinoma and squamous cell lung carcinoma patients. In future, our findings could be used as a biological marker in order to identify eligible NSCLC subgroups with potential improved response to EGFR tyrosine-kinase-inhibitors.
Phase Ib study of chidamide (CS055), a new subtype-selective oral histone deacetylase inhibitor, in combination with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer.
Authors: Hu Xing-Sheng , Shi Yuan-Kai , Wang Lin , Lin Lin , Han Xiao-Hong , Meng Zhi-Yun , Dou Gui-Fang , Sun Yan 
Published: March 2020

e19075 Background: Chidamide (CS055) is a new benzamide type of histone deacetylase (HDAC) inhibitor with subtype selective activity against HDAC1, 2, 3 and 10. Synergistic effect of chidamide combined with paclitaxel and carboplatin (PC) have been demonstrated in various in vitro studies. Chidamide has shown well-tolerated and favorable PK profiles in patients (pts) with advanced solid tumors and lymphomas.This phase Ib study was designed to assess the safety and pharmacokinetics of chidamide plus PC in pts with advanced non-small cell lung cancer (NSCLC). Methods: Chemonaive pts with stage IIIb or IV NSCLC were treated with the escalating doses of chidamide (20, 25, and 30mg) plus PC. Chidamide was oral administered twice per week. Paclitaxel (175 mg/m2) and carboplatin (AUC 5 mg·min/mL) were given both on day 1 every 3 weeks. Pts with response or stable disease after four cycles maintained single chidamide therapy until disease progression or unacceptable toxicity. Results: No DLT was observed in the 20 mg (n=3) and 25 mg (n=3) cohorts. 2 DLTs occurred in the 30 mg cohort (n=4), where 1 pt experienced grade 4 thrombocytopenia at the end of the first cycle, and the other developed grade 3 neutropenia and grade 2 thrombocytopenia resulting in the delay of the 2nd treatment cycle for > 14 days. Therefore, chidamide in 25 mg was determined to be the MTD with this combination regimen. ≥ Grade 3 toxicities were thrombocytopenia (n=3) and neutropenia (n=1). 1 pt experienced grade 1 prolonged QTc. Co-administration had no significant effect on clearance of either chidamide or paclitaxel. 1 pt in the 20 mg cohort had confirmed partial response. Of 5 pts with brain metastases, 2 of them had complete disappearance of brain tumors after 4-cycle treatment. Conclusions: Chidamide plus PC was safe and well tolerated, with no apparent chidamide-paclitaxel pharmacokinetic interaction. Preliminary efficacy results suggest that chidamide combined with PC could provide benefit to NSCLC pts, with a potential interest of further observation of brain metastasis control in NSCLC with this regimen. Clinical trial information: ChiCTR-ONC-12002283.