bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase I/II study of OGX-011 and a gemcitabine (GEM)/platinum regimen as first-line therapy in 85 patients with advanced non-small cell lung cancer
Authors: Laskin J. J. , Hao D. , Canil C. , Lee C. W. , Stephenson J. , Vincent M. , Gitlitz B. , Cheng S. , Murray N. R. 
Published: March 2020

7596 Background: OGX-011 is a second-generation antisense oligonucleotide designed to knockdown expression of the cytoprotective chaperone, clusterin, thereby facilitating apoptosis and sensitization of many human cancer cell-lines to chemotherapy. Methods: Eligibility criteria: stage IIIB/IV NSCLC; no prior chemotherapy; =1 measurable lesion; ECOG =1; adequate organ function; no active CNS metastasis. Treatment: infusion of OGX-011 initial loading doses (3 in 1 week), followed by weekly OGX-011 with standard chemotherapy: GEM (1,250 mg/m2) Days 1+8 and either cisplatin (75 mg/m2) or carboplatin (AUC=5) Day 1 q21 days, (maximum 6 cycles). Results: 85 pts (phase I=10 and phase II=75) enrolled between Dec 04 and Nov 06. Based on phase I results, dose of OGX-011 was 640 mg. Data is available on the first 53 pts; all received =1 dose of OGX-011 and were considered evaluable for safety and efficacy. Demographics: female (47%); stage IV (87%); median age 61 (45–79) yrs; ECOG PS =1 (62%); median no. of cycles delivered was 4. Principal grade 3/4 toxicities were hematologic: neutropenia (32%) + thrombocytopenia (17%). Other common toxicities included fatigue, nausea, vomiting, fever, chills, constipation, + anorexia. Two serious adverse events previously reported as associated with GEM/platinum therapy were documented: acute cortical blindness with stroke + thrombotic thrombocytopenic purpura. Responses: 12 confirmed PR (ORR = 23%). Median PFS is 101 days (53–260+). Of the first 24 patients who have all been followed for =1 yr, median survival is 383 days (19–751+); 14/24 (58%) survived >1 yr; 10/14 remain alive as of 12/13/06. Conclusions: 1-yr survival rate =50% may justify a phase III randomized trial. Survival data on 46 pts followed for =1 yr will be presented. OGX-011 is being developed by OncoGenex Technology Inc. + Isis Pharmaceuticals Inc. No significant financial relationships to disclose.
Exploratory analysis of EGFR FISH criteria in Japanese non-small cell lung cancer patients treated with gefitinib
Authors: Kazuo K. , Morrison L. E. , Kimura H. , Sone T. , Araya T. , Tamori S. , Tanbo Y. , Fujimura M. , Speake G. , Holloway B. R. 
Published: March 2020

7599 Background: In the phase III Iressa (gefitinib) Survival Evaluation in Lung cancer (ISEL) trial, high epidermal growth factor receptor (EGFR) gene copy number was a predictor of a gefitinib effect on survival in patients (pts) with refractory advanced non-small-cell lung cancer (NSCLC) (hazard ratio 0.61 vs 1.16 for high vs low copy number; p=0.045) [JCO 2006;24:5034–42]. Although EGFR mutation status may predict response to gefitinib in Japanese pts, there is insufficient data to clarify if high EGFR gene copy number assessed by fluorescence in situ hybridization (FISH) is predictive in these pts. This analysis investigated the applicability of both published Colorado FISH criteria (Colorado Univ) and new FISH criteria to Japanese NSCLC pts. Methods: 58 tumor specimens from gefitinib-treated Japanese pts were analyzed using Vysis LSI EGFR and CEP7 (chromosome 7 control) FISH probes. Specimens were classed as FISH+ or - using Colorado and exploratory (EGFR/cell; CEP7/cell; EGFR/CEP7; % of cells with various numbers of EGFR or CEP7 signals) criteria. Results: Of the 58 pts, 17 (29%) had an objective response (OR). Using Colorado criteria, OR was 50% in the 14 FISH+ pts vs 23% in the 44 FISH- pts (2-sided Fisher's exact test p=0.089). There was a trend for an association between FISH+ status and improved survival (log rank p=0.15). Defining FISH+ as specimens with =5% cells containing >5 EGFR signals, OR was significantly better among FISH+ pts vs FISH- pts (p=0.0030; 52% of the 23 FISH+ pts responding vs 14% of the 35 FISH- pts). A survival advantage was not indicated. Defining FISH+ as =74% of cells with EGFR or CEP7 loss (<2 signals) or gain (>2 signals), OR was significantly better among FISH+ pts vs FISH- pts (p=0.043; 45% of the 22 FISH+ pts responding vs 19% of the 36 FISH- pts). Association with survival had marginal significance (log rank p=0.061). Conclusions: These preliminary data have identified loss or gain of EGFR and CEP7 abnormality as promising biomarkers for response to gefitinib in Japanese NSCLC patients. Analysis of these markers for correlation with time to progression is ongoing. Investigation of these potential markers in other cohorts of patients is worthy of further evaluation. [Table: see text]
Pemetrexed and carboplatin plus bevacizumab for advanced non-squamous non-small cell lung cancer (NSCLC): Preliminary results
Authors: Patel J. D. , Hensing T. A. , Villafor V. , Hart E. , Bonomi P. 
Published: March 2020

7601 Background: Pemetrexed in combination with carboplatin has been shown to have promising activity and favorable toxicity profile in NSCLC. Bevacizumab has been shown to improve response rates and survival in pts with advanced non-squamous NSCLC when combined with carboplatin and paclitaxel. This study of pemetrexed and carboplatin plus bevacizumab was designed to evaluate the toxicity profile and to estimate the activity of the regimen in this pt population. Methods: Eligibility required that pts were chemotherapy-naive, had stage IIIB (effusion)/IV non-squamous NSCLC, PS 0–1, with no evidence of CNS metastases. Pts received pemetrexed 500 mg/m2 over 10 minutes, carboplatin AUC 6 over 30 minutes, and bevacizumab 15 mg/kg over 30–90 minutes on a 21-day cycle for 6 cycles. Pts with SD or PR received pemetrexed 500 mg/m2 and bevacizumab 15 mg/kg every 21 days until disease progression or toxicity. All pts received folic acid, vitamin B12 and steroid prophylaxis. Results: From 8/05 to 9/06, 39 pts (of planned 50) were enrolled: 20 M/19 F; median age 64 (range 41 - 80). One pt enrolled and subsequently refused treatment. Median number of cycles was 6 (range 1–22), and 25/38 (66%) completed at least 6 cycles of therapy. There was no grade 4 hematological toxicity. Grade 3 hematological toxicities were anemia (5%, N=2) and thrombocytopenia (3%, N=1). The most common grade 3/4 non-hematological toxicities included proteinuria (3%, N=1, gr 3), venous thrombosis (3%, N=1, gr 3), infection (3%, N=1, gr 4), and diverticulitis (11%: 8%, N=3, gr 3/3%, N=1, gr 4). 1 pt with diverticulitis experienced bowel perforation that required surgical intervention. The trial was temporally suspended and the group of pts with diverticulitis was analyzed separately. The only risk factor identified was previous history of diverticulitis. One CR, 20 PRs were observed for an overall response rate of 55% (95%, CI 43–75%). Conclusions: Treatment with pemetrexed and carboplatin plus bevacizumab in pts with advanced non-squamous NSCLC is feasible with an acceptable toxicity profile. The encouraging activity justifies further development of this regimen. However, pts with a prior history of diverticulitis should be excluded until this observation can be investigated further. No significant financial relationships to disclose.
Extent of lymphadenectomy (LA) and outcome for patients with stage I non-small cell lung cancer (NSCLC)
Authors: DeCamp M. M. , Recht A. , Nikolov M. , Flickinger J. C. , Varlotto J. M. 
Published: March 2020

7604 Background: It is uncertain if LA affects overall survival (OS) or disease-free survival (DFS) rates for patients with stage I NSCLC and, if performed, what is the minimum number of nodes that should be recovered. Methods: 24,273 patients with stage I NSCLC diagnosed from 1992–2002 underwent a definitive surgical procedure and were included in the SEER data-base. For patients diagnosed from 1998–2002, outcome was examined separately for patients having only N1 (2,683 patients) or N2 nodal (1,019 patients) dissections. Results: For the entire population, LA was associated with an increase in the 5-year OS rate from 41.7% to 58.4% (p <0.0001) and in DFS from 58.4% to 72.9%, compared to not having LA. For patients undergoing only N1 dissection, LA was also associated with significant improvements in OS and DFS, compared to no LA (p=0.056 and 0.043). The maximum difference between those with no LA and those with only N1 dissection was when 11–16 nodes were removed (4-year OS, 40.0% vs. 68.2%; DFS, 40.0% vs. 60.4%). For patients undergoing only N2 dissection, LA was associated with a significant improvement in OS (p=0.045) and a trend for a DFS benefit (p=0.086), with the maximum difference between those with no LA and those with 7–10 nodes removed (4-year OS, 75.0% vs. 77.7%; DFS, 75.0% vs. 85.0%). Those patients undergoing removal of ≥ 11 N2 nodes were found to have a significantly increased risk of death to cardiopulmonary/infectious causes (5.56% vs 1.79%) as compared to those patients having < 11 nodes removed (p = 0.023). Conclusions: LA was associated with increased rates of OS and DFS, compared to no LA. Our results also suggest the minimum number of recovered nodes needed to see the maximum staging accuracy of LA. No significant financial relationships to disclose.
3p and 10q deletions detected by fluorescence in situ hybridization (FISH): A potential new tool for early detection of non-small cell lung cancer (NSCLC)
Authors: Yendamuri S. , Vaporciyan A. A. , Zaidi T. , Fernandez R. , Rice D. C. , Spitz M. , Swisher S. , Walsh G. L. , Roth J. A. , Katz R. L. 
Published: March 2020

7606 Objectives: To study the feasibility of detecting chromosomal deletions at the 3p and 10q regions in bronchoscopic brush biopsies and touch preparations by FISH and to study their distribution in different areas of the airway in patients with NSCLC. Methods: Bronchoscopic brush biopsies from the mainstem bronchus on the normal side contralateral to the tumor (NBB) and normal mainstem bronchus on the tumor side (TBB) were obtained from 120 patients who underwent surgical resection. Touch preparations from the tumor (TTP) and normal lung parenchyma from the involved lung (NTP) and from bronchi adjacent to the tumor (TAB) were also obtained. Two FISH assays using probes complementary to 3p22.1 and 10q22.3 were used for evaluation of chromosomal deletions at each site. The ratios of the percentage of deletions detected at different anatomical sites were compared using the Wilcoxon signed rank test. Correlations between deletions at TTP and other sites were estimated with a Spearman coefficient. Results: Contralateral normal bronchial tissue (NBB) showed a relatively low deletion rate of 3p and 10q compared to TTP (p<0.0001). FISH on brush biopsies at TBB showed a significantly higher rate of deletions compared to NBB (p<0.05) for both 3p and 10q. A significantly higher deletion rate was seen at TTP compared to NTP at both the 3p (p<0.0001) and 10 q regions (p<0.0001). Significant correlations were seen between the rate of deletions between TTP and TBB at 3p (ρ=0.61, p<0.0001) and between TTP and TAB at 10q (ρ=0.64, p<0.0001). Conclusions: Chromosomal deletions of the 3p and 10q regions can be reliably detected by FISH in bronchoscopic biopsies and touch preparations. As one progresses from the contralateral normal bronchus to the bronchus on the side of tumor and the tumor itself, the percentage of chromosomal deletions increases in a statistically significant fashion,supporting an etiological role of these changes. Deletions at the bronchoscopically normal main and adjacent bronchus on the side of the tumor correlate with an increased deletion rate in the tumor itself. This suggests that FISH analysis of bronchoscopic brushes may be useful for identifying patients at high risk for developing NSCLC. No significant financial relationships to disclose.
Impact of epidermal growth factor receptor (EGFR) pathway alterations on the outcome of non-small cell lung cancer (NSCLC) patients (pts) treated with first-line chemotherapy (CHT)
Authors: Gelibter A. , Buttitta F. , Nuzzo C. , Visca P. , Cianciulli A. M. , Rinaldi M. , Terzoli E. , Sperduti I. , Ceribelli A. , Cognetti F. 
Published: March 2020

7607 Background: Molecular alterations along the EGFR pathway have been proposed to be the major determinant of clinical outcome in response to EGFR tyrosine kinase inhibition in NSCLC pts. However, their potential impact on sensitivity to CHT has not been studied in detail. Methods: Advanced NSCLC pts undergoing CHT were screened for EGFR gene mutations (by SSCP and sequencing) and/or increased copy number (by FISH), EGFR protein expression (by IHC), and HER-2, phosphorylated AKT (pAKT), and total AKT protein expression (by IHC). Correlation between specific molecular alterations and clinical outcome (ORR, PFS, and OS) was then retrospectively explored using both the Cox regression model as well as classification and regression trees (CART) analysis. Results: One hundred and twenty seven pts were screened and 93 received 1st-line CHT. The frequency of EGFR pathway alterations is shown in Table 1 . At a median follow up of 13 mos, survival analysis revealed that true EGFR gene amplification is the only significant predictor of worst OS (p=0.004). No significant correlation was found with PFS. ORR was significantly worse in HER-2-positive pts (p=0.03). CART analysis confirmed that true EGFR gene amplification negatively affect OS, followed by EGFR gene mutation and chromosome 7 polysomy in non-amplified and non-amplified/non-mutated pts, respectively. Conclusions: EGFR pathway alterations significantly impact on outcome following 1st-line CHT for advanced NSCLC. HER-2 overexpression negatively impacts on ORR, but not on PFS and OS. This information maybe useful in selecting appropriate treatment algorithm for advanced NSCLC pts. No significant financial relationships to disclose. [Table: see text]
Correlation of the EGFR gene mutation, gene amplification and protein expression in non-small cell lung cancer with clinical outcomes of erlotinib monotherapy: An exploratory analysis of biomarkers by the Korean Cancer Study Group
Authors: Ahn M. , Ahn J. , Kim S. , Kim H. , Lee J. , Cho J. , Song H. , Park S. , Shin S. , Park K. 
Published: March 2020

7608 Background: Mutations in epidermal growth factor receptor (EGFR) are considered to be strong predictive marker for response to the EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) patients. The aim of this study conducted by the Korean Cancer Study Group (KCSG) was to determine the clinical implications of EGFR gene mutation, increased gene copy number or protein over- expression in Korean patients with advanced NSCLC who had been treated with erlotinib. Patients and Methods: A total of 120 patients received erlotinib at a dose of 150 mg daily as part of an open label phase II monotherapy trial between January 2005 and May 2006 in Korea. Ninety-two tissue samples obtained from these patients were analyzed for EGFR mutations (exon 18–21), 88 samples for EGFR gene amplification by real time PCR, and 77 samples for EGFR protein expression by immunohistochemical (IHC) staining. Results: Twenty-four out of 92 patients (26.1%) had EGFR mutations in exon 18, 19, or 21, most commonly in exon 19 (75%, 18/24). A higher frequencies were noted in female patients (40.0% vs 17.5%, p=0.017). Higher rate of response to erlotinib was noted in patients with EGFR mutations compared to wild type (N=14/24 (58.3%) vs 11/68 (16.2%), p<0.001). With the median follow-up duration of 14.5 months, time to progression (TTP) and overall survival (OS) were also significantly longer in patients with mutations than those without mutations (p=0.003, p=0.042). Increased EGFR gene copy number was found in 44.9% (36/88). Patients with increased gene copy number achieved higher rate of response to erlotinib (N=14/36 (38.9%) vs 9/52 (17.3%), p=0.023). Also patients with high gene copy number showed longer TTP and OS (p<0.001, p=0.022). Forty six out of 75 patients showed (+) IHC staining for EGFR protein although there was no relationship between the EGFR expression and the response to erlotinib, TTP or OS (p=0.82, p=0.35, p=0.83). Conclusion: EGFR mutation and gene amplification were shown to be important predictive markers not only for response but also for survival of the Korean patients with advanced NSCLC who had been treated with erlotinib. No significant financial relationships to disclose.
An open-label, phase II trial of nanoparticle albumin bound paclitaxel (nab-paclitaxel), carboplatin, and bevacizumab in first-line patients with advanced non-squamous non-small cell lung cancer (NSCLC)
Authors: Reynolds C. , Barrera D. , Vu D. Q. , Jotte R. , Spira A. I. , Weissman C. H. , Boehm K. A. , Ilegbodu D. , Pritchard S. , Asmar L. 
Published: March 2020

7610 Background: The development of nab-paclitaxel has circumvented many of the infusion difficulties that are associated with standard solvent based paclitaxel (in cremophor). In this open label, phase II trial, patients with advanced (stage IIIB or IV) nonsquamous NSCLC received the combination of nab-paclitaxel, carboplatin and bevacizumab. Methods: 50 patients were enrolled between October 2005 and April 2006. Patients received intravenous (IV) nab-paclitaxel 300 mg/m2, carboplatin IV AUC=6, and bevacizumab 15 mg/kg on day 1 of each 21-day cycle. Responding patients received at least 4 cycles of treatment; however, therapy was discontinued for patients with progression or intolerable toxicity. The primary endpoint was response rate based on RECIST. Results: The median patient age was 67 years; 80% were white and 56% were female. Patients received a median of 4 cycles (range, <1–6). The preliminary efficacy results are PR 30% and SD 48%; no complete responses were noted. Median progression-free survival was 7.1 months (range, <1–10.6); median survival has not yet been reached. Grade 3–4 treatment related toxicities were neutropenia (52%); fatigue (19%); neuropathy (15%); thrombocytopenia (10%) dyspnea (6%), anorexia, constipation, febrile neutropenia, hemoptysis, and nausea and/or vomiting (4% each). 64% of patients are currently alive. 32 patients have come off study, prior to 4 cycles due to disease progression (12%), adverse event (10%), investigator request (8%), sudden death (6%), and withdrawal of consent (2%); 16 patients had normal study completion (completed 4 cycles of therapy). Conclusions: This combination of nab-paclitaxel, carboplatin and bevacizumab was well tolerated, with moderate neutropenia. Adverse events were manageable. The preliminary analysis from this study indicates that this combination has promising activity in first-line patients with non-squamous NSCLC. This research was supported, in part, by a research grant from Abraxis BioScience, Inc., Santa Monica, CA. No significant financial relationships to disclose.
Docetaxel compared with vinorelbine in elderly patients with advanced non-small cell lung cancer (NSCLC): A randomized phase II Hellenic Oncology Research Group trial
Authors: Karampeazis A. , Vamvakas L. , Agelidou A. , Chandrinos V. , Tsiafaki X. , Christophylakis C. , Chainis K. , Kakolyris S. , Kalykaki A. , Mavroudis D. 
Published: March 2020

7615 Background: To compare docetaxel versus vinorelbine as front-line treatment of elderly patients with advanced non-small-cell lung cancer (NSCLC). Methods: Chemotherapy-naive patients >65 years, with stage histologically or cytologically documented IIIB/IV NSCLC and performance status (PS) 0–3 were randomly assigned to receive docetaxel 38 mg/m2 (days 1 and 8) or vinorelbine 25 mg/m2 (days 1 and 8) every 21 days. Treatment was continued for a maximum of six cycles and was interrupted in case of disease progression or unacceptable toxicity. Results: A total of 112 patients with median age of 76 years (range, 66–87) were enrolled onto the study. PS 2–3 had 39 (35%) patients. The two treatment groups were well balanced. There was no statistical difference between the 2 arms in median overall survival (6.27 months vs 3.97 months; p=0.129), in median time to progression (2.2 months vs 2 months; p=0.863.) and in overall response rate (5.3% vs 11.3%; p=0.247). Docetaxel conferred a statistically significant survival benefit compared to vinorelbine only in patients with PS 0–1 (11.4 months vs 4.3 months; p=0.009). Among patients treated with docetaxel there was a significant difference in median overall survival for patients with PS 0–1 compared with patients with PS 2–3 (11.4 months vs 2.5 months; p=0.004) while there was no statistical difference in the vinorelbine arm (4.3 months vs 2.8 months; p=0.970).The most common grade 3 and 4 toxicity was neutropenia (3.4% for docetaxel; 27.8% for vinorelbine; p=0.0001). Other toxicities were mild, well tolerated and similar for both groups with the exception of asthenia grade 2 (8.6% for docetaxel; 24.1% for vinorelbine; p=0.026). Conclusions: Docetaxel improves survival compared with vinorelbine in elderly patients with advanced non-small-cell lung cancer and good performance status without increasing toxicity. No significant financial relationships to disclose.
The effects of changing the world health organization definition of bronchioloalveolar carcinoma
Authors: Varlotto J. M. , Recht A. , Nikolov M. , Flickinger J. C. , DeCamp M. M. 
Published: March 2020

7632 Background: In 1999 the World Health Organization (WHO) changed its definition of bronchioloalveolar carcinoma (BAC). We examined the effects of this change. Methods: Patients included in the Surveillance, Epidemiology, and End Results program from 1992–2002 with Stages I-IIIB non-small cell lung carcinoma (NSCLC) who underwent a definitive surgical procedure were divided into a Cohort A (1,348 patients with BAC diagnosed from 2000–2002), Cohort B (2,955 patients diagnosed with BAC from 1992–1998), and Cohort C (36,861 patients with other NSCLC from the entire period). Overall survival (OS) and disease-free survival (DFS) rates were compared according to potential prognostic factors, including use of a matched-pair analysis. We also compared the demographic, histopathologic, and treatment factors associated with the three groups. Results: The proportion of BAC increased both as a percentage of NSCLC and as a percentage of adenocarcinoma for cohort A(12.5%, 22%) as compared to Cohort B(10.9%, 20%). The proportions of patients with smaller tumor size, female sex, non-black or non-white race, resections less than a pneumonectomy, no radiotherapy, Stage I disease, and well- differentiated tumor grade were similar between Cohorts A and B and statistically different between them and Cohort C. Cohorts A and B also had very similar OS/DFS to each other. Matched patients with Stage I cancer in Cohort A had better OS than in Cohort C; OS was similar for other stages. DFS was improved for all stages in Cohort A as compared to Cohort C (except for Stage II). Conclusions: Patients with BAC diagnosed before or after 1999 have similar outcomes to each other and better outcomes than patients with other NSCLCs. Furthermore, both BAC groups had analogous patient demographic, histopathologic and treatment factors, but differed from those of non-BAC NSCLC during this time period. Surgically-resected BAC defined using the 1999 WHO criteria remains distinctly different than non-BAC NSCLC. Therefore recommendations for adjuvant therapy may need to be different for this patient population. No significant financial relationships to disclose.