bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bexarotene improves median survival (MS) in untreated, advanced NSCLC, when given in combination with carboplatin/paclitaxel
Authors: Bordoni R. , Saleh M. , Khanwani S. , Page T. , Auerbach M. , Steinbaum F. , Ghalie R. 
Published: March 2020

17070 Background: Bexarotene (bex) is a subclass specific, synthetic rexinoid analogue, that preferentially binds and modulates the expression of RXR subclass of receptors α, β, and γ. It induces concentration-dependent repression of multiple genes (cyclin D1/D3, total EGFR, pEGFR) inhibiting cell growth, angiogenesis, invasion and metastasis, inducing differentiation, and apoptosis in tumor cells. Several phase-I/II trials suggested increased survival in patients with advanced NSCLC. Methods: Stage-IIIB with pleural effusion & Stage-IV chemo-naïve patients, ECOG 0–2, were enrolled and treated with carboplatin IV AUC-6 d-1 and paclitaxel IV 100 mg/m2 d-1, 8, 15, every 28-d for 4 cycles. Pts were randomized using a 1:1 design to bex PO 400 mg/m2/d either concurrent (C) from Day 1 or sequential (S) at the completion of chemo, for up to a year. Results: 56 patients were enrolled; median age 62.3 (range 41–86), 48 TNM Stage IV, 38 males, 50 ECOG PS 0–1. Of 51 pts evaluable for response, 30 (58%) achieved PR (C: 15 and S: 15); 16 (31%) showed SD (C: 8 and S: 8), and 5 (9.5%) had PD (C: 3 and S: 2). Thirty-two (63%) patients have expired as of 12/31/05. Based on ITT, 40 evaluable pts showed a median TTP of 169 days (C: 166.5 and S 172); The MS for the entire group is 342 days (11.42 mo (C: 12.8 and S: 10.53). Currently, 10 pts are still alive between 407 to 1036 days from registration on the trial. The treatment was well tolerated; overall, AEs were reported in 48% of pts in the S arm and 51% in the C arm. The incidence of Gr 3–4 AEs, regardless of the treatment arm, was < 5%. There were no treatment-associated deaths. Conclusions: Our data suggests a better ORR, TTP, and improvement in MS, when bex is added to carboplatin/ paclitaxel, regardless of concurrent or sequential administration, compared with chemo alone. ORR was not compromised by bex administration and in fact it was above average reported for similar phase-II & -III studies. Toxicity is easily managed. [Table: see text]
Expression of CEACAM1 in pulmonary adenocarcinoma cells and their metastases
Authors: Laack E. , Schult-Kronefeld O. , Burkholder I. , Görn M. , Andritzky B. , Kugler C. , Edler L. , Bokemeyer C. , Schumacher U. , Thöm I. 
Published: March 2020

17071 Background: The cell adhesion molecule CEACAM1 is involved in intercellular adhesion and is expressed in a variety of normal human tissues such as mammary gland, colonic mucosa and prostate. In cases of malignant transformation of these tissues a down regulation or loss of CEACAM1 has been shown. In contrary, CEACAM1 is not expressed in normal lung tissue or melanocytes and it has been demonstrated that a expression in these tissues is associated with the development of metastatic disease. The aim of the present investigation was to analyze a possible association between the expression of CEACAM1 in pulmonary adenocarcinoma cells and their lymph node and hematogenous metastatic cells. Methods: CEACAM1 expression was immunhistochemically evaluated in primary tumor cells, cells in lymph nodes and in distant metastases of 96 patients with metastatic adenocarcinoma of the lung who had undergone surgery between 1999 and 2002. Results: An expression of CEACAM1 has been shown in 78 of 96 primary tumors. We found a significant positive correlation between the CEACAM1 expression on the cells of the primary tumor and the lymph node metastases (p<0.005) and the hematogenous metastases (p<0.05). Conclusion: As shown before, CEACAM1 is not expressed in normal lung tissue but in most primary adenocarcinomas of the lung. We are the first to demonstrate, that its expression is preserved in the lymph node and hematogenous metastases in metastatic disease implicating that its expression is of functional significance of both metastatic sites. No significant financial relationships to disclose.
The Ets transcription factor Esx regulates expression of metastasis-associated genes in non-small cell lung cancer (NSCLC)
Authors: Mitas M. , Graham A. , Khoors A. , Chen Y. , Lewin D. , Davoodi P. , Mikhitarian K. , Montero A. , Cole D. , Wallace M. 
Published: March 2020

17077 Background: The overall 5-yr survival for the treatment of lung cancer patients is less than 20% due to the inability to control metastatic disease. Methods: To identify genes that promote the development of metastases in NSCLC and other solid tumors, we first performed three separate microarray analyses using Affymetrix U133A chips whereby expression values of a pool of normal lymph nodes was compared to: lung cancer cell lines (n = 4), and metastatic lymph nodes from breast (n = 3) and pancreatic (n = 3) cancer patients. Separate lists of the 35 most highly overexpressed genes for each cancer type were compiled. Results: We observed that each list contained EpCAM, XAG, CK19, and CK8 (p = 1.1E-18). To search for genes that might regulate expression of these four genes, we queried the CGAP NCI60 gene expression database with the 87 genes contained on the three lists and constructed a connectivity map such that the presence of a gene on the map required: 1) high correlation (p < 8.0E-6) with at least two other genes, and 2), direct or indirect contact to EpCAM or XAG. The map contained two gene clusters (XAG cluster = 6 genes; EpCAM/CK19/CK8 cluster = 7 genes) that were connected to, and potentially regulated by, the Ets transcriptional factor Esx. Genes from both clusters, as well as Esx, were highly overexpressed in metastatic mediastianal lymph nodes obtained from NSCLC patients. To investigate whether Esx might regulate expression of one or more genes in the two clusters, we transfected an NSCLC cell line derived from lymph node metastases with siRNA to Esx and observed: 1) a reduction in expression of EpCAM (4-fold), XAG (7-fold), and the orphan nuclear receptor ESRRα (1,000-fold), and 2), an inhibition of cell growth. Conclusions: Based on our ability to simultaneously inhibit cell growth and expression of multiple metastasis-associated genes with a single siRNA, we conclude that Esx is a major regulator of lymph node metastasis. No significant financial relationships to disclose.
Phase I study of OGX-011, a second generation antisense oligonucleotide (ASO) to clusterin, combined with cisplatin and gemcitabine as first-line treatment for patients with stage IIB/IV non-small cell lung cancer (NSCLC)
Authors: Laskin J. J. , Chi K. N. , Melosky B. , Sill K. , Hao D. , Canil C. M. , Gleave M. , Murray N. 
Published: March 2020

17078 Background: The clusterin gene is frequently expressed in NSCLC and encodes a cytoprotective chaperone protein that promotes cell survival and is upregulated in response to apoptotic stimuli such as chemotherapy. OGX-011 is an ASO that binds to clusterin mRNA thus potently regulating expression and chemosensitizing cancer cells. Previous Phase I studies of OGX-011 identified biologically active doses of 480mg to 640mg. The objective of this multi-center Phase I study was to define the Phase 2 dose of OGX-011 in combination with standard chemotherapy. Methods: Patients (pts) with chemotherapy-naive advanced stage IIIB/IV NSCLC were potentially eligible. OGX-011 is given as a 2hr IV infusion weekly after 3 loading doses (days -7, -5, and -3). OGX-011 dose escalation was planned to a maximum of 640mg. Cisplatin was given at 75 mg/m2 IV day 1 and gemcitabine 1250mg/m2 IV days 1 and 8, on a 21-day schedule up to 6 cycles. Pharmacokinetic profiling was done in cycle 1. Results: Between Jan 2004 and Apr 2005, 10 patients were enrolled. Median age 62 yrs (49–75); 4 female. ECOG 0/1: 3/7. Stage IIIB/IV: 1/9. 9 of 10 pts completed at least one cycle; 1 withdrew after one dose of OGX-011 due to progressive disease (PD). Of the 9 pts, 6 received ≥ 5 cycles and 3 received 2–4 cycles (2 patients discontinued due to PD and 1 at the pts request). Median follow-up: 5.0m (1.6 - 6.7m). As of Jan 2006, 2 pts had a PR; 5 had SD; 2 had PD. 4 pts had 5 serious adverse events: elevated creatinine, hypoxia, pneumonia, pleural effusion, and febrile neutropenia. 3 pts had Gr 3 hyponatremia. Gr 3/4 hematological toxicities in 10–40% and 10–20%, respectively. No dose-limiting toxicities noted; 7 pts received OGX-011 at 640 mg. A proportional increase in OGX-011exposure (Cmax and AUC0-inf) from 480 to the 640 mg was noted with no apparent effect on GEM/CIS. Conclusions: OGX-011 was well tolerated and can be given at biologically active doses (640 mg) with standard GEM/CIS chemotherapy for patients with advanced NSCLC. A multicenter Phase II trial of this combination is underway. Sponsored by OncoGenex Technologies, Inc. with Isis Pharmaceuticals Inc. [Table: see text]
Risk of severe radiation pneumonitis in gemcitabine (GEM) based consolidation chemotherapy after concurrent chemo-radiation (C-RT) in stage III non-small-cell lung cancer (NSCLC)
Authors: Mok T. , Zhang L. , Liao M. , Boyer M. , Yang J. , Wu Y. , Zhou C. , Zee B. , Lee J. 
Published: March 2020

17079 Background: Recent phase II study (S9504) showed that 3 cycles of consolidation docetaxel after C-RT is associated with prolonged survival but 6 pts (7%) had severe (≥gr 3) radiation pneumonitis and 2 (2.4%) died.(None at S9019) LCRG, a multinational Asian study group, designed a randomized phase II study aiming to assess the treatment outcomes of consolidation GEM or GEM/Carboplatin (CAR) after C-RT. GEM is a potent radiation sensitizer with known recall phenomena, thus we evaluated the risk of severe radiation pneumonitis with GEM-based consolidation chemotherapy after C-RT in this interim report. Methods: Enrollment criteria: Histologic proven NSCLC; attained CR/PR/SD after C-RT (Cisplatin-based chemotherapy between 25 mg/m2 and 40 mg/m2 per week or 60 mg/m2 to 100mg/m2 every 3 to 4 weeks; fraction dose not more than 2.0 Gy; total dose not less than 54 Gy and not higher than 64 Gy); ECOG PS 0–1; adequate hematologic/renal/liver function. Patients were screened for eligibility within 6 weeks after C-RT. Eligible patients are randomized to receive GEM 1250mg/m2 day 1,8 q21days with or without CAR 5XAUC day 1. Results: Between 3/04 and 9/05 we screened 51 patients and excluded 19. Six (31.5%) were excluded due to radiation pneumonitis.(gr 1=5 and gr 3 = 1). C-RT induced toxicity was the main reason for difficulty with accrual to this trial. We enrolled 32 patients (m:f 29:3; mean age 58 (40–78); adeno:scc:other 14:16:2; IIIa:IIIb 4:28) Median RT fraction and dose was 30 (27–32) and 60 Gy (54–64), respectively. 19 pts received GEM and 13 received GEM/CAR. Severe (≥gr 3) radiation pneumonitis was reported in 3 pts (9.3%) and 1 (3.1%) died from the complication. Another 10 and 6 pts had grade 1 and 2 radiation pneumonitis, respectively, but without significant clinical compromise. Conclusions: Radiation pneumonitis is common after C-RT with or without consolidation chemotherapy. However, severe radiation pneumonitis is relatively uncommon in pts who received GEM based consolidation chemotherapy after C-RT. A possible explanation is that we have screened out the high risk pts prior to enrollment. [Table: see text]
Intratumoral injection of oncolytic adenovirus H101 in combination with vinorelbine/cisplatin chemotherapy in patients with advanced non-small cell lung cancer
Authors: Zhou C. , Xu Y. , Ni J. , Zhou S. , Xu J. 
Published: March 2020

17082 Background: Chemotherapy is main treatment for advanced NSCLC. But its efficacy is quite small with improvement of 1–2 months in median survival. New strategy against NSCLC is needed. Oncolytic adenovirus H101 is found to be effective against NSCLC. This trial is desigened to investigate efficacy and toxicity of intratumoral injection of H101 in combination with chemotherapy in the treatment of NSCLC. Methods: The NSCLC patients confirmed cytologically or pathologically were randomized to intratumoral injection of adenovirus H101 (1.5 × 1012 viral particles) plus NP chemotherapy (arm A) or NP chemotherapy (arm B). Objetive response was evaluated every two cycles and time to progression (TTP) and overall survival were followed up. Results: Out of 18 evaluable patients in Arm A, 4 patients showed partial response (PR),3 minor response(MR), 7 stable disease (SD) and 4 disease progression (PD), while in Arm B 16 evaluable patients showed 3 PR, 4 MR, 3 SD and 6 PD. At the first time of response evaluation, there was 1 PD in Arm A,but in Arm B there were 5 of PD. Failure rate in Arm B was significantly higher than in Arm B. Survival curves between the two arms were similar. Six month, 9 month and 1 year survival rates were slightly higher in Arm B and median TTP was also prolonged in Arm A. Except non-infectious fever, Arm A was similar in other toxicities to Arm B. there was only 2 patients developing mild pneumothorax. Conclusions: Intratumoral injection of H101 1.5 × 1012 viral particles in combination with NP chemotherapy was feasible, effective and safe in treatment of advanced NSCLC. No significant financial relationships to disclose.
Cytokines modulation and activity in non-small cell lung cancer (NSCLC) by chemotherapy and indinavir
Authors: Bearz A. , Simonelli C. , Talamini R. , Sgadari C. , Monini P. , Ensoli B. , Spazzapan S. , Vaccher E. , Berretta M. , Tirelli U. 
Published: March 2020

17094 Background: Our aim was to evaluate the activity of chemotherapy (CT) and indinavir, a protease inhibitor affecting matrix metalloproteases (mmps) of tumors, according to in-vitro studies (Sgadari, Nat Med 2002), in NSCLC patients (pts). Methods: All consecutive pts with NSCLC, IIIB and IV, underwent a platin-gemcitabine treatment. All pts with stable disease or partial remission after 3 courses were given 3 more courses plus indinavir 800 mg tid p.o, till progression. For each pt serum samples were collected before CT and every month till end of the study. Results: We enrolled 24 pts, with the same prognostic factors (age <70 years; PS 0 and IV stage disease). Clinical data are available for 18 pts. Up to now we did not find any clinical benefit with indinavir as maintenance therapy: median time to treatment failure (TTF) is 2.75 mos (±1.0) and median overall survival (OS) is 16 mos (±4.5), not significantly different from literature data. For 11 pts, biological data are available. Using a paired T-test to compare differences at different times, we did not find any variation in VEGF, TNF-α, ICAM, neopterine, γ-IFN, mmps by CT. VEGF decreases in comparison with basal time, but not significantly, mean value 326 pg/mL (±79). Indinavir induces an increase of mmp2, before Indinavir 68.8 pg/mL (±9.18), after 97.09 (±10.21), p = 0,04. Analyzing by response, all pts with a RP at CT had a progressive decrease of serological VEGF; pts with SD or PD had an increase of VEGF. Pts with longer OS had a decrease of TNF-α, even at the time of progression. Conclusion: In our pts TNF-α and VEGF seem to have different pathways. TNF-α is related with OS, while VEGF is related with response to treatment. VEGF is a good marker to follow the clinical response and TNF-α is a better prognostical marker for OS. All our pts showed mean serum VEGF values lower than the previously reported values as cut-off level for prognostic value (Laack E. Lung Cancer 2005); in fact we selected pts in SD or RP after the third course of CT. In our pts VEGF is related with tumor response to therapy (i.e. tumor volume) while TNF-α drives their outcome. Modulation of TNF-α and his pathway may improve pts outcome. No significant financial relationships to disclose.
Phase II randomized study of gefitinib alone or plus vinorelbine every 2 weeks’ treatment in patients with adenocarcinoma of the lung who failed at least two regimens
Authors: Chen Y. , Perng R. , Tsai C. , Whang-Peng J. 
Published: March 2020

17095 Background: To assess the feasibility and the efficacy of adding chronic intermittent low-dose vinorelbine to gefitinib (Iressa) treatment for lung cancer patients with adenocarcinoma who failed 2 previous regimens of chemotherapy. Methods: Patients who had adenocarcinoma and failed at least 2 regimens, including taxanes and platinum, were enrolled and randomized into 2 arms: oral Iressa 250 mg daily (I) or vinorelbine 15 mg/m2 intravenous infusion day 1 and oral Iressa 250 mg daily from day 2 to 14, every 2 weeks (IV). From August 2004 to October 2005, 48 patients were enrolled. Results: Twenty-four patients were randomized into Iressa plus vinorelbine treatment. However, 3 patients refused vinorelbine treatment and received Iressa treatment only. Thus, 27 patients received I treatment and 21 patients received IV treatment. Objective response rates were 55.6% in I and 57.1% in IV. Any grade of leukopenia, neutropenia, and fatigue sensation was significantly higher in the IV arm (p=0.035, 0.001, 0.012, respectively). All the toxicities in both arms were generally mild and no toxic death occurred. However, many patients in the IV arm stopped V treatment before disease progression, including port-A occlusion in 4 patients (after 2, 5, 20, and 23 injections, respectively), mucositis in 1 (after 4 injections), and fatigue sensation in 1 (after 7 injections). After a median follow-up of 8 months, median time to disease progression was higher in IV than I (longer than 12 months vs. 7.1 months, p = 0.0271), more than half of the patients in each arm were still alive (p = 0.2269), and more than 9 patients in each arm survived longer than 1 year. Conclusions: Iressa is highly effective in ethnic Chinese patients with adenocarcinoma of the lung who have failed previous platinum and taxane treatment. The addition of low-dose V every 2 weeks produced a signiificantly better progression-free survival. Replacement of intravenous V with oral V should be considered to prevent the early termination of V treatment. No significant financial relationships to disclose.
Yttrium-90 microsphere treatment for liver dominant hepatic metastases from lung cancer
Authors: Murthy R. , Oh Y. , Tam A. , Gupta S. , Madoff D. C. , Glisson B. 
Published: March 2020

17122 Background: Hepatic metastases are a common manifestation of primary lung malignancies; the primary and other extrahepatic sites are often less responsive to systemic therapy. A new method of regional therapy for hepatic metastases, called SIR-Spheres, a 32μ resin sphere incorporating a pure Beta emitter, Yttrium - 90, has advantages to older forms of regional hepatic therapy, used to treat colorectal liver metastases. The effectiveness and relatively response durability suggests a favorable alternative to chemotherapy for patients with liver-dominant metastatic lung cancers. We report our experience using SIR-Spheres in this setting. Methods: 6 patients (2 well differentiated carcinoid, 2 well & 1 poorly differentiated adenocarcinoma, 1 poorly differentiated small cell carcinoma) with unresectable hepatic metastases were treated with 8 infusions of SIR-Spheres after failing systemic chemotherapy, radiofrequency ablation or arterial embolization were included in the study. SIR-Spheres were administered as 2nd-6th line therapy. Median interval from diagnosis to SIR-Spheres treatment was 20.5 months (6–51 m). Results: Abdominal visceral arteriography demonstrated vasculature conducive for SIR-Spheres delivery in all patients. The median dose of 36.1 mCi (12.9–54 mCi) was delivered. SPECT - CT fusion Bremsstrahlung scans post therapy confirmed preferential deposition of SIR-Spheres within metastases. Responses to therapy included a decrease in the size of the hepatic metastases in one patient and stable disease in two patients. One patient had a mixed response and two patients had progression of disease. One Gr. III and one Gr. IV hepatic toxicity occurred. All patients experienced transient Gr. 1 or 2 fatigue. Time to progression of liver disease ranged from 3 to 9 months. Conclusion: SIR-Spheres is a feasible alternative to systemic therapy for patients with liver dominant metastases from lung cancers. Although serious hepatotoxicity was noted in patients with advanced liver metastases, the treatment was tolerated with only reversible fatigue in the majority of patients. When the treatment was effective, the duration of local disease control after one treatment equaled or exceeded what would be expected with chemotherapy. [Table: see text]
Choice of chemotherapy (CT) for advanced/metastatic lung carcinoma, WHO types I - III - IV (NSCLC)
Authors: Bollina R. , Beretta G. , Belloni P. , Toniolo D. , Cozzi C. , Brigida S. , Beretta G. A. 
Published: March 2020

17132 For NSCLC optimal CT has not been established so far, while many equivalent moderately active schemes are used. The present 40-month study randomized 71 consecutively accrued patients (pts) with parametrable disease between platinum(P)-based three-weekly combinations and non-P monoCT (weekly gemcitabine, vinorelbine or taxane). 68 evaluable pts characteristic were well balanced between treatments: median age 67 years (r. 40–82y), median P Status < 2 WHO scale (r. 0–2),male predominant 82.3%, ratio of IIIb/IV = 1.34 and squamous/non squamous histotype = 1.19, pathologies 26% (only mild to moderate, not contraindicating CT). Objective/subjective response (RECIST/MILAN criteria, JNCI 92:180; P.ASCO 19:642a) after poliCT (PCT) or monoCT (MCT) are reported in the descriptive table . Tolerance was good for both treatment, MCT resulting less deeply toxic and more easily accepted by the majority of pts. This study is still ongoing to achieve the total pts accrual in order to explore statistical significant in the principal determinant subgroup, to determine the subjective response to CT, and to confirm a possible difference in survival. The role of a programmed second line CT vs supportive care alone, and the impact of adding new biomolecular therapies (combined with CT) are the short-term challenges of the second part of this prospective study for advanced NSCLC. [Table: see text] No significant financial relationships to disclose.