bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective phase II trial of a combination of gemcitabine, cisplatin and UFT as first-line treatment in patients with advanced, unresectable, non-small cell lung carcinoma
Authors: Jin S. S. , Min Y. , Kim H. , Ahn J. , Jegal Y. , Seo K. , Park C. , Shin J. , Cha H. , Kwon W. , Park J. 
Published: March 2020

18109 Background: Most patients with advanced non-small cell lung cancer (NSCLC) receive either single agents or doublet chemotherapy. For non-elderly patients in good performance status, platinum-based double combinations represent the standard treatment. And oral UFT had the survival advantage in adjuvant setting. Therefore we performed a phase II study using the combination of gemcitabine, cisplatin and UFT as a first line therapy in patients with advanced NSCLC. Methods: Eligible patients had histologically or cytologically confirmed stage IIIB or IV NSCLC with good performance status and were chemotherapy-naive. This study was two-stage design and planned number of patients was forty-seven. Gemcitabine (1,250 mg/m2, 10 mg/kg/min on days 1 and 8) and cisplatin (75 mg/m2 on day 1) were injected intravenously and UFT (400 mg/day) was administered orally on day 1–14. Treatment repeated every 3 weeks. Primary end point was overall response rate and secondary end points were overall survival, time to progression and toxicity. Results: Thirty seven patients with advanced NSCLC were enrolled. The median age of the patients was 60 years (range: 44 to 72). The performance status (WHO) was 0 in 4, 1 in 30 and 2 in 3 patients. Twenty three patients completed six cycles. Complete response was achieved in 1 (3%) patient, partial response in 22 (59%) patients, stable disease in 9 (24%) patients. Overall response rate was 62% on intent to treat basis. Among patients who response evaluation was possible (33 patients), response rate was 70%. The median survival time was 14.5 months (95% CI 6.9, 22.3) and the 1 year survival was 35% and then median time to progression was 3.4 months(95% CI 3, 3.9). Toxicities were moderate and mostly hematological adverse events. Grade 3/4 neutropenia occurred in 37%, 5 patients with febrile neutropenia. Grade 3/4 anemia and thrombocypenia was occurred in 37% and 5%. Nonhematologic toxicities were mild. Conclusion: The combination therapy consisted of gemcitabine, cisplatin and UFT is active and well tolerable first line regimen for NSCLC patients. No significant financial relationships to disclose.
Treatment patterns of very elderly patients with non-small cell lung cancer
Authors: Oxnard G. R. , Fidias P. , Sequist L. V. 
Published: March 2020

18110 Background: Among patients with non-small cell lung cancer (NSCLC), patients aged 80 or older, termed the ‘very elderly‘, have inferior survival. Treatment patterns within this patient population are poorly described. Methods: A retrospective chart review was performed of 111 outpatients with NSCLC presenting at age 80 or older to an academic referral center over 5.3 years. Based upon available literature regarding elderly patients with NSCLC, a guideline recommended therapy (GRT) was determined for each tumor stage. Each patient’s treatment regimen was evaluated for consistency with the GRT. Particular attention was paid to how patient characteristics and attitudes influenced therapy decisions. Results: Patients characteristics included: median age 82.6 (range 80–92); 50% male; 55% adenocarcinoma, 19% squamous cell; 30% stage I-II, 28% stage III, 39% stage IV; and 59% performance status (PS) 0–1, 25% PS = 2 (PS not available for 15%). 89% of patients received some form of anti-neoplastic therapy and 11% were treated with best supportive care alone. Of 34 patients with localized disease, 53% underwent tumor resection and 38% received definitive radiation. Of 74 patients with stage III or IV disease, 34% received cytotoxic chemotherapy. Radiotherapy (47%) and oral targeted therapy (35%) were the most common treatment modalities overall. 32% of patients received the stage-specific GRT. Multivariable analysis demonstrated that independent predictors for failing to receive GRT included PS = 2 (odds ratio [OR] 17.1, 95% confidence interval [CI] 2.2–135) and age =85 (OR 4.8, 95% CI 1.0–23.4) Of the patients who failed to receive GRT, 19% electively refused GRT that was offered (13% specifically refused chemotherapy), and 76% were not offered GRT (44% due to PS or comorbidities, 32% due to age or unstated reasons). Conclusions: The vast majority of NSCLC patients age 80 or above receive some form of anti-neoplastic therapy, but only one-third of this population receives the stage-specific GRT. The strongest predictor of treatment with GRT is PS 0–1; those with poor PS are 17-fold less likely to receive GRT. A small but clinically significant portion of patients elect against the offered GRT; more data is needed about the attitudes of these patients toward therapy. No significant financial relationships to disclose.
Pemetrexed and carboplatin in the treatment of malignant pleural mesothelioma (MPM)
Authors: Papi M. , Genestreti G. , Tassinari D. , Tamburini E. , Nicoletti S. , Nicolini M. , Fabbri P. , Fabbri P. , Santo A. , Pasquini E. , Ravaioli A. 
Published: March 2020

18114 Background. MPM is a poor prognosis disease, whose clinical negative outcome is due both to it’s aggressiveness and to the lack of active drugs for clinical practice. To assess activity and safety of pemetrexed-carboplatin combination in the treatment of MPM, an open trial has been recently concluded in our departments. Methods. All the consecutive patients with proven diagnosis of MPM admitted to our departments between 2003 and 2005 were considered eligible and enrolled into the trial. All the patients were treated with pemetrexed 500mg/m2 and carboplatin AUC 5mg/ml/minute every 21 days until progression of disease or unacceptable toxicity. All the patients were treated with steroid prophylaxis, folinic acid and vitamin B12 supplementation. Results. 26 patients (18 chemotherapy-naive) were considered eligible and enrolled into the trial. 21 patients were male and 5 female; median age of the patients was 67 years (range 49–77). 22 patients were affected by locally advanced or extensive disease and the other 4 ones by localized disease. All the patients were valuable for response, toxicity and survival. Overall response rate was 19,3%, with 5 partial responses and no complete regression of the disease. A stable disease was observed in 7 patients (26.9%), with an overall disease control rate of 46.2%. 201 complete courses of chemotherapy was performed with a median number of 6 courses/patients. Toxicity was mild with grade 3/4 WHO neutropenia in 4 patients (15.3%), grade 3 anemia and thrombocytopenia in 2 patients (7.6%). No grade 3/4 non-hematological toxicity was observed along all the conduction of the trial. Median survival was 9,3 months, assessed with the Kaplan Meyer non-parametric test. Conclusions. Pemetrexed and carboplatin seem to represent an active and well tolerated schedule against MPM, confirming their priority role in the treatment of the disease; nevertheless, further trials are probably needed to improve the outcome of chemotherapy in this rare poor-prognosis disease. Supported by IOR No significant financial relationships to disclose.
Phase II study of meloxicam with carboplatin plus docetaxel in first-line treatment of patients with advanced non-small cell lung cancer (NSCLC)
Authors: Ishida T. , Kanazawa K. , Oizumi H. , Yokouchi H. , Yamazaki K. , Akie K. , Sukoh N. , Harada M. , Munakata M. , Isobe H. 
Published: March 2020

18121 Background: Preclinical and clinical studies showed that selective cyclooxygenase-2 (COX-2) inhibitor (celecoxib or rofecoxib) might improve efficacy of treatment of advanced NSCLC. Meloxicam is a non-coxib, non-steroidal anti-inflammatory drug (NSAID), and selectively inhibits COX-2. Comparing with coxibs, meloxicam shows less cardiovascular toxicity; however, anti-tumor efficacy has not been proved in clinical settings. Methods: Eligibility criteria included stage IIIB/IV histologically or cytologically confirmed NSCLC, no prior chemotherapy, no current use of NSAIDs, PS = 0–1, and no urgent symptoms. Patients received oral meloxicam (150 mg) daily, and carboplatin (AUC 5) plus docetaxel (60 mg/m2) day 1 every 3 weeks. Treatment was continued until disease progression or toxicity. The primary endpoint was anti-tumor effect, with secondary endpoints including the safety and time to progression. Calculated sample size was 45 patients (Simon’s two-stage minimax design). Results: From April 2005 to July 2006, a total of 50 patients (33 males/17 females, median age, 65 years) were accrued and 48 patients were eligible. Partial response was 40% (95% CI 24–56%), stable disease was 29% (95% CI 14–44%), and 23% had progressive disease. Grade 3/4 hematologic events included leukopenia (81%), neutropenia (96%), and thrombocytopenia (8%). Grade 3/4 non-hematologic events included hyponatremia (6%), anorexia (6%), fatigue (2%), and neuropathy (2%). Febrile neutropenia occurred in 2 patients, and one patient developed pneumonia. Conclusions: Meloxicam added to carboplatin plus docetaxel demonstrated acceptable tolerability with encouraging activity in advanced NSCLC patients. No significant financial relationships to disclose.
Artificial intelligence, complex system analysis and simulation modeling for early detection of lung cancer
Authors: Kshivets O. 
Published: March 2020

18127 Background: Early detection (ED) of non-small cell lung cancer (LC) is the key to the cancer problem solving and practically regulates effectiveness of surgery. We examined immunologic factors associated with early LC. Methods: In trial (1987–2006) the data of consecutive and monitored 94 LC patients (LCP) after lobectomies (age=58.3±0.8 years; tumor size=2.32±0.07 cm; m=80, f=14) with pathologic stage IA (T1N0M0) (squamous=36, adenocarcinoma=53, large cell=5; G1=32, G2=38, G3=24), 282 patients with lung non-malignant pathology (NMP) (m=188, f=94; pneumonectomies=5, lobectomies=179, segmentectomies=98; non-malignant tumours=100; abscess=112; tuberculoma=70) and 120 healthy donors (HD) (m=69, f=51) were reviewed. Variables selected for ED study were input levels of 64 immunity blood parameters, sex, age. Representativeness of samplings was reached by means of randomisation based on unrepeated random selection. Logistic regression, clustering, discriminant analysis, neural networks computing, structural equation modeling, Monte Carlo and bootstrap simulation were used to determine any significant regularity. Results: Logistic regression modeling displayed that ED of LC significantly depended on: CD8, CD4, CD16, neutrophils, monocytes (P=0.002–0.041). Neural networks computing, genetic algorithm selection and bootstrap simulation discovered relationships between early LC and blood lymphocytes (rank=1), T-lymphocytes (2), CD4 (3), CD16 (4), B- lymphocytes (5), CD1 (6), NST-A2 (7), CD8 (8), NST-SP (9), NST-A1 (10), monocytes (11), eosinophils (12). Conclusions: Correct recognition of LCP with stage IA (T1N0M0) from NMP and HD was 81.7% by logistic regression (odds ratio=6.39), 84.1% by discriminant analysis and 99.2% by neural networks computing (area under ROC curve=0.99; error=0.063). No significant financial relationships to disclose.
12-Lipoxygenase is a potential therapeutic target in non-small cell lung cancer
Authors: Pidgeon G. P. , Gately K. , Lysaght J. , Cathcart M. C. , Campbell V. , Kay E. , O’Byrne K. J. 
Published: March 2020

18129 Background: Platelet-type 12-LOX is an arachidonic acid metabolising enzyme resulting in the formation of 12(S)-HETE, which stimulates tumour cell adhesion, invasion and metastasis. We examined the expression of 12-LOX in NSCLC and its role in cell survival. Methods: A549 (adenocarcinoma), SK-MES1 (squamous cell lung carcinoma), H460 and H647 (large cell lung carcinoma) were grown in serum depleted media (0.5%) and screened for 12-LOX expression by RT-PCR and western blot analysis. Cells were treated with baicalein (10uM), a selective inhibitor of 12-LOX, or 12(S)-HETE (100ng/ml) and cell survival / proliferation determined by BrdU assay. Apoptosis was determined using the multi-parameter apoptosis kit and In-cell Analyser, and also by FACS. Gene alterations following 12-LOX inhibition in both A549 and SKMES-1 cells were assessed by quantitative PCR arrays and validated by RT-PCR. A panel of retrospective resected lung tumours were stained for 12-LOX expression by immunhistochemistry. Results: All lung cancer cells lines expressed moderate levels of platelet-type 12-LOX, which was reduced following treatment for 24h with the baicalein. Baicalein decreased lung cancer survival in all cell lines, while 12(S)-HETE increased cellular proliferation. Inhibition of 12-LOX induced apoptosis in a dose dependent manner, with decreased f-actin filaments and loss of mitochondrial mass potential. QPCR array data implicated a number of genes regulating these effects which were validated by RT-PCR, many of which control apoptosis and angiogenesis. The subset of genes downregulated included bcl-2, VEGF, integrin a2 and a4. 12-LOX expression was observed in a variety of human lung cancers with different histological subtypes. Conclusions: 12- LOX is a survival factor in NSCLC. 12-LOX inhibitors decreased NSCLC survival, inducing apoptosis through mechanisms including downregulation of the bcl family of proteins, integrin receptor and angiogenic growth factors. Expression of 12-LOX in fresh resected and retrospective tissue suggests that inhibition of this enzyme is a potential therapeutic strategy in the treatment of NSCLC. No significant financial relationships to disclose.
N-cadherin, a potential novel therapeutic target in small cell lung cancer
Authors: Batus M. , Kaiser K. A. , Coon J. S. , Ahmed S. , Patel A. , Avery E. F. , Kemper M. A. , Kassar M. , Bonomi P. D. 
Published: March 2020

18134 Background: New treatment ideas are needed in small cell lung cancer (SCLC). N-cadherin which is associated with increased tumor invasiveness is a potential novel therapeutic target. It seems reasonable to test recently developed cyclic peptide N-cadherin antagonists in tumors with high N-cadherin expression, and it seemed likely that high N-cadherin expression would occur more frequently in aggressive tumors like SCLC. Our objective was to determine the frequency and biological significance of N-cadherin expression in SCLC. Methods: We retrospectively analyzed 86 patients with small cell lung cancer, most of whom received treatment: chemotherapy with or without radiation. We reviewed their clinical charts and obtained: date of diagnosis, age, gender, performance status, treatment dates and treatment response (CR/PR, stable disease, progression), and death or last encounter date. We also analyzed their pathology specimens for frequency of expression of N-cadherin and grouped them into three categories: no expression, some expression of N-cadherin >1% but <35%, and strong expression 36–100%. Subsequently, we determined the correlation between the N-cadherin frequency groups and the overall survival for all 86 patients. We also determined the time to progression in a subset of 56 patients (with available treatment response data). Results: Out of the 86 patients, 18 (21%) did not express N-cadherin, 10 (11.6%) patients showed >1% but <35% expression of N- cadherin, and 58 (67.4%) had a strong expression >36%-100%. There was no association found between N-cadherin expression and overall survival using either the Log-Rank Test or the Wilcoxon Test. In the subset of 56 patients with available treatment response data there was no association between N-cadherin expression and progression free survival. Conclusions: N-cadherin was expressed relatively frequently in this group of SCLC patients, and these results suggest that phase II trials of the novel cyclic peptide N-cadherin antagonists are warranted in SCLC. N-cadherin did not appear to have prognostic value in our study. No significant financial relationships to disclose.
Phase I/II trial of bortezimib and pemetrexed in patients with advanced non-small cell lung cancer
Authors: Natale R. B. , McKinley M. , Hilger J. , Myers T. 
Published: March 2020

18145 Background: Bortezomib (Vc) is a novel proteosome inhibitor with activity in several malignancies including multiple myeloma, mantle cell lymphoma, and NSCLC. In NSCLC, Vc has additive activity combined with carboplatin and gemcitabine in first line and with docetaxel in second line treatment. Pemetrexed (P) is active in NSCLC and preclinical data suggests a pro-apoptotic synergy between Vc and P. Therefore, we initiated a phase I/II dose finding study of Vc + P in previously-treated patients (pts) with advanced or metastatic NSCLC. Methods: Fifteen pts have been accrued to 3 of 4 planned dose levels of Vc + P. Starting doses (and # pts treated) were Vc 1.4 mg/m2 day 1 & 8 + P 400 mg/m2 day 1 every 3 weeks (3 pts). The 2nd and 3rd dose levels were Vc 1.6 mg/m2 day 1 & 8 + P 500 mg/m2 day 1 (8 pts, 5 new + 3 from dose level 1) and Vc 1.8 mg/m2 day 1 & 8 + P 500 mg/m2 day 1 (7 pts). Results: 15 pts are evaluable for response and toxicity and include 8 males, 7 females, median age 67 (range, 55–82), PS 0/1 (3/12 pts), median of 2 prior therapies (range 1–3). Confirmed PRs occurred in 2 pts (13%) and stable disease in 5 (33%). Dose limiting toxicities consisted of grade 4 fatigue (1 pt) and neutropenia/fever (1 pt) at dose level 2, and grade 3 abdominal pain and fatigue (1 pt) and grade 3 diarrhea and vomiting (1 pt) at dose level 3. Conclusions: The above combination is safe at the doses tested thus far and active in pts with heavily pretreated, advanced NSCLC. We are currently exploring Vc 2.0 mg.m2 Day 1 & 8 + P 500 mg/m2 day 1 every 3 weeks to determine the MTD and plan a multi-site Phase II study to determine response rate and survival in a larger pt population. No significant financial relationships to disclose.
Biweekly docetaxel and gemcitabine as first line chemotherapy in advanced non-small cell lung cancer (NSCLC)
Authors: Gaspar E. , Firvida J. , Amenedo M. , Orts D. , Salgado M. , LLorca C. , Ramos M. , Perez E. , Cervera J. , Abal J. 
Published: March 2020

18147 Background: The activity and tolerability of third-generation agents led many investigators to evaluate doublet combinations in the hope that platinum analogues could be eliminated from the treatment of advanced NSCLC. To improve the therapeutic index of this combination, we performed a study with biweekly gemcitabine and docetaxel. Primary objective was determination of objective response rate (ORR). Secondary objectives were time to progression, tolerability and overall survival. Methods: Patients histologically confirmed of non-small cell lung cancer, aged ≥ 18, ECOG PS 0–2, measurable lesion according RECIST criteria, adequate bone marrow, renal and hepatic function were included. Prior chemotherapy was not allowed. Patients received treatment with a combination of Docetaxel 50 mg/m2 and gemcitabine 20,00 mg/m2 each 15 days for a maximum of 8 cycles. Results: Fifty patients were included between July 2005 and October 2006.Now we present the results of the first 32 patients: 88% were male, median age was 62.7 years old, 69% had ECOG 0–1 and 81% of patients had stage IV. Histology was squamous cell carcinoma (53%) adenocarcinoma (31%) and large cell carcinoma (16%). A total 221 cycles were administrated . Over 30 patients evaluable for response, none achieved CR, 11 PR (36%), 7 SD (23%) and 12 PD, with an overall response rate of 36%. Median follow up of patients is 16 months, with a median overall survival of 9 months. Grade 3–4 toxicity per patient was: neutropenia (6%).Grade 1–2 toxicity per patient asthenia (75%), and nauseas (30%). Conclusions: These results suggest that biweekly schedule of gemcitabine / docetaxel is a safe and active regimen in first line advanced NSCLC patients.Updated results will be presented. No significant financial relationships to disclose.
A phase II trial of pemetrexed (P) in patients (pts) with performance status (PS) 2 and 3 as first- and second-line treatment for advanced non-small cell lung cancer (NSCLC)
Authors: Zinner R. , Fossella F. V. , Kies M. S. , Herbst R. S. , Lu C. , Johnson F. M. , Bhat S. V. , Price J. S. , Cleeland C. , Wang X. 
Published: March 2020

18149 P (Alimta) is approved as second-line therapy in pts with advanced NSCLC. In a phase III trial comparing P with docetaxel (D), median survival was 8.3 mos (P) vs 7.9 mos (D); P had a more favorable safety profile than D (Hanna, 2004). There are few data on pts with PS 3, and ASCO 2003 guidelines recommend that chemotherapy be reserved for pts with PS 0, 1 and possibly 2. Since P is well tolerated, PS3 pts may tolerate and benefit from it. In this trial, we treated 20 pts with stage IIIb/IV NSCLC and PS 2–3 who were chemo-naive or had received 1 prior regimen. Pts received P 500 mg/m2 IV D1 Q 3 wks. All pts received folic acid, vitamin B12 and dexamethasone prophylaxis. Serial blood samples were obtained to monitor inflammatory cytokines, and symptoms were monitored using the validated MDASI instrument. All pts were assessable for toxicity-symptoms, and 17 pts were evaluable for response (assessed after first cycle). Pt characteristics: 8 pts were PS 3 (4/8 first line) and 12 pts were PS 2 (6/12 first line). Median age was 69 for PS3 and 68 for PS2. 5/8 PS3 pts and 6/12 PS2 pts were men. 2/8 PS3 pts and 4/12 PS2 pts had stage IIIb. 4/8 PS3 pts and 6/12 PS2 pts were chemo-naive. Grade 3–4 toxicities for PS3/PS2 cohorts were: neutropenia 0/1 pt, anemia 1/2, fatigue 2/0, pneumonia 1/1, hypotension 1/1, neutropenic fever 0/1, atrial fibrillation 1/1. Response rates (RR) in PS3 pts were minor response (MR) 1/8, stable disease (SD) 5/8, progressive disease (PD) 2/8; RR in PS2 pts were partial response (PR) 1/12, MR 2/12, SD 3/12, PD 3/12, inevaluable 3/12. RR by line of therapy: first-line 6/10 SD, 2/10 PD, 2/10 inevaluable, and second-line, 1/10 PR, 2/10 MR, 3/10 SD, 3/10 PD, and 1/10 inevaluable. Reasons for PS3 pts coming off study were progression (4/8), constitutional toxicity (3/8), fatal pulmonary emboli (1/8); PS2 pts came off study due to progression (5/12), constitutional toxicity (2/12), and pneumonia (1/12). 4/12 PS2 pts are still on study. These preliminary data suggest that single-agent P is well-tolerated and has a promising RR in poor PS pts. Total planned accrual is 30 PS3 and 45 PS2 pts. Survival, symptom, cytokine data will be presented. [Table: see text]