bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two different schedules of docetaxel plus cisplatin as first-line therapy in advanced non-small cell lung cancer: A preliminary result from a randomized phase II study
Authors: Park S. , Bang S. , Cho E. , Shin D. , Lee J. 
Published: March 2020

7135 Background: There has been increasing interest in the use of a weekly administration of docetaxel as a way of reducing its hematologic toxicity. The purpose of this randomized study is to evaluate the toxicity and efficacy of docetaxel and cisplatin combination on two schedules in patients with previously untreated, advanced non-small cell lung cancer (NSCLC). Methods: Consenting patients with stage IIIB/IV or recurrent NSCLC were randomized to receive first-line chemotherapy with cisplatin 75 mg/m2 on day 1, plus either weekly (35 mg/m2 on day 1, 8, 15 of a 4-week cycle) or 3-weekly (75 mg/m2 on day 1 of a 3-week cycle) docetaxel, both for up to 6 cycles. Objectives of this randomized phase II trial were response, toxicity and quality of life (QOL; measured with EORTC QLQ-C30). With a two-stage phase II design, the required number of patients was 39 per each arm. Results: Of 85 patients accrued, 71 patients were evaluable for response and 83 for safety. Baseline characteristics were well-balanced between the two arms: male (56 patients); median age (64 years); adenocarcinoma/squamous cell carcinoma (53/32); stage IIIB/IV/recurrent (12/63/10); ECOG performance status 0/1/2 (20/44/21). Median number of chemotherapy cycles was 3 (1–6) for both arms. Median dose intensities were docetaxel 88%, cisplatin 98% in weekly arm, and docetaxel 97%, cisplatin 98% in 3-weekly arm. The objective responses of weekly and 3-weekly arm were 38% (95% CI, 23–53) and 42% (95% CI, 27–57), respectively. There was significantly more grade 3/4 neutropenia (66% v 12%; P < .001) and febrile neutropenia (40% v 7%; P < .001) on 3-weekly arm but less grade 3/4 diarrhea (2% v 14%; P = .05) and severe skin/nail toxicity (5% v 29%; P = .003). No difference in the rates of treatment delay or dose reduction for both arms; however, 19% of day 15 docetaxel were omitted in weekly arm due to toxicity. Conclusions: Both weekly and 3-weekly docetaxel plus cisplatin appear to be active as first-line chemotherapy for advanced NSCLC, with different safety profiles. Updated results and QOL data, including a prolonged follow-up, will be presented. No significant financial relationships to disclose.
An economic analysis of National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) JBR.10, a randomized trial of adjuvant vinorelbine plus cisplatin versus observation in early stage non-small cell lung cancer (NSCLC)
Authors: Ng R. , Mittmann N. , Florescu M. , Shepherd F. A. , Salvarrey A. , Seymour L. , Winton T. , Evans B. , Leighl N. 
Published: March 2020

7155 Background: NCIC CTG JBR.10 is among the landmark trials to establish 3rd generation platinum-based adjuvant chemotherapy as standard of care after complete resection of stages IB-II NSCLC, improving 5-year survival by 15% and median survival by 21 months (p 0.04). The cost-effectiveness of adjuvant chemotherapy from the perspective of Canada’s public health care system was undertaken in a retrospective analysis based on the JBR.10 study population. Methods: Direct medical resource utilization data, from prospective trial data of patients enrolled onto the BR.10 trial at the 5 largest accruing Canadian centres, were identified and collected retrospectively. Direct medical costs included treatment, hospitalization and procedures. Data were captured from the time of randomization until death or study closure (April, 2004). Non-medical direct and indirect costs were not included. Available costs are presented both with and without discounting at 5% per year. Costs (2005 $CAN) were obtained from provincial sources. Average costs per treatment arm (adjuvant chemotherapy vs. observation) were calculated. Basic demographic statistics were calculated. Results: Utilization data were collected from 172 patients (36% of the trial population), 83 randomized to observation and 89 to chemotherapy. Preliminary results are available for the non-drug related costs of direct medical care including hospitalization and procedures. The mean cost of treatment for patients in the observation arm is $15,323 (25–75% IQR $1,933-$17,831), and $18,701 (25–75% IQR $2,873-$18,781) for patients in the adjuvant chemotherapy arm (2005 $CAN). Conclusion: Non-drug related costs are only slightly higher in patients treated with adjuvant chemotherapy in the NCIC BR.10 trial, despite substantially longer survival for this group of patients. These preliminary results will be updated and cost effectiveness data will be available in May 2006. No significant financial relationships to disclose.
Previously documented mutations in the epidermal growth factor receptor (EGFR) gene in a non-small cell lung cancer (NSCLC) population treated with gefitinib are not associated with response
Authors: Bebb D. G. , Pugh T. , Sutcliffe M. , Barclay L. , Fee J. , O’Connor R. , Vielkind J. , Murray N. , Laskin J. J. , Marra M. 
Published: March 2020

7163 Background: Mutations in the tyrosine kinase domain of EGFR that may correlate with clinical features and response of NSCLC to EGFR tyrosine kinase inhibitors have been described. But, varying methodologies have contributed to an uncertain relationship between EGFR mutational status and response. This study sought to characterize EGFR mutations in microdissected tumour tissue from pts with advanced NSCLC treated with gefitinib and correlate their clinical data. Methods: Biopsy material from pts treated with gefitinib for advanced NSCLC at the British Columbia Cancer Agency was analyzed. Malignant cells (cytology specimens) or tissue (paraffin embedded biopsies) was reviewed and tumour cells isolated by laser- capture microdissection or manual scrape. Genomic DNA was extracted and exons coding for the EGFR tyrosine kinase domain (18 - 24) were amplified by PCR and sequenced. When insufficient, the priority was 18, 19, 21, followed by 20, 23, 22, and 24. EGFR mutational analyses were correlated with response to gefitinib and clinical features. Results: 61 pts were identified, 14 (23%) radiological responders (CR, PR): 10 Asian, 10 female, 8 non-smokers, 8 adenocarcinoma, 2 BAC. Of 51 tumour samples available, 39 had adequate tissue for sequencing analysis. EGFR copy number by FISH is pending. Laser-capture microdissection allowed for high quality DNA to be extracted almost exclusively from tumour. Exons 18, 19, 20, 21, 22, 23 and 24 have been sequenced in 37, 34, 30, 33, 12, 10, and 13 patients, respectively. 4 mutations were identified: 2 in 2 non-smoking Asian pts (exon 19; deletion or substitution of L747-T751) and 2 in Caucasians (exon 20 point mutation resulting in a L798F substitution). None of these pts had a response to gefitinib. Conclusions: As with other series, most responders were female, non-smokers of Asian origin. Our results support the relationship between Asian ethnicity and EGFR mutations but question the role of EGFR mutational status in predicting response. Prospective studies will need to focus the detection of additional genetic features using accurate and reproducible techniques before recommendations for selecting populations to be treated can be made. No significant financial relationships to disclose.
Preliminary analysis of biomarkers in plasma by SELDI to predict the response to EGFR tyrosine kinase inhibitors (TKIs) in NSCLC patients
Authors: Zhang L. , Ning L. , Zhang X. , Pan Z. Q. , Wang X. , Xu F. , Guan Z. Z. 
Published: March 2020

7189 Background: The identification of NSCLC patients who are most likely to respond to EGFR tyrosine kinase inhibitors (TKIs) have been investigated intensively. Although screenings for EGFR mutation and gene copy number are promising, these tests are not yet widely available. New predictor markers are urgently needed. The objective of this study was to identify proteomic markers in plasma to predict benefits for patients treated with EGFR TKIs. Methods: Proteomic spectra derived from plasma samples from EGFR TKIs-responsive patients and non-responsive patients were generated by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). These proteomic spectra (WCX2 chips, Ciphergen Biosystems, Inc.) were then analyzed by comparing protein profiles in different response groups (PR Vs PD, training set). Another group of patients treaded with EGFR TKIs will be serving as testing set to validate the result of training set. Results: Totally, fifty-four advanced NSCLC patients were included in this study. All patients were treated with single agent of gefitinib or erlotinib. Twenty-nine patients were included in training set of this study. All were suitable for response evaluation. Ten patients (34.5%) were PR, 8 (27.6%) were SD, and 11 (37.9%) were progressive disease (PD). Total six significant protein peaks were significant (m/z 4288, 4595, 9191, 9349, 9397, and 9563) between PR group and PD group (table). Another twenty-five patients were included for testing set. Analyzing of testing set is still going on. Table shows PR and PD patients’ plasma comparison on WCX2 chips. Conclusions: This preliminary “training” set of spectra that uses SELDI-TOF MS technology found that six protein peaks seemed to be very important biomarkers to predict the response to gefitinib. Prospective tests to confirm these proteins and peptides will be present at this meeting. These results are promising for identifying new biomarkers of EGFR TKIs with SELDI. [Table: see text] No significant financial relationships to disclose.
Initial safety results of an expanded access program (EAP) of erlotinib in non-small cell lung cancer (NSCLC)
Authors: Reck M. , Perng R. , Groen H. , Riska H. , Pirker R. , Sederholm C. , Caspar C. , Boyer M. , Berzinec P. , Allan S. 
Published: March 2020

7190 Background: Erlotinib is an orally active and selective inhibitor of HER1/EGFR tyrosine kinase. In the BR.21 phase III trial, erlotinib significantly prolonged survival, delayed symptom progression, and improved quality of life in NSCLC patients (pts) (Shepherd et al, NEJM, 2005;353:123). The EAP is an open label, non-randomized, multicentre phase IV trial. Methods: Eligibility criteria included stage III/IV NSCLC pts who failed or were unsuitable for chemotherapy. Pts were given oral erlotinib, 150 mg/d, for as long as treatment provided clinical benefit without unacceptable toxicity. Pts were monitored monthly. Results: In Dec 05, data were available for 1,140 pts from 25 countries, median age 64 y (range 25–91). Key base-line characteristics (% pts) were: males 58%; Caucasian/Oriental 82/15; non-smoker/former or current-smoker 26/73. The % pts with ECOG PS 0/1/2/3 were 20/52/20/8. Most pts (55%) had adenocarcinoma. The % pts receiving erlotinib as 1st/2nd/3rd-line treatment were 12/47/40. As expected, rash was a common adverse event (AE: any grade [gr]: 65%; gr 3/4: 9%). Full safety data were available for 581 pts. Unexpected erlotinib-related AEs were only seen in <2% pts. Erlotinib-related AEs leading to treatment discontinuation were GI disorders in 21 pts (12 pts had gr 3/4 AEs) and skin disorders in 14 pts (6 pts had gr 3/4 rash). Only 10% of pts had dose reductions, mainly due to rash (66%; gr 3 in 8 pts) and diarrhea (17%; gr 3 in 2 pts). The median daily dose of erlotinib was 150mg. Serious erlotinib-related AEs were GI disorders (19 AEs; 11 gr 3/4), mainly diarrhea (8 AEs, 5 were gr 3). Pt accrual and analyses of response, survival data and assessment of various predictive biomarkers are ongoing. Response and survival data will be presented. Conclusions: These interim safety results of erlotinib in the real-life clinical setting in a large number of unselected pts with advanced NSCLC confirm the good tolerability observed in clinical trials. To date, the trial demonstrates that erlotinib is well tolerated, thus, allowing full dose administration to most pts. [Table: see text]
Prognostic value of blood levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in advanced non-small cell lung cancer (NSCLC) patients
Authors: Alberola V. , Camps C. , Sirera R. , Llobat L. , Blasco A. , Safont M. J. , Garde J. , Taron M. , Sanchez J. J. , Rosell R. 
Published: March 2020

7196 Background: VEGF and bFGF are among the most important angiogenic factors. We have explored these angiogenesis mediators in plasma and its prognostic significance in advanced NSCLC. Methods: Were enrolled 451 patients with advanced NSCLC, stages IIIB and IV and treated with cisplatin and docetaxel. Blood was collected before chemotherapy. Plasma VEGF and bFGF levels were assessed by commercial ELISA (sensitivity 5 pg/ml). In parallel plasma from 32 age and gender-matched controls was used. Results: Median age was 61 years (35–82) and 84% were males. 99% had performance status 0–1. 84% were in stage IV and 16% in stage IIIB. The histological subtypes were: 32% squamous cell carcinoma, 50% adenocarcinoma, 14% anaplastic large cell, and 4% undifferentiated. 41% of the patients received second line chemotherapy. 1% achieved complete response (CR), 36% partial response (PR), 35% had stable disease (SD) and 28% progressive disease (PD). Patient’s median plasma levels of VEGF (20 pg/ml, [6–203]) differ significantly (p = 0.04) from controls (14 pg/ml, [7–53]), but in contrast bFGF levels were not different, 14 pg/ml [5–960] vs 10 pg/ml [6–278] respectively. There were not differences in patients according to histology, site of metastasis and ECOG; however we could observe a tendency with stage for both factors: bFGF 9 pg/ml [5–24] in stage IIIB vs 15 pg/ml [6–960], p = 0.071 and VEGF 17 pg/ml [6–145] in IIIB vs 21 pg/ml [6–203] in IV, p = 0.086. It could not be observed any differences in response to therapy for both angiogenic factors; CR+PR patients presented median VEGF of 18 pg/ml [6–71] and bFGF 11 pg/ml [6–960] vs 20 pg/ml of VEGF [6–203] and 15 pg/ml of bFGF [5–395] in the SD+PD group. In the multivariate analysis we could not find that VEGF and bFGF plasma levels were predictors for time to progression (TTP) and overall survival (OS). Conclusions: VEGF but not bFGF levels in patients are significantly higher in patients than in controls. In our cohort of patients with advanced NSCLC we have not found any relationship between serum VEGF and bFGF levels with stage, histology, response, site of metastasis, TTP and OS. No significant financial relationships to disclose.
The influence of fluticasone inhalation on premalignant lesions in the bronchial epithelium of a high risk population: A double blind placebo-controlled randomised phase II study
Authors: Van Den Berg R. M. , Van Tinteren H. , Van Zandwijk N. , Sutedja T. G. , Baas P. , Visser C. , Grünberg K. , Mooi W. J. , Postmus P. E. , Smit E. F. 
Published: March 2020

7200 Background: Bronchial epithelium exposed to cigarette smoke undergoes a series of histological changes that may ultimately lead to invasive cancer. In rats exposed to cigarette smoke inhaled corticosteroids reduce the number of lung tumors. We studied the effect of fluticasone on premalignant lesions in volunteers with a smoking history of ≥10 pack-years and patients cured of head and neck cancer or lung cancer. Methods: Participants were screened for premalignant lesions by bronchoscopy. At least 3 standard locations and suspicious lesions (if present) were biopsied. Use of systemic corticosteroids in the past 12 months or serious comorbidity precluded participation. Biopsies were classifed using WHO criteria. In case of a metaplasia index > 15%, participants were randomised to receive a powder inhalation device containing either fluticasone 500 μg or a placebo. Compliance and side effects were monitored monthly. After 6 months, biopsies were taken from the same locations as previously sampled. Efficacy of treatment was assessed by reversal of metaplasia/dysplasia; secondary end-points were reversal of increased p53 immunoreactivity and hTERT expression. CT-scans were obtained at baseline and after intervention. Results: From February 2002 until October 2004, 201 subjects were screened. Two were excluded because of lung cancer detected during screening. Of the 108 volunteers included, 74 were male, mean age was 53 years (35–71), mean number of pack-years 48 (18–99), mean metaplasia index 48%, 32% had some degree of dysplasia at baseline. There were no significant differences between these characteristics in the intervention and placebo groups. Outcome: there was no significant difference with respect to reversal of metaplasia/dysplasia. Additional molecular studies will be performed to assess possible changes at a molecular level. Results will be presented at the ASCO annual meeting 2006. Conclusions: Fluticasone does not alter the natural course of premalignant lesions in the central airways when standard histological criteria are applied. No significant financial relationships to disclose.
Non-small cell lung cancer in the new millennium: The effect of FDG-PET on stage distribution
Authors: Goodgame B. , Morgensztern D. , Grove L. , Govindan R. 
Published: March 2020

7205 Background: The stage-wise distribution of NSCLC at the time of initial presentation following the widespread use of positron emission tomography with 2-[18F] fluoro-2-deoxy-D-glucose (FDG-PET) has not been characterized. Frequently quoted estimates of stage distribution are based predominantly on data prior to 2000. FDG-PET was approved in 1998 and has been widely utilized since 2000. We describe here the stage-wise distribution of NSCLC at the time of initial presentation over the past 15 years. Methods: Patients were identified and clinical data were obtained through our institutional tumor registry system. All patients diagnosed with NSCLC between January 1, 1990 and December 31, 2004 were included. All statistical comparisons were performed by X2 tests. Results: Of 6311 patients identified, 3926 were diagnosed prior to January 1, 2000 and 2385 thereafter. Pathological (surgical) staging was completed in 37% of patients. Given the widespread availability of FDG-PET since 2000, we grouped the analysis by date of diagnosis, before or after January 1, 2000. Before 2000, stage proportions were: I-29%; II-9%; III-31%; IV-30%; and unknown-1%. After January 1, 2000, stage proportions were: I-26%; II-9%; III-26%; IV-37%; and unknown-2%. The percentage of stage IV disease peaked at 40% in 2004. The difference in rates of stage IV disease before and after January 1, 2000 was highly significant (p < 0.0001). Conclusions: We have documented a significant change in the distribution of stages of non-small cell lung cancer in the last five years. The increase in stage IV disease and decreases in stages I & III disease coincide with the widespread adoption of FDG-PET, suggesting an earlier diagnosis of metastatic disease. [Table: see text]
Pharmacokinetic of inhaled low molecular weight heparin
Authors: Scheuch G. , Haeussermann S. , Brand P. , Herpich C. , Meyer T. 
Published: March 2020

7209 Background: Treatment with Heparin and low molecular weight (LMW) Heparin is frequently used in oncology settings. Usually, these drugs are delivered by subcutaneous (s.c.) administration. Since 1963, the clinical relevance of inhalation of unfractionated as well as LMW-Heparin has been investigated in various studies with over 500 subjects. In this study, a single inhalation of the LMW-Heparin Certoparin (Mono-Embolex, Novartis) was investigated in 10 healthy subjects. The goal was to assess the pharmacokinetic behavior. Inhalations were performed using a novel inhalation system, which allows an accurate dosing in the lungs by controlling patient’s breathing pattern (AKITA). Lung deposition is about 85% of the emitted dose. Methods: 10 non-smoking healthy subjects participated in this study. Inhalation of 9000 IU of LMW-Heparin was compared to 3000 IU s.c. administration to achieve factor-Xa-activity in the plasma of 0.2 to 0.3 U/ml. Intravenous blood samples were taken 0.25, 0.5, 1, 2, 4, 6, 24, 48 hrs after administration. Factor-Xa-activity in plasma was assessed using the Berichrom assay (Dade Behring, Marburg, Germany). Results: Inhalation of LMW-Heparin was well tolerated and did not result in any side effects or changes in lung function. The maximum anti-Xa-activity in the plasma was 0.3 U/ml for the s.c. administration of Certoparin and 0.32 U/ml after inhalation of 9000 IU. However, pharmacokinetics was considerably different. Inhaled LMW-Heparin resulted in a prolonged anti-Xa-activity. After 6 (24) hours, the anti-Xa-activity after s.c. administration was down at 0.16 U/ml (0.10) and after inhalation at 0.30 (0.18) U/ml. Even after 48 hrs, the anti-Xa-activity after inhalation was significantly higher than the baseline value. Comparing area under the curve (AUC), bioavailability for the inhalation was 9.4 U · h/ml ± 14% compared to 5.7 U · h/ml ± 27% after s.c. administration. Conclusions: These results suggest that with controlled inhalation, this administration route is an attractive alternative to s.c. administration, with the result of longer bioavailability and less variability. A once daily administration is possible. Inhalation therapy with these kind of systems might also be useful with different anticancer agents, which cannot be administered orally. [Table: see text]
Clinical characterization of node-negative non-small cell lung cancer: Results of a prospective investigation
Authors: Yoshino I. , Ichinose Y. , Nagashima A. , Takeo S. , Motohiro A. , Yano T. , Ishida T. , Yamazaki K. , Sugio K. , Yasumoto K. , Maehara Y. 
Published: March 2020

7218 Background: 20 to 30% of clinical stage IA non-small cell lung cancer cases were revealed to be node-positive by pathologic examination of resected specimens. In this prospective study, the clinical features of a truly node-negative population were prospectively investigated to search for candidates of a lesser resection or of a stereotactic radiotherapy. Methods: The clinical data and radiographic features of high-resolution computed tomography (HR-CT) were registered before operation in 169 clinical stage IA lung cancer patients, who were scheduled to undergo a standard lobectomy and systemic mediastinal node dissection. The nodal metastasis was pathologically defined, while the clinical factors associated with the presence of the nodal metastasis were evaluated. Results: In 130 evaluable cases, 16 of 114 adenocarcinoma and 3 of 16 other NSCLC were node-positive. Among all parameters, positivity of the serum carcinoembryonic antigen (CEA) was the only factor significantly associated with nodal metastasis (p = 0.0074). When we focused on adenocarcinomas, the serum CEA, retraction sign and intratumoral air-space on HR-CT were suggested to be predictive factors for lymph node metastasis with hazard ratios of 12.44 (p = 0.0003), 6.53 (p = 0.0533) and 0.17 (0.0073), respectively. In combination with the radiologic features of HR-CT imaging, none of 18 CEA-negative/retraction-negative cases and 3 of 65 CEA-negative/air-space positive cases showed nodal metastasis, in which the incidence of nodal metastasis was significantly lower than the counterparts with respective p-values of 0.0015 and 0.037. The tumor size and the proportion of ground glass attenuation were not associated with the incidence of nodal metastasis. Conclusions: The serum CEA and HR-CT features thus allowed us to identify node-negative lung adenocarcinomas. In clinical stage IA adenocarcinoma cases, a standard operation should be considered when positive serum CEA and/or retraction sign on HRCT is noticed. No significant financial relationships to disclose.