bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expressionn of ERCC1 and its influence on efficacy of induction chemotherapy in non-small cell lung cancer (NSCLC)
Authors: Zhou C. , Su C. , Su C. , Zhou S. , Xu Q. , Chen X. , Chen X. 
Published: March 2020

18102 Background: Chemotherapy efficacy is related to pharmacogenomic differences among NSCLC patients. It is thought that up-regulated ERCC1 may be responsible for platinum resistance in NSCLC.This study was to investigate expression of ERCC1 in Chinese NSCLC patients and determine its influence on efficacy of induction chemotherapy. Methods: We retrospectively compared expression of ERCC1 between NSCLC patients receiving and not receiving induction chemotherapy. Expression of ERCC1 was detected with immunohistochemistry and defined as positive if more than 10% of tumor cells expressed ERCC1 in their nuclei. Results: Consecutive 73 NSCLC patients resected from December 1997 to Feb.1998 in our hospital were randomly selected for the study. Among them, 33 patients were given 1 to 2 cycles of cisplatin-based induction chemotherapy (mainly MVP as regimen) and their characteristics were not different from those receiving no chemotherapy. Expression of ERCC1 was higher in those younger than 60 years old than older than 60 years, in those with adenocarcinoma than in those with squamous carcinoma and in those receiving induction chemotherapy than those not receiving chemotherapy. Response (and progression) rates of induction chemotherapy were 59% (6%) and 31% (19%) in those without and with ERCC1 expression, respectively. Median survival, 3 year survival, and 5 year survival were 54 months, 53% and 35% in the patients with negative ERCC1 and 36 months, 50% and 25% in those with positive ERCC1, respectively. Difference in response rate of induction chemotherapy tended to be significant between those with and with expression of ERCC1( P<0.1). Conclusions: ERCC1 is expressed in Chinese NSCLC patients. Its expression might be induced by chemotherapy. ERCC1 in NSCLC might be useful to select patients for induction chemotherapy, which needs further study. No significant financial relationships to disclose.
Disease control with a second epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) after failure of a first TKI in Asian patients with non-small cell lung cancer (NSCLC)
Authors: Wong A. , Lim S. W. , Chin T. M. , Soong R. , Soo R. A. 
Published: March 2020

18104 Background: Asian NSCLC patients are known to have higher response rates to the EGFR TKI gefitinib (G) and erlotinib (E). Anecdotal reports suggest some activity for a second EGFR TKI after failure of the first. Methods: A retrospective review of the electronic pharmacy records, clinical and radiographic records of patients with advanced NSCLC at the National University Hospital who received both G and E in the previous 2 years was conducted. Objectives were to assess the disease control (response/stable disease) of the second TKI after failure of the first and characterize the clinical, pathological and molecular features of patients benefiting from a 2nd TKI. Results: 14 patients with advanced NSCLC who received a 2nd EGFR TKI after progression on the 1st TKI were identified. Patient characteristics: Chinese 12, female 10, and non-smokers 13. Histologic subtype: adenocarcinoma 7, bronchioloalveolar carcinoma (BAC) 3, squamous-cell carcinoma 1, NSCLC unspecified 3. 12 patients received cytotoxic chemotherapy with a median of 2 lines, (range 1–5). G and E was used as 1st/2nd/3rd/=4th line treatment in 8/2/2/2 and 0/4/2/8 patients respectively. G was used before E in 13 cases and disease control was seen in 8/14 (57%) patients. With a 2nd TKI after disease progression, disease control was seen 4/14 (28%) patients. Patient characteristics were: adenocarcinoma 3, BAC 1, all were never smokers and all received and responded to prior G. Median duration of control in these 4 patients for G was 8 (range 7–12) months, and subsequently to E was 2.5 (range 2–8) months. Disease control was associated with symptomatic improvement. Conclusion: This study documents disease control in 28% of Asian NSCLC patients treated with a second EGFR TKI after failure of a first. The molecular basis for these observations is currently being investigated. No significant financial relationships to disclose.
Design and analysis methods for assessing drug synergy: Illustration using histone deacetylase (HDAC) inhibitor LBH589 combined with CDDP in mesothelioma (meso) cell lines
Authors: Symanowski J. T. , Giraud Y. , Dino P. , Atadja P. , Vogelzang N. , Sharma S. 
Published: March 2020

18108 Background: LBH589 (Novartis) is an investigational agent belonging to a cinnamic hydroxamic acid class of compounds that was shown to inhibit HDAC enzyme activity. LBH589 is in phase I clinical testing and combinations with various agents are being explored in the laboratory. Common experimental designs used for in-vitro cell viability experiments to assess drug synergy in cancer cell lines include complete factorial design (CFD) and fixed dose ratio design (FRD). While CFD provides data for the entire response surface, it can result in unfeasibly large experiments and complex synergy calculations, especially when 3 or more drugs are under evaluation. We investigated the FRD and alternative analysis methods to estimate and test synergy between two or more drugs. Methods: Experiments in meso cell lines were conducted using a colorimetric MTS assay. The FRD included 4 LBH concentrations (10 to 100 nM) and 4 CDDP concentrations (.5 to 5 μM), for each drug alone and in combination at a 50:1 CDDP:LBH ratio. Data were analyzed by applying the median effect equations (Chou, Adv Enzyme Regul, 1984) to the joint modeling approach by Straetemans, Biom. J., 2005. This method provides a straightforward estimate of the combination index (CI) and a statistical test for synergy (CI values less than 1.0 indicate synergy). Results: Results showed CI values significantly less than 1 for cell lines 2052 and MSTO for low to mid effect levels. Additive results were seen in cell line 2452. IC50’s were not greatly exceeded; therefore, CI’s for higher effect levels were not estimated. Conclusions: LBH appears to be synergistic with CDDP in some meso cell lines. The FRD is an efficient method to assess drug synergy and will be used for larger experiments to study 3 drug combinations involving LBH589. We propose a straightforward analysis method based on the median effect equations that jointly models the data, providing confidence intervals and a statistical test for synergy. [Table: see text] No significant financial relationships to disclose.
Gemcitabine (GEM) (day 1–8) plus carboplatin (CBDCA) (day 2) for the treatment of advanced non-small cell lung cancer (aNSCLC) in elderly or poor performance status (PS) patients (pts)
Authors: Sperandi F. , Melotti B. , Martoni A. A. 
Published: March 2020

18116 Background: Several studies have demonstrated that the combination of CBDCA plus GEM according to various regimens appears as effective as cisplatin (CP) containing regimens. CBDCA plus GEM regimens are associated with more haematological toxicity (G3–4 leucopenia 17–40.6%, G3–4 neutropenia 29–75%, G3–4 thrombocytopenia 21–57% and G3–4 anaemia 5–33%), but with lower non-hematological toxicity as compared to CP-based regimens. Methods: The primary objective of this trial was the evaluation of the overall survival, while the secondary objectives were assessment of objective response and toxicity in elderly or poor PS pts. The eligible pts had previously untreated aNSCLC not suitable for CP-based chemotherapy. Pts received each at 3-week intervals GEM 1000 mg/sq on day 1 and 8 plus CBDCA area under the curve of 5 on day 2. Between April 2004 and January 2007, 54 consecutive pts were accrued in the study. Pt characteristics were: 42 (78%) males and 12 (22%) females; median age 72 years (range: 56–84 years) with 67% of pts = 70 years; median Karnofsky PS 90 (range: 50–100) with 33% of pts = 80; stage disease: IIB not suitable for surgery in 1 (2%) pt, IIIA in 5 (9%), IIIB in 10 (19%), IV in 33 (61%) and recurrent disease in 5 (9%); histologic subtype: adenocarcinoma in 30 (56%) pts, epidermoid in 11 (20%), bronchioalveolar carcinoma in 2 (4%) and other histologic subtypes in 11 (20%). Results: A median of 4 courses was administered (range 1–8). Dose- intensity was 98.7% (range 50–100%) for CBDCA and 87.2% (range 60–100%) for GEM. Objective response according to intention-to-treat analysis was as follows: 15 (28%) pts had PR, 16 (29%) had SD, 14 (27%) had PD and 9 (16%) were not assessable because lost to follow-up or too early. Median overall survival was 10 months. WHO G3 leucopenia was observed in 5 (9%) pts, G3–4 neutropenia in 15 (28%), G3 thrombocytopenia in 7 (13%) and G3 anaemia in 2 (4%). No WHO G3–4 non-hematological toxicity was observed. Conclusions: This regimen is feasible and active in elderly or poor PS pts. It can be administered in a outpatient setting because toxicity is moderate and manageable. No significant financial relationships to disclose.
The association of epidermal growth factor receptor (EGFR) polymorphisms and clinicopathological factors with skin rash on gefitinib use
Authors: Huang C. , Yang C. , Yeh K. , Hu F. , Lin Z. , Wan J. , Tseng L. , Yu C. , Cheng A. 
Published: March 2020

18118 Background: Skin rash is the most common toxicity of EGFR-targeted therapy. Skin rash of EGFR inhibitor is associated with longer survival or tumor response. However, the clinical and genetic factors associated with this skin rash are not well understood. Methods: Fifty-two non-small-cell lung cancer patients enrolled in a prospective clinical trial of first-line gefitinib treatment were genotyped for EGFR intron 1 CA repeat polymorphism (CAn) and single nucleotide polymorphisms at promoters G-216T, C-191A, and R521K. Grade 2 to 3 skin rash within 4 weeks of treatment (early G2/3 rash) was correlated with the genotype and clinicopathological features of the patients by multivariate logistic regression. Results: Seventeen patients (32.7%) developed early G2/3 rash. In multivariate logistic regression analysis, only the CAn genotype was associated with early G2/3 rash and the effect was modified by patient age. Early G2/3 rash developed in 21% of patients with homozygous long allele (19 to 22 repeats, L) genotype (4/19), 31% of heterozygous short allele (15 to 18 repeats, S) / L genotype (8/26), and 71% of S/S genotype (5/7), respectively. The median ages of patients with early G2/3 rash and patients without early G2/3 rash were 57 years (range: 39–77) and 69 years (range: 43–86), respectively. The estimated logarithm of odds ratio (ln OR) for early G2/3 rash, as compared to S/S genotype, for S/L genotype was -0.038 multiplied by patient age (P = 0.011); and the ln OR for L/L genotype was -0.050 multiplied by patient age (P = 0.004). Fifty patients were evaluable for response. In logistic regression analysis, early G2/3 rash correlated with tumor response (P = 0.027). However, the CAn genotype was not significantly correlated with tumor response (P = 0.43). Conclusions: Homozygous short allele of EGFR CAn is more likely to develop skin rashes on gefitinib treatment. Genotyping of EGFR CAn appears to be a useful predictive marker for development of skin rashes on gefitinib use. [Table: see text]
Phase II trial of irinotecan, carboplatin, and bevacizumab in patients with extensive-stage small cell lung cancer
Authors: Spigel D. R. , Hainsworth J. D. , Yardley D. A. , Burris H. A. , Farley C. , Zubkus J. , Meng C. , Murphy P. , Saez R. , Greco F. A. 
Published: March 2020

18130 Background: Bevacizumab (B) improves survival when combined with chemotherapy in non-small cell lung cancer treatment. Our center previously studied the role of B as maintenance therapy in patients (pts) with limited-stage small cell lung cancer (SCLC). The present multicenter community-based trial was designed to examine the role of B and chemotherapy in previously untreated pts with extensive- stage SCLC (ES-SCLC). Methods: The primary endpoint is to assess the median time to progression (TTP). Eligibility criteria: untreated ES-SCLC, ECOG PS 0–1, measurable disease, and informed consent. Exclusion criteria: hemoptysis, brain metastases, and therapeutic anticoagulation. Treatment: irinotecan (I) 60 mg/m2 IV D1, 8, 15, and carboplatin (C) AUC=4 IV D1, and B 10 mg/kg IV D1 and 15 every 28D. Pts were restaged every 8 weeks. If no evidence of progressive disease (PD) after 4–6 cycles, pts received B x 6 months. This 2- stage trial was designed to achieve a 40% improvement in historical median TTP of 6 months. Results: 34 pts were enrolled from 2/06 to 12/06 (trial ongoing, n=50 planned). Data are available for 23 pts in this analysis. Baseline characteristics: median age 66 years; male/female, 52%/48%; and ECOG PS 0/1, 35%/65%. The objective response rate was 78% (95% CI 58%-90%), all partial responses. One pt had stable disease and no pts had PD. Four pts were not evaluable due to: comorbidity (off study), 2 pts; too early, 2 pts. With a median follow-up of 7 months, the median TTP and overall survival have not been reached. Grade (G) 3/4 non-hematologic toxicity: diarrhea (26%), hyponatremia, pain, arthralgia, fatigue (13% each), and dehydration, confusion, proteinuria (9% each). G3/4 hematologic toxicity was limited to neutropenia (13%). Other G3/4 toxicities were = 5%. There have been no episodes of G3/4 bleeding or treatment-related deaths. Conclusions: I/C/B appears to be safe and generally well tolerated in pts with ES-SCLC in this preliminary analysis. Further accrual and longer follow-up are necessary to assess median TTP. No significant financial relationships to disclose.
18F-FDG uptake on positron emission tomography in gefitinib-treated non-small cell lung cancer patients
Authors: Na I. , Byun B. , Kang H. , Cheon G. , Kim C. , Koh J. , Choe D. , Ryoo B. , Lim S. , Lee J. , Yang S. 
Published: March 2020

18136 Background: This study evaluated the clinical significance of 18F-fluoro-2-deoxy-glucose (FDG) uptake on positron emission tomography (PET) in gefitinib-treated non-small-cell lung cancer (NSCLC) patients. Method: We retrospectively analyzed PET scans of 66 NSCLC patients with stage IIIB-IV and its association with gefitinib responsiveness. Response rate and time-to- progression (TTP) were analyzed according to the maximum standardized uptake value (SUV) at presentation. Cut-off vale of SUV was obtained from receiver operating characteristic analysis. Univariate and multivariate analyses were performed. Results: According to smoking history and pathology, different response rates were observed (P = 0.012 and 0.048, respectively). Thirteen patients were categorized into low SUV group. Patients with low SUV showed higher RR compared with those with high SUV (46% vs 13%, P = 0.007). In univariate analysis, prolonged TTP was observed in never-smoker (P = 0.007). Low SUV was associated with prolonged TTP (P = 0.010). Multivariate analysis confirmed that low SUV and never-smoker remained favorable prognostic factors (P = 0.046 and 0.043, respectively). Conclusion: These results suggest that FDG uptake may be predictive of outcome in gefitinib-treated non-small-cell lung cancer patients. No significant financial relationships to disclose.
Improvement in symptoms and quality of life (QoL) for patients (p) with non-small cell lung cancer (NSCLC) treated with erloninib: TargeT study
Authors: Alberola V. , Gallego O. , López-Vivanco G. , Mesía C. , Oramas J. , Trigo J. M. , Virizuela J. A. , Camps C. , Regueiro P. , Massutí B. 
Published: March 2020

18140 Background: Erlotinib is an EGFR TKI that is effective in the treatment of advanced NSCLC, in terms of longer survival, better quality of life and delayed symptom progression.We present here the outcome of a group of p from the TargeT study, whose QoL was assessed by the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire and the Lung Cancer Subscale (LCS). Methods: TargeT study was a multicenter, single-arm phase II study evaluating efficacy, safety, and tolerability of erlotinib (150 m/day) in p with stage IIIB or IV NSCLC, in 1st, 2nd and 3rd line treatment. Primary end-point was time to progression. QoL was a secondary end point as assessed monthly by the Functional Assessment of Cancer Therapy-Lung questionnaire (FACT- L) and its Lung Cancer Subscale. Physical and functional aspects of the QoL were measured by the Trial Outcome Index (TOI), which is the sum of the physical well being, functional well-being and LCS scores from the FACT-L questionnaire. Results: Data from 91 pts were available. QoL analysis showed that 53% of the p (95% IC 37–58%) had improvement in FACT-L or TOI. Similarly, 45% (95% IC35–56%) of improved their symptoms from baseline. Improvement was observed for each individual LCS item and specifically in the pulmonary items. In symptomatic p, shortened of breath was 17,6% at baseline vs 2.2% after treatment (p<0.001) and cough was 24.7% vs 8.8 % (p<0.001) after treatment. Those improvements in symptoms were rapid and, 73% of the patients who improved showed that recovery in the first cycle of treatment. In terms of association between efficacy of erlotinib and QoL, there is a statistically significative relationship between objective response and improvement in TOI or FACT-L (p<0.02). Conclusions: This QoL analysis confirms that erlotinib improves both symptoms and functional aspect of patients with NSCLC. The improvement in QoL is related with objective response. No significant financial relationships to disclose.
A single institution experience of lung cancer treatment in octogenarians
Authors: McCormack S. , Pleister A. , Young D. , Confer P. , Otterson G. A. 
Published: March 2020

18141 Background: In the NCI’s SEER database nearly 15% of NSCLC patients were = 80 years during the years 1973–2003. As the “elderly” population increases, the percentage of octogenarians with NSCLC will increase. To better understand this population we investigated the patient and tumor characteristics and treatment modalities by stage in octogenarians with NSCLC over a recent 5 year period at The Ohio State University Medical Center. Methods: Patients aged 80 years and older with biopsy-proven NSCLC seen between 1998–2003 were included in the analysis. 74 patients met criteria for study. Data was gathered from the cancer registry and chart reviews. Characteristics included stage, histology, treatment, and co-morbid conditions (pulmonary and non-pulmonary co-morbidities, weight loss, and ECOG PS). PS was either explicitly stated or inferred from the records, or recorded as “unknown” when PS could not be determined. Results: The 74 patients averaged 82.8 years of age (range 80–91), with 53% males and 47% females (83 years of age with 56% males and 44% females from the SEER database). 46% of patients had “surgical” disease (Stage IA, IB, and IIB), 20.3% had stage III disease, 29.7% had stage IV disease, and 4.0% had indeterminate staging. 82.4% of “surgical” disease patients received some variety of treatment (70.6% surgery[S], 23.5% radiation[RT], and 12.5% chemo[Ch]); 80% of stage III patients received treatment (53.3% S, 40% RT, and 33.3% Ch); 50% of stage IV patients received treatment (0% S, 31.8% RT, and 40.9% Ch). Patients with an ECOG PS of 0–1, 2, 3–4, or “unknown” equaled 44.6%, 20.3%, 16.2%, and 18.9% respectively with 81.8%, 100%, 41.7%, and 78.6% of these patients receiving treatment. Conclusions: There is little data on treatment of the ‘extreme elderly.‘ Our analysis of this subset of the elderly reveals that most octogenarians seen at a referral center can receive treatment. The majority of “surgical” disease octogenarians received surgical resection of their primary tumor and the majority of all patients received some treatment. Further studies of outcomes based on staging, co-morbidities, and PS will be important in this population. Additional studies of this population in non-referral centers are of interest. No significant financial relationships to disclose.
Gemcitabine and radiotherapy: Analysis of safe use
Authors: Czarnecki A. 
Published: March 2020

18146 Background: Radiation in combination with chemotherapy offers a significant survival advantage. Preclinical and clinical data indicate that gemcitabine (GEM) is a potent radiosensitizing agent in numerous cancer types used subsequently with radiation given in different doses and techniques. We compared safety/toxic effects of GEM with GEM plus radiation. Methods: Lilly Safety Database was searched for all reports where patients received radiation before, during and after GEM therapy. The string search for ‘radio’, ‘radia’ and a search for MedDRA terms covering possible radiation recall and typical recall phenomena were conducted. Cases were reviewed by a physician and allocated to one of the categories: ‘concurrent’ (radiation and GEM was given at the same time or 7 days apart), and ‘non-concurrent’ (treatment was given more than 7 days apart). Results: In one third of cases who received concurrent treatment the toxicity reported was higher in 3 System Organ Classes (SOC): ‘Injury’, ‘Gastrointestinal disorders’ (GI), and ‘Respiratory’ in comparison to non radiation treated patients: 4.1%, 16%, 14.8% versus 1.4%, 11.2% and 10.5% respectively but toxicity was lower for ‘Blood and lymphatic disorders’ and ‘General disorders’. In cases with ‘non-concurrent’ treatment the results were similar to ‘concurrent’ treatment for the Injury, Respiratory and Blood SOCs but GI toxicity was only 60% of the one seen in non radiation treated patients. In patients with reported radiation recall the most frequent were skin reactions, pneumonitis and myositis. Radiation injury mainly affected targeted tissue organs exposed to direct radiation e.g eosophagitis and pneumonitis for chest irradiation, GI effects for abdominal irradiation. In Non-concurrent administration no correlation between GEM dose and toxicity could be established. In Concurrent cases, treatment dose and technique of radiation, target tissue and volume were factors together with dose and frequency of GEM administration. Conclusions: Review of adverse drug reactions for GEM and radiation treatment reported from estimated GEM exposure of nearly 1.1 million patients suggests that any increase in GEM toxicity in non- concurrent combination regimen other than radiation recall is due to typical radiation toxicity and mainly affects directly irradiated tissues. No significant financial relationships to disclose.