bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors affecting the risk of brain metastases after chemoradiotherapy for locally advanced non-small-cell lung cancer (LA-NSCLC)
Authors: Fujii M. , Segawa Y. , Nogami N. , Hamamoto Y. , Kataoka M. , Komori E. , Sawada S. , Yamashita M. , Shinkai T. , Takashima S. 
Published: March 2020

17019 Background: With an improvement in treatment outcome in patients with LA-NSCLC undergoing radical chemoradiotherapy, brain metastasis has become a greater problem. We assessed the cumulative incidence of brain metastases and its risk factors in such patients with LA-NSCLC. Methods: Between 1993 and 2003, 85 consecutive patients with stage IIIA or IIIB NSCLC underwent chemoradiotherapy in our institution. The characteristics of these patients were as follows: median age, 64 years (range, 39 to 74 years); stage IIIA/IIIB, 30/55 patients; squamous-cell/nonsquamous-cell histologies, 39/46 patients. Concurrent and sequential chemoradiotherapy were administered for 78 and 7 patients, respectively. Only two patients underwent surgical resection after chemoradiotherapy. Fifty-seven patients received conventional thoracic radiotherapy with a total dose of 59.5 ± 1.4 Gy (range, 40 to 70 Gy), and 28 received twice-daily radiotherapy with a total dose of 71.5 ± 6.5 Gy (range, 43 to 86 Gy). Thirty-eight patients received a combination chemotherapy consisting of cisplatin and docetaxel, and the remaining 47 received the other platinum-based regimens. Results: At a median follow-up time of 51 months (range, 9 to 131 months), median survival time was 25 months, with a 3-year survival rate of 36.9%. The median disease-free survival time was 13 months. During treatment and observation periods, 21 (24.7%) patients had developed brain metastases. Thirteen (15.3%) patients experienced brain metastases as the first site of relapse, and in nine (10.6%), brain was the sole site of relapse. The cumulative risk of brain metastases was 15.4% at 1-year, 21.1% at 2-year, and 25.7% at 3-year, respectively. In a multivariate analysis using Cox proportional hazard model, T-factor (T4 vs. T1–3) was the most predictive of brain failure (hazard ratio, 3.51; 95% confidence interval, 1.35 to 9.13; p = 0.01). Conclusions: In patients with LA-NSCLC undergoing chemoradiotherapy, brain was one of the most common sites of failure when locoregional control was achieved. Although efficacy of prophylactic cranial irradiation (PCI) on survival remains unclear for such patients with NSCLC, identification of patients more likely to have a benefit from PCI would be useful. No significant financial relationships to disclose.
Analysis of nerve growth factor (NGF) blood levels in patients with advanced non-small cell lung cancer patients (NSCLC): Its correlation with clinical outcome
Authors: Blasco A. , Sirera R. , Camps C. , Giner V. , Llobat L. , Safont M. J. , Berrocal A. , Taron M. , Sanchez J. J. , Rosell R. 
Published: March 2020

17025 Background: Platinum compounds and taxanes have severe side effects in a dose and time-dependent manner, especially neurotoxicity. NGF plays an important role in growth and differentiation of neuronal components. Our goal was to study NGF levels in plasma and correlate it with patient’s clinico-pathologic characteristics. Methods: The study was performed with 451 patients with advanced NSCLC, stages IIIB-IV and treated with cisplatin and docetaxel. Peripheral blood was collected before therapy. NGF were assessed by commercial ELISA (detection limit, 5 pg/ml). Plasma from 32 age and gender-matched controls was used. Results: 91% of males, mean age 61 y [35–82]. 86 patients in ECOG PS 0–1 and 14 PS2. 71% in stage IV and 29% in IIIB. The histological subtypes were 38% squamous cell, 37% adenocarcinoma, 5% anaplasic large cell and 20% undifferentiated. 77.5% of the metastasis was out of the lung. Patients received a median of 6 cycles of chemotherapy [1–7]. 4% presented complete response (CR), 38% partial response (PR), 25% stable disease (SD) and 30% progressive disease (PD). Patient’s median plasma levels of NGF did not differ significantly from controls: 44 pg/ml [6–176] vs 31 pg/ml [14–144] respectively. There were not differences according to histology, site of metastasis and ECOG; however we could observe significant differences with stage: 25 pg/ml [10–70] in stage IIIB vs 47 pg/ml [6–176] in stage IV (p = 0.008). We could not observe any differences in response to therapy: CR+PR patients presented median NGF of 35 pg/ml [6–92] vs 39 pg/ml [10–165] in the SD+PD group. Splitting the cohort according to NGF median we found two significantly different groups in terms of Overall Survival (OS): patients with NGF <44 pg/ml had a median OS of 10.9 months (m) [7.9–13.9] vs 7.3 m [3–11.5] for patients with NGF >44 pg/ml (p = 0.03). In the multivariate analysis, NGF levels was not predictor for time to progression (TTP) and OS. Conclusions: NGF plasma levels did not differ in patients and controls. In our cohort with advanced NSCLC we have not found any relationship between NGF levels with histology, response, site of metastasis and TTP. By contrast NGF levels are higher in those patients in stage IV and in those presenting poorer OS. No significant financial relationships to disclose.
Phase II trial of pemetrexed (P) and gemcitabine (G) as first-line chemotherapy for elderly and/or poor performance status patients with stage IIIB/IV non-small cell lung cancer (NSCLC)
Authors: Blakely J. , Schnell F. , Kaywin P. , Keaton M. , Fortner B. , Epperson A. , Schwartzberg L. S. 
Published: March 2020

17031 Background: Pemetrexed and gemcitabine have shown to be active agents in the treatment of locally advanced or metastatic NSCLC with favorable toxicity profiles. A recent phase I study examined a biweekly schedule of P and G in combination in order to establish a maximum tolerated dose in solid tumors. (Dudeck, A. ASCO 2004 Abstract 2141.) This established the dose for this study. Methods: After informed consent all patients received biweekly cycles of P 500 mg/m2 IV 10 minutes before G 1500 mg/m2 IV. A maximum of 12 cycles was planned for stable or responding patients. All patients received vitamin B12 1000 μg and folic acid 1000 mg 7 days prior to the initiation of treatment and continued through treatment. Entry criteria include measurable stage IIIB/IV NSCLC by RECIST criteria, age ≥65 years and ECOG 0–2 or <65 years and ECOG of 2. A total of 40 patients are scheduled to be enrolled. Primary endpoint is objective response rate. Results: To date, 19 of 29 enrolled patients have data available for analysis. The median age is 71 (range 61–85). 2 had stage IIIB and 17 stage IV, median number of sites of disease is 2. Male/Female ratio was 10/9. Performance status was as follows ECOG 0 = 3 patients, 1 = 12 patients, 2 = 4 patients. 3 patients had grade 3 or 4 neutropenia with only 1 patient having neutropenic fever. There were no grade 3 or 4 anemias or thrombocytopenias. One patient had grade 3/4 nausea; there were no other severe non-hematologic toxicities. 14 patients were evaluable for response with 3 achieving PR (21%), 10 with SD (71%) (median number of cycles 7) and 1 with PD (7%). Conclusion: Pemetrexed and gemcitabine in combination biweekly has substantial activity with a favorable toxicity profile for patients with advanced NSCLC who are elderly or have poor performance status. The study is expected to be completed and fully evaluable by ASCO. No significant financial relationships to disclose.
Tandem high-dose therapy with autologous stem cell support for small-cell lung cancer (SCLC)
Authors: Machatschek J. N. , Kobbe G. , Haas R. , Rohr U. P. 
Published: March 2020

17033 Background: We evaluated the therapeutic efficacy of tandem high-dose chemotherapy followed by autologous peripheral stem-cell transplantation (PBSCT) in patients with newly diagnosed SCLC in complete remission or very good partial response after induction chemotherapy. Methods: Between 1996 and 2000, 19 patients with newly diagnosed SCLC in CR or very good PR after two cycles of induction chemotherapy (cisplatin 90 mg/m2 day 1, etoposide 120 mg/m2 day 1–3, ifosfamide 1500 mg/m2 day 1–4) received a tandem high-dose chemotherapy (cyclophosfamide 2000 mg/m2 day 1 and 2, etoposide 700 mg/m2 day 1–3, carboplatin 1200 mg/m2 day 1) followed by PBSCT. Following transplantation, patients received concurrent chest and cranial radiotherapy to a total dose of 45 Gy and 30 Gy, respectively. Results: Of 19 patients with SCLC, 18 had stage III and one stage IV disease. The median age was 50.7 years. Median time to leukocyte-recovery above 1000/μl and platelet-recovery above 20.000/μl was 12 days and 9 days, respectively. The median follow-up was 6.38 years (range 5.11–7.23) for surviving patients. There were no transplant-related deaths and toxicity was moderate. Using the Kaplan-Meier method, the 2- and 5-year survival rates after high-dose therapy were 42% and 32% respectively. Median time to relapse was 0.7 years (range 0.2–4.6). The mean survival was 36.8 months. This outcome compared favourably to a group of 77 patients who did not receive high-dose therapy but responded to conventional chemotherapy (mean survival 11.4 months). Using the Cox regression model, among all patients response to induction, normal LDH and PBSCT were associated with favourable outcome. Conclusions: Our findings suggest that patients with or near complete response after conventional therapy might benefit from tandem high-dose therapy with PBSCT with tolerable toxicicity. No significant financial relationships to disclose.
A feasibility/phase II study of gemcitabine (G) and split dose cisplatin (C) in advanced or metastatic non-small cell lung cancer (NSCLC) in an outpatient setting
Authors: Hussain S. A. , Palmer D. H. , Swinson D. E. , Riley P. , Brown C. , Wills A. , El-Modir A. , Rea D. W. , Chetiyawardana A. D. , Cullen M. H. 
Published: March 2020

17048 Background: This is a feasibility/phase II trial with GC on a 21-day cycle, with G and C split between d1, 8. Split dose C allowed administration in an outpatient setting. Objectives: To document the toxicity and define the objective response rate; and determine progression free and overall survival. Methods: Pts with stage III/IV NSCLC received: G/C 1250/40mg/m2 (G and C given on d1, 8 every 3 wks). Eligibility: ECOG PS 0–2, adequate bone marrow/liver function, calculated GFR > 50 ml/min. Results: 56 pts enrolled, all evaluable for toxicity; 47 evaluable for response; 4 patients too early for response assessment and 5 patients did not complete 1 cycle of chemotherapy. Characteristics: 70% male, median age 66 yrs (41–77), 25% GFR 50- 60 ml/min, 62% Stage IV. Radiotherapy was allowed after completing chemotherapy. 165 cycles have been delivered. Cycles with hematological toxicity: Grade 3: 5 anaemia, 17 neutropenia, 6 thrombocytopenia; Grade 4: 7 neutropenia, 4 thrombocytopenia. There were 3 episodes of febrile neutropenia. Cycles with non-hematological toxicity: Grade 4: 1 myocardial infarction (MI), 1 gastrointestinal (GI) bleed, 1 pulmonary embolism, 1 stroke; Grade 3: 3 nausea, 1 deep vein thrombosis, 4 chest infection, 1 hypomagnesemia; Grade 2: 3 renal toxicity, 2 seizure, 1 hypomagnesemia. Five cycles were deferred due to grade 4 neutropenia; 2 for renal toxicity (in one patient with diabetes and hypertension renal function declined after 1 cycle necessitating discontinuation of chemotherapy). 2 deaths occurred on treatment: 1 MI (patient with a previous history of MI); 1 GI bleed (on aspirin). Overall ITT RR was 33% (17/52: 1 CR+ 16 PR) (36% [17/47] for assessable pts). Median survival is 310-days. 1- year survival rate is 38%. Conclusion: G plus C in a 21-day schedule is active and well tolerated in an outpatient setting. This modified regimen with C split between d1 and d8, and, eligibility criteria of GFR as low as 50mls/min widens the spectrum of patients receiving cisplatin-based chemotherapy. Phase III trial is warranted. [Table: see text]
Increased levels of inflammatory mediators in lung cancer and their modulation by oral anticoagulant treatment
Authors: Hoppensteadt D. A. , Ciftci A. , Demir M. , Altiay G. , Tobu M. , Iqbal O. , Fareed D. , Bick R. , Fareed J. 
Published: March 2020

17050 Background: Venous thromboembolic events (VTE) are associated with lung cancer and significantly contributes to the increased mortality in these patients. While the increased prevalence of VTE is fully recognized in lung cancer, its pathogenesis is not fully understood. Even the patients undergoing therapeutic interventions are at high risk to develop VTE. These patients provide a unique clinical setting to investigate the pathogenesis of lung cancer associated thrombosis. Methods: In a prospective, randomized, controlled study patients with inoperable lung cancer (n = 100) were randomized to receive chemotherapy, radiation and warfarin (INR 1.5–2.5) or chemotherapy, radiation without warfarin (n = 50). Blood samples were drawn prior to and after the second treatment cycle with warfarin. All samples were analyzed for tumor necrosis factor alpha (TNF α), CD 40 ligand (CD 40L), C-reactive protein (CRP), interleukin 1 beta (IL-1β), asymmetric dimethylarginine (ADMA) and nitric oxide (NO). Results: Summarized in the table given below. All of the surrogate markers of inflammation showed a decreased trend (13–50%) in the warfarin treated group, whereas the non-warfarin treated group exhibited an increase (18–46%) in all markers except CRP and ADMA. Conclusions: The levels of various inflammatory markers are upregulated in lung cancer suggesting a pathogenic role of this process in lung cancer. Warfarin down regulated the inflammatory process in contrast to the non-warfarin treated group. The clinical relevance of these observations require additional analysis. [Table: see text] No significant financial relationships to disclose.
Phase I-II trial of daily thalidomide in combination with docetaxel in patients with relapsed non-small cell lung cancer: A final analysis
Authors: Seidler C. W. , Scepansky E. , Khanani S. , Rooney J. , Gordon J. , Walsh W. 
Published: March 2020

17060 Background: Recent studies have shown that inhibition of vascular endothelium growth factor (VEGF) in combination with chemotherapy can improve the antitumor efficacy of chemotherapy in NSCLC. This study tested the effectivness and toxicity of thalidomide (an inhibitor of VEGF) combined with docetaxel as second-line therapy for progressive NSCLC. Methods: Patients(pts) with recurrent/progressive NSCLC, prior chemotherapy, measurable/evaluable disease, ECOG performance status (PS) 0–2 and adequate hematologic, renal and hepatic function were enrolled. Pts with uncontrolled CNS disease or hypercoagulable state were excluded. Doxetaxel 75 mg/M2 was administered every 3 weeks (maximum of 8 cycles). Thalidomide was administered orally at a starting dose of 50 mg daily escalated by 50 mg every 3 weeks to a maximum dose of 200mg day and continued until disease progression, dose limiting toxicity, or completion of chemotherapy. Primary end-point was overall survival (OS), secondary end points were time to disease progression(TTP) by Kaplan Meyer method and response rate (RECIST criteria). Results: Of 28 enrolled patients, 26 were eligible for treatment and 25 were evaluable for disease progression and survival. For evaluable pts: mean PS = 1, median age 64.5 years, median number of prior chemotherapy regimens + 1.2. Response rate was 19.1% (1 complete response, 4 partial responses). Stable disease was observed in 9 patients (34.6%). TTP was 2.7 months (95% confidence interval [CI] 2.1–5.0+): median OS was 5.4 months (95% CI 3.1–9.3+). One episode each of febrile neutropenia requiring hospitalization and pulmonary embolism was observed. No grade 3–4 neuropathy was shown. Nonhematologic adverse events included constipation, alopecia, nausea and anorexia. Conclusions: These data suggest thalidomide in doses of 200mg/ day may be combined with docetaxel 75 mg/m2 every 3 weeks in the second line treatment of NSCLC. The response rate, TTP and OS compare favorably with previously reported studies with docetaxel in this population. No significant financial relationships to disclose.
Phase II trial of weekly docetaxel and gemcitabine as first line therapy for patients with advanced non-small cell lung cancer
Authors: McNeill G. , Kalmadi S. , Davis M. , Peereboom D. , Adelstein D. J. , Bukowski R. M. , Mekhail T. 
Published: March 2020

17076 Background: A platinum doublet has been the standard treatment for patients with advanced non-small cell lung cancer (NSCLC) and good performance status. This treatment results in almost a doubling of 1-year survival, along with an improvement in quality of life despite treatment related toxicities. However, platinum based treatment is associated with significant toxicity. Methods: In this trial, we prospectively evaluated a weekly regimen of docetaxel and gemcitabine for advanced NSCLC from December 2001 to January 2005. The endpoints of this study included objective response rate, survival and toxicity. Forty-two patients with previously untreated, advanced NSCLC with PS 0–1 were included. Patients received docetaxel (36 mg/m2) and gemcitabine (600 mg/m2) on days 1,8 and 15 of a 28-day cycle. Responses were assessed every two cycles. Results: The median age was 63 years; with 22 males and 20 females; 67% were >60 years old; and 38 patients had stage IV disease. In the intent-to-treat (ITT) analysis of response, 16 patients had a partial response (38%) and 15 patients had stable disease (36%). The 1-year survival was 48%; median survival for all patients was 11.3 months and the median progression-free survival was 5.1 months. Toxicities (> grade 3) included neutropenia (29%), asthenia (26%), thrombocytopenia (14%), diarrhea (14%), pneumonitis (7%), peripheral neuropathy (5%), peripheral edema (5%), nail changes (2%), and myositis (2%). Conclusions: This study demonstrated that this non-platinum doublet (docetaxel + gemcitabine) given on a weekly schedule for advanced NSCLC was well tolerated with efficacy comparable to platinum based chemotherapy regimens. [Table: see text]
Health-related quality of life measures in advanced non-small cell lung cancer patients receiving sorafenib
Authors: Gondek K. , Dhanda R. , Simantov R. , Gatzemeier U. , Blumenschein G. R. , Reck M. 
Published: March 2020

17085 Background: A multicenter, international, single-arm Phase II study evaluated the efficacy, safety, and tolerability of sorafenib in patients with advanced non-small-cell lung cancer (NSCLC). In addition, patients’ health-related quality of life (HRQL) and symptoms were assessed. Methods: HRQL was measured by the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire that was self-administered at baseline, at every other cycle during the study treatment period, and at the end-of-treatment (EOT) visit. Patients responded to each item on a five-point Likert-type scale ranging from 0 (not at all) to 4 (very much). Five subscale scores and an overall function score were calculated, with higher scores reflecting better function and symptom response. A change of two points, the minimum important difference (MID), in each of the five domains (physical well-being [PWB], emotional well-being [EWB], social well-being [SWB], lung cancer symptoms [LCS], and functional well-being [FWB]) was determined to be clinically meaningful. The total score of the treatment outcome index (TOI) was also assessed. Results: A total of 52 patients were evaluated. Data were collected at baseline, Cycle 2, Cycle 4, and EOT for 50/52 (96%), 42/52 (81%), 21/52 (40%), and 20/52 (38%) of patients, respectively. The mean total FACT-L scores were 99.3, 106.5, and 83.7 at Cycles 2, 4, and EOT, respectively. The mean changes from baseline in the total FACT-L score were -4.6, -0.2, and -14.6 at Cycles 2, 4, and EOT, respectively. The mean change from baseline in the each subscale scores were: -0.6, -1.0, -5.8 for PWB; -0.4, -0.8, -0.6 for SWB; -0.0, 2.1, -1.1 for EWB; -0.7, 0.9, -3.9 for FWB; -0.5, -1.0, -3.6 for LCS; and -2.6, -1.0, -13.2 for TOI, at Cycles 2, 4, and EOT, respectively. An improvement greater than the MID was observed in EWB at Cycle 4. Decreases below MID were observed for EWB at Cycle 2 and EOT, and all other subscales of the FACT-L at Cycles 2, 4, and EOT. Conclusions: These findings are encouraging and suggest that sorafenib did not adversely impact patient-reported outcomes in function and symptom response during the treatment period. As there is no comparator arm, interpretation of results is limited. [Table: see text]
Phase II trial of a 2-hour infusion of gemcitabine plus carboplatin as first-line chemotherapy for advanced non-small cell lung cancer
Authors: Xu N. , Shen P. , Zhang C. X. , Yu F. L. , Bao Y. H. , Shi M. G. , Huang S. , Chen J. , Fang J. W. 
Published: March 2020

17099 Background: Prolonged infusion of gemcitabine have shown increased levels of the active triphosphate metabolite that theorically could increase the response rate and toxicity. The objectives of this study were to evaluated the efficacy and safety of this combination of using gemcitabine as a rate infusion of 10 mg/m2 per min with carboplatin in front-line chemonaive patients with advanced NSCLC. Methods: Fifty-four chemonaive patients have been included. 44 were male and 10 female. Median age was 63 years (19–75). 13% had ECOG 0 and 53.7% ECOG 1 and 33.3% ECOG 2. 32 (59.2%) patients had adenocarcinoma, 13 (24.1%) squamous cell, 1 (1.9%) large cell carcinoma, and 8 (14.8%) others. Eight (14.8%) had stage IIIB and 46 (85.2%) stage IV. Treatment was consisted of 1200 mg/m2 gemcitabine given as a 2-hour continuous infusion (10 mg/m2 per min) on days 1 and 8 of each cycle an AUC 5 carboplatin as on day 1, repeating each cycle every 21 days. A total of 223 chemotherapy cycles were administered, with a median of 4 cycles per patient (range 1–6), and 15 (27.8%) patients received all six cycles. Results: Of the fifty-four patients enrolled, all were evaluated for toxicity (according to the WHO scale) and 51 assessed for response (according to the RECIST criteria), the overall response rate (ORR) was 41.2% (95% confidence interval, 28% to 57%), including two complete responses (CRs: 3.9%) and 19 partial responses (PRs: 37.3%). As per the intent-to-treat (ITT) analysis, the ORR was 38.9%. With a median follow-up time of 10.8 months, the median TTP was 5.0 months (range 3.7–6.3 months), median OS time was 11.5 months (range 9.9–13.1 months) and 1-year survival was 41.7% (95% CI 26% to 57%) and 2-year survival was 19.3% (4.4% to 34.2%).The main grade 3–4 toxicity consisted of neutropenia (55.6%) and thrombocytopenia (57.4%).Patients were required platelet transfusion in 27 cycles (12.1%) and haematopoietic growth factors support care in 56 (25.1%) cycles. No bleeding episodes were recorded. Grade 3 nausea/vomiting occurred in 5.6% and grade 1–2 skin rash occurred in 42.6%. Conclusions: Prolonged gemcitabine infusion combined with carboplatin is manageable tolerated and its efficacy is similar to that of other chemotherapeutic schemes used for NSCLC treatment. No significant financial relationships to disclose.