bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival in previously treated advanced NSCLC: Pemetrexed versus best supportive care (BSC)
Authors: Fossella F. V. , Berry D. A. , Adachi S. , McAndrews P. , Peterson P. 
Published: March 2020

17015 Background: Patients with advanced NSCLC who progress following initial treatment have several approved secondary treatment options including single agent intravenous chemotherapy (docetaxel or pemetrexed) and an oral EGFR tyrosine kinase inhibitor (erlotinib). Docetaxel and erlotinib were shown in randomized trials to have an overall survival (OS) advantage over BSC. On the other hand, pemetrexed was approved based on a randomized trial (JMEI) in which it showed clinically equivalent survival to docetaxel. Investigators felt that it was not ethical to compare pemetrexed to BSC because docetaxel was approved in that setting. However, indirect comparisons of pemetrexed with BSC are possible and are legitimate statistically. Methods: We used summary data from JMEI and TAX317(b) in the analysis. Studies BR21 and ISEL provide relevant data from recent trials with a BSC arm. We based comparisons on the logarithms of these HRs and their variances in proportional hazards models, accounting for interstudy variability. Results: Patients in these studies had similar prognostic characteristics. Docetaxel in TAX317(b) showed a significant survival benefit over BSC (HR = 0.56, 95% CI 0.35–0.88). In JMEI, the pemetrexed over docetaxel HR was 0.99 (95% CI 0.82–1.20). The HR of pemetrexed over BSC for survival was 0.55 (95% CI 0.33–0.90). The similarity of median OS for the placebo (or BSC) arms of studies TAX317(b), BR21 and ISEL supports the above analysis. Conclusions: In comparison with BSC pemetrexed lowers the hazard of mortality in previously treated advanced NSCLC by an estimated 45% (95% CI 10%-67%). [Table: see text] [Table: see text]
Neoadjuvant chemotherapy followed by extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM): An Italian experience with cisplatin-based regimens
Authors: Marino A. , Pinto C. , Mutri V. , Galetta D. , Di Bisceglie M. , Bini A. , Dell’amore D. , Sacco R. , Gentile A. L. , Martoni A. A. 
Published: March 2020

17022 Background: We have evaluated the feasibility and the impact on survival of two different preoperative chemotherapy regimens in potentially resectable MPM. Methods: Eligibility criteria were: histologically confirmed MPM, stage T1–3 N0–2 M0, adequate organ function, KPS ≥80. A first group of pts (group A) received cisplatin 75 mg/m2 d1 and gemcitabine 1200 mg/m2 d1,8, every 3 weeks for 4 courses, followed by EPP and by 6 courses of adjuvant chemotherapy with mitoxantrone 10 mg/m2 d1, methotrexate 35 mg/m2 d1 and mitomycin 7 mg/m2 d1, every 3 weeks with mitomycin in alternate cycles. A second group of pts (group B) received cisplatin 75 mg/m2 d1 plus pemetrexed 500 mg/m2 d1 with full vitamin supplementation for 4 cycles. In each group, only pts with metastatic lymph nodes and/or positive resection margins underwent radiotherapy after EPP. Results: Twenty-five pts were enrolled from February 2000 to August 2005 (8 in group A and 17 in group B). Pt characteristics were: 21 (84%) males and 4 (16%) females, asbestos exposure in 16 (64%) pts, median age 64 years (range, 51–72), median KPS 100 (80–100), histological subtype: 19 (76%) epithelial, 2 (8%) sarcomatous, 3 (12%) mixed, 1 (4%) unknown; IMIG stage: 6 (24%) I, 14 (56%) II, 5 (20%) III. Clinical response to neoadjuvant chemotherapy consisted of 4 (16%) CR, 2 (8%) PR, 11 (44%) SD, 5 (20%) PD; 3 (12%) pts were not evaluable. The overall response rate (CR + PR) was 24% (95% CI: 9.4 - 45.1). Toxicity was mild in each group. Fourteen (56%) pts have undergone EPP, 5 (20%) pleurectomy and 6 (24%) pts were inoperable. Three postoperative complications and two postoperative deaths (one for controlateral pneumonia and one for ARDS) occurred after EPP. The 1-year survival rate was 60%. Long-term survivors (≥18 months) included 5 pts who had undergone EPP (18, 26, 54, 57 and 63 months) and 2 pts who had undergone pleurectomy (22 and 32 months). Conclusions: These preliminary data, albeit in a small series, suggest that preoperative chemotherapy followed by EPP is a feasible approach to be investigated in larger trials in pts with MPM. No significant financial relationships to disclose.
Role of early serial change in serum carcinoembryonic antigen levels as a predictive marker for gefitinib sensitivity in Japanese patients with non-small cell lung cancer
Authors: Hotta K. , Kiura K. , Tabata M. , Takigawa N. , Fujiwara Y. , Umemura S. , Hosokawa S. , Hisamoto A. , Ueoka H. , Tanimoto M. 
Published: March 2020

17029 Background: The aim was to evaluate the utility of an early change in CEA levels for predicting subsequent gefitinib sensitivity in NSCLC patients. Methods: CEA level was measured before and after the beginning of gefitinib treatment (day1) in 110 (91%) of consecutive 121 patients. Daily decline rate of CEA was simply defined for each patient as follows: (M0−Mx)/Dx/M0*100(%), with the baseline level (M0), the level on days × (Mx), and days from day 1 to day X (Dx). Results: Patient characteristics were as follows; median age: 62, M/F: 61/39%, Ad/others: 84/16% and smoker: 66%. Objective response rate and disease control rate were 28.2% and 74.5%, respectively. Median baseline CEA level was 12.6 ng/mL. Daily decline rate of CEA level from day 1 to the date on which confirmation of objective response was performed significantly differed among the response categories; median decreases in percentages were 0.86, 0.06, and −1.52%/day in CR/PR, SD, and PD patients, respectively (p < 0.0001). This association was more evident in the 70 patients with abnormal baseline CEA level (≥5.0 ng/mL). A cutoff level of −0.58% decrease per day most accurately reflected tumor shrinkage in the 70 patients, with sensitivity, specificity, and positive and negative predictive values for disease control (CR/PR/SD) of 89.1, 73.3, 92.5 and 64.7%, respectively. Among 49 (41%) patients reassessed CEA levels within the first 2 weeks since day 1, 41 could continue the treatment without any disease progression during this period. The daily decline rate in this early phase tended to differ between the responses (median; 1.57 and −0.50% in CR/PR/SD and PD, respectively; p = 0.0975), and less exactly reflected disease control with sensitivity, specificity, and positive and negative predictive values of 82.1, 40.0, 88.5, and 28.6%, respectively when a cutoff of −0.58% was applied. Conclusion: Degree of change in CEA level from the start of gefitinib treatment to confirmation of objective response significantly correlated with tumor shrinkage. As a predictor for obtaining disease control, monitoring early change in CEA level might be useful due to high sensitivity and positive predictive value, in spite of low specificity for detection of PD patients. No significant financial relationships to disclose.
Randomized phase II study of cisplatin plus gemcitabine administered either as short infusion or at a fixed dose rate in non-small cell lung cancer (NSCLC)
Authors: Pereira J. R. , Fein L. , Carvajal P. , Giglio A. , Blajman C. , Richardet E. , Schwartsmann G. , Orlando M. , Hall B. J. , Van Kooten M. 
Published: March 2020

17037 Background: Previous studies have indicated that, in combination with cisplatin (cis), fixed dose rate gemcitabine (gem) may be more efficacious than standard infusion gem. This open-label, randomized, multicenter Phase II study (B9E-LA-S350) was aimed to compare the efficacy and safety of these regimens as treatment for advanced NSCLC in Latin American patients (pts). Methods: Major eligibility criteria included histologic/cytologic diagnosis of stage IIIB/IV NSCLC not amenable to curative surgery; and at least one measurable lesion. Pts were randomized to receive up to 6 cycles of treatment with cis 75 mg/m2 on Day 1 plus either gem 1000 mg/m2 over 30 min on Days 1 and 8 of a 21-day cycle (standard arm) or gem 1000 mg/m2 at a fixed dose rate of 10 mg/ m2/min on Days 1 and 8 of a 21-day cycle (FDR arm). The primary endpoint was the objective response rate (ORR; assessed by RECIST criteria) and secondary endpoints included overall survival (OS), progression-free survival (PFS), duration of tumor response (TR), and toxicity. Results: The results from this interim analysis assessed all objectives. Sixty-four pts were randomized to treatment (N = 33 standard arm; N = 31 FDR arm): 22 females; mean age 60 ± 9 yrs; 20% stage IIIB, 80% stage IV. In the standard arm, 9 (27%) pts responded (CR or PR) compared to 6 (20%) pts in the FDR arm (Odds ratio: 0.67, 95% CI 0.21–2.2, p = .56). As shown in the table below, there were no statistically significant differences in median ORR, OS, PFS, TR times, and Grade (G) 3/4 toxicities. Conclusions: The standard and FDR gem and cis treatment regimens produced similar results for both efficacy and toxicity in this patient population. This trial does not support the use of a FDR administration of gem in Latin American pts with NSCLC. [Table: see text] [Table: see text]
Phase II study of genexol (paclitaxel) and carboplatin as first-line treatment of advanced or metastatic non-small-cell lung cancer (NSCLC)
Authors: Kim C. , Bae S. , Lee N. , Lee K. , Park S. , Kim D. , Won J. , Hong D. , Park H. 
Published: March 2020

17049 Background: Genexol is a polymeric micelle loaded paclitaxel without Cremophor EL (CrEL). CrEL has been shown to cause hypersentivity reaction and neuropathy. To evaluate and efficacy, we conducted a phase II study of CrEL-free paclitaxel (genexol) and carboplatin in patients (pts) of advanced or metastatic NSCLC. Methods: Eligibility criteria included: stage IIIB or IV NSCLC without previous chemotherapy and radiotherapy; written informed consent; measurable lesion; age 18–75; ECOG PS 0–3; adequate bone marrow, liver, and renal function; and no CNS disease. The patients received genexol 225 mg/m2 IV on day 1, followed by carboplatin AUC = 6 IV on day 1 every 3 weeks. Primary end points are response and toxicity. Response evaluations were performed after cycles 2, 4, and 6 of chemotherapy according to the RECIST criteria. Results: 36 pts were enrolled between November 2002 and November 2005. Pts characteristics: median age 63 years (range 45–73), median ECOG PS 1 (range 0–3), 13 stage IIIB and 23 IV, 21 adenocarcinoma and 14 squamous cell carcinoma, and 1 large cell carcinoma. At present, 30 pts were evaluable for response and toxicity. Meidan number of treatment cycles was 4 (range 1–6). Seven pts needed dose reduction. Thirteen pts achieved partial response and 13 pts had stable disease. The response rate 43.3%. Grade (gr) 4 neutropenia occurred in 11 pts (36.7%). Gr 1/2 sensory neuropathy occurred in 13 pts (43.3%) and gr 3/4 sensory neuropathy occurred in 5 pts (50%) among 10 pts over 65 year old. Other toxicities included neutropenic fever in 9 pts (30%), gr 4 thrombocytopenia 3 patients (10%), gr 2 hepatic dysfunction 3%, and gr 3 fatigue 10%. Treatment related mortality was not occurred. Complete analysis will be presented. Conclusions: In this trial, the combination of genexol and carboplatin showed a significant activity with acceptable and manageable toxicities as first line treatment for patients with advanced or metastatic NSCLC and dose reduction needed in older patients. No significant financial relationships to disclose.
A phase II trial of biweekly pemetrexed (P) and gemcitabine (G) in the first-line treatment (tx) of patients (pts) with advanced non-small cell lung cancer (NSCLC)
Authors: Peacock N. W. , Spigel D. R. , Hainsworth J. D. , Yardley D. A. , Burris H. A. , Barton J. H. , Patton J. F. , Shipley D. L. , Simons L. , Greco F. A. 
Published: March 2020

17054 Background: P and G are active and well-tolerated non-platinum agents used in the tx of NSCLC. Previous trials have combined P and G in the first-line NSCLC setting using a 21D schedule. This trial examined the safety and activity of biweekly P/G. Methods: Theprimary endpoints of this single center community-based phase II study were toassess the safety and response rate (RR) of P/G in pts with previously untreated stage III (unresectable) or IV NSCLC. Tx included: P 500mg/m2 IV D1 and G 1500mg/m2 IV D1 Q 14D for 8–12 cycles. Pts also received folate and B12 prophylaxis. Pts were restagedafter 4 cycles. Eligibility included:measurable disease, ECOG PS 0–2, adequate organ function, informed consent, and no active brain metastases. Analysis was by intent to treat. Results: Thirty-five pts were enrolled between 5/05 and 8/05. The median follow-upis 6 months (3.5–7.5 months). Baseline characteristics include: medianage 65 years (41–85); male/female, 71%/29%; ECOG PS 0,1,2:17%/71%/12%; and histology, adenocarcinoma (34%), large cell (29%), squamous (11%), mixed or not specified (26%). The median number of cycles delivered was 8 (1–12). Grade (G)3/4 non-hematologic toxicity included:chest pain (6%), constipation (6%), fatigue (17%), hypercalcemia (6%), dyspnea (9%), and tachyarrhythmia (9%). G3/4 hematologic toxicity included: neutropenia(51%), anemia (8%), and thrombocytopenia (3%). G3/4 febrile neutropenia occurred in 14%. There were notx-related deaths. Response data are availablefor 35 pts. Complete/partial responses for all pts were observed in 0 pts/7pts, respectively, for an overall RR of 20% (95% CI 10%-36%, 1 pt unconfirmed by RECIST criteria). Fifty-four percentof pts had stable disease, and 14% had disease progression(4 pts were unevaluable.) Six-month progression-free survival (PFS) andoverall survival (OS) were 51% and 67%, respectively. Median PFS and OS have not been reached. Conclusions: Biweekly P/G is a safe and well-tolerated regimen with RRsimilar to other standard first-line regimens for the tx of pts with advanced NSCLC, and further study is warranted. Median and 1-year PFSand OS endpoints have not been reached in this trial. [Table: see text]
A phase I dose-escalating study of combination S-1 and carboplatin (CBDCA) in patients with chemo-naïve advanced non-small cell lung cancer (NSCLC)
Authors: Tamura K. , Okamoto I. , Ozaki T. , Shimizu T. , Kashii T. , Takeda K. , Matsui K. , Kudoh S. , Kurata T. , Fukuoka M. 
Published: March 2020

17055 Background: S1, a novel oral fluoropyrimidine derivative, has promising results in the treatment of advanced gastric or colorectal carcinoma. Response rate/median survival time of single S1 and the combination S1 plus cisplatin for advanced NSCLC were 22.0%/309 days and 47.3%/335 days, respectively in the previous phase II. Platinum doublets including a novel active drug is a potent standard for advanced NSCLC as 1st line chemotherapy. Carboplatin has advantage of low gastrointestinal or renal dysfunction in comparison with cisplatin. The primary objective of this study was to determine the maximum tolerated dose (MTD) of combination S-1 and carboplatin, the toxicity profile and the recommend dose (RD) for a multi-center randomized trial of platinum doublets including S1. Methods: Eligibility criteria includes histologically diagnosed NSCLC stage IIIB/IV, no prior chemotherapy, ECOG PS 0–1, 75 > age >20, adequate organ function, and written informed consent. Pts receive carboplatin intravenously over 30 minutes on day 1, and S1 daily for 2 weeks, every 3 weeks. Results: Total 10 patients were registered (M/F: 6/4; median age:67 (37–73); Ad/Sq:7/3; IIIB/IV: 0/10 PS 0/1:3/7) Three patients were enrolled at the dose level 1 (CBDCA AUC = 5 and S1 65 mg/m2), 3 patients at level 2 (CBDCA AUC=5 and S1 80 mg/m2) and 4 patients at level 3 (CBDCA AUC=6 and S1 80 mg/m2), respectively. No DLTs (dose-limiting toxicities) occurred at both level 1 and 2. DLTs were observed in 2 out of 4 patients at level 3. One is significant delay starting of 2nd cycle caused by thrombocytopenia. One is G3 anorexia and vomiting at 1st cycle and results in stop the treatment. A total 27 courses were assessable for safety. Two pts with G3 neutropenia, 2 pts with G3 anorexia, 1 pts with G3 liver dysfunction and 1 pts with G3 infection were observed during total courses. Five out of 6 patients at Level 1 or 2 have completion of 4 cycle’s treatment. Objective response was obtained in three patients out of 10. Conclusions: MTD was level 3. RD for the future trial was Level 2 (CBDCA AUC = 5 and S1 80 mg/m2). This combination was well tolerated and produced an antitumor effect for advanced NSCLC. No significant financial relationships to disclose.
Gefitinib-induced platelet-derived microparticle and ICAM-1 in Japanese patients with non-small cell lung cancer
Authors: Kanazawa S. , Kinoshita Y. , Yamaguchi K. , Nomura S. 
Published: March 2020

17056 Background: We recently discovered that platelet activation is observed in patients receiving gefitinib. Nomura et al. reported that activated platelets generated platelet-derived microparticle (PDMP) and this PDMP could induce adhesion molecules and an interaction between white blood cells and endothelial cells. Theaim of the present study was to identify the clinical significance between PDMP and intercellular adhesion molecule-1 (ICAM-1) in lung cancer patients receiving gefitinib. Methods: Patients with a diagnosis of non-small cell lung cancer were entered into this study. Blood samples were withdrawn before and one week and two weeks after the administration of gefitinib. PDMP and ICAM-1 were measured using an enzyme-linked immunosorbent assay kit. A total of 25 patients was recruited in the study. The characteristics of the study subjects were: age: 42–78 years (median: 68 years); gender: male vs. female = 14 vs. 11; tumor histology: adenocarcinoma vs. squamous cell carcinoma = 17 vs. 8. Nine patients were responders and the other 16 patients were non-responders. Results: The plasma concentration of PDMP significantly increased after receiving gefitinib (before vs. one week vs. two weeks = 14.1±12.0 U vs. 17.9±16.9 U (p<0.05) vs. 14.6±12.0 U n = 25). The plasma concentration of ICAM-1 significantly increased after receiving gefitinib (before vs. one week vs. two weeks = 296.2±85.1 ng/ml vs. 319.4±78.9 ng/ml vs. 344.8±74.0 ng/ml (p<0.05) n = 16). Conclusions: Platelets were activated by gefitinib therapy, and the effect of gefitinib is related to a reaction of not only blocked EGFR but also platelet activation and in part endothelial cells and leukocytes through activated platelets. The mechanisms underlying some adverse events in gefitinib-treated patients are poorly understood. Our results suggest that one of the mechanisms causing gefitinib-related adverse effects depends on platelet activation. No significant financial relationships to disclose.
The inter-relationship of hypoxia and phospho-Akt in the pathobiology of malignant pleural mesothelioma
Authors: Stewart D. , Edwards J. , Richardson D. , Jones L. , Burke B. , Waller D. , Zeigler-Heitbrock L. , Wardlaw A. , O’Byrne K. 
Published: March 2020

17057 Background: Poor outcomes with conventional oncological treatments for malignant pleural mesothelioma (MPM) have driven the imperative to advance understanding of the disease pathobiology. Carbonic Anhydrase (CA)-IX is a surrogate marker of hypoxia over-expressed in solid tumours. Protein Kinase B, or Akt, known to have important intracellular roles including resistance to apoptosis, is activated in human malignancies and upregulated in hypoxic conditions. This study examined the expression of CA-IX and phosphorylated Akt (pAkt) in tumour samples from patients with MPM, correlating expression with established prognostic factors. The role of pAkt in the survival of an MPM cell line exposed to hypoxic conditions was also examined. Methods: Full local regional ethics committee approval was obtained for this work. Tumour samples from 200 patients with MPM were stained using pAkt and CA-IX specific antibodies. The effect of hypoxia on Akt and pAkt was evaluated in the JU77 mesothelioma cell line in the presence or absence of the phosphatidylinositol-3-kinase inhibitor, LY294002. Results: There was a positive association between the level of CA-IX and pAkt staining, implying that intra-tumoural hypoxia may be a stimulus for Akt phosphorylation. On multivariate analysis increased expression of nuclear pAkt was found to be associated with a poor survival. In-vitro cell culture work showed that, although pAkt is expressed in normoxic conditions in the JU77 cell line, the rates of apoptosis were significantly increased in hypoxic conditions when the phosphorylation of Akt was blocked by LY294002. Conclusions: This work provides evidence for the anti-apoptotic role of pAkt in hypoxic conditions in solid human malignancies. Phospho-Akt may represent a novel therapeutic target in MPM. No significant financial relationships to disclose.
Stereotactic body radiotherapy (SBRT) and medical inoperability of early stage non-small cell lung cancer
Authors: Franks K. N. , Bezjak A. , Pearson S. , Cho B. C. , Payne D. , Sun A. , Waddell T. K. , Shepherd F. A. , Keshavjee S. 
Published: March 2020

17074 Background: Early stage NSCLC is commonly diagnosed in elderly patients who often have significant medical co-morbidity. SBRT is emerging as a treatment alternative that can provide 80–97% local control for peripheral tumors. We performed a literature review and a retrospective review of 24 patients referred to Princess Margaret Hospital for consideration of SBRT to assess what criteria were used to determine patient selection for this new treatment. Methods: Published papers reporting treating stage I NSCLC with SBRT were reviewed. Clinical and demographic characteristics of patients referred for consideration of SBRT over the last 15 months were analyzed. All patients were assessed by experienced thoracic surgeons to determine their operability status. Patients were retrospectively scored as average or high risk for surgery on the basis of accepted PFT guidelines (FEV1 and DLCO <40% predicted); Charlson Index of Comorbidity (CCI) was calculated (score >2 associated with impaired survival). Results: Of 13 papers reporting Stage 1 SBRT results, 8 included details of medical inoperability. 2 papers had strict guidelines for PFTs, in addition to other criteria. In 6 studies reporting 276 pts, the most common reason for inoperability was non-specific medical comorbidity (60%). Our cohort (24 patients) referred for SBRT (median age 75, range 57–89) had a mean tumour size of 2.32cm (S.D. 1.11); 50% of patients had a good (0–1) Zubrod Performance status. Based upon PFT tests alone 10 patients (42%) were high risk and 5 (21%) average risk for surgery. The CCI score was ≥3 in 10 patients (42%). 3 patients who scored average risk and CCI ≤2 were deemed medically inoperable due a single severe medical comorbity. In 23/24 pts the surgeon recommended against surgery; one patient refused surgery. Conclusions: With an aging population and increased detection due to incidental finding or screening, it is important to know that there is effective alternative therapy for patients deemed too high risk for surgical resection. Comorbidity is an important factor influencing surgical mortality; defining explicit criteria for inoperability remains a clinical challenge. No significant financial relationships to disclose.