bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nadaplatin or cisplatin combined with paclitaxol in treating non-small cell lung cancer: A randomized controlled study
Authors: Chen L. , Xu G. , Guan Z. 
Published: March 2020

7689 Background: Nadaplatin is a 2nd generation platinum compound created in Japan. It also has been used in China for recent years and shown treatment effect in several kinds of cancer including lung cancer. However, no randomized clinical trial has been done compared with cisplatin when combined with paclitaxol in treating non-small cell lung cancer. This prospective clinical study is to investigate the treatment effect, long term survival, side effect and quality of life (QOL) of NSCLC patients treated with nadaplatin combined with paclitaxol controlled with cisplatin combined with paclitaxol. Methods: NSCLC patients with stage IIIB or IV were randomized into two groups: TN group- nadaplatin 30 mg/m2 d1–3, paclitaxol 175 mg/m2 d1, repeated every 4 weeks; TP group- DDP30 mg/m2 d1–3, paclitaxol 175 mg/m2 d1, repeated every 4 weeks. The treatment effect, 1 and 2 year survival and the side effect were observed. The functional assessment of cancer therapy-lung (FACT-L) was used to evaluate the quality of life (QOL). Results: Sixty patients were enrolled and 57 were assessable with 30 in TN group and 27 in TP group. The overall response rate were 43.3% vs 48.1% (P=0.716), and the disease control rate were 86.7% vs 88.8% in TN and TP group (P=0.799), respectively. The median survival time were 14.3 vs 13.0 months, and the 1 and 2 year survival were 62.5% vs 59.1%, 0% vs 5.8% in TN and TP group (P=0.839), respectively. Neutropenia and thrombocytopenia were similar in TN and TP group whereas more patients in TP group suffered from anemia (38.5% vs 17.5%, P=0.001), nausea and vomiting (68.0% vs 34.7% with grade 1 and 2, 14.6% vs 0.9% with grade 3 and 4, P=0.000), fatigue (35.9% vs 14.1% P=0.000) and peripheral neurotoxicity (50.0% vs 21.9%, calculated by case, p=0.023). In the FACT-L assessment, the relationship with doctor, the emotional well-being and the lung cancer related symptom were similarly improved in both TN and TP group whereas physical well-being was improved only in TN group. Conclusions: Nadaplatin combined with paclitaxol is an effective treatment regimen for NSCLC patients. When compared with similar regimen using cisplatin, the response rate and survival were similar; however, nadaplatin regimen shows superiority in some aspects of side effects and QOL. No significant financial relationships to disclose.
Genomic copy number alterations in non-small cell lung cancers identified using CBS and MSA
Authors: Park M. S. , Ma C. , Aziz M. U. , Rao S. , Gold K. , Samanta M. , Guttman M. , Grant G. R. , Vachani A. , Brose M. S. 
Published: March 2020

7695 Background: Lung cancer is the leading cause of cancer death in both men and women with a 5-yr survival rate of 15.5%. Previous studies have begun to characterized genomic copy number alterations of non-small-cell lung CA using array CGH and SNP arrays. We have used aCGH using our 1MB BAC arrays and two algorthims for making copy number alteration (CNA) determinations. We have also pursued the exact copy number gains and losses of several genes using Q-PCR. Methods: Genomic DNA from fresh frozen tumors of 27 patients with NSCLC. We performed aCGH using 1MB Arrays. We used CBS, and MSA to identify regions of CNA. We further pursued several genes of interest (including HRAS, CRK, and CDC42) identified using Q-PCR. Unsupervised hierarchical clustering was performed to look for distinct subgroups. Significant Analysis of Microarrays (SAM) was applied to identify the association between CNAs clinical parameters including tumor subtype, gender, lymph node involvement, tumor stage, and overall survival. Results: 240 regions of amplification and 181 regions of deletions were found, and included all previously published regions implicated in lung cancer. CNAs in > 70% of tumors included amplifications in 1q, 3q, 5p, 6p, 11p, 16q, 20q, and Xq, and deletions in 1p, 8p and 13q. We verified CNAs of HRAS, CRK and CDC42 using Q-PCR. Hierarchical clustering revealed 2 subgroups: one with amplifications in 2q, 4p, 4q, 8q, 21q, 15q, and 16p, and the other with amplifications in 3q, and 5q. These were confirmed by supervised SAM analysis. Using SAM we found that gain of 2q, 4p and 10q, and loss of 16p and 19q were significantly present in adenocarcinomas. (q = 0, FDR = 0%). Gain of 10q, and loss of 6p and 14q were associated with female gender. (q = 0, FDR = 0%). Conclusions: We used aCGH to identify CNAs that characterize non-small cell lung CA tumors with the aim of finding key regions which may harbor important oncogenes and tumor suppressors. Several regions of CNA have been identified, several of which have been associated with clinical parameters. Because much heterogeneity exists in non-small-cell lung tumors, we have demonstrated that clustering analysis is useful in identifying subtypes which may possess prognostic and therapeutic significance. No significant financial relationships to disclose.
Pemetrexed plus cetuximab in patients (pts) with recurrent non-small cell lung cancer (NSCLC): A phase I-IIa dose-ranging study from the Hoosier Oncology Group
Authors: Jalal S. I. , Waterhouse D. , Edelman M. , Nattam S. , Ansari R. , Koneru K. , Yu M. , Shen J. , Breen T. , Hanna N. 
Published: March 2020

7698 Background: Both pemetrexed (P) and cetuximab (C) have single agent activity in NSCLC, non-overlapping toxicities and different mechanisms of action, making the combination of P and C an attractive option to evaluate. This study evaluates the feasibility of combining these agents, and tests the activity and toxicity of this regimen in pts with recurrent NSCLC. Methods: Eligible pts had stage IIIB/IV NSCLC, previously treated ≥ 1 prior platinum containing regimen, PS 0–1. Prior use of EGFR tyrosine kinase inhibitors was permitted. The phase I portion determined the MTD (Bedano Proc ASCO et al., 2006). The primary endpoint of the phase II portion was to estimate TTP using Kaplan-Meier analysis (5% alpha, 80% beta), requiring 25 pts to demonstrate a TTP of ≥ 24 weeks vs. historical control of 12 weeks. Following a loading dose of C at 400 mg/m2 on week 1, pts received P at 750 mg/m2 iv q3wks and C at 250 mg/m2 iv weekly. Cycles were repeated every 21 days. After completing at least 4 cycles, pts with non-progressive disease (PD) were allowed to continue C alone until PD. Results: Eligible and treated phase II pts (n=23) received a median of 4 cycles (range 1–12). Pt characteristics: M:F 57%:43%; median age 64 (range 43–80), stage IIIB: IV 17%:83%; adeno:squamous cell 61%:30%; smoking status: current/former/never: 29%/62%/10%. Prior regimens, median 2 (range 1–6). G3/4/5 toxicities included: 4.3% neutropenia, 13% infection, 4.3% hemorrhage, 22% skin. There were no G3/4 episodes of anemia, TCP, febrile neutropenia, liver toxicity or diarrhea. Response data was available for 18 patients. Partial responses were seen in 2 pts (8.7 %), SD in 8 patients (34.8%). Median TTP was 25 weeks. Conclusion: It is feasible and safe to combine P at 750 mg/m2 every 21 days and C at 400 mg/m2 week 1 and 250 mg/m2 weekly thereafter. This combination resulted in longer TTP when compared with historical controls of P at 500 mg/m2 alone. No significant financial relationships to disclose.
Sorafenib in malignant mesothelioma (MM): A phase II trial of the Cancer and Leukemia Group B (CALGB 30307)
Authors: Janne P. A. , Wang X. F. , Krug L. M. , Hodgson L. , Vokes E. E. , Kindler H. L. 
Published: March 2020

7707 Background: Systemic chemotherapy with cisplatin/pemetrexed is the approved first line treatment regimen for patients with MM. There is no approved second line therapy. In addition, many patients, especially those >70, cannot tolerate combination chemotherapy. Angiogenesis inhibitors have emerged as attractive potential therapies for MM and SU5416 and PTK787 have previously demonstrated single agent activity. We examined the efficacy of sorafenib, an inhibitor of VEGFR2 and PDGFR-b, in chemotherapy naïve and previously treated patients with MM. Methods: This was an open label single arm phase II study of sorafenib in chemotherapy naïve and previously pemetrexed treated patients with MM. Primary end point was response rate (RR). Secondary objectives were 3-month failure free and overall survival (FFS and OS). Forty-four (44) eligible patients were expected to enroll to differentiate a RR of <5% versus >20%, with a Type I error of 0.0675 and a power of 0.955 Results: Between 10/04 and 8/05, 51 patients were enrolled and treated with sorafenib 400 mg bid. One cycle was defined as 28 days; restaging occurred every 2 cycles. Baseline demographics: M/F (36/15); Median age (69; range 36–88; 45% >70); Histology (epithelial/sarcomatoid/mixed/unknown: 37/4/8/2); pleural/peritoneal MM (46/5); ECOG PS 0/1 (11/40); chemo-naive/prior chemo (20/31). Grade 3/4 toxicities occurring in >10% of patients: Fatigue (12 (25%); 11/1) and hand-foot reaction (6 (13%); 6/0). No study related deaths occurred. Estimates of RR and FFS are based on 47 patients with available follow-up data. Response: CR: 0; PR 2: 4% (95% CI; 1- 14%); SD 28 (60%); PD 11 (23%); unevaluable 6 (14%). Three month FFS was 78%; median FFS was 3.7 months and median OS was 10.7 months. The median FFS were 3.6 and 3.6 months and the median OS were 4.9 and 14.6 months in chemo naïve and previously treated patients, respectively. Conclusions: Sorafenib demonstrated modest activity in this phase II trial but did not meet its primary endpoint. The improved outcome in previously treated patients likely reflects patient selection. Ongoing correlative science studies including expression of p-ERK 1/2, baseline VEGF and PDGF levels, are being performed to help identify patient subsets who may benefit (PR or SD) from sorafenib. No significant financial relationships to disclose.
DNA methylation profile predicts survival of patients with resected malignant pleural mesothelioma (MPM)
Authors: Ceresoli G. L. , Destro A. , Baryshnikova E. , Garassino I. , Zucali P. A. , Morenghi E. , Testori A. , Alloisio M. , Roncalli M. , Santoro A. 
Published: March 2020

7712 Background: Methylation in different tumor suppressor genes is among the most frequent alterations reported in MPM patients (pts). DNA methylation increases upon immortalization and transformation of human mesothelial cells, and demethylating agents were found to have some activity in MPM. In this study we analysed the methylation status of the promoter region of four candidate genes in MPM: p15INK4BINK4B, p16INK4AINK4A, RASSF1A and NORE1A. Methods: Samples of 79 consecutive MPM pts who underwent surgical procedures (41 extrapleural pneumonectomy (EPP), 32 partial pleurectomy, 6 diagnostic biopsy) at our Institution from 1997 to 2005 were analyzed. DNA was isolated from each paraffin-embedded MPM; the methylation status of the four genes was evaluated by a methylation-specific PCR method (MSP). Correlations between methylation status, clinico-pathological parameters (including proliferation index) and overall survival (OS) were examined in all pts and in the EPP subgroup. Proliferation index was evaluated as percentage of nuclear immunoreactivity/10 high-power field using a mouse monoclonal antibody anti-human Ki-67, clone MIB-1 (DAKO Corporation, Carpinteria, CA). Results: The MSP analysis documented gene promoter methylation in at least one gene in 30 cases (38%). The methylation frequency of each gene was: p15INK4B 15 cases (19%), p16INK4A 9 (11.4%), RASSF1A 16 (20.2%), Nore1A 4 (5.1%). Of the 30 methylated MPMs, 18 (60%) showed only one methylated gene, 10 (33.3%) were methylated in two genes and 2 (6.7%) in three. Methylation in at least one gene was associated to a higher proliferation index (P=0.058, ANOVA), but not to OS, in the whole study population. In pts treated with EPP, the 22 methylated cases showed a trend to a worst OS in comparison to 19 unmethylated cases (median OS 16 months vs 35 months, P=0.066, HR=2.01, 95% CI 0.94–4.30, Cox regression), independently by histology and nodal status. Conclusions: In pts treated with EPP, the methylation profile of p15INK4BINK4B, p16INK4AINK4A, RASSF1A and NORE1A appeared to be an independent prognostic factor for OS. The methylation status was correlated to proliferation rate, indicating a potential role of these oncosuppressor genes in the neoplastic progression of MPM. No significant financial relationships to disclose.
Surgery as primary treatment for limited disease small cell lung cancer: Time to re-evaluate
Authors: Lim E. , Goldstraw P. 
Published: March 2020

7719 Background: Chemoradiation is considered the gold standard for the management of limited disease (LD) small cell lung cancer (SCLC). Surgery has been abandoned due to poor overall survival, but many small series report good results with selected extremely limited disease (in one study without adjuvant treatment). Controversy remains if and when surgery should be considered as a primary modality. We sought to determine the survival and impact of pathologic staging in patients after complete resection of SCLC and the prognostic impact of pathologic stage. Methods: A retrospective review was undertaken of patients who underwent surgery between 1980 and 2003. Patients were staged according to the 6th UICC revision, actuarial survival estimated with Kaplan Meier methods and comparisons were undertaken using Cox regression. Results: We identified 51 patients who underwent complete resection with systematic nodal dissection for SCLC. The mean age (SD) was 61 (11) years and 37 (73%) were men. Complete staging information was available in 47, listed by stage with IA (n=6), IB (n=10), IIA (n=5), IIB (n=15), IIIA (n=10), IIIB (n=1). The median time to follow up (1st to 3rd quartile) was 4.5 (1.3 to 11.9) years with an overall survival (95% CI) at 1 and 5 years of 82% (72, 93) and 61% (48, 76). There were no clear differences in the outcome of patients in T categories 1 and 2 (P=0.411) with good overall results in patients across the spectrum of nodal disease from N0 to N2 (P=0.281). Conclusions: This study shows excellent survival for stage I to III patients who underwent lung resection with complete nodal resection for SCLC. These results, in an era of improved pre-operative and intra-operative staging, suggests that TNM staging is relevant in extremely limited disease SCLC and suggest that the role of surgery in such cases should be re- evaluated. No significant financial relationships to disclose.
A phase II study of picoplatin (pico) as second-line therapy for patients (pts) with small cell lung cancer (SCLC) who have resistant or refractory disease or have relapsed within 180 days of completing first-line, platinum (plat)-containing chemotherapy
Authors: Bentzion D. , Lipatov O. , Polyakov I. , MacKintosh R. , Eckardt J. , Breitz H. 
Published: March 2020

7722 Background: Pico is a sterically hindered plat analogue designed to overcome plat resistance with improved safety and efficacy. In >600 pts pico had single-agent activity in lung, prostate, ovarian and other malignancies with rare significant nephro-, oto-, or neurotoxicity (∼2% grade 3 and 0% grade 4). In a previous phase 2 study of single agent pico as 2nd line therapy in SCLC, 4 of 48 pts (8%) had a partial response and 21 (44%) stable disease. Median survival was 27.0 (95% CI = 16–35) wks. This multi-center phase 2 trial was designed to confirm the activity of pico as 2nd line monotherapy for plat-resistant SCLC. Methods: Pts with SCLC who either 1) failed or progressed through 1st line plat-containing chemo (refractory disease), or 2) initially responded to 1st line plat-containing chemo and then relapsed/ progressed within 3 months (resistant disease), or 3) initially responded and then relapsed/progressed between 90 to 180 days (sensitive, relapsed 90 to 180 days), had measurable disease and ECOG PS 0–2 were treated with pico, 150 mg/m2 iv over1–2 hrs, q 21 days. Tumor response was assessed q 6 wks. Adverse events (AEs) were graded using the NCI CTCAE. Results: 77 pts received pico (45 refractory, 27 resistant, 5 sensitive). The median number of cycles received was 2 (mean = 2.9). The most frequently reported AEs of any severity were thrombocytopenia (39% of pts), anemia (35%), neutropenia (22%), nausea (20%), emesis (14%) and dyspnea (25%). Neutropenic fever occurred in 1 pt; there were no treatment related deaths. One pt had grade 3 neuropathy; there was no grade 3 or 4 ototoxicity or nephrotoxicity. Median overall survival is 28.1 (95% CI = 26–37) wks. Median progression free survival is 9.3 (95% CI = 7–12) wks. Of 63 pts with at least 1 post-treatment assessment of disease status, 33 (52%) had stable disease. Conclusion: Median survival compares favorably with other therapeutic options and toxicity is reduced in pico treated SCLC pts who have failed prior plat-containing first-line chemo or who have progressed within 180 days of first-line chemo. A phase III trial to confirm these results has been initiated. No significant financial relationships to disclose.
Age, gender, performance status and stage outperformed stage alone in predicting overall survival (OS) in patients with small cell lung cancer: A pooled analysis of 1,623 patients from the North Central Cancer Treatment Group
Authors: Foster N. R. , Mandrekar S. J. , Schild S. E. , Nelson G. D. , Jett J. R. , Adjei A. A. 
Published: March 2020

7723 Background: It is critical that we understand the impact of patient, tumor, and treatment-related factors on patient prognosis for the proper design and analysis of Small Cell Lung Cancer (SCLC) trials. An analysis of 15 SCLC trials was performed to investigate and improve our understanding of several factors on OS. Methods: Data from 1623 patients (pts) were used. Age, gender, performance status (PS), tumor stage, body mass index (BMI), creatinine levels, hemoglobin levels, white blood cell counts (WBC), platelet counts, and bilirubin levels were tested for prognostic significance for OS both univariately and multivariately using a Cox Proportional Hazards Model. Models were stratified by protocol, and analyses carried out on the complete data available based on the selected covariates. Model discrimination (i.e., ability to discriminate patients with different survival times) was evaluated using the concordance index (COI). Results: Median follow-up was 63.1 months (range: 1.9 to 155.7). 58% and 42% of pts had extensive-stage or limited-stage SCLC, respectively. Patients with extensive-stage disease, PS>0, increased age, and male gender had significantly worse OS both univariately and multivariately. Patients with increased WBC had significantly worse OS univariately, however, WBC was not a significant predictor when adjusted for other factors. None of the other factors were prognostic for OS. Model discrimination improved by 6.3% when age, gender, PS, and stage were included in a model compared to a model with stage alone (COI improved from 0.63 to 0.67). Conclusions: Age, gender, PS and stage did better at predicting OS than stage alone. Further refinement of this model, including the addition of number of metastatic sites at baseline and treatment related factors, is currently underway. No significant financial relationships to disclose. [Table: see text]
A phase II trial of VNP40101M in patients with relapsed or refractory small cell lung cancer (SCLC) with or without brain metastases
Authors: Mekhail T. , Gettinger S. , Blumenschein G. , Axelrod R. , Haigentz M. , Guarino M. J. , Cahill A. L. , Spigel D. , Greco F. A. 
Published: March 2020

7724 Background: Relapsed or refractory SCLC patients (pts) have a poor prognosis. Median survival at relapse is 2–3 months; brain metastases (mets) are common. Alkylating agents have demonstrated activity in SCLC. Cloretazine is a new alkylator that is active against selected alkylating agent resistant tumor cell lines. Xenograft models show distribution across the blood-brain barrier. This study investigates VNP40101M safety and activity in SCLC patients who have relapsed or are refractory to standard 1st line chemotherapy. Methods: Pts are entered in 2 groups based on response to prior chemotherapy: sensitive relapse (chemotherapy-free interval >3 months); or resistant/refractory (chemotherapy-free interval ≤3 months). Eligibility criteria include: measurable or evaluable disease; life expectancy of ≥2 months; and ECOG PS of 0–2. Pts with brain mets are eligible. 31 pts received VNP40101M IV at a starting dose of 125 mg/m2/wk × 3, every 6 weeks. Due to a high incidence of grade 3–4 thrombocytopenia (34%), an amended protocol reduced the dose of VNP40101M to 100 mg/m2 at the same schedule. 13 pts received the reduced dose. Pts are evaluated by RECIST criteria after each 6-week cycle. Results: 44 of 87 planned pts have been treated at 7 sites. Of 41 evaluable pts, 21 patients have sensitive relapse disease, and 20 have resistant/refractory disease. Median age is 64 years (44–86). Median number of cycles received is 1 (1–3). Grade 3–4 thrombocytopenia was seen in 11/31 pts at the 125 mg/m2 dose and 3/13 pts at the 100 mg/m2 dose. Gr 3–4 non-hematologic toxicity is rare, except for fatigue (10%) and GI effects (10%). The response rate (PR) is 6/21 (29%) in the sensitive relapse group, and 1/20 (5%) in the resistant/refractory group. 2/6 PRs, in the sensitive relapse group, occurred at the reduced dose level. 16 pts had brain mets at study entry. Of these, there were 3 PRs (2 with measurable regression of brain mets) and 3 stable diseases. Conclusions: The study is ongoing to confirm efficacy and safety. VNP40101M has activity against SCLC in the 2nd line setting including pts with brain metastases; further study is warranted. No significant financial relationships to disclose.
The impact of shortened vitamin supplementation lead-in time before pemetrexed (P) in patients with relapsed small cell lung cancer (SCLC)
Authors: Richards D. A. , Socinski M. , Raju R. N. , Coke K. , Reynolds C. , Chen R. , Cunneen J. L. , Tai D. F. , Treat J. A. , Obasaju C. K. 
Published: March 2020

7726 Background: Clinical studies of P have shown less overall toxicity and reductions in Grades 3–4 hematologic and nonhematologic toxicities when pts are pretreated with folic acid and vitamin B12. Current recommendations are to give folic acid 350 μg - 1,000 μg by mouth for at least 5 of 7 days prior to the 1st dose of P, and 1 injection of vitamin B12 1000 μg during the week preceding the 1st P dose. Treatment delay to allow this supplementation may be clinically undesirable, particularly in pts with aggressive malignancies. A trial evaluating single-agent P for the treatment of relapsed SCLC gave us opportunity to observe the effects of a shortened lead-in time for vitamin supplementation. Methods: We reviewed data from a U.S. trial designed to assess the safety and efficacy of single-agent P in chemosensitive and chemorefractory relapsed SCLC pts. Eligible pts had limited or extensive-stage SCLC, PS 0 to 2, and 1 prior chemo regimen. Pts received P doses of 500 mg/m2 or 900 mg/m2 q 21 d. The protocol required the administration of folic acid for at least 5 of 7 days prior to the 1st P dose, and vitamin B12 administration on Day 1, Cycle 1, or up to 14 days prior to the 1st P dose. Included in the analysis were pts who received at least 1 dose of folic acid prior to 1st P dose. We then analyzed preliminary toxicity results for pts receiving vitamin B12 for 0–3, 4–6 and =7 days prior to 1st P dose. Results: From 7/2004 to 3/2006, 116 pts were treated with P. At baseline M/F 57%/59%; median age 64.5 years (range 35–85); PS 0/1/2 was 39%/57%/20%. Cycle 1 vitamin administration timing data is available for 109 pts. Data for all 116 pts will be reported at time of meeting. Because toxicities observed between the 2 P doses were not significantly different, the combined toxicities for both dosing groups are reported here. Conclusions: Based on this data, Vitamin B12 given less than 7 days prior to P does not appear to be associated with increased serious toxicities. No significant financial relationships to disclose. [Table: see text]