tbuckley/cabot-search huggingface dataset:
Dose-escalation and pharmacodynamic study of topotecan in combination with cyclophosphamide in patients with refractory cancer.
Authors: J R Murren, S Anderson, J Fedele, G Pizzorno, D Belliveau, D Zelterman, B A Burtness, I Tocino, S D Flynn, D Beidler, Y C Cheng
Journal: Journal of Clinical Oncology (1997)

PURPOSE Based on preclinical data that demonstrated synergy between alkylating agents and topoisomerase (topo) I poisons, we determined the maximum-tolerated dose (MTD) of topotecan, using a 5 day bolus schedule, that could be given in combination with a single, fixed dose of cyclophosphamide. Pharmacodynamics of this combination were explored by analyzing biochemical effects of treatment in peripheral-blood mononuclear cells (PBMCs). PATIENTS AND METHODS Patients with refractory cancer were treated with cyclophosphamide 600 mg/m2 on day 1, followed by topotecan given as a 30-minute infusion for 5 consecutive days. Cycles were repeated every 3 weeks. Once the MTD was defined, granulocyte colony-stimulating factor (G-CSF) was added to the regimen in an attempt to escalate further the dose of topotecan. Plasma concentrations of topotecan were determined during the first treatment cycle by high-performance liquid chromatography. PBMCs were sampled at baseline and throughout the 5-day treatment period for analysis of topo I protein concentrations and to determine drug-induced DNA fragmentation. RESULTS Twenty-six patients were treated with topotecan at doses that ranged from 0.5 mg/m2/d to 1.2 mg/ m2/d for a total of 74 cycles. Reversible neutropenia was dose-limiting, with mild to moderate suppression of the other blood-cell elements commonly occurring. Transfusions of RBCs and platelets were required in 24% and 7% of treatment cycles, respectively. The most prominent nonhematologic toxicities were fatigue and weight loss. Compared with previously published data in which topotecan was administered alone, cyclophosphamide did not appear to alter the pharmacokinetics of topotecan. Significant increases in topo I concentration were identified in PBMCs following the administration of cyclophosphamide on day 1 and there was a significant decrease in topo 1 during the 5-day course of treatment (P &lt; .01, sign test). DNA fragmentation as a result of drug treatment was identified in 11 of 15 (73%) cycles analyzed. CONCLUSION For previously treated patients, the recommended dose of topotecan in this schedule is 0.75 mg/m2/d without growth factor support and 1.0 mg/ m2/d if it is administered with G-CSF. Biochemical changes in cells induced by exposure to camptothecins can be measured in vivo and these effects may have important implication in the design of combination therapies and the optimal scheduling of this class of agents.
Initial cohort toxicity evaluation for chemoradiotherapy (CRT) and ZD1839 in stage III non-small cell lung cancer (NSCLC): A CALGB stratified phase II trial
Authors: N. Ready, J. Herndon, E. Vokes, J. Bogart, J. Crawford, T. Dipetrillo, M. Green
Journal: Journal of Clinical Oncology (2004)

7078 Background: ZD1839 (Iressa) is a small molecule inhibitor of the EGFR that has single agent activity in advanced NSCLC and preclinical evidence of being a radiosenitizer. Methods: Patients with stage III NSCLC were assigned to stratum 1 (PS 0–1>5% weight loss or PS 2) or stratum 2 (PS 0–1weight loss < 5%). Patients on both strata received induction paclitaxel (P) 200 mg/m2 and carboplatin (C) AUC of 6 IV every three weeks for 2 cycles as well as ZD1839 250 mg PO/day. Stratum 1 then received RT 200 cGy for 33 fractions (total dose 6600 cGy) and ZD1839 250 mg PO /day. Stratum 2 received the same RT with concurrent ZD1839 250 mg/day, and P 50 mg/m2 plus C AUC of 2 weekly for 7 doses. There was a 2-week break from ZD1839 after RT finished to assess recovery from treatment. Maintenance ZD1839 was started if all toxicities were grade < 2. Initial enrollment was limited to 6 institutions and conference calls were held every 2 weeks. Results: Toxicity and safety of therapy was evaluated for ZD1839 concurrent with RT or CRT, since the safety of ZD1839 as a single agent or with doublet chemotherapy has been demonstrated. Acute grade 3 in-field radiotherapy related toxicity such as esophagitis was not considered a DLT because acute grade 3 in-field toxicity exceeded 33% in co-operative group trials such as RTOG 9410 and CALGB 9431. However a DLT was deemed to have occurred if grade ≥ 3 in-field radiotherapy related toxicity persisted at 90 days follow-up. There were no unexpected toxicities in the patients in stratum 2 (CRT and ZD1839). In the initial cohort of 6 patients in stratum 2, 1 patient had a DLT having missed 3 out of 7 planned doses of CT during RT due to cytopenias, and esophagitis, and had a 2 week delay in completing RT. Among the other five patients in stratum 2, RT was delayed 1 week or less, and ≥ 5 CT doses of 7 planned were delivered during CRT. In the initial cohort of 6 patients in stratum 2, all treatment related toxicities improved to grade ≤ 2 by 4 weeks after the completion of RT. Conclusions: Our data suggests that ZD1839 can be safely administered with CRT. The evaluation of the cohort for stratum 1 is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis AstraZeneca; Aventis Bristol-Myers Squibb
Costs related to febrile neutropenia (FN) in patients with acute leukemia (AL) or in autologous stem cell transplantation (ASCT) recipients treated in German hospitals
Authors: C. Junghanss, U. Koester, C. Schmidt, M. Thalheimer, B. Ehlken, M. Schaff, K. Berger, A. Goertz, M. Leithaeuser, M. Freund
Journal: Journal of Clinical Oncology (2008)

18023 Background: This study assesses treatment patterns, resource consumption and costs related to FN in patients with AL receiving chemotherapy (CT) or in ASCT recipients. Methods: This is a multicentre observational,cost study. Interim results are presented for consecutive adult patients receiving CT or ASCT between 01–11/2006 at 4 academic hospitals. FN was defined as absolute neutrophil count <0.5×109/L, fever ≥38ºC and no hint of a non-infectious fever origin. Resource use was extracted from medical charts. FN related costs for medication, diagnostics, blood products and re-hospitalization are presented from provider perspective. Costs for prolonged inpatient stay due to FN are excluded (under investigation). Results: Of 86 cases, 46 received CT and 40 ASCT. Most common disease in CT pts was AML (78%) and in ASCT pts multiple myeloma (50%) and NHL (40%). Mean±SD age was 55±17 yrs (CT) and 57±11 yrs (ASCT). 96% (CT) and 98% (ASCT) of cases respectively received neutropenia/infection prophylaxes (G-CSF, GM-CSF, anti-infectives). Mean onset of FN was 25.3±37.5 and 6.8±2.7 days following start of CT or ASCT. Mean duration of FN episodes was 5.7±4.8 days (CT) and 3.7±2.3 days (ASCT); mean treatment duration of FN was 13.3±8.2 days (CT) and 9.2±3.2 days (ASCT). Two CT pts were re-hospitalized, all other were inpatients at onset of FN. 91% (CT) and 95% (ASCT) received antibiotics, 46% (CT) and 28% (ASCT) received antifungal agents. 83% (CT) and 85% (ASCT) of cases received blood products. Mean treatment cost per FN episode was €4,740±6,914 (Range: 0–32,455) for CT cases and €1,656±1,225 (range: 0–5,721) for ASCT cases. Main cost drivers were anti-infective drugs (CT 62% of cost, ASCT 43% of cost). Conclusions: FN induces significant costs with highest average cost for patients with AL receiving chemotherapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen GmbH Amgen GmbH
Improved survival with combined modality therapy in the modern era for primary mediastinal B-cell lymphoma
Authors: Matthew W. Jackson, Chad G. Rusthoven, Bernard L. Jones, Manali Kamdar, Rachel Rabinovitch
Journal: American Journal of Hematology (2016)

Primary mediastinal B-cell lymphoma (PMBCL) is an uncommon lymphoma for which existing data is limited. We utilized the National Cancer Database (NCDB) to evaluate PMBCL and the impact of radiotherapy (RT) on outcomes in the years following FDA approval of rituximab. We queried the NCDB for patients with PMBCL diagnosed from 2006 to 2011 and treated with multiagent chemotherapy. Kaplan-Meier overall survival (OS) estimates, univariate (UVA), and multivariate (MVA) Cox proportional hazards regression analyses were performed. Propensity score matched analysis (PSMA) was performed to account for indication bias and mitigate heterogeneity between treatment groups. 465 patients were identified with a median follow-up of 36 months. Median age was 36 years; 43% received RT. 5-year OS for the entire cohort was 87%, and for the no-RT and RT groups, 83% versus 93%, respectively. On UVA, OS was improved with RT (HR 0.34, P = 0.002). On MVA, RT remained significantly associated with improved OS (HR 0.44, P = 0.028) while Medicaid insurance status and increasing stage remained significantly associated with OS decrement. PSMA confirmed the OS benefit associated with RT. This analysis is the largest PMBCL dataset to date and demonstrates a significant survival benefit associated with RT in patients receiving multiagent chemotherapy in the rituximab era. More than half of patients treated in the United States during this time period did not receive RT. In the absence of phase III data to support omission, combined modality therapy with its associated survival benefit should be the benchmark against which other therapies are compared.
Methylglyoxal-bis(guanylhydrazone) (Methyl-GAG): current status and future prospects.
Authors: R P Warrell, J H Burchenal
Journal: Journal of Clinical Oncology (1983)

Initial clinical trials of methyl-GAG (MGBG) showed that repetitive daily administration produced severe, occasionally fatal, toxic reactions. After two decades of neglect, recent studies have shown that doses of 500-600 mg/sq m administered every 7-14 days are very well tolerated. Moreover, current results indicate that MGBG has useful antitumor activity in patients with advanced malignant lymphoma and carcinomas of the head and neck, esophagus, and lung (non-small cell). The drug's mechanism of cytotoxic action and its toxic effects are not shared by most other cancer chemotherapeutic drugs. Furthermore, Phase II and Phase III evaluation are required to determine the therapeutic potential of this unique agent.
Advances in echo imaging using contrast enhancement: Edited by N.C. Nanda and R. Schlief. 405 pp. 79.50 (hardback), Dordrecht, Netherlands: Kluwer, 1993. ISBN 0-7923-2137-5
Authors: B. Delemarre
Journal: Cardiovascular Research (1995)

Advances in echo imaging using contrast enhancement: Edited by N.C. Nanda and R. Schlief. 405 pp. £79.50 (hardback), Dordrecht, Netherlands: Kluwer, 1993. ISBN 0-7923-2137-5 Get access B. Delemarre B. Delemarre Amsterdam, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 30, Issue 1, July 1995, Page 160, https://doi.org/10.1016/S0008-6363(95)90145-0 Published: 01 July 1995
Polymorphisms in candidate genes in patients with congestive heart failure (CHF) after childhood cancer: A Report from the Childhood Cancer Survivor Study (CCSS)
Authors: R. Aplenc, J. Blanco, W. Leisenring, S. Davies, M. Relling, L. Robison, C. Sklar, M. Stovall, S. Bhatia
Journal: Journal of Clinical Oncology (2006)

9004 Background: In cancer survivors, CHF associated with the use of anthracyclines is an important clinical complication. Risk factors for anthracycline associated cardiac toxicity, including cumulative dose, gender, and age, have been described. However, these risk factors do not fully explain the observed clinical variability. Notably, the potential role of genetic risk factors has not been studied. A recent “unifying hypothesis” postulates that the early cardiac damage is mediated mostly by oxidative stress while the more chronic type of toxicity is induced by anthracycline alcohol metabolites synthesized by carbonyl reductases (CBRs). Therefore we hypothesized that genetic polymorphisms in genes encoding for enzymes involved in oxidative stress pathways, and the metabolism of anthracyclines may impact on the risk of anthracycline-related cardiotoxicity. Methods: We conducted a nested case-control study within a cohort of 5,739 patients enrolled in the CCSS. Forty-seven cases with CHF and 195 matched controls (matched for demographics, follow-up and treatment) were genotyped for 10 genetic polymorphisms in 7 genes: catalase (CAT), GSTP, GSTT, GSTM, superoxide dismutase (SOD 1), NQO1, and CBR3. Results: In the subjects who received anthracyclines, multivariable analyses of CHF risk, adjusted for gender, smoking history, recurrence, and family history of heart disease, showed the GSTP +313A&gt;G polymorphism was a significant risk factor, HR = 5.0, p = 0.01 for the A/G genotype vs. A/A; HR = 3.3, p = 0.19 for the G/G genotype vs. A/A. In addition, a suggested association between CBR3 V244M polymorphism and the risk of CHF after treatment with anthracyclines, HR=10.2, p=0.06 for G/G vs. A/A; HR = 4.0, p=0.18 for G/A vs. A/A was seen in an identical multivariable analysis. Conclusions: These data suggest that specific polymorphic genetic variants on a panel of candidate genes relevant to the anthracycline pharmacodynamics may modify the risk of CHF in childhood cancer survivors. Future studies to further refine the role of these novel genetic risk factors affecting a large population are warranted. No significant financial relationships to disclose.
Metabolism of Concanavalin A-Affinity Molecular Variants of Alpha-Fetoprotein in Rats&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Maxwell Barus, David Sylwester, Philip C. Kelleher, Carol J. Smith
 5
Journal: JNCI Journal of the National Cancer Institute (1978)

Serum half-lives of unfractionated rat alpha-fetoprotein (AFP), concanavalin A (Con A)-nonreactive AFP, and Con A-reactive AFP in normal 45- to 55-day-old male and female F344 rats were determined to be 19 hours. No significant differences were seen between the half-lives of unfractionated AFP and either of the two Con A-affinity molecular variants of AFP studied. No evidence of interconversion of the Con A-affinity AFP variants during 24 hours in the circulation was found. These results supported the conclusion that the proportions of Con A-affinity molecular variants of AFP in the sera of fetal, newborn, and hematoma-bearing rats result from differences in the relative synthesis rates of the two variants.
Differential pathologic complete response rates after neoadjuvant chemotherapy among molecular subtypes of triple-negative breast cancer.
Authors: Hiroko Masuda, Keith A. Baggerly, Ying Wang, Ya Zhang, Ana M. Gonzalez-Angulo, Funda Meric-Bernstam, Vicente Valero, Brian D. Lehmann, Jennifer A. Pietenpol, Gabriel N. Hortobagyi, William Fraser Symmans, Naoto T. Ueno
Journal: Journal of Clinical Oncology (2013)

1005 Background: By gene profiling, Lehmann et al. (J Clin Invest 121:2750-2767, 2011) reported that triple-negative breast cancer (TNBC) can be classified into 6 clusters—basal-like 1 (BL1), basal-like 2 (BL2), immunomodulatory (IM), mesenchymal (M), mesenchymal stem-like (MSL), and luminal androgen receptor (LAR)—plus an unstable (UNS) cluster. While it is clear that patients with TNBC differently respond to chemotherapy, the clinical relevance of these molecular TNBC subtypes is unknown. Methods: We qualitatively reproduced the Lehmann et al. experiments using Affymetrix CEL files from the public datasets. We identified 130 TNBC gene expression microarrays obtained from 03/00 to 03/10. All patients had received neoadjuvant chemotherapy containing sequential taxane and anthracycline-based regimens and had evaluable pathological tumor response data. Median follow-up was 68.1 months. (5.1-147.5). We classified TNBC samples using Lehmann’s gene signatures, then performed Fisher's exact test to correlate TNBC subtype and pCR status. To assess the independent utility of TNBC subtype for predicting pCR status, we fit a logistic regression model to our data and used age, clinical stage, treatment regimens, and nuclear grade as potential explanatory factors. We also performed comparison of the subtypes with the PAM50 intrinsic subtypes and RCB index. Results: The BL1 subtype had the highest pCR rate (52%); BL2 and LAR the lowest (0% and 10%, respectively). TNBC subtype and pCR status were significantly associated (p = 0.044). TNBC subtype was an independent predictor of pCR status (p = 0.022) by a likelihood ratio test.The Lehmann’s subtype classification better predicted pCR status than did the PAM50 intrinsic subtypes (basal-like vs. non basal-like). Conclusions: Dividing TNBC into 7 subtypes predicts high vs. low pCR rate. The 7-subtype classification may lead to innovative personalized medicine strategies for patients with TNBC. There is a need for prospective validation of the hypothesis that pCR rates associated with the seven TNBC subtypes will predict long-term patient outcome.
Disease Activity Score 28 (DAS28) using C-reactive protein underestimates disease activity and overestimates EULAR response criteria compared with DAS28 using erythrocyte sedimentation rate in a large observational cohort of rheumatoid arthritis patients in Japan
Authors: T. Matsui, Y. Kuga, A. Kaneko, J. Nishino, Y. Eto, N. Chiba, M. Yasuda, K. Saisho, K. Shimada, S. Tohma
Journal: Annals of the Rheumatic Diseases (2007)

<b>Objectives:</b> To compare disease activity and the improvement of disease activity evaluated between by Disease Activity Score 28 using erythrocyte sedimentation rate (DAS28-ESR) and by DAS28 using C-reactive protein (DAS28-CRP) in Japanese patients with rheumatoid arthritis (RA). <b>Methods:</b> Data from 3073 RA patients registered in the large cohort database (<i>NinJa</i>: National Database of Rheumatic Diseases by iR-net in Japan) of 2003 was used to calculate DAS28-ESR and DAS28-CRP and disease activities were evaluated. Improvements in disease activities were also evaluated according to the European League Against Rheumatism (EULAR) response criteria in 1482 RA patients whose DAS28-ESR and DAS28-CRP could be calculated from data for both 2002 and 2003. <b>Results:</b> The mean value of DAS28-CRP (3.59, SD 1.25) was significantly smaller than that of mean DAS28-ESR (4.31, SD 1.32) (p &lt; 0.0001). The number of patients who satisfied the criteria of remission was 297 (9.7%) in DAS28-ESR versus 705 (22.9%) in DAS28-CRP and the number of patients with high disease activity was 842 (27.4%) versus 357 (11.6%) for DAS28-ESR and DAS28-CRP, respectively; there was a significant difference between the two (p &lt; 0.0001). Change of respective DAS28 was significantly correlated (ΔDAS28-ESR −0.05, SD 1.14 versus ΔDAS28-CRP −0.10, SD 1.10) (p &lt; 0.0001); however, the number of "good response" patients was significantly different (p &lt; 0.03) between DAS28-ESR (97 patients, 6.5%) and DAS28-CRP (136 patients, 9.2%). <b>Conclusions:</b> DAS28-CRP significantly underestimated disease activity and overestimated the improvement in disease activity compared with DAS28-ESR. DAS28-CRP should be evaluated using different criteria from that for DAS28-ESR.
A Mortality Study of 11,500 Nickel Workers&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Harry S. Shannon
 4, James A. Julian, Robin S. Roberts
Journal: JNCI Journal of the National Cancer Institute (1984)

A historical prospective mortality study was conducted at a nickel company with mines, mills, and a smelter in Ontario, Canada. All men were included in the study who worked for a total of at least 6 months and were employed at some time between 1950 and 1976. Mortality was ascertained and observed number of deaths (O) were compared with expected number of deaths (E), on the basis of the person-years method with the use of rates for Ontario males. There were 804 O compared to 743 E (P less than .001). However, the excess was more than accounted for by the increase in accidental and violent deaths (O = 242; E = 150). Deaths from circulatory diseases and all cancers were roughly equal to E. Laryngeal cancer mortality was significantly increased due to an excess in miners (O = 4; E = 1.00). Lung cancer mortality was somewhat increased (O = 46; E = 37.5); no nasal cancers were observed. Three deaths were due to pneumoconiosis. Sinter plant workers showed a significant increase of cancer deaths (O = 13; E = 6.7; P = .015).
A multicenter phase II study of docetaxel plus cisplatin as first-line therapy in patients with metastatic squamous cell esophageal cancer
Authors: J. Kim, H. Song, Y. Do, M. Kim, K. Lee, S. Bae, H. Ryoo, K. Park, J. Baek, W. Lee
Journal: Journal of Clinical Oncology (2008)

15520 Background: The studies on the efficacy of docetaxel and cisplatin in esophageal cancer, especially squamous cell carcinoma in histology, which is the predominant type of esophageal cancer in Asia, are limited. This study were planned to evaluate feasibility and response rate in patients with metastatic esophageal cancer with three weekly docetaxel and cisplatin combination chemotherapy. Methods: Eligible patients had untreated metastatic esophageal cancer with measurable lesion(s), histologic proof of squamous cell type, ECOG PS 0–2, adequate organ function, and signed informed consent. Treatment consisted of docetaxel 70 mg/m2 i.v. on day 1 plus cisplatin 70 mg/m2 i.v. on day 1 of a 21-day cycle. Measurable and/or unmeasurable lesions were assessed after every 2 courses by RECIST. Results: From Dec. 2004 to Dec. 2007, total of 39 patients (M/F=39/0) were enrolled. The median age was 65 years. The common metastatic lesions were abdominal lymph nodes (25.6%), lung (15.4%), liver (5.1%) and bone (5.1%). Out of 34 evaluable patients, there were 3 (7.7%) CR, 10 (25.6%) PRs, 11 (28.2%) SDs, and 10 (25.6%) PDs. Objective tumor response was 33.3% in the ITT population. Median PFS was 5.0 months (95% C.I.: 2.7–7.3 monhs), and median survival was 10.5 months (5% C.I.: 6.0–15.0 months). The median number of cycle was 3 (range, 1–6). The relative dose intensity of docetaxel and cisplatin was 92% and 91% respectively. All 39 patients were assessed for safety. This treatment was well tolerated with grade 3/4 neutropenia in 21%/10%, grade 2/3 anemia in 26%/3%, grade 3 infection in 5%, grade 2/3 nausea in 18%/3%, grade 2 general weakness and dysphagia in 8% both, grade 2 vomiting 5%, grade 2 anorexia, general ache and diarrhea was in 3% of patients. Conclusions: Docetaxel plus cisplatin combination chemotherapy showed significant antitumor effect with manageable and tolerable toxicities in patients with metastatic squamous cell esophageal cancer. No significant financial relationships to disclose.
TCT-652 Outcomes in Patients with Transcatheter Aortic Valve Replacement and Left Main Stent: The multicenter, multinational TAVR-LM Registry
Authors: Tarun Chakravarty, Rahul P. Sharma, Yigal Abramowitz, Samir Kapadia, Azeem Latib, Hasan Jilaihawi, Kanhaiya L. Poddar, Gennaro Giustino, Henrique B. Ribeiro, Didier Tchetche, Benoit Monteil, Luca Testa, Giuseppe Tarantini, Michela Facchin, Thierry Lefevre, Brian R. Lindman, Babak Hariri, Jigar Patel, Nobuyuki Takahashi, George W. Matar, James Mirocha, Wen Cheng, E. Murat Tuzcu, Horst Sievert, Josep Rodes-Cabau, Antonio Colombo, Ariel Finkelstein, Jean Fajadet, Raj Makkar
Journal: Journal of the American College of Cardiology (2015)