tbuckley/cabot-search huggingface dataset:
Abstract 9621: Intensive Lipid Lowering Therapy Using Rosuvastatin Associates with Greater Atherosclerotic Aortic Plaques Regression - A Magnetic Resonance Imaging Study -
Authors: Makiko Yogo, Makoto Ayaori, Hiroki Sato, Teruyoshi Kihara, Makoto Sasaki, Maki Iizuka, Shunichi Takiguchi, Harumi Uto-Kondo, Emi Yakushiji, Kazuhiro Nakaya, Tomohiro Komatsu, Yukihiko Momiyama, Masayoshi Nagata, Katsunori Ikewaki
Journal: Circulation (2012)

Whether intensive lipid-lowering therapy yields greater regression of atherosclerotic plaques remains inconclusive. We therefore performed a prospective, randomized trial comparing standard (achieving LDL-C levels recommended by the Japanese guideline) and intensive (achieving further 30% lower levels than the former) rosuvastatin therapy for 1 year with primary outcome of aortic plaques evaluated by magnetic resonance imaging (MRI).Sixty patients, who were eligible for statins therapy (51 primary, 9 secondary prevention), were randomized to standard or intensive group, and dose of rosuvastatin were titrated to achieve the respective target LDL-C. Average doses of rosuvastatin throughout the study were 2.9±3.1 and 6.5±5.1 mg/day in standard and intensive group, respectively. Although both treatments significantly reduced LDL-C and high sensitive CRP(hsCRP) levels, reduction of LDL-C levels was greater in intensive group than in standard group (-46 vs. -34%). MRI study revealed that both thoracic and abdominal plaques were significantly regressed in both groups with greater regression in thoracic plaques in intensive group compared to standard group (-9.1 vs. -3.2%) (Figure A). Moreover, thoracic plaques regression correlated with reductions in hsCRP (FigureB).In conclusions, the present study demonstrated that intensive lipid-lowering using rosuvastatin led to additive plaques regression compared to standard therapy. Therefore, rosuvastatin may provide long term benefit in patients with increased risk through its potent LDL-C lowering and anti-inflammatory effects.
Randomized trial of adjuvant chemotherapy (Cx) with cisplatin plus gemcitabine (CG) versus cisplatin plus docetaxel (CD) in patients (pts) with completely resected non-small cell lung cancer (NSCLC) with quality of life (QoL) as the primary objective
Authors: F. Barlesi, C. Chouaid, J. Crequit, H. Lecaer, J. Pujol, H. Bérard, A. Vergnenegre, J. Letreut, E. Fabre-Guillevin, A. Loundou
Journal: Journal of Clinical Oncology (2009)

7532 Background: Adjuvant Cx with vinorelbine plus cisplatin (VC) improves survival of resected NSCLC but has an immediate negative impact on QoL (Bezjak, JCO 2008). In advanced stages NSCLC, GC and DC have comparable efficacy and might be superior to VC in QoL outcomes. This trial was designed to provide with data on other adjuvant Cx regimens for pts with resected NSCLC. Methods: Pts with stage IB to III resected (R0) NSCLC, without major postoperative complication, were eligible. Surgery has to be standardized. Cx consisted of cisplatin (75 mg/m 2 , D1) plus gemcitabine 1,250 mg/m 2 (D1,8) or docetaxel (75 mg/m 2 D1) for 3 cycles. The primary endpoint was QoL (EORTC QLQC30) and the trial was designed to detect a 10 points difference in QoL scores (α=0.05; power 80%). Relapse-free survival, overall survival (OS), safety profile and costs were the secondary endpoints. Results: 136 pts (median age: 57 yrs, 74% males, pTNM: 32% IB, 34% II, 34% III; histology: 55% ADC, 23% SCC) were included. 67 and 69 pts were randomized in the GC and DC arms, respectively. Surgery was a (bi)lobectomy in 85% of cases. No imbalance was found between arms regarding major pts characteristics. Overall, a Gr3/4 hematological toxicity occurs for 33.8% and 21.7% of pts (p=0.11) and a Gr3/4 non-hematological toxicity occurs for 33.8% and 26.1% of pts (p=0.33), in the GC and DC arms. Compliance to QoL assessment was good (93%). At inclusion, global health status (GHS) scores (/100) were comparable between arms (mean score, 63.5 and 62.7, in the GC and DC arms, p=0.8). At the end of treatment (3 rd month), GHS scores have slightly improve (mean score, 64.5 and 65.4, in the GC and DC arms, p=0.8). At the time of analysis, 15 pts (7 GC, 8 DC) have died. At 1 year, 100 and 96.8% of the pts were alive in the GC and DC arms; At 2 years, 92.9 and 89.8% of the pts were alive in the GC and DC arms (log-rank, p=0.88). Conclusions: Adjuvant GC and DC have comparable effect on post-operative QoL and equivalent efficacy among pts with resected NSCLC. The GC and DC efficacy, safety profiles and QoL outcomes favorably compare with the results reported for the VC regimen. Detailed analyses will be presented at the meeting. [Table: see text]
The influence of O2 on exercise capacity (6-minute-walking-distance, 6MWD) in COPD
Authors: Inga Heinzelmann, Andreas Jerrentrup, Claus Vogelmeier, Klaus Kenn
Journal: European Respiratory Journal (2011)

We investigated the additional effect of supplemental oxygen on 6MWD in severe COPD-patients. The aim of the study was to find out if the response to nasal oxygen during 6-minute-walking-test (6MWT) depends on the level of exercise capacity.  To identify characteristics of patients with high oxygen response, we defined patients as “O 2 - Responder” if they increase their 6MWD by ≥ 35m due to oxygen supply.  111 COPD-patients (age: 63,5y±8,7; FEV 1 : 35,9%pred.±11,6; m:f=65:46) took part in a randomized, single-blinded, prospective study.  The patients underwent a 6MWT pretest followed by 2 6MWT either on 2L oxygen or on medical air (MA). After 3 week rehabilitation including resistance- and endurance-training both tests were repeated. We measured lung function before and after rehabilitation, SpO 2 , paO 2 , paCO 2  and BORG-scale before and after every 6MWT.  The difference between 6MWD O2  and 6MWD MA  (O 2 -response) was greater pre (Δ=7,16%) than post rehabilitation (Δ=3,25%). Separating patients in 2 groups, O 2 -response was significantly higher in patients with 6MWD 2 -Response decreases (r=0,52, p=0,001).  “O 2 -Responders” were characterized by: lower FEV 1 % pred. (p 2  (before and after 6MWT; p 2  (after 6MWD).  We detected a negative relationship between O 2 -response and exercise capacity. “O 2 -Responders” showed lower FEV 1  and higher limitations during exercise.  We speculate that training therapy improves muscle oxygen-efficiency and increases exercise capacity even without oxygen supply with the consequence that supplemental oxygen becomes less important.
On the Significance of Glucolysis for Cancer Growth, With Special Reference to Morris Rat Hepatomas&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Dean Burk, Mark Woods, Jehu Hunter
Journal: JNCI Journal of the National Cancer Institute (1967)

Anaerobic fermentation (glycolysis of glucose) was measured in a progressive growth spectrum of normal and host rat livers (zero net growth) through very slowly growing, slowly growing, intermediately growing, and rapidly growing lines of Morris rat hepatomas, maintained as slices in Krebs-Ringer bicarbonate-glucose-pyruvate medium at 37 C with 5% CO2 in N2 as gas phase. All hepatoma lines, including even the most slowly growing, showed glucose fermentation values in excess of those of normal or host rat livers. A continuous, positive correlation was observed between in vivo growth rate and in vitro anaerobic glucolytic potential; also, of equal importance, Km-glucose (concentration of glucose required for half-maximum rate of fermentation) and degree of inhibition by the anti-insulin stilbestrol decreased with increasing growth rate. Recent data of Gullino are cited which provide overwhelming evidence as to the actuality of in vivo fermentation of glucose to lactate by slow-growing hepatomas of the Morris series, compared to in vivo consumption of lactate normally observed with livers. The results reported make clear that a dominant biochemical difference between a normal metabolism and one characteristic of even the lowest degree of malignancy studied involves a critical, however small, increase in glucolytic capacity over that in the normal tissue of origin, in this instance, liver. Progression in malignant growth capacity is associated with increasing fermentation capacity. These results and conclusions confirm and extend the well-known findings of Otto Warburg over the past 40 years and our similar findings made with mouse melanoma spectra and Sanford-Earle tissue culture spectra, and, as reported here, also in the Hilf rat mammary tumor spectrum. Implications of these findings for chemotherapy and hyperthermy therapy of cancers are briefly indicated.
Improving quality of cancer care by rapid adoption of new scientific evidence.
Authors: Joanne Schottinger, Violeta Rabrenovich, David Campen, Dean Fredriks
Journal: Journal of Clinical Oncology (2013)

62 Background: The goal of the Kaiser Permanente (KP) Cancer Care Program is to provide patient-centered, evidence-based, safe care for all KP oncology patients. Multiple processes and information technology tools support KP’s clinicians in delivering the best care to our patients. Prior to 2008, chemotherapy ordering and administration across KP was paper-based, and the standardization of chemotherapy regimens was driven by prescribers’ preferences. KP Oncologists used more than 1,400 chemotherapy protocols. Pharmacy had varying systems for dosing alerts, and reliable chemotherapy administration data was not available for clinical quality improvement. Methods: By 2012, all KP regions had implemented the KP HealthConnect Beacon (KPHCB) system, which incorporates chemotherapy ordering, alerting, verifying, dispensing, and administration in ambulatory and inpatient settings. Important outcomes of the KPHCB implementation include: 1) our success in gaining agreements on standardization of chemotherapy protocols across the Program, and 2) implementation of a rapid process for adoption of new scientific evidence. Our approach includes an evaluation of the quality of the relevant scientific literature and an assessment of a particular treatment. The KP multidisciplinary team discusses and integrates the scientific evidence and clinical expertise of KP clinicians into KPHCB chemotherapy protocols. The new evidence-based protocols with supporting literature references are imbedded as a web link at the end of the each protocol and are available to clinicians within days following the publishing of new evidence. Results: An example of a rapid dissemination and adoption of evidence is the 2010 Pfizer’s and FDA’s announcement that the sale of Mylotarg would be voluntarily discontinued due to a fatal liver veno-occlusive disease. Within 48 hours, we identified 12 patients who received Mylotarg in 2010, and the treating oncologists were individually contacted and provided with the new information to discuss with patients, as appropriate. Conclusions: The benefits of KP’s rapid adoption of new evidence methodology are reaching over 40,000 cancer patients, receiving over 250,000 chemotherapy treatments annually.
Treatment of Chinese patients with advanced gastric cancer with FOLFIRI followed by FOLFOX7 or the reverse sequence.
Authors: F. Bi, Q. Li, C. Zhou, J. Yu, X. Cai, M. Qiu, J. Liu, C. Yi, D. Luo, F. Xu
Journal: Journal of Clinical Oncology (2010)

TPS207 Background: A well-recognized standard first-line or salvage chemotherapy regimen for advanced or metastatic gastric cancer has not been established until now. Two regimen sequences—folinic acid, 5-fluorouracil (FU), and irinotecan (mFOLFIRI) followed by folinic acid, FU, and oxaliplatin (mFOLFOX7; arm A), and mFOLFOX7 followed by mFOLFIRI (arm B)—were evaluated for their antitumor activity and toxicity in Chinese patients (pts) with locally advanced or metastatic gastric cancer. Methods: Previously untreated pts between age 18 and 75 with an ECOG performance status of 0-2 and life expectancy > 4 months were eligible if they had histologically proven gastric or gastroesophageal junction adenocarcinoma with at least one site of unidimensionally measurable disease (RECIST), adequate bone marrow function (hemoglobin ≥90 g/L, absolute neutrophil count of ≥2.0×109 cells/L, and platelet count of ≥100×109 cells/L), hepatic function (alkaline phosphatases ≤3 upper limits of normal [UNL], total bilirubin ≤1.5 UNL, AST and ALT ≤3UNL) and renal function (creatinine ≤135umol/L). Previous adjuvant chemotherapy, if given, must have been completed at least 6 months before inclusion. Pts were randomized (1:1) according to the following sequences: a 2-hour infusion of folinic acid 200 mg/m2 followed by 46-hour infusion of FU 2,400 mg/m2 every 2 weeks, either with irinotecan 150 mg/m2 or with oxaliplatin 85 mg/m2 as a 2-hour infusion on day 1. Toxicity evaluations were based on the National Cancer Institute Common Toxicity Criteria for Adverse Events v3.0. Radiological evaluations were conducted at base line and after every two courses. At progression, irinotecan was replaced by oxaliplatin (arm A), or oxaliplatin by irinotecan (arm B). Primary endpoint was progression-free survival. Secondary endpoints were overall survival, response rate, and safety. Randomization was performed using a minimization technique, stratifying patients by center and by presence or absence of measurable disease. The planned sample size is 100 in each arm, considering two-sided log-rank test to have 80% power to detect a 20% difference in the proportion of patients without progression at 8 months. No significant financial relationships to disclose.
Incidence, predictors, and cost implications of gastrointestinal complications following intensity-modulated radiation therapy for prostate cancer.
Authors: Monica J. Wood, Gally Reznor, Quoc-Dien Trinh, Paul Linh Nguyen
Journal: Journal of Clinical Oncology (2015)

31 Background: The objective of this study was to examine the incidence and predictors of gastrointestinal (GI) complications following intensity-modulated radiation therapy (IMRT) for prostate cancer and their impact on national healthcare expenditure. Methods: Using Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked data, we identified 11,781 men diagnosed with non-metastatic prostate cancer from 2002 to 2006 who underwent definitive IMRT, had no pre-existing GI toxicity, and had at least 36 months of follow-up after IMRT initiation. Annual incremental spending was defined as the difference between the total Medicare payments in the year after the development of the first GI complication and the total Medicare payments in the year preceding prostate cancer diagnosis, excluding prostate cancer treatment-related costs. We used multivariate logistic regression to evaluate the odds ratio of developing IMRT-related GI toxicity, and quantile regression to compare the annual incremental costs between groups. All analyses were done using SAS 9.3. Results: Over the 36-month follow-up period, the incidence of post-IMRT GI complications was 26.5% (n=3,118). Patients on anti-coagulation therapy or receiving brachytherapy boost were more likely to develop IMRT-related GI toxicities (OR 1.11, 95% CI 1.01-1.22 (p=0.029) and OR 1.18, 95% CI 1.08-1.30 (p&lt;0.001), respectively). The median Medicare annual incremental cost per patient associated with post-IMRT GI complications was $3,375 in 2014 dollars (95% CI $3,222-3,529, p&lt;0.0001). Among patients with post-IMRT GI complications, the presence of diabetes was associated with an additional $610 (95% CI $206-1,014, p=0.003) per patient in Medicare spending. Conclusions: Medicare spending associated with post-IMRT GI complications is considerable, often in excess of 10% of IMRT cost. Quantifying these expenditures may better frame the potential for cost savings of emerging technologies that aim to reduce the incidence and severity of IMRT-related GI toxicities.
Phase II trial of R-(-)-gossypol acetic acid (NSC 726190, AT-101) in patients with recurrent extensive stage small cell lung cancer (ES-SCLC).
Authors: M. Q. Baggstrom, R. Govindan, M. Koczywas, A. Argiris, M. Millward, E. Johnson, Y. Qi, C. Erlichman
Journal: Journal of Clinical Oncology (2010)

e17523 Background: AT-101 is an oral inhibitor of the anti-apoptotic Bcl proteins (Bcl-2, Bcl-XL, Bcl-W, and Mcl-1) and potent inducer of the proapoptotic proteins noxa and puma. This multicenter, single-arm study evaluated the efficacy of AT-101 in patients with recurrent chemosensitive ES-SCLC. Methods: To be eligible, patients must have had chemosensitive ES-SCLC (defined as no progression during and no recurrence < 2 months after completion of first-line platinum-based chemotherapy), ECOG performance status (PS) 0-2, and adequate organ and marrow function. Patients were not eligible if they had symptomatic and/or progressive brain metastases. Treatment consisted of AT-101 20 mg orally daily for 21 out of 28 days each cycle. Tumor evaluations were performed every 8 weeks. AT-101 was continued in the absence of tumor progression or unacceptable toxicity. The primary endpoint was the proportion of confirmed responses (CR, PR) during the first 6 cycles of treatment. Under the two-stage Simon Optimal design, 14 evaluable (for response) patients were enrolled in stage 1, and if ≥ 2 responses were observed, an additional 28 would be enrolled in stage 2. Results: To date, 15 of 42 planned patients were enrolled in 5 sites. Patient characteristics: median age 67.0 years (range 46-76), male 40%, ECOG PS 0 46.7% and 1 53.3%, Caucasian 86.7%, previous radiation 80%. Median number of cycles received was 2 (range 1-6). A planned interim analysis was performed on an intent to treat basis. One patient discontinued treatment after one cycle due to thrombocytopenia and was considered non-evaluable for the primary endpoint. Among the 14 evaluable patients, no objective responses were reported. Three patients (21%) achieved stable disease after two cycles of therapy but have since progressed on treatment. Grade 3 toxicities included anorexia, fatigue, and nausea/vomiting. One patient had a grade 3 leukopenia which was unrelated to treatment. The study met the stopping rule in the first stage of enrollment and was closed to further accrual. Conclusions: This interim analysis indicates that AT-101 is well-tolerated but has little activity in recurrent chemosensitive SCLC. Supported by N01-CM62205. No significant financial relationships to disclose.
Lynch syndrome founder mutations in families of Navajo and German-American heritage
Authors: H. T. Lynch, S. M. Coronel, R. Okimoto, H. Hampel, K. Sweet, J. F. Lynch, R. Fodde, T. Drouhard, A. Wagner, A. De La Chapelle
Journal: Journal of Clinical Oncology (2004)

9511 Background: Lynch syndrome is caused by mutations in mismatch repair (MMR) genes which confer extraordinarily high risk of colorectal cancer, endometrial, ovarian as well as lesser occurring cancer types. Carriers of these MMR mutations require genetic counseling, clinical surveillance, and targeted management. Methods: An MLH1 mutation among the Navajo consisted of a four basepair deletion beginning at the first nucleotide of codon 727. In Caucasians a deletion encompassing exons 1 - 6 of MSH2 occurred. To facilitate the diagnosis of these mutations, specific PCR-based tests were developed and used for large-scale screening of individuals at risk. An extensive genealogical and historical study was performed in search for a common origin of each mutation and its spread. Results: The MLH1 deletion mutation was found in members of six widely dispersed Navajo families in Arizona. To date, 386 individuals from these families have been identified to be at risk of whom 142 individuals have been tested with 56 harboring the mutation. The MSH2 deletion mutation was found in members of nine Caucasian families living in various parts of the U.S. To date 566 family members of the nine probands have been identified to be at risk and counseled; 137 of these have been tested, and 61 carry the mutation. Carriers of the mutation have already been identified in 14 states. Three of these families have been genealogically shown to descend from a German immigrant family that arrived in Pennsylvania in 1727. Conclusions: The postulated high frequency and continent-wide geographic distribution of these founder mutations beg the suggestion that until more is learned about their occurrences, the routine testing of individuals at risk for Lynch syndrome in the U.S. might include an assay for these mutations in the interest of early cancer detection and improved cancer control. No significant financial relationships to disclose.
In Vitro and In Vivo Proteasome Activity Profiles of Bortezomib and a Novel Proteasome Inhibitor NPI-0052.
Authors: Dharminder Chauhan, Ta-Hsiang Chao, Laurence Catley, Benjamin Nicholson, Mugdha Velanker, Teru Hideshima, Celia Berkers, Huib Ovaa, Saskia Neuteboom, Michael Palladino, Kenneth C. Anderson
Journal: Blood (2005)
Retrospective analysis of nanoparticle albumin-encapsulated paclitaxel versus dacarbazine in advanced melanoma.
Authors: P. Chalasani, S. S. Morgan, D. Butcher, J. M. Jeter, E. Hersh, L. D. Cranmer
Journal: Journal of Clinical Oncology (2010)

e19002 Background: Despite limited activity, dacarbazine (D) remains standard treatment for metastatic melanoma. Nanoparticle albumin-encapsulated-paclitaxel (nab-p; Abraxane) has demonstrated promising anti-melanoma activity in phase II studies. We compared the activity of nab-p with that of D in patients with advanced melanoma. Methods: Retrospective chart review to estimate rate of stable disease or better at first assessment, complete response rate, median progression-free survival (PFS), and 6-m PFS. Patients with advanced melanoma treated at a single center from 1/2005 to 12/2009 with D (27), nab-p (38), or both sequentially (22; 21 D followed by nab-p). For data to be included, patients had to complete at least 42 days of treatment with a given drug and undergo formal response assessment. For all patients, these criteria were satisfied by 59 nab-p and 45 D patients. In those receiving both, these criteria were satisfied in 18 D and in 21 nab-p patients. Median PFS was assessed by log-rank. All other comparisons were Chi-Squared with Yates' correction. Results: There was no pre-treatment difference between nab-p and D groups with regard to lactate dehydrogenase levels (high vs. normal; p = 0.08) or stage distribution (IIIc vs. IVa vs. IVb vs. IVc; p = 0.35). There was no difference in the proportion of patients achieving at least stable disease at first planned assessment (71% nab-p vs. 60% D, p = 0.32) or complete response rate (3% nab-P vs. 2% D, p = 0.81). Median PFS was significantly higher for nab-p (5.0 vs. 4.3 m, p = 0.03). 6-m PFS was also significantly greater in the nab-p group (46% vs. 22%, p = 0.01). In the subset of patients (n = 22) who received both drugs, median PFS was greater during nab-p treatment (5.4 vs. 2.6m, p = 0.02). Conclusions: In this retrospective analysis of a single-center's experience, nab-p yields improved median and 6-m PFS versus D. Notably, in patients receiving both drugs, most of whom received D prior to nab-p, median PFS favored salvage therapy with nab-p over primary therapy with D. These data suggest increased activity for nab-p in patients with advanced melanoma, compared to standard therapy with D. A phase III trial is in progress comparing these two drugs in advanced melanoma. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abraxis BioScience Abraxis BioScience Abraxis BioScience Abraxis BioScience