tbuckley/cabot-search huggingface dataset:
MO19391: An open-label safety study of bevacizumab plus taxane-based therapy as first-line treatment of patients with locally recurrent (LR) or metastatic breast cancer (MBC)
Authors: J. Pierga, K. I. Pritchard, H. Cortes-Funes, L. Biganzoli, C. Thomssen, F. A. Franke, I. E. Smith, N. Bogdanova, D. Stroyakovskiy
Journal: Journal of Clinical Oncology (2008)

1140 Background: In a randomised phase III trial, E2100, the addition of bevacizumab to first-line paclitaxel significantly improved PFS in patients (pts) with LR or MBC (HR 0.48; p<0.0001). MO19391 is a study investigating the safety profile of bevacizumab in LR or MBC, in combination with first-line taxane-based chemotherapy (CTX). This will provide additional efficacy and safety data in a broader patient population. Methods: This is an interim analysis of an open-label, single-arm trial that plans to enroll 2,300 pts from 50 countries. The primary endpoint is safety. Secondary endpoints include TTP and OS. Pts must have LR or MBC and an ECOG PS of 0–2. Exclusion criteria include prior CTX for LR or MBC and evidence of CNS metastases. Bevacizumab is administered at 10mg/kg q2w or 15mg/kg q3w combined with the physician's choice of taxane regimen (or investigator's standard of care, excluding anthracyclines). Treatment with bevacizumab continues until PD or unacceptable toxicity. In addition to collecting information on AEs, data are sought for AEs of special interest (hypertension, proteinuria, wound-healing complications, thromboembolic events, CNS bleeding, other haemorrhages, GI perforation, fistulae, reversible posterior leukoencephalopathy syndrome and CHF). Results: As of 11/07, the safety population was 861 pts from 33 countries, with a mean duration of bevacizumab therapy of 82.4 days (min=1, max=325). Characteristics of this population are reported in the table. Conclusions: MO19391 is a large ongoing trial that will further elucidate the safety profile of bevacizumab in a community setting. A detailed overview of the patient population of this trial will be presented. ITT population (n=861) Median age (years) 53 Range 24–93 ECOG PS (%) 0 61.6 1 33.2 2 5.2 ER status (%) + 63.3 − 34.2 Unknown 2.5 PR status (%) + 52.3 − 42.9 Unknown 4.8 Disease stage (%) LR 6.9 MBC 93.1 Neo/adjuvant chemotherapy (%) Yes 89.3 No 10.7 Neo/adjuvant anthracycline (%) Epirubicin 48.9 Doxorubicin 36.5 Neo/adjuvant taxane (%) Paclitaxel 11.8 Docetaxel 23.5 Chemotherapy backbone (%) Taxane monotherapy 65.7 Taxane combination 14.9 Other 11.6 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Aventis, Biomira, Ortho Biotech, Pfizer, Pharmacia, Roche, YM Biosciences AstraZeneca Oncology, Aventis, Pfizer, Pharmacia, Roche AstraZeneca Oncology, Aventis
TAILOR: Phase III trial comparing erlotinib with docetaxel in the second-line treatment of NSCLC patients with wild-type (wt) EGFR.
Authors: Marina Chiara Garassino, Olga Martelli, Anna Bettini, Irene Floriani, Elena Copreni, Calogero Lauricella, Monica Ganzinelli, Mirko Marabese, Massimo Broggini, Silvio Veronese, Giorgio Gherardi, Flavia Longo, Maria Agnese Fabbri, Maurizio Tomirotti, Oscar Alabiso, Maria Giuseppa Sarobba, Roberto Labianca, Silvia Marsoni, Gabriella Farina, Alberto Scanni
Journal: Journal of Clinical Oncology (2012)

LBA7501 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Monday, June 4, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Efficacy and safety of cetuximab, oxaliplatin, and capecitabine as first-line therapy for metastatic colorectal cancer (mCRC): Results of a phase II study
Authors: S. A. Barroso, E. Sanches, M. Ferreira, M. Passos, A. Sá, R. Nabiço, C. Sotto-Mayor, J. Espírito Santo, R. San- Bento
Journal: Journal of Clinical Oncology (2009)

e15013 Background: To date, few studies have investigated the use of cetuximab in combination with oxaliplatin and capecitabine in the first-line treatment of mCRC. We therefore conducted an uncontrolled, open-label, multicenter study to evaluate the efficacy and safety of this combination in this setting. Methods: Patients (pts) received intravenous (iv) oxaliplatin 130 mg/m 2 (3h day 1) plus capecitabine 1,000 mg/m 2 twice daily (days 1–14) every 3 weeks (XELOX) and cetuximab 400 mg/m 2 iv week 1 then 250 mg/m 2 weekly over 8 cycles. Treatment was continued until disease progression (PD), unacceptable toxicity or completion of therapy. Pts were followed until death. The primary endpoint was overall response rate (ORR). A sample size of 45 pts was necessary to obtain a 95% confidence interval (CI) for ORR with a maximum width of 15% assuming an ORR of 50–80%. Results: From Sept 2005-Jan 2007, 49 pts were enrolled (ITT population): 67% male, mean age 60 (range: 44–75) years, 56.3% ECOG PS 0. Of 42 pts evaluable for ORR, 4 (9.5%) achieved a complete response, 31 (73.8%) a partial response, 6 (14.3%) had stable disease and 1 (2.4%) had PD. The ORR was 83.3% (95% CI: 72.0–94.6%). Median time to progression was 9 months (95% CI: 7.1–10.9 months). Of the 49 pts evaluable for safety, 27 (55.1%) had at least one grade 3/4 toxicity, 42 (85.7%) had acne-like rash (8 pts [16.3%] grade 3). Most common grade 3/4 toxicities included diarrhea (n=9;18.4%) and changes in potassium (n=6;12.2%). 24 (3.4%) AEs led to dose reductions (12 unrelated, 10 unlikely and 2 definitely related to cetuximab), 56 (7.8%) led to a dose delay (12 unrelated, 28 unlikely, 8 possibly, 6 probably, 2 definitely related to cetuximab) and 2 (0.3%) led to infusion rate reduction (not treatment related). 27 (55.1%) pts discontinued therapy: 10 (20.4%) due to AEs, 7 (14.3%) PD, 10 (20.4%) other reasons. 33 (67.3%) pts died: 30 (61.2%) due to PD, 2 (4.1%) intercurrent event/disease, 1 (2.0%) acute pancreatitis. The results according with the HGFR evaluation by IHC will be presented. Conclusions: In this first-line mCRC study, 83.3% of pts treated with cetuximab, oxaliplatin and capecitabine achieved an overall response. This combination appears to be a highly active and well-tolerated regimen. No significant financial relationships to disclose.
Breast cancer inhibition by statins
Authors: L. Esserman, M. Campbell, M. Shoemaker, M. Lobo, C. Marx, C. Benz
Journal: Journal of Clinical Oncology (2004)

1003 Background: Statins are potent cholesterol-lowering drugs with pleiotropic activities including inhibition of Ras, Rac and Rho isoprenylation, altered PI3K/AKT activity and eNOS production, and reduced ubiquinone synthesis. These activities are independent of cholesterol reduction and may explain the prevention of breast cancer and other malignancies seen in a number of studies. Methods: We compared hydrophilic (pravastatin, P) vs. hydrophobic (lovastatin, L; simvastatin, S; fluvastatin, F) statins for their in vitro growth inhibitory effects on a panel of human breast cancer cell lines: MDA-MB-231, SKBR3, BT-474, and MCF-7. To evaluate statin potential to silence expression of specific oncogenes, stable MCF-7 sublines expressing ErbB2 or cyclinD1 promoter-driven luciferase reporters were assayed for growth and promoter activity after statin treatment. Finally, we evaluated the in vivo impact of statin administration in a murine ErbB2 breast cancer model. Results: In vitro results indicate that only hydrophobic statins have direct anticancer activity. There is a >2 log IC50 range in statin sensitivity (e.g. IC50 for S and F: <1um in MDA-231 vs. 91 and 85 for MCF-7, respectively). Cells with activated Ras or ErbB2 pathways appeared more sensitive than those overexpressing ER or cyclin D1. The NCI/DTP screen of L and S against >50 non-breast human cancer cell lines produced mean cytotoxic values (LC50, 48h) of 29 uM and 25 uM, respectively; with no apparent correlation between L and S on these cell lines (COMPARE analysis). Only S and F produced promoter-specific oncogene inhibition, with ErbB2 showing greater promoter sensitivity than cyclinD1. Finally, oral dosing of S (1–2mg/kg/day) in mice implanted with MCNeuA mammary cancer cells produced 50% inhibition in mean tumor size by day 27 (518 vs. 1019 mm3; p<0.001). Conclusions: Hydrophobic statins exert direct anticancer activity in vitro, especially in cell lines with activated Ras or ErbB2 pathways, and inhibit ErbB2-dependent breast tumorigenic growth in vivo at a daily dose comparable to that approved for cholesterol reduction in humans. Among the statins tested, F demonstrated the most potent antiproliferative and oncogene-specific inhibitory activity. No significant financial relationships to disclose.
Combination Of Ofatumumab and Bortezomib In Patients With Indolent B-Cell Lymphomas Who Relapsed &gt;6 Months After Rituximab-Containing Regimen: A Brown University Oncology Research Group Phase II Study
Authors: Jorge J Castillo, James N Butera, Eric S Winer, Frederick Lansigan, Kayla Rosati, Howard Safran
Journal: Blood (2013)
Denosumab for the treatment of men with low bone mineral density: 24-month results from the Adamo Trial
Authors: B Langdahl, C Teglbjaerg, PR Ho, R Chapurlat, E Czerwinski, D Kendler, Jean-Yves Reginster, A Kivitz, M Lewiecki, P Miller, M Bolognese, M McClung, H Bone, O Ljunggren, B Abrahamsen, U Gruntmanis, YC Yang, R Wagman, S Siddhanti, E Orwoll
Journal: Endocrine Reviews (2014)
Abstract 10095: Progression of Carotid Thickness in Adolescents and Young Adults: Determinants of Accelerated Aging in Youth
Authors: Elaine M Urbina, Zhiqian Gao, Connie E McCoy, Philip R Khoury, Amy S Shah, Thomas R Kimball, Lawrence M Dolan
Journal: Circulation (2012)

In adults, accumulation of CV risk factors increases carotid intima-media thickness (IMT) and carotid stiffness and accelerates progression of IMT. The rate of progression of carotid IMT and stiffness in adolescents and young adults is not known, nor has the effect of CV risk factors on progression been documented. We examined carotid IMT and stiffness (beta stiffness index=Beta; Incremental elastic modulus=Einc; Peterson elastic modulus=PEM; Young’s elastic modulus=YEM), BMI, BP, CRP, fasting lipids, and HbA1c in 124 subjects age 10-22 years at baseline. Measures were repeated after 4 years of follow-up (mean age 22.1 + 3.3, 49% male, 33% Caucasian, 1/3 T2DM) to elucidate determinants of accelerated aging. Mean values between baseline and follow-up were evaluated by t-tests. General linear models were constructed to determine significant predictors of follow-up measures. The full model contained age, race (Caucasian/African-American), sex, presence of T2DM, baseline IMT or stiffness measure, baseline and...
Liver functional reserve and survival after sunitinib therapy in cirrhotic patients with advanced hepatocellular carcinoma.
Authors: M. Biolato, M. Basso, A. Cassano, C. Cefalo, L. Miele, M. Pompili, G. L. Rapaccini, G. Gasbarrini, C. Barone, A. Grieco
Journal: Journal of Clinical Oncology (2010)

e14600 Background: Sunitinib, an oral multitargeted tyrosine kinase inhibitor, showed encouraging results on time to tumor progression against advanced hepatocellular carcinoma (HCC) (Lancet Oncol 2009; 10:794–800; J Clin Oncol 2009; 27:3027- 3035). Aim of this study is to evaluate the effect of a 4-week sunitinib 50 mg/d treatment on liver functional reserve in an open-label, multidisciplinary, phase II trial. Methods: 19 patients with advanced HCC were enrolled. Mean age was 66.6 years, and 17 were male. 5 patients had portal vein thrombosis and 14 had extrahepatic dissemination. All but one were cirrhotic (14 Child A and 4 Child B). Patients received sunitinib 50 mg/d for 4 weeks followed by 2 weeks of rest per cycle. Classical liver function tests and dynamic functional reserve, assessed by aminopiryne and methacetin breath test, were performed on days 1 and 28. Results: At 28 days, MELD (p=0.005) and 13C-methacetin breath test (p=0.022) significantly worsened (Table). Despite the limited study population, these results suggest a liver function worsening after 28 days therapy on sunitinib 50 mg/d, unclear if drug or disease progression related. With a median follow-up time of 31.5 weeks, the overall survival of this cohort was 28.0 weeks (95% CI, 1.6 to 54.3 weeks). Higher MELD and lower 13C-methacetin breath test at baseline were associated with poor overall survival (r=0.134 and r=0.054, respectively). Conclusions: Sunitinib 50 mg/d could worse liver function in cirrhotic patients with HCC. Patients with better liver functional reserve at baseline seem to get a survival benefit from sunitinib therapy. Results Day 1 Day 28 p Child-Pugh 5.83 5.66 0.161 Meld 8.83 9.66 0.005 13C-aminopiryne breath test* 6.72% 6.71% 0.480 13C-methacetin breath test* 16.15% 12.80% 0.022 * Cumulative exhaled rate at 120 minutes. No significant financial relationships to disclose.
Next-generation sequencing (NGS) to identify potential therapeutic targets in advanced pancreatic cancer.
Authors: Madappa N. Kundranda, Donald Peter Braun, Kim Kramer, Jizhou Ai, Bradford A. Tan, Eiko Kilmant, George L. River, Maurie Markman
Journal: Journal of Clinical Oncology (2015)

357 Background: Even with the advent of newer systemic therapies; long term survival in advanced PDAC is dismal. Hence there is an urgent need to use technologies such as NGS to identify potential therapeutic targets. Methods: A retrospective analysis was performed of all advanced PDAC patients (pts) evaluated with NGS through Foundation One (Foundation Medicine Inc., MA). DNA was extracted from biopsy specimens and sequencing was performed of 315 cancer-related genes plus select introns. Statistical analysis including Kaplan Meier survival analysis along with the log-rank test was used to compare the differences between groups. Results: 53pts were analyzed between Nov 2012 - Sep 2014; 25 (47%) were females; median age was 59 yrs (range: 33-77). 178 genomic alterations (GAs) were identified in 52 pts (average 3.43 GAs/pt). The GAs included mutations 140 (78%), amplifications 25 (14%), loss/deletions 13 (7%) and 1 pt had no GAs. Most frequent GAs and associated survival are listed in Table 1. There was no statistically significant difference in median overall survival (mOS) between the groups with or without KRAS (22.1 vs. 21 months; p=0.95) and with or without TP53 (21 vs. 23.4 months; p=0.76). 6/52 pts (12%) who had received at least 3 prior lines of therapy (range 3-4) and had an ECOG performance status &lt;2; were treated off label with trametinib. The median PFS on the last therapy prior was 5 months (range 1.6-7). On trametinib, the median PFS was 1.9 months (range 1.1-7.1) with mOS of 5.1 months. Conclusions: Our data demonstrate that there are a range of GAs that are eligible for investigational targeted therapies. Secondly, the choice of agents (eg. Trametinib - targets downstream RAS effectors ) based on individual genomic profile can be considered when an appropriate clinical trial is not available or inaccessible even in heavily pretreated patients with a good performance status. Tumor profiling should be utilized in drug development to personalize treatment options in patients with advanced PDAC. [Table: see text]
Treatment results with an aggressive chemotherapeutic regimen (MACOP-B) for intermediate- and some high-grade non-Hodgkin's lymphomas.
Authors: A M Schneider, D J Straus, A E Schluger, D A Lowenthal, B Koziner, B J Lee, G Wong, B D Clarkson
Journal: Journal of Clinical Oncology (1990)

Seventy previously untreated patients with stage II, III, and IV intermediate- or high-grade lymphoma were treated with methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) between September 1985 and November 1987. Forty-nine of these patients had diffuse large-cell lymphoma (DLCL), and eight of these patients were human immunodeficiency virus (HIV)-positive. Complete responses were achieved in 54% of all patients and 52% of those with DLCL. With follow-up extending to 36 months, 45% of all DLCL patients are alive, and 50% are still living, if the HIV-positive patients are excluded from the analysis. Chemotherapy was quite toxic. Seventy-five percent of patients had severe mucositis, 42% had peripheral neuropathy, 50% required hospitalization, and 54% experienced leukopenia with a WBC count below 1,000/microL. Seven percent (five patients) died of toxicity related to the chemotherapy. Our analysis of prognostic parameters indicated that B symptoms, a performance status below 80, and, to a lesser extent, elevation of serum lactic acid dehydrogenase (LDH) (in HIV-negative DLCL patients) were associated with an inferior survival. Advanced age, sex, and bulky disease were not found to have a statistically significant effect on survival. Our preliminary results indicate that MACOP-B chemotherapy is an effective regimen for high- and intermediate-grade lymphomas. However, the survival for patients with DLCL treated with MACOP-B is no different than that achieved with previous regimens at our institution.
Analysis of 210 febrile neutropenic episodes during induction therapy of acute myeloid leukemia (AML): An institutional experience from a developing country
Authors: M. L. Konatam, S. Rajappa, R. Digumarti, L. S. Maddali, L. Vemu
Journal: Journal of Clinical Oncology (2008)

18011 Background: Infections are a major cause of morbidity and mortality in AML patients during induction therapy. Prompt antibiotic therapy based on clinical condition and local microbiological susceptibility pattern is vital to their survival. Methods: Retrospective analysis of 100 patients with AML undergoing induction chemotherapy between Jan 2003 and December 2007 was done. Prophylactic antibiotics, anti-fungals or hematopoietic growth factors were not used. Results: The median age was 25 years (range, 1–64) with 56 males and 44 females. Forty one patients (41%) had grade 3 or 4 neutropenia at presentation of which 18 patients (44%) had evidence of infection. 210 episodes of febrile neutropenia were documented with a mean of 2 episodes (range, 1–5) per patient. Clinically, a focus of sepsis was documented in 91 episodes (44%). Twenty patients (20%) had central venous lines. Lung was the most common focus (27%), followed by gastrointestinal tract (14%), skin and subcutaneous tissue (7%), line-related (4%) and 2% each for ear, throat and gums. Blood and sputum cultures were positive in 35 (17%) and 3 (2%) episodes respectively. Of the positive cultures, 92% grew bacteria and 8% fungus. E.coli was the most common isolate (34%), followed by Pseudomonas (21%), Staphylococcus (16%), polymicrobial (16%), Candida in 10%, 5% each of Enterobacter, Enterococcus and Acinetobacter, 2% of Aspergillus, Klebsiella & Streptococcus. 80% responded to initial empiric antibiotic therapy. 60% of all patients had a second spike of fever. Second line antibiotics and antifungals were started in 50% each. 67% responded to second line antibiotics while 57% to antifungal. 11 patients (11%) died during induction therapy, of which 9% were infection related. Conclusions: Culture positive infections are not common in febrile neutropenia during induction therapy of AML. Gram-negative bacteria are the predominant pathogens. This may be due to infrequent use of central lines and absence of prophylactic antibiotic use. In spite of initial response, breakthrough infections are common. Most induction deaths are infection related. No significant financial relationships to disclose.
TCT-68 Predictors of Elective Support Device Insertion Prior to High Risk Percutaneous Coronary Intervention: Changing Trends between 1993–2013
Authors: Aatish Garg, Akhil Parashar, Shikhar Agarwal, E. Murat Tuzcu, Samir Kapadia
Journal: Journal of the American College of Cardiology (2014)
A pilot assessment of nutritional needs in cancer outpatients receiving active anticancer therapy
Authors: T. Li, U. Hopkins, G. Jung, S. Herszkopf, Y. Mossavar-Rahmani, M. Kim, A. Moadel, J. Wylie-Rosett
Journal: Journal of Clinical Oncology (2008)

20680 Background: Meeting the complex nutritional needs of cancer patients on treatment is critical to ensuring treatment adherence and optimal outcomes. The primary objective of this study was to assess the nutritional status and needs of cancer outpatients receiving anticancer therapy in our institution using a clinically validated Patient-Generated Subjective Global Assessment (PG-SGA) form and several population-specific survey questions. Methods: Cancer patients receiving active systemic therapy in oncology clinics and ambulatory infusion units at our institution were eligible for this study. Investigators conducted the one-time survey in candidates identified by nurses or physicians. The PG-SGA numerical score (0–37) and global nutrition assessment category (A, B and C) were assessed by two investigators. Results: Over a period of 6 months, ∼200 outpatient cancer patients treated by more than 15 faculty oncologists participated in the study. Complete assessments were available for 180 patients (median age: 68 ±10 yr; female/male: 66%/34%; Black/Hispanic/White/Asian/Others: 34%/30%/28%/5%/3%). Cancer types included 44 (24%) gastrointestinal, 34 (19%) breast, 31 (17%) gynecological, 29 (16%) lung, 24 (13%) hematological, 11 (6%) head and neck, and 7 (4%) other cancer. The distributions of nutritional categories and PG-SGA scores are summarized in the table below. Our data confirm that the PG-SGA score is a good screening tool for identifying malnourished (B and C) outpatients for dietician consult. Among well-nourished (A) patients, 35% had weight gain and 51% had stable weight. Almost all (98%) of these patients had a PG-SGA score of ≥2, mainly from the presence of symptoms affecting food intake. We propose a new nutrition education intervention in these patients for early prevention of malnutrition and improvement of weight and symptom control. Conclusions: Individualized nutrition intervention is needed even for patients appearing well-nourished for weight control and symptom management. Nutrition Category No. of Patients (%) PG-SGA Scores Nutritional Triage Recommendations (No. of Patients, %) Median ± SD Range No Intervention (0-1) Education (2-3) Dietician (4-8) Urgent Intervention (≥9) A (well-nourished) 110 (61%) 4.0 ± 3.2 1-17 2 (2%) 43 (39%) 51 (46%) 14 (13%) B (moderately malnourished) 40 (22%) 13.0 ± 3.3 8–21 0 0 2 (5%) 38 (95%) C (severely malnourished) 30 (17%) 18.0 ± 5.2 6–29 0 0 1 (3%) 29 (97%) No significant financial relationships to disclose.