tbuckley/cabot-search huggingface dataset:
An autologous tumor-derived heat shock protein vaccine for high risk ovarian cancer
Authors: Z. Li, J. D. Nash, Y. Qiao, J. M. Kulko, D. K. Wilcox, J. Gaffney, C. D. Runowicz, S. A. Simonich, B. Liu, P. K. Srivastava
Journal: Journal of Clinical Oncology (2005)

9592 Background: Five-year survival for stage III and IV ovarian cancer of the epithelial cell origin is less than 30%, despite surgery and chemotherapy, due largely to disease relapse. Tumor-derived heat shock protein (HSP) gp96-peptide complexes can induce tumor-protective T cell immunity in multiple preclinical models. We have initiated the first study of consolidation therapy with autologous gp96 vaccine for stage III/IV ovarian cancer. Methods: All patients have the diagnosis of stage III or IV ovarian cancers. Gp96-peptide complexes are purified from autologous tumors procured at the initial surgery. Patients who have completed standard therapy (Carboplatin/Taxane) and have no evidence of progressive disease are eligible to receive the vaccine. The first 11 patients receive gp96, 25 μg i.d., weekly for 8 weeks. The second group of 11 patients will receive the same dose and schedule of gp96 vaccine, mixed with 100 μg GM-CSF. Patients are followed clinically for toxicity and relapse-free survival, and immunologically for T cell and NK cell responses. Results: Twenty patients signed consent and their tumors were procured. So far, gp96 was purified successfully for all 8 patients. Five have completed the vaccination with gp96. Three are being immunized. No patients received gp96 and GM-CSF just yet. Grade II or higher toxicity was not observed. All 5 patients demonstrated increased NK cell activity measured by ELISPOT against K562 cells. Three of 5 patients showed increased IFNγ-producing cells in the peripheral blood against autologous gp96-peptide complexes that are MHC class I-dependent. Conclusions: This is the first trial to test an HSP-based vaccine against ovarian cancer in a consolidation setting. Our results demonstrated that it is feasible and well-tolerated. In addition, measurable immunological responses were observed. Future studies will determine the clinical efficacy of gp96 vaccine for ovarian cancer and the potential benefits of adding GM-CSF in HSP vaccines. Acknowledgement: This work is supported in part by the Pamela Weinstein Ovarian Cancer Endowment Fund. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Antigenics Antigenics
The British Society of Gastroenterology. 1984 annual meeting, Liverpool. Abstracts.
Authors: J Neuberger, E Christensen, G Altman, N Tygstrup, Roger Williams, M Camilleri, J Malagelada, S Phillips, B Williamson, J Simpson, G Mclatchie, G Gillespie, J Baxter, S Jenkins, R Mackie, N Roberts, D Day, W Taylor, R Shields
Journal: Gut (1984)

Primary biliary cirrhosis (PBC) is one of the commonest parenchymal liver diseases currently being treated by liver transplantation in the Addenbrookes/King's College Hospital programme, but difficulties arise in choos- ing the optimal time for surgery.Currently, A1133
Neutrophil Biology and the Next Generation of Myeloid Growth Factors
Authors: David C. Dale
Journal: Journal of the National Comprehensive Cancer Network (2009)

Neutrophils are the body's critical phagocytic cells for defense against bacterial and fungal infections; bone marrow must produce approximately 10 x 109 neutrophils/kg/d to maintain normal blood neutrophil counts. Production of neutrophils depends on myeloid growth factors, particularly granulocyte colony-stimulating factor (G-CSF). After the original phase of development, researchers modified these growth factors to increase their size and delay renal clearance, increase their biologic potency, and create unique molecules for business purposes. Pegylated G-CSF is a successful product of these efforts. Researchers have also tried to identify small molecules to serve as oral agents that mimic the parent molecules, but these programs have been less successful. In 2006, the European Medicines Agency established guidelines for the introduction of new biologic medicinal products claimed to be similar to reference products that had previously been granted marketing authorization in the European community, called bio-similars. Globally, new and copied versions of G-CSF and other myeloid growth factors are now appearing. Some properties of the myeloid growth factors are similar to other agents, offering opportunities for the development of alternative drugs and treatments. For example, recent research shows that hematopoietic progenitor cells can be mobilized with a chemokine receptor antagonist, chemotherapy, G-CSF, and granulocyte macrophage colony-stimulating factor. Advances in neutrophil biology coupled with better understanding and development of myeloid growth factors offer great promise for improving the care of patients with cancer and many other disorders.
Update on the first phase I study of AGRO100 in advanced cancer
Authors: D. A. Laber, V. R. Sharma, L. Bhupalam, B. Taft, F. J. Hendler, K. M. Barnhart
Journal: Journal of Clinical Oncology (2005)

3064 Background: AGRO100 is an oligonucleotide that functions as an aptamer and binds to nucleolin, a protein found intranuclear in all cells, but uniquely expressed on the surface of tumor cells. Such binding leads to internalization of the complex, and a strong anti-proliferative response in the tumor cell. Objectives of this study are to (1) determine the maximum-tolerated dose and dose-limiting toxicity of AGRO100 in patients with advanced cancer; (2) determine the pharmacokinetic distribution and profile of AGRO100; (3) obtain preliminary evidence of clinical and biological responses to AGRO100 therapy. Methods: AGRO100 was administered as continuous intravenous infusion in the hospital. Dose level 1 was 1 mg/kg/day over 4 days. Patients were enrolled in cohorts of 3. If no toxicity was observed 28 days after therapy, the dose of AGRO100 was increased up to 10 mg/kg/day over 7 days. Toxicity was graded by the NCI CTCAE v3.0. Responses were assessed every 28 days by using the RECIST guidelines. Results: From September 2003 through July 2004, 17 patients with advanced cancer were enrolled. Prior to AGRO100 treatment, all patients had objective documentation of progressive metastatic disease after multiple therapies. Patient characteristics: median age 63 (30 - 74), PS ECOG 1 (0 - 2). Type of cancer: renal (3), colon (3), pancreatic (2), and lung, lymphoma, gastric, cervical, melanoma, prostate, synovial sarcoma, hemangiopericytoma (1 each). All patients are evaluable for toxicity and response. 22 cycles of AGRO100 have been administered (1–2 cycles/patient). Eight (50%) patients had stable disease at two months after treatment; disease was stable in these patients for 2 - 9 months before progression. One patient is maintaining a near complete response after more than 6 months. No toxicity of any type related to drug administration has been observed. AGRO100 was present in the serum during the entire infusion and the concentration was related to the dose. Conclusions: AGRO100 is the first nucleic acid aptamer ever tested for the treatment of cancer in humans. This non-toxic targeted cancer therapy is showing very promising responses. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aptamera
Efficacy of octreotide LAR (OCT) in patients (pts) with advanced neuroendocrine tumors (NET): A post hoc analysis of the placebo (PBO) arm of the phase III RADIANT-2 study with updated survival data.
Authors: Jonathan R. Strosberg, James C. Yao, Emilio Bajetta, Mounir Aout, Bert Bakker, John D. Hainsworth, Philippe B. Ruszniewski, Eric Van Cutsem, Kjell E. Oberg, Marianne E. Pavel
Journal: Journal of Clinical Oncology (2014)

265 Background: In pts with metastatic midgut NET, OCT showed antitumor activity and significantly extended time to tumor progression (TTP) vs PBO (PROMID trial, Rinke et al. 2009). We present a post hoc analysis assessing efficacy of OCT (30 mg q28d) in the PBO+ OCT arm of the phase III RADIANT-2 study. Methods: For this post hoc analysis, progression-free survival (PFS by central review, cutoff Apr 2, 2010) and overall survival (OS, cutoff Jun 13, 2013) in the PBO + OCT arm were estimated by prior somatostatin analogue (SSA) use and primary tumor location subgroups using the Kaplan-Meier (KM) method. Results: 213 pts were randomized to PBO + OCT (median age, 60 yrs; male, 58%; WHO PS: 0/1/2 in 66%/29%/5% pts; &gt;80% had well-differentiated disease). Of these, 47 (22%) were SSA naïve (foregut, 32%; midgut, 51%; hindgut, 4%; not classified or missing, 13%) and 166 (78%) had received SSA (foregut, 10%; midgut, 72%; hindgut, 11%; not classified or missing, 7%) prior to study entry. Median PFS (95% CI) for pts who were SSA naïve vs who had received SSA was 13.6 (8.2-22.7) mos vs 11.1 (8.4-14.2) mos. By primary tumor location, median PFS (95% CI) in SSA naïve pts vs who received SSA was 5.7 (2.8-27.8) mos vs 8.7 (2.8-13.9) mos for foregut, 22.2 (8.3-29.5) mos vs 12.0 (8.4-17.7) mos for midgut, and not-reached (NR; 4.7-NR) vs 6.6 (3.0-13.0) mos for hindgut. OS analysis is in table. Conclusions: This post hoc analysis of the PBO + OCT arm of the RADIANT-2 study showed a PFS of 13.6 mos in SSA naïve pts treated with OCT. While the RADIANT-2 study PBO arm differs from PROMID in patient population and method of assessment of tumor progression, the data from this post hoc analysis provide additional evidence of the antiproliferative effect of OCT in NET. Clinical trial information: NCT00412061. [Table: see text]
Phase 1 Clinical Trial of the Novel Structure Proteasome Inhibitor NPI-0052.
Authors: Andrew Spencer, Michael Millward, Paul Mainwaring, Simon Harrison, Laurence Catley, Amanda Townsend, Shawgi Sukumaran, Angie M. Longenecker, Michael A. Palladino, G. Kenneth Lloyd, Saskia Neuteboom, Peeter Padrik, Matthew A. Spear, Timothy Price
Journal: Blood (2009)
Race and albuterol premedication are risk factors for hypersensitivity reactions to cetuximab
Authors: S. N. Waqar, B. R. Tan, B. Zubal, D. I. Kuperman, D. R. Adkins
Journal: Journal of Clinical Oncology (2008)

20503 Background: Cetuximab (C-mab) is a recombinant (human/mouse) epidermal growth factor receptor antibody indicated for use in patients with colorectal cancer (CRC) and head and neck cancer (HNC). Serious grade 3–4 hypersensitivity reactions (HSR) to C-mab have been reported in the frequency of 0.5%-22%. The purpose of this paper is to study risk factors for HSR to C-mab at our institution. Methods: A retrospective record review was performed of serial patients treated with C-mab at the Siteman Cancer Center, St. Louis, MO for CRC from July 2004 to July 2006 and HNC from June 2005 to August 2007. HSR were defined as allergic reactions to C-mab and were graded 1–5 according to severity, based on the Common Terminology Criteria for Adverse Events v3.0 (CTCAE). Data regarding demographics and premedication history was collected from patient charts. Results: Fifty-one patients (27 males and 24 females) with CRC and 50 patients (38 males and 12 females) with HNC treated with C-mab were identified and their mean age was 60 ±12.07 years. Seventy (69.3%) patients were Caucasian and 31 (30.7%) were African American. All patients were pre-medicated with benadryl prior to C-mab administration. Data regarding pepcid, dexamethasone and solucortef premedication was available for 84 patients. Of these, 14(16.7%) received pepcid, 32 (38.1%) received dexamethasone and 25 (29.8%) received solucortef. Twenty four (48%) of HNC patients also received albuterol. Eleven patients (10.9%) developed HSR. Serious grade 3–4 HSR were seen in 9 patients (8.9%). Race was strongly associated with HSR. All 11 patients who developed HSR were Caucasian (Fisher's exact p=0.017). No grade 3–4 HSR were seen in the group who received albuterol (Fisher's exact p=0.077). There was no statistically significant effect of dexamethasone, pepcid or solucortef premedication on the risk of HSR, although the small numbers were limiting. Age and gender had no effect on the risk of HSR. Conclusions: Race is a strong predictor for HSR. Additional pre-medication with albuterol may prevent grade 3–4 HSR. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Abraxis Oncology, Amgen, Bristol-Myers Squibb, Genentech™ BioOncology, ImClone Systems Incorporated, Pfizer Oncology, sanofi-aventis
Long term progression-free survival correlates with KIT/PDGFR mutational status in advanced GIST patients treated with imatinib (IM)
Authors: A. Cioffi, J. F. Emile, J. Domont, I. Ray-Coquard, J. Y. Blay, P. Terrier, S. Bonvalot, C. Le Péchoux, D. Perol, A. Le Cesne
Journal: Journal of Clinical Oncology (2007)

10053 Background: IM is the first-line treatment for advanced GIST and must be given continuously until disease progression or intolerance. The median progression free survival (PFS) of pts included in consecutive prospective trials is around 2 years. Pt characteristics and the exact mutational status of GIST who benefit the most from IM in term of prolonged response to IM and prolonged PFS are unknown. Methods: two hundred and seventy six pts were included in 2 consecutive prospective trials since 2001 in 2 centers. Pts receiving IM for at least 3 yrs (3 to 5 yrs) who have no exhibited any kind of progression and receiving IM continuously until december 2006 have been retrospectively analyzed both clinically and biologically. KIT and PDGFR mutations were analyzed using DHPLC and direct sequencing of frequently mutated exons (KIT 9, 11, 13, 14, 17, PDGFR 12, 14, 18). Results: after a median follow-up of 4 yrs (3–5yrs), 31 pts are free of progression and received IM continuously. The characteristics of these long term survivors favorable cohort of pts are as following: man (61%), small bowel origin (60%), liver involvement (80%), synchronous metastasis at inclusion (58%), and normal initial hemoglobin level (92%&gt;10 g/dl). As of now, 15 pts are evaluable for mutational analysis. All but one (exon 9) pts had an exon 11 mutation. The most commun genetic alteration was an in frame deletion between 550 to 558. Conclusions: Pts with metastatic GIST arising from small bowel harboring an exon 11 mutation in the vicinity of codon 557–558 may be a very favorable subgroup. No significant financial relationships to disclose.
SU11248 (Sunitinib) does inhibit tumor growth and angiogenesis in an ovarian cancer murine xenograft model
Authors: D. O. Bauerschlag, C. Schem, S. Tiwari, I. Meinhold-Heerlein, C. Mundhenke, M. Weigel, J. H. Egberts, H. Kalthoff, W. Jonat, N. Maass
Journal: Journal of Clinical Oncology (2008)

16557 Background: Ovarian cancer is newly diagnosed in∼ 22,000 cases each year in the US. Standard treatment is cyto reductive surgery followed by a platinum based chemotherapy. Some patients do not respond to primary chemotherapy and the majority of patients suffer from disease recurrence and eventually succumb to platinum-resistant tumors. The establishment of new strategies which target molecules and signaling pathways may provide new treatment options for the treatment of ovarian cancer. Sunitinib is an oral multitargeted tyrosine kinase inhibitor that inhibits VEGFR, PDGFR, FLT3, KIT. Signaling blockade of these pathways is associated with anti-tumor and anti- angiogenesis activity. The aim of this study is to evaluate the efficacy of SU11248 in inhibiting ovarian tumor growth and angiogenesis in a xenograft mouse model. Methods: 5 million Skov3 ovarian cancer cells - which are in vitro platinum resistant - stably transfected with luciferase were injected i.p. into SCID beige mice. 28 days after implantation one group of mice were treated with a clinically relevant dosage of 40mg/kg SU11248 (orally/daily) and another group given vehicle control only. Tumor development was monitored weekly by measuring luciferase activity in vivo using a Peltier cooled charged-coupled device camera (NightOWL LB 983; Berthold). After 80 days of treatment all mice were sacrificed and CD31 staining was performed to measure micro-vessel density (MVD). Results: We report here for the first time that SU11248 does inhibit tumor growth and angiogenesis in an ovarian cancer murine xenograft model. Treatment with SU11248 showed a 1.6 fold reduction in tumor growth as visualized and measured by bioluminescence. Histological examination of tumors from treated mice showed a 2.5 fold reduced MVD when compared with the control mice. The control mice developed clinically relevant amount of ascites when compared to the SU11248 treated group. Conclusions: The inhibition of selective tyrosine kinases in an ovarian cancer mouse model significantly reduced tumor growth and angiogenesis. These results suggest that SU11248 is a small molecule drug which can potentially be utilized to target primary tumors with intrinsic platinum-resistance and recurrent tumors with acquired platinum-resistance. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer
Gemcitabine and cisplatin in metastatic breast cancer
Authors: G. L. Moura, R. Pasquini, A. Frare, K. Vianna, L. Albini, S. Padilha
Journal: Journal of Clinical Oncology (2007)

1084 Background: Gemcitabine plus cisplatin have synergistic activity and have been tested in several schedules and doses in metastatic breast cancer. Our objectives were to assesss the efficacy and toxicity of gemcitabine and cisplatin in pretreated patients. Methods: Measurable disease and at least two prior anthracycline and /or taxane-containing regimen in either metastatic or adjuvant setting was required. Treatment consisted of gemcitabine 700mg/m(2) IV infusion over 30 min plus cisplatin 30mg(2) given on day1 and 8 every 3 weeks. Results: Seventy four patients with median age of 48 years (range 26- 73) were recruited. A median of six cycles of the study treatment was delivered. The overal response rate was 30% (95% confidence interval, 12–53%). Median time to progreesion was 30.6 weeks (95%CI, 12.6–44 weeks). Median survival was 73.2 weeks (95% CI, 47.1–93.2 weeks). Toxicities included grade 3 and 4 leukopenia in 27(36.4%), anemia in 19 (25.6%) and oral mucositis in 4 (5.4%). No grade 3 or 4 peripheral neurophaty, hepatic or renal dysfunction was observed. No treatment-related death ocurred. Conclusions: Gemcitabine plus cisplatin is a well tollerated and active treatment in heavily pretreated patients with metastatic breast cancer. No significant financial relationships to disclose.
The Gail Model as a diagnostic indicator in African-American women: Truth or consequence
Authors: L. Adams-Campbell, K. Makambi, J. Palmer, L. Rosenberg
Journal: Journal of Clinical Oncology (2004)

1017 Background: The Gail model has been utilized to predict the risk of breast cancer in women of all race/ethnic groups although the model has only been validated in US white women. The aim of the present study was to assess the utility of the Gail Model as a diagnostic predictor in African-American women. Methods: Risk profiles were derived via a self reported questionnaire at the time of enrollment into the Black Women's Health Study in 1995. Bi-annual questionnaires were mailed to the participants to update the risk factor information and to determine the incident cases of breast cancer. The study of 150 cases and controls revealed that the sensitivity of the Gail Model was 14.7% (11/75) and the specificity was 93.3% (70/75) among the African-American women. The risk based on the Gail model ranged from 0.3 to 2.7 among the cases and from 0.2 to 2.4 among the controls. Conclusions: The Gail model underestimates the risk of developing breast cancer among the African-American women. Therefore, the Gail Model appears to be an inappropriate model to be used in African-American women to predict breast cancer risk. No significant financial relationships to disclose.
The combination of a chemotherapy doublet (gemcitabine plus capecitabine) with a biologic doublet (bevacizumab plus erlotinib) in patients with advanced pancreatic adenocarcinoma: The TARGET study.
Authors: D. J. Watkins, N. Starling, I. Chau, J. Thomas, J. Webb, J. R. Oates, G. Brown, K. Thomas, D. Cunningham
Journal: Journal of Clinical Oncology (2010)

4036 Background: Preclinical data support the combined inhibition of VEGF and EGFR pathways in the treatment of pancreatic cancer (PC). Following a dose-finding phase I study (Starling et al, JCO 2009) the efficacy and toxicity of a four drug regimen utilizing gemcitabine and capecitabine (GemCap) in combination with bevacizumab (BV) and erlotinib (E) was further assessed in patients (pts) with advanced PC. Methods: Eligible pts had locally advanced (LA) or metastatic PC, were WHO PS ≤2 and had received no prior chemotherapy for advanced disease. The phase II cohort received the dose schedule recommend from phase I as follows; Gem (1,000 mg/m2 D1, 8, 15), Cap (1,400 mg/m2 D1-21), BV (5 mg/m2 D1, 15) and E (100 mg daily) every 28 days. Planned recruitment was 44 pts (phase I and II). The primary endpoint was radiological response rate by RECIST. CT assessment was performed every 8 weeks. Consolidation radiotherapy was considered in LA pts following 6 cycles of treatment. Results: Outcome data for all 44 pts (20 pts in the phase I cohort and a further 24 pts in the phase II cohort) recruited between Jan 06 and Mar 09 are presented. Median age 63 (range 33-80), PS 0:1:2; 3:40:1, LA:metastatic; 20:24. Median cycles delivered 6 (range 1-16). Significant toxicities are tabulated below. 60 day all-cause mortality was 4.5%. Confirmed radiological responses were seen in 23% (95% CI:11-38%) of pts. At time of analysis 15 pts remain alive. The median PFS and OS for the entire cohort was 8.5 and 12.8 months respectively. Median and 1 year OS was 11.1 months and 49% (95% CI:28-71%) in pts with metastatic disease and 14.8 months & 89% (95% CI:76-100%) in pts with LA disease respectively. Conclusions: The combination of GemCap, BV and E demonstrates good efficacy and has a manageable toxicity profile in pts of performance status 0 or 1. Toxicity (n = 44) All grades (%) Grade 3/4 (%) Diarrhea 34 (77) 8 (18) Stomatitis 29 (66) 7 (16) Nausea/vomiting 35 (80) 3 (7) Acneiform rash 31 (70) 7 (16) Hand-foot syndrome 29 (66) 8 (18) Lethargy 44 (100) 14 (32) Venous thromboembolism 5 (11) 5 (11) GI bleed 5 (11) 2 (5) Febrile neutropenia - 0 (0) Neutropenia 38 (86) 21 (48) Platelets 36 (82) 6 (14) Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche Roche Roche