tbuckley/cabot-search huggingface dataset:
Abagovomab maintenance therapy in patients with epithelial ovarian cancer after complete response (CR) post-first-line chemotherapy (FLCT): Preliminary results of the randomized, double-blind, placebo-controlled, multicenter MIMOSA trial.
Authors: P. Sabbatini, J. S. Berek, A. Casado, K. Cwiertka, T. Pinter, A. Pluzanska, G. Scambia, E. Pujade-Lauraine, J. B. Vermorken, J. Pfisterer
Journal: Journal of Clinical Oncology (2010)

5036 Background: Phase I/II data demonstrated that abagovomab, a murine monoclonal anti-idiotypic antibody against CA125, induces an active immune response against CA125 tumor-associated antigen (TAA). Methods: Abagovomab is evaluated in a randomized (2:1) double-blind, placebo-controlled, multicenter phase III trial in patients with FIGO stage III/IV ovarian cancer in CR after platinum-taxane based FLCT. Abavovomab 2 mg or placebo is given as 1 mL/sc every 2 weeks for 6 weeks (induction phase), then every 4 weeks (maintenance phase) until recurrence or up to 21 months after randomization of last patient. Primary end-point: PFS; secondary end-points: OS and immunological response. Results: Enrolment was completed December 2008. Characteristics of 888 patients are: mean age, 56.3 yrs; ECOG PS ≤ 1: > 90%; serous papillary subtype: 81.4%; FIGO stage III: 85.9%; CA125 ≤ 35 U/mL after 3rd cycle FLCT: 78.9%. As of September 2009 (mean exposure, 10 months), 20 potentially treatment-related SAEs (placebo/ Abagovomab) are reported. 9.3% of patients withdrew the study due to AE. Among nonserious AEs, most were mild/moderate intensity. Most frequent were injection site reaction and fatigue, reported respectively in 76.6% and 16.2% of patients. Last DSMB review (Oct 2009) found no safety issues and recommended continuation. Preliminary blinded immunologic results (data for weeks 10 and 22) showed 68% and 69% of overall patients were positive for Ab3 (median value = 62.000 ng/mL and 337.000 ng/mL, respectively) while 53% and 66% patients were positive for HAMA (median values = 510 ng/mL and 644 ng/mL, respectively). Further update of safety and immunological data will be available at the time of meeting. Conclusions: Preliminary blinded results confirmed that abagovomab, given as repeated monthly sc administrations, is safe and induces a measurable immune response comparable with the one observed in previous studies. The double-blind period will end December 2010 and the final efficacy data will be available the first half of 2011. Submitted by MIMOSA Trial Steering Committee. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Menarini
Combination of Antioxidant Cocktail and Pregabalin in the Management of Pain in Chronic Pancreatitis After Ductal Clearance: A Randomized, Double-Blinded, Placebo-Controlled Trial
Authors: R. Talukdar, S. Lakhtakia, R. Pradeep, G.V. Rao, D.N. Reddy
Journal: Clinical Gastroenterology and Hepatology (2015)
Abstract #3610: Assessment of circulating tumor cells in disease-free breast cancer patients vaccinated with HER2/neu peptide vaccines or immunoadjuvant GM-CSF.
Authors: Guy Clifton, Holmes Jarrod, Linda Benavides, Jeremy Gates, Suzanne Mccall, Stanley Rivera, Elizabeth Mittendorf, Alexander Stojadinovic, Gerald Merrill, Sathibalan Ponniah, George Peoples
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Background: The quantity of circulating tumor cells (CTC) and post-treatment reduction predict outcome in medically treated metastatic breast cancer patients (BCa) and has previously been used to monitor the effect of vaccination with the HER2/neu peptide, E75. CTCs may be a useful early marker of therapeutic effect for vaccines in the adjuvant setting. We assessed the level of CTCs in clinically disease-free high-risk node negative (NN) and node positive (NP) BCa patients being vaccinated with immunogenic HER2/neu peptides prior to and post-vaccination. Methods: Clinically disease-free high-risk NN or NP patients were enrolled after completion of surgery and standard chemo/radiation therapy. The patients were randomized to receive one of the HER2/neu-derived peptides GP2 or AE37 with GM-CSF as an immunoadjuvant or to the control arm where they will receive only GM-CSF monthly for 6 months. The CellSearch System (Veridex, LLC Warren, NJ) was used to enumerate total CTC in 20 ml of blood from selected samples obtained from patients (n=32) prior to vaccination. If CTCs were present pre-vaccination, levels were also measured at completion and 6 months after completion of the vaccination series. Results: 12/32 patients (37.5%) had at least one CTC identified pre-vaccination. Thus far, 7 of the 12 patients have had multiple samples collected. Of those with multiple samples, 3 patients received adjuvant GM-CSF only and 4 patients received GP2 and adjuvant GM-CSF. Of the 3 in the adjuvant only arm, 33.3% (1/3) decreased after completion of the series. Of the 4 who received GP2 and adjuvant, 75% (3/4) had no detectable CTCs after completion of the vaccine series. The one GP2 patient with CTCs after completing the primary vaccine inoculations had a clinically detected cancer recurrence shortly after completion of the vaccine series. Conclusions: CTCs may be an early marker for therapeutic effect of cancer vaccines in the adjuvant setting. Initial results from our clinical trial show that patients treated with the GP2 peptide vaccine are more likely to have a decrease in the level of detectable CTCs than patients receiving GM-CSF immunoadjuvant only. These early results warrant the continued assessment of CTC in our vaccine trials.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3610.
Prevalence of emotional distress, anxiety, and depression and their impacts on pain in terminally ill cancer patients.
Authors: S. Jung, K. Park, J. Kim, Y. Do, K. Kwon, H. Song, S. Koh
Journal: Journal of Clinical Oncology (2010)

e19642 Background: Psychosocial aspect of patient care is becoming paramount in the oncologic field and palliative care. We aimed to determine the prevalence of emotional distress, anxiety, depression, and their impacts on pain in terminally ill cancer patients in Daegu, Korea. Methods: In this multicenter study, patients (N = 122) with age between 23 and 81 years (median =60.5 years), with eight types of cancer, were recruited. All patients were registered in the palliative care units in the same region. The procedure of gathering data included the consent of patients and the application of Brief Pain Inventory (BPI), the Distress Thermometer/Problem List (DT/PL), the Sheehan Disability Scale (SDS), and the Hospital Anxiety and Depression Scale (HADS). Results: A total of 110 patients were analyzed. Sixty six patients (60%) had moderate to severe distress defined as score of 4 or more on DT. Thirty seven percents of patients had anxiety and 55.7% had depressive mood. Statistically significant correlations were found for distress and pain severity (p=0.007), the number of emotional problems (p<0.001), practical problems (p<0.001), physical problems (p=0.048), spiritual or religious concerns (p=0.019), and family problems (p=0.016). No significant correlation was observed between distress and social activity (p=0.23). Anxiety and depressive mood were more frequently diagnosed in the moderate to severe distressed group. Of 21 physical symptoms examined, only pain and sleep disturbance were associated with distress. Conclusions: The prevalence of distress, anxiety, and depression is high in terminally ill cancer patients. It may be important to include psychological screening and intervention in multidimensional management for this population of patients. No significant financial relationships to disclose.
The pharmacodynamic profile of NPI-0052 is cell-type specific
Authors: Ta-Hsiang Chao, Ana Barral, Kenneth Lloyd, Matt Spear, Michael Palladino, Saskia Neuteboom
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

3257 

The purpose of this study was to compare the pharmacodynamic profile of the proteasome inhibitor NPI-0052 in different cell types. NPI-0052 is a potent, small molecule proteasome inhibitor that inhibits the chymotrypsin-like (CT-L), trypsin-like (T-L) and caspase-like (C-L) activities of the 20S proteasome in vitro and in vivo with different kinetics when compared to Velcade® (Chauhan et al, Cancer Cell, 2005, 8:407) or PR-171 (Demo et al, Cancer Res, 2007, 67:6383). Due to the different profiles, it was considered important to evaluate the inhibition and recovery of proteasome activities after repeated administration of NPI-0052, which may contribute to understanding efficacy, dose and schedule in clinical studies. Preclinical studies demonstrated that after intravenous or oral administration to mice, NPI-0052 inhibited the CT-L, T-L and C-L activities of whole blood 20S proteasomes in a dose-dependent manner. Furthermore, a single administration of NPI-0052 resulted in sustained whole blood proteasome inhibition with significant recovery of the proteasome activity by day 7. Repeated intravenous administration of NPI-0052 in rats and primates demonstrated a dose-dependent inhibition of the CT-L activity, which was most potent at 24 hr post dosing and partially recovered over a period of 7 days. A similar trend was observed after second and third weekly treatments. Since whole blood cell lysates mainly represent red blood cells, which are anucleated cells with a half-life of about 80 days and lack the capability to generate new proteasomes, we assessed the effects of NPI-0052 on nucleated cells, focusing on peripheral blood mononuclear cells (PBMCs) that have a half life of 2-5 days. Rats were treated with NPI-0052, blood was collected at various time points after dosing, and PBMCs were isolated. Both whole blood and PBMC lysates were prepared and the CT-L activity of the 20S proteasome was determined. Results demonstrated a different recovery profile of the 20S proteasome CT-L activity in PBMCs as compared to whole blood, with activity in PBMCs markedly recovering within 48-72 hours after dosing.These results clearly demonstrate the difference between cell types in the duration of proteasome inhibition following NPI-0052 administration, which is probably secondary to the ability of PBMCs to synthesize new proteasomes and their relatively short half-life in blood. It will be of interest to correlate these findings with those in patients. NPI-0052 is currently being evaluated in Phase I clinical trials for treatment of patients with solid tumors, lymphomas, or multiple myeloma (MM). The 20S proteasome activity is being evaluated in PWB, PBMC and plasma for all tumor types, and also in CD138+ MM cells and CD138- bone marrow derived cells in the case of multiple myeloma patients.
Abstract 11252: E2F1 Suppresses Cardiac Neovascularization by Downregulating VEGF and PlGF Expression
Authors: Min Wu, Junlan Zhou, Min Cheng, Chan Boriboun, Dauren Biyashev, Hong Wang, Raj Kishore, Douglas Losordo, Gangjian Qin
Journal: Circulation (2011)

Background: The E2F transcription factors are best characterized for their roles in cell-cycle regulation, cell growth, and cell survival. Previously, we have shown that E2F1 is involved in the ang...
Sofosbuvir plus ribavirin for hepatitis C virus-associated cryoglobulinaemia vasculitis: VASCUVALDIC study
Authors: David Saadoun, Vincent Thibault, Si Nafa Si Ahmed, Laurent Alric, Maxime Mallet, Constance Guillaud, Hassane Izzedine, Aurélie Plaisier, Hélène Fontaine, Myrto Costopoulos, Magali Le Garff-Tavernier, Christophe Hezode, Stanislas Pol, Lucile Musset, Thierry Poynard, Patrice Cacoub
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Hepatitis C virus (HCV) is the aetiological agent for most cases of cryoglobulinaemia vasculitis. Interferon-containing regimens are associated with important side effects and may exacerbate the vasculitis. <h3>Objective</h3> To evaluate safety and efficacy of an oral interferon-free regimen, sofosbuvir plus ribavirin, in HCV-cryoglobulinaemia vasculitis. <h3>Patients and methods</h3> We enrolled 24 consecutive patients (median age of 56.5 years and 46% of women) with HCV-cryoglobulinaemia vasculitis. Sofosbuvir (400 mg/day) was associated with ribavirin (200–1400 mg/day), for 24 weeks. The primary efficacy end point was a complete clinical response of the vasculitis at the end of treatment (week 24). <h3>Results</h3> Main features of HCV-cryoglobulinaemia vasculitis included purpura and peripheral neuropathy (67%), arthralgia (58%), glomerulonephritis (21%) and skin ulcers (12%). Twenty-one patients (87.5%) were complete clinical response at week 24. Complete clinical response was achieved in six (25%) patients at week 4, four (16.6%) at week 8, seven (29.2%) at week 12, three (12.5%) at week 16 and one (4.2%) at week 20. The cryoglobulin level decreased from 0.35 (0.16–0.83) at baseline to 0.15 (0.05–0.45) g/L at week 24. The C4 serum level increased from 0.10 (0.07–0.19) to 0.17 (0.09–0.23) g/L at week 24. Seventy-four per cent of patients had a sustained virological response at week 12 post treatment. The most common side effects were fatigue, insomnia and anaemia. Two serious adverse events were observed. <h3>Conclusions</h3> Sofosbuvir plus ribavirin combination was associated with a high rate of complete clinical response and a low rate of serious adverse events in HCV-cryoglobulinaemia vasculitis.
Cisplatin-based chemoresistance resulted from enhanced DNA repair in human head and neck squamous cell carcinoma
Authors: Wei Guang, Bert O’Malley, Daqing Li
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

1490 

Chemotherapy plays an important role in the neoadjuvant or adjuvant setting and management of advanced and metastatic disease for the treatment of head and neck squamous cell carcinoma (HNSCC). Cisplatin is one of the most potent and useful antitumor agents for the treatment of HNSCC to date. The development of Cisplatin resistance is a major factor responsible for the failure of Cisplatin chemotherapy. A protein complex made up of hMre11, hRad50 and Nbs1 (MRN) has been shown to be a critical component of the cellular response to the repair of DNA double-strand break (DSB). The present study investigated the molecular mechanism of Cisplatin-induced tumor cell resistant and explored whether enhanced DNA DSB repair could be a primary cause for development of resistance in tumor cells to cisplatin, which induces crosslinks and DNA DSBs. Two human HNSCC cell lines, JHU006 and JHU020, were used for this study. JHU006 cell line has been characterized as a Cisplatin-resistant cell line, whereas JHU020 demonstrates sensitive to Cisplatin-based chemotherapy. The cell viability was evaluated. Western blot, co-immunoprecipitation (co-IP), and real-time quantitative-reverse transcription-polymerase chain reaction (Q-RT-PCR) were performed. The formation of an MRN complex in both cell lines was confirmed by Western blot and co-IP studies in both cell lines. However, a significantly increased expression level of MRN was found in the JHU006 cell line treated with Cisplatin when compared with JHU020 cell line. The increase in MRN expression level corresponds to the level of cytotoxicity in Cisplatin-resistant JHU006 cell line and suggests that Cisplatin-induced tumor cell resistant occurs through enhance DNA DSB repair. Our study further suggests that the interruption the MRN complex may block DNA DSB repair and therefore sensitize chemoresistant cells in Cisplatin-based chemotherapy for the treatment of human HNSCC.
The significance of the residual mediastinal mass in treated Hodgkin's disease.
Authors: M Jochelson, P Mauch, J Balikian, D Rosenthal, G Canellos
Journal: Journal of Clinical Oncology (1985)

The chest roentgenograms of 65 patients treated for Hodgkin's disease with mediastinal adenopathy were analyzed retrospectively to determine the incidence and significance of residual mediastinal abnormality after treatment. All patients were treated with radiation therapy, and 36 patients received additional chemotherapy. On completion of treatment, 57 (88%) of the 65 patients had some residual mediastinal abnormality. These were either minimal changes in the mediastinal shadow in 30 patients or a widening greater than 6 cm in 27 patients. In the latter group, 11 (40%) of 27 patients continued to have residual mediastinal widening one year after completion of therapy. These patients did not have a higher incidence of recurrence. Long-term follow-up (median, 48 months) revealed continued abnormalities in 24 (40%) of the original 57 patients. Mediastinal abnormalities are common at the end of radiation or combined modality therapy for Hodgkin's disease and do not by themselves indicate persistent active disease or an increased risk for relapse. We strongly recommend that additional chemotherapy or higher radiation doses beyond the initially planned course not be used for residual mediastinal widening.
Barriers and facilitators for clinical trial participation among diverse Asian patients with breast cancer.
Authors: Guek Eng Lee, Mandy Y.L. Ow, Desiree Lie, Rebecca Alexandra Dent
Journal: Journal of Clinical Oncology (2014)

108 Background: Recruitment rates for breast cancer trials are low for racial/ethnic minorities. Little is known about factors influencing trial recruitment in Asian patients. Our aim is to examine the barriers and facilitators for participation in trials among multi-ethnic Asian women with breast cancer. Methods: We recruited a convenience sample from consecutive women seen at a National Cancer Centre. Two experienced bilingual (English and Chinese) moderators conducted focus groups to theme saturation. The question guide incorporated open-ended questions soliciting opinions about trial participation and knowledge. Women were first asked if they were willing, unwilling, or still open to participate in future trials. Sessions were audiotaped and transcribed. Transcripts were independently coded for emergent themes. Results: Sixteen of 103 women approached participated in five focus groups. Chinese, Malay and Indian participants aged 29 to 69 represented different cancer stages. Five had no prior knowledge of trials. We identified three major areas consisting of 24 minor themes for barriers and facilitators. Major themes fell into: 1) individual- or patient-related, 2) trial-related and and 3) sociocultural factors. When analysis was stratified by willingness to join trials, we found that women willing to join trials expressed themes representing facilitators (better test therapy, cost-effective profile, or trust in doctors and local systems). Women unwilling to participate expressed themes associated with barriers, while women still open to participation expressed themes representing both facilitators and barriers. Malay women were more likely to express themes related to ‘fatalism’ as a barrier. Conclusions: We found that facilitators and barriers to trial participation among Asian women were similar to those previously reported in Western women. Knowledge of trials is limited among women receiving breast cancer treatment. Unique sociocultural factors suggest that approaches customised to local and community beliefs are needed to improve trial participation in minority groups.
Randomized phase II study of combined infusional leucovorin sodium (LVNa) and 5-FU versus the sequential administration of leucovorin calcium (LVCa) followed by 5-FU with irinotecan or oxaliplatin in patients (pts) with metastatic colorectal cancer (mCRC).
Authors: H. Bleiberg, A. Vandebroek, I. Deleu, P. Vergauwe, H. Rezaei Kalantari, G. D'Haens, M. Paesmans, M. Peeters, A. Efira, Y. Humblet
Journal: Journal of Clinical Oncology (2010)

e14019 Background: 5-FU modulated by leucovorin calcium (LVCa) remains the mainstay of therapy for CRC. It is expected that LV Sodium (LVNa), which is stable when given with continuous infusion (ci) of 5-FU, could further enhance its activity. Methods: Eligibility criteria include confirmed mCRC, unresectable metastases, no previous chemotherapy, age ≥ 18 years, WHO-PS: ≤2. Pts received irinotecan 180 mg/m2 IV/30-90 min or oxaliplatin 100 mg/m2 IV/120 min and were randomized for LVCa 400 mg/m2/2 hours, followed by 5-FU bolus 400 mg/m2, and by 5-FU 3,000 mg/m2 IV ci/46 hours or, LVNa 400 mg/m2 plus 5-FU 3,000 mg/m2, IV ci/46 hours. Primary endpoint was objective response rate (ORR) by investigators and independent panel and assessed on pts who had a baseline and at least one post-baseline evaluations. Main secondary endpoints included safety, and overall/progression-free survival (OS, PFS) based on all pts treated. Experimental treatment was defined as warranting further evaluation in phase III if true ORR > 35 %(α=5%, β=10% in case of true ORR > 55%, 51 evaluable patients planned/arm). Results: See Table. Conclusions: LVNa disclosed an ORR >35% (study positive according to planning despite reduced sample size) and induces no more toxicity than LVCa. OS in favor of LVNa triggers the concept of improved activity of 5-FU/LV with LVNa ci which needs to be further validated in a phase III study. ORR Treatment Group % ORR (CI) P for ORR>35%- LVCa Investigators 66 (46-42) 0.01 Independent review 50 (31-68) 0.062 LVNa Investigators 63 (44-78) <0.01 Independent review 59 (40-75) <0.01 Survival Parameter Treatment Median (CI) P for LVNa vs. LVCa OS (months) LVCa 11.93 (9,17-19.83) LVNa 22.90 (16,66—) 0.02 PFS (months) LVCa 8.02 (7.26-9.03) LVNa 11.5 (7.26-19.09) 0.1 Toxicity Adverse events Treatment No. (%) P for LVNa vs. LVCa No. grade 3-4 AE >2 LVCa 6 (21.4) LVNa 5 (17.8) ns % with 1 or > grade 3-4 AE LVCa 18 (64.2) LVNa 13 (46.4) ns Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sirtex SA, Taiho Pharmaceutical, Teva