tbuckley/cabot-search huggingface dataset:
Prostate Adenocarcinoma: TransCutaneous Hormones, PR09 (PATCH): A randomized controlled trial of transdermal estrogen patches versus luteinising hormone releasing hormone agonists in locally advanced and metastatic prostate cancer.
Authors: Ruth E Langley, Trinh Duong, Gordana Jovic, Abdulla A Alhasso, Howard Kynaston, David Paul Dearnaley, Stuart D Rosen, Roger Kockelbergh, Noel W. Clarke, Ian F Godsland, Subramanian K Sundaram, Sanjay Dixit, Marc Laniado, Andrew Stockdale, Alvan Pope, Edgar M Paez, Ben Spittle, Anna Bara, Mahesh M K Parmar, Paul D Abel
Journal: Journal of Clinical Oncology (2014)

TPS5099 Background: Contemporary androgen deprivation therapy (ADT) with luteinising hormone releasing hormone agonists (LHRH) suppresses androgen to castrate levels but also depletes estrogen (synthesised from aromatised testosterone). Sex hormone depletion results in serious long term toxicities including osteoporosis and adverse metabolic changes potentially associated with increased cardiovascular (CVS) risk. Transdermal estrogen is a compelling alternative to LHRH for achieving castrate levels of testosterone, and should avoid the CVS toxicity associated with oral estrogen by circumventing first-pass hepatic metabolism, as well as mitigating estrogen depletion related toxicities. Methods: PATCHis a multi-centre, randomised, non-inferiority trial comparing the efficacy and safety of transdermal estrogen patches (FemSeven 100 µg/24 hour, 4 patches changed twice-weekly reducing to 3 after 4 weeks) against LHRH. Men (without significant CVS disease) with advanced prostate cancer (newly diagnosed or previous radical treatment and rising prostate specific antigen) are eligible. The trial was designed for evaluation in stages. Stage 1 (n=254) showed the patches produced castrate levels of testosterone similar to LHRH without additional CVS toxicity (Langley et al. Lancet Oncology 2013;14:306-16), and had more favourable blood glucose and lipid profiles. In stage 2, a pre-planned interim analysis (n=638) reviewed by the Independent Data Monitoring Committee (June 2013) led to the decision to extend the trial, with the aim of recruiting a total of 2,150 patients, to enable the evaluation of the patch efficacy to progress seamlessly from phase II to III. The design for the extension is based on the multi-stage, multi-arm (MAMS) approach and incorporates an interim analysis before continuing to the final stage. Primary outcome measures are overall and progression-free survival. The possibility of adding a new treatment arm for a phase II evaluation of an estrogen gel is being considered. Other international groups have been approached for potential collaboration. Clinical trial information: ISRCTN70406718.
Fludelone, an optimized epothilone for ovarian cancer treatment
Authors: David C. Dorn, Yuong Shin Cho, Daniel Procissi, Michaela Liedtke, Kang Zhang, Vladimir Ponomarey, Jason A. Koutcher, Samuel J. Danishefsky, Malcolm A. S. Moore
Journal: Cancer Research (2005)

5907  The microtubule stabilizing drug Paclitaxel is a valuable drug against a wide range of tumors. Despite its value as an anti-cancer agent, paclitaxel has two features that hamper its applicability: its low aqueous solubility, and the development of drug resistance mediated by the overexpression of the P-glycoprotein and the presence of beta-tubulin mutations. Epothilones have similar mechanisms of action to paclitaxel, but are more water soluble, are a poorer substrate for the P-glycoprotein and have a simpler molecular architecture for total synthesis and analog optimization. Recently we (Y.S.C.) synthesized epothilone analogs dEpoB and 26-trifluoro-9,10-dehydro-12,13-desoxyepothilone B (Fludelone). All tested human tumor cell lines (colon, breast and ovarian) were highly sensitive to Fludelone, with IC50s between 1-20nM in the XTT-test. The IC50 of Fludelone was lower than that of dEpoB in every case. Ovarian cancer cell lines were particularly sensitive to Fludelone which possessed a ∼8-fold greater anti-tumor activity than dEpoB. Both drugs caused tumor cells to arrest in G2M phase and rapidly induced apoptosis and beta-tubulin increase. Normal bone marrow stromal cells showed a comparable, relative resistance to both these compounds, indicating a safe therapeutic window and a potential therapeutic advantage of Fludelone over dEpoB. Fetal human lung fibroblasts (MRC-5) were sensitive to dEpoB and Fludelone, but a therapeutic window was still evident with Fludelone. In our Xenograft model we injected 1-5x107 Ovcar3, ovarian cancer cells, transduced with a HSV-TK/eGFP/Luciferase triple fusion gene, intraperitoneally into NOD-SCID mice (to study tumor growth in the physiological niche for ovarian cancer). To monitor tumor growth and location of metastases, whole animal imaging by luciferase bioluminescence was performed at three points: (1) 5-10 days post tumor injection and prior to drug treatment, (2) after 10 drug administrations and (3) at the terminal stage. Fludelone was administered 3 times weekly by intraperitoneal injection. Minor and reversible body weight loss was observed with Fludelone. A tumor reduction of 90% after ten dosages was achieved, matching Taxol controls and with greatly prolonged survival. By using in vivo19F NMR signal from Fludelone as an indicator of efficient tumor tissue uptake we were able to (1) estimate the time after injection at which the tumor tissue concentration is maximum (between 4 and 5 hours ) and (2) establish the optimal in vivo drug dosage for maximum uptake and retention (50-100 mg/kg) . To elucidate possible differences between dEpoB and Fludelone action on Ovcar3 cells we conducted micro array analysis and selective gene modulation in the NFkB pathway. Given the large therapeutic window of Fludelone compared to dEpoB, Fludelone is a promising epothilone analog for ovarian cancer treatment.
Gemcitabine and cisplatin plus ramucirumab or merestinib or placebo in first-line treatment for advanced or metastatic biliary tract cancer: A double-blind, randomized phase II trial.
Authors: Ashwin Reddy Sama, Crystal Shereen Denlinger, Arndt Vogel, Aiwu Ruth He, Nathalie Bousmans, Wei Zhang, Richard A. Walgren, Juan W. Valle
Journal: Journal of Clinical Oncology (2017)

TPS509 Background: Angiogenesis and aberrant MET signaling are implicated in the pathogenesis and progression of invasive biliary tract cancers (BTC), including adenocarcinomas of the gallbladder, intra- and extra-hepatic bile ducts, and ampulla of Vater. JSBF (NCT02711553) is a phase II, multicenter, randomized, and double-blinded study, designed to evaluate the efficacy and safety of standard of care (SOC) gemcitabine and cisplatin in combination with either ramucirumab (human IgG1 VEGFR2 monoclonal antibody) or merestinib (oral type II MET kinase inhibitor) or respective placebo for the first-line treatment of advanced or metastatic BTC. Methods: Eligible patients with advanced or metastatic BTC will be randomized to oral merestinib 80 mg, oral placebo, intravenous (IV) ramucirumab 8mg/kg, or IV placebo, in a 2:1:2:1 fashion. Randomization will be stratified by primary tumor site, presence of metastases, and geographic region. In addition to the randomly assigned treatment, all patients will receive SOC first-line treatment with up to 8 cycles of IV gemcitabine 1000mg/m 2 + cisplatin 25mg/m 2 on days 1 and 8 of 21-day cycles. IV ramucirumab and placebo will be given on days 1 and 8 of each cycle; oral treatments will be taken daily. Investigational treatment or placebo may continue past 8 cycles until disease progression or a criterion for discontinuation is met. The primary endpoint is progression-free survival, by intention-to-treat analysis. Target enrollment is 300 patients with primary analysis at 210 events to detect potential superiority of each investigational treatment over pooled control. Secondary endpoints are overall survival, objective response, disease control rate, safety, pharmacokinetics, immunogenicity (ramucirumab), and patient reported outcomes. An exploratory endpoint is to correlate biomarkers with safety and clinical outcome; blood, plasma, serum, and tumor tissue collection is mandatory. The study began in May 2016. Clinical trial information: NCT02711553.
Cancer survivorship care in rural community: Patient perspective.
Authors: Katia Noyes, David Holub, Irfan Rizvi, Alex Swanger, Coty Reisdorf, Kenneth Tomaszewski, Louis S. Constine
Journal: Journal of Clinical Oncology (2017)

25 Background: Advances in oncologic sciences have resulted in successful treatments for many cancers with improved event-free and overall survival for millions of patients. Efficient delivery of state of the art cancer care requires well-orchestrated performances of multiple oncology, primary care and social services providers. However, many rural oncology providers do not offer such multidisciplinary cancer services and rely on patients to coordinate their own care. This study assessed perspectives of rural cancer patients and caregivers on their confidence to make decisions and address their care needs. Methods: We conducted focus groups with the attendees of 3 rural Congregate Meals. The county-sponsored programs bring together seniors for nutritional meals, social connectedness and educational programs. We also developed and piloted a 5-question survey, asking respondents to rate their confidence in interacting with their clinicians about care needs, care coordination and barriers to care. Results: Overall, 85 individuals participated in the focus groups and 76 persons returned the survey (90% response rate). The vast majority of the participants were cancer survivors or caregivers to patients with cancer. Transportation to and from oncology appointments presents a major concern for the rural communities, as most patients had to travel long distance to see a doctor. Patients also reported having difficulty making decisions regarding their care due to a lack of knowledge about specific cancer services and limited availability of providers. Cancer support groups, behavioral health providers, exercise and nutrition therapies were reported to be particularly scarce in rural areas. We found that patients who had trusted relationships with their physicians tended to be more confident in their ability to obtain necessary help from their providers compared to patients who reported poor communication and lack of trust. Conclusions: There are numerous reasons that may lead to rural-urban disparities in cancer survivorship outcomes including limited availability of supportive services, limited patient resources, burden of patient decision making and care coordination, and lack of adequate patient-provider communication.
Activation of human peripheral blood immune cells in vitro by sodium stibogluconate (SSG) and SSG/IL-2 combination
Authors: T. Yi, K. Fan, J. Finke, R. Bukowski, E. C. Borden
Journal: Journal of Clinical Oncology (2006)

2557 Background: SSG, an inhibitor of SHP-1 and SHP2 which are negative regulatory signaling tyrosine phosphatases, suppressed the growth of murine renal carcinoma (Renca) in combination with IL-2 via an interferon (IFN)-γ + T cell-dependent mechanism (J Immunol 175:7003–8, 2005). Activation of primary human immune cells by SSG or SSG/IL-2 would provide additional supporting evidence for SSG clinical evaluation in combination with IL-2. Methods: Peripheral blood of healthy and melanoma donors were treated in vitro with SSG or SSG/IL-2 and then subjected to ELISPOT assays and FACS analysis for quantification of TH1 (IFN-γ + ) and TH2 (IL-5 + ) cells. Results: Characterization by ELISPOT assays of peripheral blood identified IFN-γ + cells with marked increase (9.1x) following SSG/IL-2 treatment in contrast to the modest increases induced by SSG alone (2.1x) at its clinically achievable dose (20 μg/ml) or by IL-2 (3.1x) at its Cmax of low-dose schedule (30 IU/ml). SSG at an even higher dose (100 μg/ml) was less effective alone (1.5x) or in combination with IL-2 (7.8x). IL-5 + cells were not induced by the agents individually or in combination. Induction of peripheral IFN-γ + cells by SSG/IL-2 was detectable after 4 and 16 h. Increased effectiveness of the SSG/IL-2 combination vs. the individual agents in inducing IFN-γ + cells in vitro was detected by ELISPOT assays in the peripheral blood from 7 healthy donors and 6 melanoma patients. FACS analysis showed that the combination induced IFN-γ + cells in the CD4 + and CD8 + lymphocytes and also increased lymphocytes expressing the activation marker CD69 in both CD4 + (2–5x) and CD4 − populations (∼ 3x). Conclusion: SSG, a compound used clinically for treatment of leishmaniasis, can interact with IL-2 in vitro to activate immune cells in peripheral blood of healthy and melanoma donors. Results provide further rationale, in addition to the mouse tumor data, for proof of concept clinical trials for effecting augmentation of IL-2 through inhibition of negative regulatory signaling phosphatases. No significant financial relationships to disclose.
FC gamma RIIa and FC gamma RIIa polymorphisms (SNPs) and cetuximab (C) benefit in the EXPERT-C trial
Authors: Francesco Sclafani, David Gonzalez de Castro, David Cunningham, Sanna Hulkki Wilson, Clare Peckitt, Jaume Capdevila, Bengt Glimelius, Susana Rosello Keranen, Ruwaida Begum, Gina Brown, Diana M. Tait, Andrew Wotherspoon, Janet Thomas, Jacqueline Rose Oates, Lan Chau
Journal: Journal of Clinical Oncology (2014)

FC gamma RIIa and FC gamma RIIa polymorphisms (SNPs) and cetuximab (C) benefit in the EXPERT-C trial
Management of Inpatient Hyperglycemia and Diabetes in Older Adults
Authors: Guillermo E. Umpierrez, Francisco J. Pasquel
Journal: Diabetes Care (2017)

Adults aged 65 years and older are the fastest growing segment of the U.S. population, and their number is expected to double to 89 million between 2010 and 2050. The prevalence of diabetes in hospitalized adults aged 65–75 years and over 80 years of age has been estimated to be 20% and 40%, respectively. Similar to general populations, the presence of hyperglycemia and diabetes in elderly patients is associated with increased risk of hospital complications, longer length of stay, and increased mortality compared with subjects with normoglycemia. Clinical guidelines recommend target blood glucose between 140 and 180 mg/dL (7.8 and 10 mmol/L) for most patients in the intensive care unit (ICU). A similar blood glucose target is recommended for patients in non-ICU settings; however, glycemic targets should be individualized in older adults on the basis of a patient’s clinical status, risk of hypoglycemia, and presence of diabetes complications. Insulin is the preferred agent to manage hyperglycemia and diabetes in the hospital. Continuous insulin infusion in the ICU and rational use of basal-bolus or basal plus supplement regimens in non-ICU settings are effective in achieving glycemic goals. Noninsulin regimens with the use of dipeptidyl peptidase 4 inhibitors alone or in combination with basal insulin have been shown to be safe and effective and may represent an alternative to basal-bolus regimens in elderly patients. Smooth transition of care to the outpatient setting is facilitated by providing oral and written instructions regarding timing and dosing of insulin as well as education in basic skills for home management.
Weekly paclitaxel, carboplatin, cetuximab (PCC), and cetuximab, docetaxel, cisplatin, and fluorouracil (C-TPF), followed by risk-based local therapy in previously untreated, locally advanced head and neck squamous cell carcinoma (LAHNSCC).
Authors: Erminia Massarelli, Robert I. Haddad, J. Jack Lee, Heather Y. Lin, Adam S. Garden, George R. Blumenschein, William Nassib William, Roy B. Tishler, Bonnie S. Glisson, Kathryn A. Gold, Faye M. Johnson, Guilherme Rabinowits, Lawrence E. Ginsberg, Michelle D. Williams, Jeffrey Myers, Merrill S. Kies, Vassiliki Papadimitrakopoulou
Journal: Journal of Clinical Oncology (2015)

6001 Background: We designed a randomized phase II trial to determine the efficacy of two induction chemotherapy (ICT) cetuximab (C) containing regimens with demonstrated efficacy and acceptable toxicity in previously untreated LAHNSCC. ICT was followed by risk-based definitive local therapy, where risk was defined by Human Papillomavirus (HPV) status and stage and stratification by smoking status (low vs intermediate/high). Primary endpoint was 2-year progression free survival (2yr PFS). Methods: 136 patients (pts) median age 58 years, 84% males, 89% caucasian, 66% ECOG PS 0, 40% never smokers, with stage IV (40% T3-4, 98% N2b-c/N3), 77% HPV-positive, HNSCC (oropharynx 79%, others 21%) were randomized 1:1 to receive PCC [paclitaxel 135 mg/m2, carboplatin AUC 2 weekly (wy) and C 400 mg/m2 week (w) 1 then 250 mg/m2 wy] for 6 weeks or C-TPF [docetaxel 75 mg/m2, cisplatin 100 mg/m2 day (d) 1, fluorouracil 700 mg/m2 24-hr infusion d 1-4 every 3 w and C 400 mg/m2 w 1 then 250 mg/m2 wy] for 9 weeks. Results: As of January 2015 with a median follow-up of 18.4 months and 128 evaluable pts, 14 pts recurred (5 in PCC, 9 in C-TPF) and 4 died (2 per arm). Median PFS has not been reached yet. Sites of recurrence were: primary site (3 in PCC, 6 in C-TPF), cervical lymph nodes (1 in PCC, 3 in C-TPF) and lung metastasis (1 in PCC). Overall grade 3-4 toxicities were seen in 90% PCC pts vs 88% C-TPF pts. C-TPF pts were more likely to experience dehydration (31% vs 12% p = 0.006), nausea (25% vs 9% p = 0.01), hypokalemia (21% vs 2% p = 0.0005), but less likely rash (3% vs 35% p < 0.0001), compared to PCC pts. Conclusions: Overall ICT with C, a platinum and a taxane combination, followed by risk-based local therapy has promising results with a manageable toxicity profile. Survival results are excellent and distant failure is very uncommon. Formal comparison with historical data within risk groups and predictive biomarker analysis are ongoing. Clinical trial information: NCT01154920. PCC (%) C-TPF (%) Response Rate (RR) post ICT 78 82 Overall RR (post local therapy) 94 85 Estimated 2yr PFS rate All pts 89 80 HPV-positive 94 78 HPV-negative 76 83 Low risk 95 82 Intermediate/high risk 72 75
T-lymphocyte responses to the human telomerase reverse transcriptase (hTERT) in patients (pts) with advanced non-small cell lung cancer (NSCLC)
Authors: E. Fabre, J. Medioni, M. Dosset, M. Dosset, E. Tartour, S. Oudard, M. Riquet, O. Adotevi
Journal: Journal of Clinical Oncology (2009)

3061 Background: hTERT is a potential target for cancer immunotherapy because it is highly expressed in tumor cells. To assess the applicability of hTERT-based immunotherapy in NSCLC, we aimed to analyse the natural anti-hTERT T-lymphocyte responses in advanced NSCLC pts. Methods: We included in a prospective, monocentric study chemonaive NSCLC pts. Pts were required to present stage III or IV tumor, without any immune deficiency or immunosuppressive drug. Before start of chemotherapy, the anti-hTERT T-lymphocyte responses were assessed in whole blood by ELISPOT and thymidine proliferation test. We evaluated the presence or absence of hTERT-specific T lymphocytes. Thereafter, we analyzed its link with age (&lt; 60 vs. ≥ 60 yrs), ECOG performance status PS (0–1 vs. 2–3), tumoral stage (III vs. IV), histological subtype (adenocarcinoma vs. other), and smoking status (never smoker vs. smoker). Statistical analysis was performed using chi-square or Fischer test. Results: Between February and September 2008, 31 NSCLC pts were included. They presented a stage III (n = 6) or IV (n = 27) disease. Median age was 65 yrs (33–89). Eighteen pts presented anti-hTERT T lymphocytes (54%); among them we found 12 pts ≥ 60 yrs (70%), 14 adenocarcinoma (77%), 13 stage IV (72%), 7 pts with PS 2/3 (41%), and 13 smokers (72%). So far, univariate analysis showed no relationship between presence of anti-hTERT T-cell responses and pts’ characteristics. Conclusions: These preliminary results demonstrate that natural anti-hTERT immune response exists in NSCLC pts, even in case of poor prognosis. Thus, clinical trial using telomerase-based therapeutic vaccine may include NSCLC pts with advanced disease. The study is ongoing to evaluate if baseline anti-hTERT immune response could be used as selection criteria for telomerase vaccination in NSCLC. No significant financial relationships to disclose.
AVALUZ study: First line with bevacizumab in combination with paclitaxel (P) and gemcitabine (G) in patients with HER2-negative or recurrent mBC: OS analysis.
Authors: Javier Salvador, Eva M. Ciruelos, Manuel Codes, Ana Jaen, Miquel Gil, Antonio Galan, Adolfo Murias, Carlos Jara-Sanchez, Juan De la Haba- Rodriguez, Jose Manuel Baena, Maria Jose Villanueva Silva, Juan L. Bayo, Isabel Blancas, Encarnacion Gonzalez, Diego Perez, Jose Ramón Mel, Luis Manso
Journal: Journal of Clinical Oncology (2012)

e11535 Background: The combination of bevacizumab (B) with taxanes, capecitabine or anthracyclines has shown increased PFS in pts with mBC. The combination with G and P has been evaluated and has demonstrated high response rate and good toxicity profile. The aim of this study is to evaluate the efficacy and toxicity profile of the combination of B with G and P, providing the final result of PFS, update of OS and the toxicity experienced in all pts treated. Methods: A phase II multicenter, national, open-label study in pts diagnosed of recurrent or metastatic HER-2 negative BC, treated with first line B 10 mg/kg, P 150 mg/m2 and G 2000 mg/m2 day 1 and 15 c/28 d until progression disease, unacceptable toxicity or medical decision. This abstract evaluates efficacy by PFS as primary endpoint and as secondary endpoints: OS, response rate and toxicity profile (NCI CTC v3.0 criteria). Results: From January 2009 to December 2009, 82 evaluable pts were recruited in 23 sites. The characteristic of the all of pts included (90) are: median age 51.5 (26-81), ER + 68%, PR + 59%, triple negative pts 19%, previous chemotherapy (neoadj or adj) 64.4% and &gt; 3 metastatic sites 21% of patients (19). The median cycles administered per pts was 7 (1-28) and the relative median dose intensity was 0.93 for B, 0.89 for P and 0.91 for G. Of the 76 pts with response assessment, the overall response rate obtained was 72% with a clinical benefit of 89.5% (80.3-95.34%). Of the 82 pts with a median follow up of 20.21m (0.23- 30.07), median PFS (50% events) for these pts was 11.51 m (9.01-17.6), the median duration of first response (MDR) was 12.4 m (7.6-15.2) and the median OS (42% events) was 27.4 m (21.9- NA). The one year OS % was 84.15 (74.27 – 90.47). Toxicity was generally manageable. Related AEs have been reported in 69/82 pts which were mostly mild or moderate. Safety analysis revealed 24 SAEs in 21 pts Conclusions: Bevacizumab in combination with paclitaxel and gemcitabine showed significant OS compared with the published data with paclitaxel and gemcitabine and high clinical benefit with manageable safety profile.