bluuebunny/crossref_metadata_2025_split huggingface dataset:
Results of a phase Ib study of Q-122 treatment of vasomotor symptoms in breast cancer patients.
Authors: Painter Wendy , Speed April L. , Phillips Kiwita , Pemu Priscilla , Robertson Alice , Sands Earl , Ofili Elizabeth 
Published: February 2017

99 Background: Breast cancer patients taking tamoxifen (TAM) or an aromatase inhibitor (AI) often develop severe vasomotor symptoms (VMS) yet the only FDA approved non-hormonal treatment for VMS, 7.5 mg paroxetine, has a warning against concomitant use with TAM. Q-122, an orally-available small molecule, is being developed to address this unmet medical need. Results from the Phase 1b study, Q-1001, are presented. Methods: Q-1001 was a Phase 1 open-label, two-dose, dose-escalation study of the safety and preliminary effectiveness of Q-122 in females with breast cancer currently taking TAM or an AI and experiencing an average of at least 7-8 moderate to severe hot flashes per day. Key exclusion criteria included significant renal or hepatic disease, untreated hyperthyroidism and clinically significant abnormal laboratory findings. The study period included a 2 week drug-free screening phase, 28 day treatment phase, and 2 week drug-free follow-up period. Subjects were initially enrolled into Group 1 (100 mg Q-122) followed by Group 2 (200 mg Q-122). Safety was assessed by review of adverse events (AEs), physical findings and laboratory values. The primary efficacy endpoints were mean changes in frequency and severity (hot flash severity score, HFSS) of moderate and severe hot flashes from baseline to Week 4. Menopausal symptoms were assessed using the Greene Climacteric Scale (GCS). Results: 10 and 11 subjects received 100 and 200 mg Q-122 respectively; 8 subjects in each group completed the study. At the end of treatment for groups 1 and 2 respectively, the daily average frequency of hot flashes was reduced from 9.9 to 4.1 and from 8.6 to 3.2, and the mean HFSS was reduced by 62% and 68% from baseline values. Menopausal symptoms assessed using the GCS were significantly reduced from baseline (psychological: -82%; somatic: -65%; vasomotor: -65%). All AEs (n = 29) were either mild (79%) or moderate (21%) in severity and only 3 (all in one subject) were considered possibly related to study drug. Conclusions: Treatment with Q-122 resulted in significant reduction in the frequency and severity of VMS and improvement in menopausal symptoms as assessed by the GCS. No safety issues associated with the use of Q-122 were identified in this study.
Anamorelin in patients with advanced non-small cell lung cancer and cachexia: Results from the phase III studies ROMANA 1 and 2.
Authors: Temel Jennifer S. , Currow David Christopher , Fearon Kenneth , Yan Ying , Friend John , Abernethy Amy Pickar 
Published: February 2017

175 Background: Cancer anorexia-cachexia syndrome is common in patients with non-small cell lung cancer (NSCLC). It is characterized by loss of lean body mass (LBM) and negatively impacts quality of life. Anamorelin HCl (ANAM) is a novel investigational ghrelin receptor agonist with anabolic and appetite-enhancing activity. Methods: Two randomized, double-blind, Phase 3 ROMANA 1 (N = 484; NCT01387269) and ROMANA2, (N = 495; NCT01387282) trials assessed ANAM (100 mg) efficacy/safety versus placebo in patients with unresectable stage III/IV NSCLC and cachexia ( ≥ 5% weight loss within prior 6 months or BMI < 20 kg/m2) over 12 weeks. Co-primary endpoints were change from baseline over 12 weeks in LBM and hand grip strength (HGS). Secondary endpoints included changes in body weight and in the anorexia-cachexia subdomain of the Functional Assessment of Anorexia/Cachexia Therapy questionnaire, and pooled survival from ROMANA 1 and 2. Exploratory post-hoc analyses determined change in total body and fat mass from baseline to 12 weeks. Results: Over 12 weeks ANAM significantly increased LBM vs placebo in ROMANA 1 (1.10 vs -0.44 kg, p < 0.001) and ROMANA 2 (0.75 vs -0.96 kg, p < 0.001); HGS was similar in the two arms. In both studies ANAM vs placebo increased body weight (2.20 vs 0.14 kg, p < 0.001; and 0.95 vs -0.57 kg, p < 0.001) and improved anorexia/cachexia symptoms (4.12 vs 1.92, p < 0.001; and 3.48 vs 1.34, p = 0.002). Increases in total body mass (2.87 vs 0.07 kg, p < 0.001; and 2.04 vs -0.59 kg, p < 0.001) and in fat mass (1.21 vs -0.13 kg, p < 0.001; and 0.77 vs 0.09 kg, p = 0.012) were observed for ANAM vs placebo. ANAM was well tolerated; the most frequent drug-related adverse event in ROMANA 1 and 2 was hyperglycemia (5.3% and 4.2%). There was no difference between study arms in median 1-year survival. Conclusions: In two global, Phase 3 studies, ANAM treatment for 12 weeks was well tolerated, and increased LBM, body weight, total body mass and fat mass indicating anabolic activity and suggesting restoration of energy balance in advanced NSCLC patients with cachexia. ANAM also improved anorexia-cachexia symptoms/concerns. Similar pooled survival was observed between the study arms. Clinical trial information: NCT01387269, NCT01387282.
Development of a question prompt sheet for cancer patients receiving outpatient palliative care.
Authors: Arthur Joseph Anthony , Yennu Sriram , Williams Janet L. , Tanco Kimberson Cochien , Liu Diane D , Bruera Eduardo 
Published: February 2017

25 Background: An effective communication strategy is the fundamental backbone in the delivery of an impeccable palliative care intervention. Different communication tools are sometimes utilized to enhance discussions between patients and their physicians. An example is a question prompt sheet (QPS) which is a structured list of potential questions available for the patient to ask their doctor during a clinical encounter. Although it has been shown to improve physician-patient interaction during clinical consultations, there is paucity of data on its use in the palliative care setting. The objective of this study was to develop a QPS that is feasible and applicable in palliative care clinical practice. Methods: An expert group of experienced physicians and mid-level providers were invited to participate in the study. The process was conducted in 3 Delphi rounds. In the last round, the top 25 questions with the highest level of endorsement were chosen and used towards the development of the QPS. Results: One hundred percent of the 22 experts invited to participate in the study accepted the invitation and completed all the 3 Delphi rounds. They consisted of 82% physicians and 18% mid-level providers. Participants were mostly males (59%), had a median age of 42 years, and a median of 8 years’ experience in palliative care. 98% of the top 25 questions for the QPS were endorsed by at least 50% of the expert panel in round 3. Twenty-eight percent of the questions were about symptoms, treatment and lifestyle, 24% were about commonly asked questions by caregivers, 20% were regarding end-of-life issues, 16% were regarding the nature of palliative care service, and 12% were regarding the type of available support. The question which had the highest number of endorsements among the panel members was “Is there someone I can talk to about my fears, concerns, spiritual or religious needs?” Conclusions: A 25-item, single page QPS containing some of the most relevant questions in diverse aspects of advanced cancer care and feasible for use in clinical practice was developed in this study. Further studies are needed to determine the clinical effectiveness of the QPS in assisting patient physician communication.
RAINBOW: A global, phase 3, double-blind study of ramucirumab (RAM) plus paclitaxel (PTX) versus placebo (PL) plus PTX in the treatment of advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma following disease progression on first-line platinum- and fluoropyrimidine-containing combination therapy—An age-group analysis.
Authors: Muro Kei , Bodoky Gyorgy , Cesas Alvydas , Chao Yee , Clingan Philip , Hironaka Shuichi , Komatsu Yoshito , Kurteva Galina Petrova , Lipatov Oleg N. , Nishina Tomohiro , Oh Sang Cheul , Ohtsu Atsushi , Shimada Yasuhiro , Sugimoto Naotoshi , Van Cutsem Eric , Carlesi Roberto , Chandrawansa Kumari , Wilke Hansjochen 
Published: February 2017

11 Background: RAM is a human IgG1 monoclonal antibody VEGF-R2 antagonist. The RAINBOW trial demonstrated that RAM added to PTX significantly improved overall survival (OS), progression free survival (PFS), and objective response rates (ORR) in 2nd-line gastric and GEJ adenocarcinoma patients (pts). Outcomes are reported by pts aged <65 and ≥65 yrs. Methods: Pts with advanced gastric and GEJ adenocarcinoma after disease progression on platinum- and fluoropyrimidine-based chemotherapy were randomized 1:1 to receive RAM (8 mg/kg) or placebo (PL) on days 1 and 15 plus PTX 80 mg/m2IV on days 1, 8, and 15 of a 28-day cycle. Eligible pts had ECOG PS ≤ 1 and adequate organ function. OS was the primary endpoint. Secondary endpoints included PFS, ORR, and safety. Results: Baseline characteristics were generally well balanced. Outcomes are summarized in the Table. The incidence of Grade ≥3 adverse events (AEs) was higher in the RAM+PTX arms for both age groups and similar across age groups. Grade ≥3 AEs occurring in ≥10% of pts and at higher rate in the RAM+PTX arm, and febrile neutropenia are shown in the Table. Conclusions: RAM+PTX conferred similar improvements over PL+PTX for OS, PFS, and ORR in both age groups. Toxicity profiles were similar in both groups, although a relatively higher incidence of Grade ≥3 neutropenia and leukopenia in pts ≥65 years was noted. [Table: see text]
False-negative rate for HER2 testing in 738 gastric and gastroesophageal junction cancers (GEC) from two global randomized clinical trials.
Authors: Cunningham David , Shah Manish A. , Smith Dustin , Zoudilova Maria , Hack Stephen Paul , Kang Alice , Phan See-Chun , Jubb Adrian M. , Ruschoff Josef 
Published: February 2017

16 Background: False-negative HER2 testing in GEC may deny patients the benefit of HER2-targeted therapy. The aim of this study is to estimate the false-negative rate for HER2 testing in GEC and to evaluate predictive factors that might be used to select patients for re-testing. Methods: Two clinical trials conducted in patients with HER2-negative GEC were conducted by Genentech (NCT01662869 and NCT01590719). Information on local HER2 results was collected and testing was repeated centrally by immunohistochemistry (IHC; Ventana, 4B5 antibody) and FISH. HER2 positivity was determined using published criteria (Mod Pathol 2012;25:637). Results: Of 1,189 patients screened, 738 GECs were HER2 negative by local testing and had central results available. Twenty-nine patients (3.9%, 95% confidence interval [CI] 2.5–5.3) were locally HER2 negative, but centrally HER2 positive. The cases showed a wide geographic distribution, a mixture of biopsies (n=19) and resections (n=10), and a mixture of gastric cancer (n=20) and GEC (n=9). All false-negative cases were centrally confirmed to be Lauren’s intestinal (n=25) or mixed (n=4) morphology; amongst intestinal/mixed GEC, the false-negative rate was 6.4% (95% CI 4.1–8.6). Detailed local testing results were available for 25 cases, of which 21 cases showed local IHC scores of 0 or 1+ but were centrally IHC 2+/FISH positive (n=17) or IHC 3+ (n=4). The remaining 4 cases were locally HER2 IHC 2+, FISH negative, but centrally IHC 2+, FISH positive. Conclusions: A clinically significant false-negative rate of 6.4% was observed for HER2 testing in GEC (intestinal/mixed type). Several measures might improve the accuracy of HER2 testing, including running FISH and IHC on all cases, carefully evaluating internal positive controls, improving the education of pathologists, and retesting cases with mixed or intestinal morphology. Clinical trial information: NCT01590719 and NCT01662869.
Real-world treatment patterns of previously treated advanced gastric and gastroesophageal junction adenocarcinoma (GC) in the United Kingdom (UK).
Authors: Liepa Astra M. , Brown Jacqueline , Bapat Bela , Kaye James A. 
Published: February 2017

184 Background: With no licensed therapies for previously treated advanced GC, little is known on how patients (pts) are managed after 1st-line chemotherapy (CTx) has failed. We present real-world data on characteristics, treatments, and resource utilization (RU) for such pts in the UK. Methods: Physicians who treat pts with advanced GC completed a web-based chart review detailing clinical and RU data for 3-4 de-identified pts each. Eligible pts were ≥18 years old, diagnosed Jan 2007-Mar 2012 with advanced GC, received 1st-line fluoropyrimidine+platinum, and had ≥3 months of follow-up after 1st-line discontinuation (DC). Data were summarized descriptively. Results: From Jun to Jul 2013, 58 physicians provided data for 200 pts. Pts’ mean age was 61 years; 69.5% were male. At advanced stage diagnosis, ECOG performance status (PS) was 21% 0, 72.5% 1, and 6.5% 2. The most common 1st-line regimens were capecitabine (cape)+oxaliplatin+epirubicin (epi) (34%), cape+cisplatin+epi (20.5%) and 5-FU+cisplatin+epi (13%). The most common reasons for 1st-line DC were completion of planned regimen (63%) and disease progression (24%). ECOG PS at 1st-line DC was 5% 0, 57.5% 1, 32% 2, 5.5% 3. 28.5% received 2nd-line, and 79% of these had PS 0/1 at start of 2nd-line. 21 unique 2nd-line regimens were reported; most common were docetaxel (28%), paclitaxel (11%), trastuzumab (9%), cape (7%) and irinotecan (7%). Among pts who received 2nd-line, 5% received 3rd-line. (See table.) The most common contributing reasons for hospitalization were palliative care and disease progression. Conclusions: In our study sample of advanced GC, the minority of pts received subsequent CTx after 1st-line CTx. There was considerable variation in 2nd-line regimens, although primarily monotherapy. Pts who received 2nd-line CTx had numerically similar or lower rates of supportive care. [Table: see text]
Comprehensive genomic profiling of biliary tract cancers to reveal tumor-specific differences and genomic alterations.
Authors: Ross Jeffrey S. , Wang Kai , Catenacci Daniel Virgil Thomas , Chmielecki Juliann , Ali Siraj M. , Elvin Julia Andrea , Yelensky Roman , Lipson Doron , Hawryluk Matthew J. , Miller Vincent A. , Stephens Philip J. , Javle Milind M. 
Published: February 2017

231 Background: Intrahepatic cholangiocarcinoma (IHCCA), extrahepatic cholangiocarcinoma (EHCCA) and gallbladder carcinomas (GBCA) typically present at an advanced stage and systemic chemotherapy provides only modest benefit in most cases. We queried whether comprehensive genomic profiling (GCP) of IHCCA, EHCCA and GBCA would reveal clinically relevant genomic alterations (CRGA) that could lead to targeted therapies. Methods: DNA was extracted from 40µ of FFPE sections from 412 IHCCA, 57 EHCCA and 85 GBCA. CGP was performed on hybridization-captured, adaptor ligation based libraries to a mean coverage depth of >600X for 3,230 exons of 182 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer. The CGP assay included base substitutions, INDELs, copy number alterations and fusions/rearrangements. CRGA were defined as GA linked to drugs on the market or under evaluation in mechanism driven clinical trials. Results: Patient characteristics were similar for all three tumor types. IHCCA and GBCa were more common in females and EHCCA were more common males. CGP revealed the results in the Table. Multiple antitumor responses to targeted therapies in each of the 3 tumor types will be presented. Conclusions: IHCCA, EHCCA and GBCA share GA in cell cycle regulation (CDKN2B) and chromatin remodeling (ARID1A). IHCCA features FGFR fusions, IDH1/2 substitutions, BRAF substitutions and MET amplification with a low KRAS mutation frequency. EHCCA and GBCA feature ERBB2 amplifications (GBCA > EHCCA) and PIK3CA/MTOR pathway alterations. EHCCA has a high KRAS mutation frequency whereas the KRAS GA in GBCA is low. The diverse landscape of CRGA in biliary tract cancers can serve as targets for therapies for patients with CCA, BDCA and GBCA and have the potential to improve outcomes for these aggressive forms of malignancy. [Table: see text]
Effect of coadministered beta blocker and COX-2 inhibitor to patients with pancreatic cancer prior to receiving albumin-bound (Nab) paclitaxel.
Authors: Bhattacharyya Gouri Shankar , Babu K Govind , Bondarde Shailesh Arjun , Biswas Ghanashyam , Ranade Anantbhushan , Parikh Purvish M. , Bascomb Newell F. , Malhotra Hemant 
Published: February 2017

302 Background: Paclitaxel protein-bound particles nab-paclitaxel plus gemcitabine is rapidly becoming the standard of care for patients with metastatic adenocarcinoma of the pancreas (mPCa). Preclinical and clinical studies of beta-blockers and NSAIDs show a benefit of these drugs in pancreatic cancer. The aim of this study was to evaluate the impact of the co-administration of the beta blocker propranolol (P) and the selective COX-2 inhibitor etodolac (E) on survival of patients with mPCa receiving GemNab as standard of care. PE is presumed to target the adrenergic and prostaglandin stress systems activated in cancer that induce changes in tumor microenvironment, immune system, and HPA axis leading to tumor promotion and immune tolerance. Data on the use of nab-paclitaxel plus gemcitabine (GemNab) with a beta blocker and NSAID in the clinical setting is lacking. Methods: Patients with mPCa were eligible for this randomized investigator initiated trial. Patients received PE daily for one week prior to starting GemNab. PE was administered in a chronodosed regimen to maximize the therapeutic benefit and minimize side effects. The primary endpoint was survival. Twenty-three patients were randomized to either GemNab or GemNab after one week of propranolol and etodolac (PEGemNab). The median age was 62.8 years; 68.2% male. Pain at time of diagnosis as reported in 80% of the patients in the GemNab arm and in 76.9% of the PEGemNab arm and jaundice was observed in 40% and 23% of the GemNab and PEGemNab arms, respectively. Results: Progression free survival was 7.2 and 11.8 months in the GemNab and PEGemNab arms, respectively. Overall survival was 10.5 months for the GemNab arm and 15.9 months for the PEGemNab arm. The treatment was well-tolerated with no unexpected adverse events. Conclusions: Administration of PE one week prior to Paclitaxel protein-bound particles with gemcitabine significantly increased progression free and overall survival. No unexpected adverse reactions were seen. Additional data on cytokine and cancer markers will be presented.
Simple blood test for diagnosis of gastrointestinal and pancreas cancer using surface-enhanced Raman scattering.
Authors: Ito Hiroaki , Hasegawa Katsuyuki , Hasegawa Yuuki , Kimura Satoshi , Onimaru Manabu , Ohmori Tohru , Ikeda Haruo , Saito Mitsuo , Kitamura Yohei , Sato Chiaki , Gomi Kuniyo , Sakaue Satoshi , Isozaki Masayuki , Matsukawa Masaaki , Inoue Haruhiro 
Published: February 2017

32 Background: Surface-Enhanced Raman Scattering (SERS) has been widely applicated in industrial microanalysis, and researched to apply for various fields, for example biological research. We tried to detect the SERS spectra from blood samples obtained from patients with cancers or benign diseases by using a low intensity laser beam, and compared the SERS spectra pattern among the samples from the patient group. Methods: Blood samples were obtained from patients with gastric cancer (n=30), colorectal cancer (n=20), pancreas cancer (n=5) and benign diseases (n=20). All blood samples were centrifuged at 1600g for 7 minutes, and serum samples were extracted. The serum samples were placed on the phosphor bronze chip with silver nanoscale hexagonal columns (NHCs), and SERS spectra was detected by using low intensity helium-neon red laser beam with 633 nm as wavelength. Results: SERS spectra were detected in all samples within 4 minutes from irradiation. Limiting dilution of detecting SERS was 1/1000 of serum. SERS spectra patterns were different between cancer and benign disease patients, and maximum peak level of the SERS in the samples from cancer patients were significantly higher than those from benign disease patients. There was a difference on the wavelength of Raman shifting at the peak intensity and the pattern of the SERS spectra between the samples from the patients with cancers and benign diseases. And furthermore, there was a difference on the SERS spectra pattern among the samples from the patients with gastric, colon and pancreas cancer. Additionally, it was suggested that the elements combined with the silver NHCs were histone-and-DNA complex. Conclusions: Our data suggest that our simple blood test using SERS is useful for diagnosis of gastrointestinal and pancreas cancer. We have been trying molecular analysis of the element combined with the silver NHCs by next-generation sequencer. Clinical trial information: UMIN000009818.
Phase IB study of FOLFIRINOX plus PF-04136309 in patients with borderline resectable and locally advanced pancreatic adenocarcinoma (PC).
Authors: Wang-Gillam Andrea , Nywening Timothy M. , Sanford Dominic E. , Lockhart Albert C. , Suresh Rama , Tan Benjamin R. , Lim Kian-Huat , Sorscher Steven , Fowler Kathryn , Amin Manik A. , Roshal Anna , Adkins Douglas , Nieman Rebecca , Panni Roheena Z. , DeNardo David G , Goedegebuure Peter S. , Hawkins William G. , Fields Ryan C. , Strasberg Steven M. , Linehan David 
Published: February 2017

338 Background: PF-04136309 (a novel CCR2 inhibitor) has shown anti-tumor activity in the preclinical setting in PC by depleting inflammatory monocytes and tumor associated macrophages (TAM) that contribute to an immunosuppressive tumor microenvironment. We hypothesized that combining PF-04136309 with FOLFIRINOX may improve clinical outcomes in PC. Methods: This is a phase Ib study with a dose de-escalation schema given the minimal toxicity of PF-04136309. The study includes Arm A (FOLFIRINOX only), Arm B (FOLFIRINOX plus PF-04136309) and an expansion cohort at the rapid phase II dose (RP2D). FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, LV 400 mg/m2, 5FU bolus 400 mg/m2 and 2,400 mg/m2over 46 hours) was administered every two weeks. PF-04136309 at 500 mg twice daily via oral route was the starting dose level for Arm B. Treatment response was assessed after 6 cycles of treatment. Bone marrow biopsy and EUS/FNA at baseline and post 2 cycles were performed to assess the impact of treatment on the prevalence and function of inflammatory monocytes in the blood, bone marrow and tumor. Results: A total of 41 patients have been enrolled in the study to date (6 in Arm A, 8 in Arm B and 27 in the expansion cohort). The mean age of patients was 61.1 (range 45-75 yrs), male/female: 21/20, Caucasian/others: 32/9, borderline/locally advanced: 7/34. PF-04136309 at the starting dose did not result in additional toxicities when combined with FOLFIRINOX and it is the RP2D. Out of 35 patients treated with FOLFIRINOX plus PF-04136309, 6 are still in treatment, 6 are non-evaluable (withdrew consent or had poor tolerance). Of the 23 evaluable patients, 21 (91.3%) completed all 6 cycles; 12 (52.2%) had PR by RECIST and 11 (47.8%) had SD. Curative resections were achieved in 4 out of 5 with borderline resectable and 2 with locally advanced PC. Moreover, blockade of TAM mobilization was demonstrated by FACS and qPCR analysis of baseline and post-treatment FNA biopsies. Conclusions: Combing PF-04136309 with FOLFIRINOX is safe and tolerable. The regimen resulted in impressive treatment response and it further validated CCR2 inhibition in PC. Survival data and more correlative science will be forthcoming. Clinical trial information: 01413022.