bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of telotristat etiprate on clinical and biochemical responses in patients with symptomatic carcinoid syndrome: Preliminary results of an ongoing phase II, multicenter, open-label, serial-ascending dose study.
Authors: Wiedenmann Bertram , Pavel Marianne E. , Seufferlein Thomas , Freiman Joel , Law Linda , Banks Phillip Lee , Frazier Kenneth , Jackson Jessica , Zambrowicz Brian 
Published: March 2020

e14564 Background: Excess serotonin (5-HT) may contribute to gastrointestinal (GI) symptoms such as diarrhea in carcinoid syndrome (CS) patients. Telotristat etiprate, an oral serotonin synthesis inhibitor (SSI), is designed to reduce peripheral 5-HT levels and alleviate GI distress. Methods: This study evaluates the safety and tolerability of ascending doses (150 mg, 250 mg, 350 mg, and 500 mg tid) of telotristat etiprate in symptomatic CS patients, averaging ≥4 bowel movements (BMs)/day, either therapy-naïve or receiving somatostatin analogs. Secondary objectives include symptomatic response (change in: number of BMs/day, stool form/consistency, sensation of urgency to defecate, sensation/severity of nausea, global assessment of symptoms, assessment of abdominal pain/discomfort, reduction of cutaneous flushing episodes), and assessment of plasma drug concentrations, pharmacokinetics, and pharmacodynamics (urinary 5-hydroxyindolacetic acid [u5-HIAA] and blood 5-HT). All patients began dosing at 150 mg. Dose will be increased following 2 weeks of therapy with no dose-limiting toxicity. If dose-limiting toxicities occur, the dose will be reduced to prior level. Treatment will continue at the individual maximum-tolerated dose for 4 weeks; patients may elect to continue in an extension phase. Results: As of 1/2012, 13 patients, refractory to octreotide LAR have enrolled and been treated with telotristat etiprate. Eight (8) of 9 patients have completed the 12-week ascending dose study and 6 of 6 eligible patients have enrolled into the long-term extension, up to 72 weeks; 4 more patients are eligible for the long-term extension. Mean age: 63 years (range 51-81), mean BMs at baseline: 6.0 (range 4.7-8.5) for the 9 patients. Upon completion of 12 weeks of dosing, 7 of 9 patients (78%) had sustained reductions of ≥30% in BMs/day. All 7 of these patients had multiple assessments indicating ≥50% BM reductions) during the 6 weeks while on their highest dose. No major safety issues were detected. Conclusions: Telotristat etiprate produced biochemical and clinical responses/benefit in CS.
The impact of HER2 positivity on survival in metastatic gastric and GEJ cancer in the province of British Columbia: An updated analysis.
Authors: Lim Howard John , Kumar Aalok , Zhou Chen , Huntsman David , Kollmannsberger Christian K. , Gill Sharlene 
Published: March 2020

e14568 Background: HER2 positive gastric (GC) and GEJ adenocarcinoma has been associated with a worse survival outcome. This study examines the survival rate of patients with metastatic HER2 positive GC and GEJ adenocarcinomas in the province of BC. Methods: Formalin fixed embedded tissue from patients (pts) with resected gastric or GEJ adenocarcinoma from 2004-2011 were identified retrospectively through the BC Cancer Agency registry and prospectively for pts with a new diagnosis of advanced disease. Biopsies and resection samples were analyzed via previously validated methods. IHC scores of 3 were considered positive (+), 2 were equivocal and 0 or 1 were negative (-). A 10% cut-off was used to determine positive samples. Equivocal staining was considered positive via FISH or SISH with a ratio of > 2.2 considered amplified. Patient characteristics were abstracted to an anonymized database. Kaplan-Meier curves were calculated to evaluate overall survival from time of diagnosis or relapse to death for pts with HER2 + or - disease. Results: 179 of 304 pts were identified with metastatic or relapsed gastric or GEJ adenocarcinoma without Traztumumab treatment. 21 (12%) pts were HER2 + either by IHC, FISH or SISH. Refer to the table for characteristics of both groups. Median survival was not significantly different among HER2 + and - pts (4.0 mo vs. 7.3 mo, p=0.089). Conclusions: The rate of HER2 positivity is similar to that seen in trial data. HER2 positivity trends to a worse prognosis but was not significant in this study. [Table: see text]
A phase II study of lapatinib and capecitabine in second-line treatment of metastatic pancreatic cancer.
Authors: Wu Zheng , Marshall John , Hwang Jimmy J. , Pishvaian Michael J. , Wellstein Anton , Weiner Louis M. , He Aiwu Ruth 
Published: March 2020

e14569 Background: The anti-EGFR therapy erlotinib was FDA approved for the treatment of patients with advanced pancreas cancer. Human epidermal growth factor receptor 2 (HER-2), a member of the ErbB family of growth factor receptor tyrosine kinases to which EGFR belongs, is found overexpressed in 20% of pancreatic cancers . Targeting EGFR and HER-2 with separate specific monoclonal antibodies showed synergistic inhibition of pancreatic cancer tumor progression in mice bearing xenograft of human pancreatic cancer cell lines. We performed an open-label single arm phase II study to evaluate the combination of lapatinib, a dual tyrosine kinase inhibitor of EGFR and HER-2, and capecitabine in the second-line treatment of metastatic pancreatic cancer. Methods: Patients with metastatic, unresectable, gemcitabine-refractory pancreatic cancer with adequate performance status (ECOG 0-2) and normal hepatic and renal function were eligible. Patients received lapatinib 1,250 mg PO daily, and capecitabine 1,000 mg/m2 PO twice daily on days 1-14 of each 21-day cycle. Restaging studies were performed every 2 cycles. The primary endpoint was median overall survival (OS). Secondary endpoints included response rate (RR) and progression free survival (PFS). Results: Between 9-2009 and 8-2011, 17 patients received treatment. Six of 17 patients (24%) had disease progression after 2 cycles, 2 of 17 patients (12%) progressed after 4 cycles and 4 of 17 patients (24%) had stable disease and received more than 6 cycles. The median number of treatment cycles was 3 (range 1-22 cycles). The median PFS was 9 weeks (95% CI 7.1-18.9). Median OS was 25 weeks (95% CI 11 -34). Grade 3 nausea, vomiting in 3 patients (17%), grade 3 diarrhea in 2 patients (12%), grade 3 limb edema in 1 patient (6%), and grade 3 fatigue in 1 patient (6%). Serum was collected at baseline, three weeks and time of disease progression for microRNA analysis to identify biomarkers correlated with clinical outcome. Conclusions: The combination of lapatinib and capecitabine is a tolerated regimen for patients with gemcitabine-refractory metastatic pancreatic cancer. Some patients were able to receive 6 or more cycles of therapy. Molecular analysis of patients’ biosamples is ongoing.
A phase I/II study of oral paclitaxel in patients (pts) with advanced gastric cancer.
Authors: Lee Kyung Hee , Park Young-Iee , Zang Dae Young , Lee Keun-Wook , Shin Dongbok , Park Kyung-Mi , Son Jeewoong , Bang Yung-Jue 
Published: March 2020

e14572 Background: Paclitaxel is not absorbed from GI tract because of the over- expression of P-glycoprotein by intestinal cells. In previous study, Oraxol, which composed of paclitaxel solution and HM30181A tablet, a novel P-glycoprotein inhibitor, had been administered to 25 pts with advanced solid cancer. Thereafter, the formulation of Oraxol was changed from paclitaxel slolution to paclitaxel capsule. Methods: Primary objective for Phase I study was to determine the maximum tolerable dose (MTD) or recommended dose (RD) of Oraxol using standard 3+3 dose escalation design at three pre-specified doses (180, 240, 300 mg/m2/week of paclitaxel capsule, fixed dose of 15 mg/day HM30181AK tablet). Oraxol was administrated twice a week, total 6 times per cycle (day 1, 2, 8, 9, 15 and 16), every 4 weeks.Eligible ptswere ≥ 19 years with advanced malignancies refractory to standard therapies in Phase I portion. Primary objective for phase II study was to evaluate the clinical response of pts with advanced or metastatic/recurrent gastric cancer after failure of 1 previous chemotherapy. In the phase II study, patients were enrolled in 2 stages Results: In pase I study, 10 pts were enrolled and 4 had treatment-related AEs. One pt had treatment-related grade 3 anemia, 2 pts had treatment-related grade 2 AEs: neutropenia, thrombocytopenia and asthenia. No DLT was observed in the dose range of this study and the RD for phase II was defined at 300 mg/m2/week (150 mg/m2 x 2) based on the safety profiles and plasma concentration profiles. The phase II study is ongoing. Thirty patients have been enrolled to date. Of 25 pts evaluable for efficacy, 1 had complete response (not confirmed) after 8 weeks of therapy, 3 subjects had partial response (duration of treatment: 8.83 mo+, 3.07 mo+, 3.03 mo+), and 10 had stable disease (SD) as best response. Conclusions: Oraxol has been well tolerated and has shown promising efficacy in gastric cancer patients. Updated results will be presented at the meeting.
Above-label doses of octreotide-LAR in patients with metastatic small-intestinal carcinoid tumors.
Authors: Weber Jill M. , Feldman Max , Kvols Larry , Strosberg Jonathan R. 
Published: March 2020

e14579 Background: Octreotide LAR is indicated for treatment of the malignant carcinoid syndrome, and has been studied at doses of 10-30mg intramuscularly every 4 weeks. It has also been proven to delay time to progression of metastatic midgut carcinoid tumors at a dose of 30mg every 4 weeks. In clinical practice, higher doses are often prescribed for patients who experience refractory carcinoid syndrome (flushing and/or diarrhea) or tumor growth while on the maximal labeled dose. We performed a retrospective, longitudinal review of octreotide LAR administration at a tertiary institution to determine the frequency of ‘above-label’ dosing and outcomes. Methods: A retrospective chart-review was performed using a database of patients with metastatic small-bowel carcinoid tumors treated at the Moffitt Cancer Center between the years 2000 and 2010. Data included the maximal dose of octreotide LAR administered, reasons for change in dose or frequency (above the labeled dose of 30mg every 4 weeks), and clinical responses to dose change. Results: 337 patients were considered evaluable, among whom 99 patients (27%) underwent at least one increase in dose or frequency of octreotide-LAR above the standard labeled dose. The most common maximal doses were 40mg every 4 weeks (37 patients), 60mg every 4 weeks (34 patients), and 30mg every 3 weeks (17 patients). The indications for dose increase were worsening carcinoid syndrome (60 patients), radiographic progression (33 patients) and rising urine 5-HIAA (6 patients). Among patients whose doses were increased for refractory carcinoid syndrome, 62% experienced improvement in diarrhea and 56% experienced improvement in flushing. Conclusions: In clinical practice, octreotide LAR is commonly prescribed in doses or schedules above the labled dose and frequency. Patients with refractory carcinoid syndrome appear to experience a clinical benefit from the change. Prospective data is needed to evaluate this strategy.
Risk factors for sporadic pancreatic neuroendocrine tumors (PNETs): Updated results from a single-center case control study.
Authors: Halfdanarson Thorvardur Ragnar , Bamlet William R , McWilliams Robert R. , Hobday Timothy J. , Burch Patrick A. , Petersen Gloria M. 
Published: March 2020

e14594 Background: PNETs are uncommon malignancies and little is known about risk their factors and association with other cancers. Our aim was to evaluate smoking, alcohol use, personal history of diabetes and a family history of PNET and other cancers as potential risk factors. Methods: PNET cases seen at Mayo Clinic Rochester from 2000 to 2011 were evaluated. Insulinoma and high-grade PNETs were excluded. Primary care patients served as controls and were matched (2:1 ratio) to cases on age, sex and region of residence. Cases and controls completed questionnaires at the time of evaluation. Categorical variables were compared with the chi-square test; continuous variables were compared using a two-sample t test. Results: 355 cases were evaluated, mean age was 56.6 years, 52% were males and 96% were White. Personal smoking history was not associated with PNETs (cases 51%, controls 47%, p=0.24). Ever-alcohol use was less common among cases (54% vs. 67%, p=0.001). 19% of cases reported a history of diabetes compared with 11% of controls (p<0.001). Cases were more likely than controls to report a family member with sarcoma (p=0.02), PNET (p=0.024), gall bladder cancer (p=0.024), ovarian cancer (p=0.04) and stomach cancer (p=0.01). Conclusions: Cases with PNETs were more likely than controls to report a history of diabetes and less likely to report alcohol use. There was no association with smoking. Several types of cancer were more commonly reported in family members of cases than controls.
Serum levels of macrophage inhibitory cytokine-1 (MIC1) and matrix metallopeptidase-7 (MMP7) as diagnostic and prognostic markers in gastric cancer (GC) patients (pts).
Authors: Valladares-Ayerbes Manuel , Tarrío Nuria , Blanco-Calvo Moisés , Haz-Conde Mar , Santamarina Cainzos Isabel , Medina Villaamil Vanessa , Rodríguez-Rigueiro Teresa , Figueroa Angelica , Reboredo Margarita , Antón-Aparicio Luis 
Published: March 2020

e14595 Background: MIC1 and MMP7 are secreted cytokines involved respectively in the modulation of immunological processes and in extracellular matrix remodeling. Their expression were found deregulated in different tumors, including GC. However, few data are available about their serum levels, their diagnostic potential, and their prognostic significance in GC pts. Here, we analyze the diagnostic performance of these markers and we present data linking them with short survival in GC pts. Methods: Serum samples were assayed in duplicate for MIC1 and MMP7 levels by ELISA. The diagnostic performance of markers was assessed by ROC curve analysis and the cut-offs were set using the Youden index approach. The cut-offs for prognostic purposes were determined using X-tile software. Differences in progression free (PFS) and overall survival (OS) were analyzed using Kaplan-Meier curves and logrank test. Cox regression was used to determine the prognostic independence of biomarkers. Results: From November 2006 to July 2010, 52 GC pts and 28 healthy donors were consecutively recruited. The follow-up of pts was performed until their death or the end of study (September 2011). The AUCs for MIC1 and MMP7 were respectively 0.897 and 0.865 (p < 0.001). Using the optimal cut-off to diagnose GC pts, we obtained a 73.08% of sensitivity (Ss) and a 92.86% of specificity (Sp) for MIC1, and a 78.85% of Ss and an 85.71% of Sp for MMP7. In the survival analysis, high serum levels of MIC1 and MMP7 were significantly associated with shorter PFS (p < 0.001) and OS (p < 0.001 and p = 0.003, respectively). In univariate analysis, pts with high serum levels of MIC1 and MMP7 had an increased risk of progression (HR = 3.608, p<0.001 for MIC1; HR = 4.172, p<0.001 for MMP7) and death (HR = 3.843, p=0.001 for MIC1; HR = 2.602, p=0.006 for MMP7). However, MIC1 and MMP7 failed to reach prognostic independence in multivariate analysis. Conclusions: We obtained cut-off values of MIC1 and MMP7 in serum for diagnostic purposes in GC. In addition, we established a correlation between increased levels of MIC1 and MMP7 in serum and shorter PFS and OS in GC. These findings justify studies with a larger number of pts.
Evaluation of transcatheter arterial chemoembolization (TACE) plus sorafenib in Chinese patients with unresectable hepatocellular carcinoma: A subgroup analysis of START trial.
Authors: Han Guohong , Yang Jijin , Shao Guoliang , Teng Gaojun , Wang Maoqiang , Yang Jianyong , Liu Zhaoyu , Feng Gansheng , Yang Renjie , Lu Ligong , Chao Yee , Wang Jianhua 
Published: March 2020

e14605 Background: The therapeutic effect of TACE plus Sorafenib (Sor) for unresectable hepatocellular carcinoma (uHCC) was evaluated in the START (Study in Asia of the Combination of TACE with Sor in Patients with Hepatocellular Carcinoma) trial. The preliminary results presented at ILCA 2011 showed encouraging safety and efficacy profiles of TACE plus Sor in HCC, with a median time to progression (TTP) of 9.3 months and median overall survival (OS) not reached. Here we present results of a subgroup analysis of Chinese patients with more updated data. Methods: Patients with uHCC and candidates for TACE were enrolled. TACE with lipiodol and doxorubicin (30-60 mg) was performed every 6 to 8 weeks. Sor (400mg bid) was administrated 4 days after first TACE, and then continuously with interruption 3 days before and after the TACE procedure. Tumors were assessed 4 weeks after every TACE, and every 3 months thereafter if no TACE was indicated. Patients who do not require TACE due to complete response or intolerability continued to receive Sor until disease progression (PD) or unacceptable toxicity. This analysis was conducted to evaluate the efficacy of TACE plus Sor on TTP based on modified RECIST criteria, OS and response rate (RR) in Chinese patients with uHCC. Cut-off date for the efficacy analysis is Sep 30th, 2011. Because no new or unexpected side effects were noted during this study period, safety data were not collected in this subgroup analysis. Results: A total of 64 patients enrolled from Sep. 2009 to Apr. 2010, were evaluated. The median age was 62 yr (range, 31-75) and all patients were ECOG Performance Status 0-1. The main etiology for HCC was hepatitis B in 94.9% of patients. The mean dose of Sor in this group of patients is 787.63mg.The median treatment duration was 6.4 months. The median TTP was 10.6 months, and the median OS was 16.5 months. The objective RR was 44.3%, and 11.5% of patients had PD. Conclusions: This subgroup analysis suggests that Chinese patients with uHCC may benefit from TACE and Sor combination therapy, with better improvement of TTP, compared to the interim analysis results of the overall population from the START trial.
Correlation between toxicity and outcome after multimodality therapy of locoregionally advanced (LRA) adenocarcinoma (ACA) of the esophagus (E) and gastroesophageal junction (GEJ).
Authors: Osei-Boateng Kwabena , Rybicki Lisa A. , Rice Thomas W. , Rodriguez Cristina P. , Videtic Gregory M.M. , Saxton Jerrold P. , McNamara Michael J. , Ives Denise I. , Bodmann Joanna , Adelstein David J. 
Published: March 2020

e14611 Background: Multiagent concurrent chemoradiation (CRT) and surgery is a standard curative-intent approach for patients (pts) with LRA ACA of the E/GEJ. This single institution retrospective analysis examined whether toxicities occurring during induction chemoradiation (ICRT) were independently prognostic for outcome. Methods: Between 11/99 and 7/06, 152 pts with T3, N1 or M1a ACA of the E/GEJ were entered onto one of two Cleveland Clinic trials. ICRT with 96 hour infusions of cisplatin (20mg/m2/d) and fluorouracil (1000mg/m2/d) beginning on day 1 of radiation (30Gy@1.5Gy bid), was followed by surgery and identical post-operative CRT. 75 pts also received 2 years of oral gefitinib. Multivariable Cox analysis was used to identify prognostic factors for overall survival (OS), freedom from recurrence (FFR), locoregional (LRC) and distant metastatic control (DMC). Both clinical features (including demographics, tumor characteristics, symptomatic and pathologic response), and ICRT- related toxicities (including nausea/vomiting, mucositis/dysphagia, neutropenia, thrombocytopenia, neutropenic fever and any unplanned hospitalization) were analyzed. Results: Of the 152 pts enrolled, resection proved possible in 138 (91%). With a median follow-up of 90 (range 57-126) months, the 5-year Kaplan-Meier projected OS is 22%, FFR 24%, DMC 27% and LRC 69%. As expected, in multivariable analysis, earlier clinical stage disease and a pathologic and symptomatic response to ICRT all proved favorable for treatment outcomes. In addition, the development of grade 3-4 (vs. grade 0-2) mucositis and/or dysphagia during ICRT was a significant risk factor for distant recurrence [HR 2.62 (1.34-5.12), p=0.005]; any recurrence [HR 2.08 (1.08-4.00), p=0.027] and death [HR 2.00 (1.07-3.74), p=0.031]. Neutropenic fever was also correlated with distant recurrence [HR 1.82 (1.03-3.22, p=0.039] and any recurrence [HR 2.19 (1.23-3.90) p=0.007]. Conclusions: Neutropenic fever and the development of grade 3-4 mucositis and/or dysphagia during ICRT are independently associated with worse outcomes after multimodality therapy for E/GEJ ACA.
Retrospective evaluation of resected ampulla of vater adenocarcinoma (AOVA): Clinicopathologic variables and long-term outcomes—REAL study.
Authors: Desai Neelam Vijay , Zuluaga Toro Tania , Duckworth Lizette Vila , Sommerfeld Alex , Alkhasawneh Ahmad , Hou Wei , Ivey Alison , George Thomas J. 
Published: March 2020

e14612 Background: AOVA accounts for about 1% of GI cancers. 30% of patients receive curative intent resection with 5-year survival between 20-50%. Limited data are available concerning the value of adjuvant therapy. AOVA may be intestinal or biliary based on histology with each associated with a different natural history and prognosis. This study aims to characterize clinicopathologic features of this disease and associate these with outcomes. Methods: An IRB-approved retrospective review of all patients at the University of Florida between 2000-2011 was undertaken to identify patients with resected AOVA. Periampullary tumors were excluded. Independent histologic review to define intestinal versus biliary subtype and molecular phenotype (including CK 7, 19, 20, SMAD4, CDX2 and MUC1) was undertaken. Chi-square test was used to determine significance between variables. Results: 68 total patients were identified and analyzed. Clinical variables, relapse and survival data are presented (Table). For patients <70 years old, median OS was 69 months vs 13 months for patients >70 years (P=0.0115). Histologic and molecular subgroup analysis is ongoing. Conclusions: AOVA long-term outcomes are consistent with previous publications with 5-year survival of 32%. Age and stage appear to have a substantial impact on survival. Histologic and molecular analysis may further define patient subsets and will be reported. [Table: see text]