bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and efficacy of pasireotide (SOM230) in patients with metastatic carcinoid tumors refractory or resistant to octreotide LAR: Results of a phase II study
Authors: Kvols L. , Wiedenmann B. , Oberg K. , Glusman J. E. , O’dorisio T. M. , De Herder W. , Gao B. , Arnold R. , Anthony L. 
Published: March 2020

4082 Background: Pasireotide is a novel multiligand somatostatin analogue that exhibits high binding affinity to 4 of 5 somatostatin receptor subtypes: sst1,2,3 and sst5. Compared with octreotide, pasireotide has 30, 5 and 40 times greater affinity for sst1,3 and sst5 receptors respectively and a comparable affinity for sst2. Methods: This was a Phase II, open-label, multicenter study in patients with metastatic carcinoid tumors whose symptoms (diarrhea and flushing) were inadequately controlled by octreotide LAR. Patients had histopathologically confirmed disease, elevated 5-HIAA and/or CgA levels and at least one measurable lesion (excluding bone). Patients initially received pasireotide 300 μg sc bid and escalated to a maximum dose of 1200 μg sc bid every 3 days until clinical response was achieved. Partial response (PR) was defined as a mean of <4 bowel movements (BM)/day with no more than 6 BM on any given day, and a mean of <2 flushing episodes/day for 15 consecutive days on a fixed dose of pasireotide. Complete response (CR) was defined as a mean of ≤3 BM/day, with no more than 3 BM on any given day, and no flushing episodes. Results: Safety data are reported from 45 patients as of September 2005; 44 patients (mean age 61 years) qualified for efficacy assessment. Carcinoid tumors were predominantly of midgut origin. Preliminary efficacy data in controlling symptoms of carcinoid syndrome showed PR in 9 patients (20%) at 600–1200 μg sc bid doses and CR in 2 patients (5%) at the 600 and 900 μg sc bid doses. Objective tumor response in 11 patients showed 9 with stable disease and 2 with progressive disease at 6 months. Adverse events (AEs) were primarily gastrointestinal (GI): abdominal pain (31%) and nausea (27%). Weight loss (22%) and fatigue (22%) were also reported. Most AEs were mild or moderate. Glucose-related AEs (predominantly CTC grade 1–2) were observed in 24% of patients. Most discontinuations were due to GI AEs (n = 6) or lack of therapeutic response. Conclusions: Pasireotide 600–1200 μg sc bid was effective in controlling symptoms of diarrhea and flushing in 25% of patients with metastatic carcinoid tumors inadequately controlled by octreotide LAR. The safety profile of pasireotide is similar to octreotide LAR. [Table: see text]
A retrospective analysis of epidemiology and treatment patterns for gastric cancer at a tertiary health care center in India
Authors: Digumarti R. , Rajappa S. J. , Uppalapati S. , Surath A. 
Published: March 2020

4086 Background: Gastric cancer is the second most common gastrointestinal cancer in our hospital based cancer registry. This retrospective analysis aims at studying the epidemiology and treatment patterns for gastric cancer at our hospital, which is a tertiary care cancer center for the state of Andhra Pradesh in south India. Methods: A retrospective analysis of the case records of 125 consecutive patients with gastric cancer who presented to our department between Jan 2004 and Dec 2005 were analysed. Data regarding epidemiology, stages at diagnosis and treatment plans were collected. Patients with early gastric cancer received 5FU based chemoradiation or chemotherapy only. Palliative chemotherapy included 5FU/cisplatin based regimens. Results: A total of 125 patients were analysed. The median age was 61years (range 18–82 years). 71% were males and 29% females. Being a tertiary care center, 92% were referred with a confirmed diagnosis on endoscopic biopsy. 30% were smokers, 11% consumed alcohol, 40% had both habits while 29% had neither. The most common part of the stomach involved was the antro-pyloric region (44%) followed by the body (30%), GE junction/cardia (20%) while 6% had diffuse involvement including linitis plastica. At diagnosis, 35% were early stage, 56% metastatic and 8% locally advanced tumors. 90% patients who had surgery for early stage disease had T2,3 tumors. One third had inadequate nodal staging.70% of patients who had curative resections underwent adjuvant chemoradiation and 30% had chemotherapy only. Of all patients with metastatic disease, 65% palliative chemotherapy while 45% opted for best supportive care. Conclusions: The distribution of tumors within the stomach is similar to Japanese data, which may reflect the common etiological factors like high salt diet. The fact that one third of patients had inadequate nodal dissection stresses the relevance of adjuvant chamoradiotherapy protocols. The high incidence of smoking as a contributory factor in the etiology reflects the need for aggressive anti tobacco legislation. The study reiterates the need for inexpensive and novel therapies for palliation of symptoms in patients with advanced disease and widens the scope for collaborative clinical trials. No significant financial relationships to disclose.
Epithelial-mesenchymal transition (EMT) in resected pancreatic cancer
Authors: Yosuico V. D. , Khoury T. , Yu J. , Pande A. , Javle M. 
Published: March 2020

4094 Background: EMT plays an important role in tumor invasion and metastases; its detection may have prognostic significance. We examined expression of EMT related proteins in resected pancreatic cancers and correlated results with clinical outcome. Methods: Clinical data/surgical specimens from 34 consecutive pancreatic cancer patients (pts) who underwent pancreatectomy from 1996–2002 were included. Immunohistochemical staining for vimentin (Vim 3B4), E-cadherin (36B5), MIB1 and cytokeratin (CK-AE1/AE3) was performed on formalin fixed paraffin embedded tissues. Percentages of stained cells (cytoplasmic for vimentin and CK, nuclear for MIB1 and membranous for E-cadherin) were recorded. The results were correlated with clinicopathological parameters and survival. Survival analysis (log-rank test, Cox-proportional hazard model), categorical data analysis (Pearson’s chi-square, logistic regression) and Kendall’s tau were performed at the significance level of 0.05. Results: Clinical data/specimens from 34 pts were included: 13 males, median age 66 (range 38–84); SEER stage 1 (2 pts), 2 (27 pts), 3 (5 pts); histological grade 1 (4), 2 (13), 3 (16), 4 (1). Median survival was 15 months (95% CI: 11–24 months). Sixteen pts had adjuvant chemoradiotherapy, 4 pts had chemotherapy, 1 pt had radiation. IHC Results: vimentin (11.8%), MIB1 (100%), E-cadherin (91%) and CK (100%). There was a significant negative association between vimentin and E-cadherin expression (Kendall’s tau = −0.47, p = 0.0024). Vimentin expression correlated with histological grade (exact chi-square p = 0.0247). No associations were found between these proteins and SEER stage, age, treatment or smoking. Univariate analysis revealed histological grade 50% (p = 0.0039) and MIB1 expression >10% (p = 0.0224) were related to better survival. Multivariate analysis using Cox-proportional hazard model revealed the following significant variables: histological grade (hazard ratio (HR) = 11.8, p = 0.0001), age (HR = 1.1, p = 0.0053), MIB1 (HR = 0.9, p = 0.0003) and adjuvant chemotherapy (HR = 0.2, p = 0.0288). Conclusion: Decreased E-cadherin expression (<50% expression) was associated with poorer survival; E-cadherin expression had an inverse correlation with vimentin. Acknowledgement: Supported by OSI Pharmaceuticals. [Table: see text]
Preoperative radiotherapy and docetaxel in resectable pancreatic adenocarcinoma: A phase II trial
Authors: Viret F. , Ychou M. , Moutardier V. , Magnin V. , Rouanet P. , Monges G. , Azria D. , Turrini O. , Gonçalves A. , Giovannini M. , Delpero J. R. 
Published: March 2020

4099 Background: We previously reported results a phase I trial of weekly docetaxel concurrently with radiation therapy in patients (pts) with locally advanced pancreatic adenocarcinoma (Pancreas, Vol 27, N°3, 2003). We prospectively explored this regimen in 34 pts with biopsy proven potentially resectable pancreatic adenocarcinoma. Methods: Treatment consisted of concomitant radiotherapy (45 Gy within 5 weeks directed at the pancreatic tumor and regional lymphatics) with 5 weekly doses of docetaxel (30 mg/m2/week) by 1-hour infusion, followed by a complete staging evaluation 3–4 weeks after chemo-radiation. Pts without disease progression underwent surgery. Results: From May, 2003 to July, 2005, this study enrolled 34 pts (59% men) with median age 62 years (range 45–72). Median tumor size was 3 cm. Pretreatment Endoscopic Ultrasound (EUS) staging was uT1 (7 pts), uT2 (25 pts), uT3 (2pts), uN0 (26 pts) and uN1 (8 pts). Median pretreatment CA 19.9 levels was 114 (range 1–9432). All pts (97%) but one completed radiation and 91% (31 pts) received the 5 weekly doses of docetaxel. Adverse events included grade 3/4 asthenia (28%), grade 3/4 nausea/vomiting (10%), grade 3/4 anemia (7%) and grade 3/4 neutropenia (7%). Median time between diagnosis and surgery was 3.7 months (range 2.8–8.7). Ten pts (29%) presented progressive disease after chemo-radiation and one additional patient (pt) voluntary stopped treatment procedure. Twenty three pts (68%) underwent surgical procedure, which was with curative intent in 17 pts (50%). One pt died within the 30-day post operative period. Pathological response was observed in 7 pts (30%), including 2 complete response. The median Disease Free Survival (DFS) was 11 months and the 2-year DFS was 21%. The median overall survival (OS) was 14 months. The 2-year DFS for the 17 pts resected with a curative intent was 50.4%. In this subgroup, median overall survival was not reached. Conclusions: Pre-operative combination of radiotherapy and docetaxel is feasible with tolerable toxicity and with promising pathological response. A randomized phase III study comparing this regimen (radiotherapy and docetaxel) and surgery versus surgery alone is starting. Supported in part by Sanofi Aventis, France. No significant financial relationships to disclose.
Prediction of gemcitabine resistance in patients with pancreatic cancer
Authors: Nakahira S. , Nakamori S. , Tsujie M. , Okami J. , Takemasa I. , Takeda Y. , Nagano H. , Dono K. , Sakon M. , Monden M. 
Published: March 2020

4125 Background: Pancreatic cancer is the most lethal of all solid tumors partially because of its chemoresistance. Although a deoxycytidine analogue, gemcitabine, is widely used as a first selected and a single agent for the treatment of this disease despite low response rate, molecular mechanisms of gemcitabine resistance in pancreatic cancer still remain obscure. The purpose of this study is to identify the molecular marker for gemcitabine resistance in human pancreatic cancer. Methods: Gemcitabine resistant variants were established from human pancreatic cancer cell lines, MiaPaCa2. Gene expression changes between parental cells and resistant cells were assessed by an oligonucleotide microarray covering 30,000 human oligonucleotides, and candidate genes were validated by RT-PCR and Western blotting. The association to resistance was validated by RNAi assay. Clinical effects on 18 recurrent pancreatic cancer patients treated by gemcitabine were evaluated using mRNA of specimens resected at the primary operation. Results: The 81-fold gemcitabine resistant variant MiaPaCa2-RG was selected from pancreatic cancer cell line MiaPaCa2. By microarray analysis between parental and resistant MiaPaCa2 cells, 99.6% genes were altered expression of less than 2-fold. Among 43 genes with altered expression of more than 2-fold, the most up-regulated gene in MiaPaCa2-RG cells is ribonucleotide reductase M1 subunit (RRM1) with 4.5-fold up-regulation compared with MiaPaCa2 cells. Transfection with RRM1-specific RNAi suppressed more than 90% of RRM1 mRNA and protein expression both in MiaPaCa2 and MiaPaCa2-RG cells. After RRM1-specific RNAi transfection, gemcitabine chemoresistance of MiaPaCa2-RG was significantly reduced to the same level of MiaPaCa2. The 18 recurrent pancreatic cancer patients were divided into two groups by RRM1 mRNA expression levels. There was a significant association between gemcitabine response and RRM1 expression (p = 0.018). Furthermore, patients with high RRM1 levels had a poor survival times after gemcitabine treatment than those with low RRM1 levels (p = 0.016). Conclusions: RRM1 should be a key molecule in gemcitabine resistance in pancreatic cancer through both in vitro and clinical models. RRM1 should be considered as the predictor of gemcitabine resistance. No significant financial relationships to disclose.
Long term survival following cytoreductive surgery and intraperitoneal hyperthermic chemotherapy for disseminated appendiceal tumors
Authors: Baraki Y. , Kostuik P. N. , Merriman B. , Nieroda C. , Sardi A. 
Published: March 2020

4128 Background: Appendiceal tumors represent 2.8% of gastrointestinal tumors and less than 0.5% of gastrointestinal malignancies, but frequently involve intraperitoneal spread. Controversial treatment of disseminated tumor has consisted of extensive debulking surgery, peritonectomy, and intraperitoneal chemotherapy. We evaluated the disease free and overall survival, morbidity and mortality of patients with disseminated appendiceal tumors treated by cytoreductive surgery (CRS) and intraperitoneal hyperthermic chemotherapy (IPHC). Methods: A retrospective review of a prospective database was performed between 1999 and 2005. Thirty-one patients underwent CRS followed by IPHC using mitomycin 40 mg infused over 90 minutes at 40–42°C. Patients were given a Peritoneal Carcinomatosis Index (PCI) score pre and post operatively. Postoperatively, patients were assigned cytoreductive scores, indicating completeness of resection: CC-0 = no residual disease, CC-1 ≤ 0.25 cm, CC-2 = 0.25–2.5 cm, CC-3 ≥ 2.5 cm. Cox proportional-hazards models were used to test the influence of different variables on survival. The models were adjusted for age, grade of differentiation, histology and cytoreductive score. Results: There were 14 females and 17 males with a mean age 50 years (range 33–80). Two-thirds of all patients had a preoperative PCI score of >20. The overall survival at 1 year was 96% (95% CI, 74% to 99%) and at 3 years was 69% (95% CI, 38% to 86%). Disease free survival at 3 years was 30% ( 95% CI, 8% to 56%). There was no mortality from the procedure. Overall morbidity, including Grades 1–5 as described by the CTCAE guidelines, was 48%. A multivariate analysis was performed for grade of differentiation and was not found to be statistically significant. However, log rank test for equality of survivor functions in patients with CC scores of 0 or 1 experience recurrence of disease at a slower rate than patients with scores of 2 or 3 (p < 0.001). Conclusions: Although further study is necessary, Cytoreductive surgery followed by IPHC, where a low PCI score and a CC score of ≤1 is achieved, can lead to increased survival for selected patients having advanced appendiceal cancer with peritoneal dissemination. No significant financial relationships to disclose.
Gemcitabine, oxaliplatin and weekly high-dose 5-FU as a 24-hr-infusion in chemonaive patients with advanced or metastatic carcinoma of the gallbladder: Preliminary results of a multicenter phase II-study
Authors: Wagner A. D. , Buechner-Steudel P. , Schmalenberg H. , Moehler M. , Kuss O. , Behrens R. , Hahnfeld S. , Kleber G. , Wein A. , Fleig W. E. 
Published: March 2020

4129 Background: Combinations of gemcitabine (GEM)/5-FU, GEM/oxaliplatin (LOHP) or 5-FU/LOHP work synergistically in pancreatic and/or colorectal malignancies, and have non-overlapping safety profiles. This phase II-study was designed to evaluate the efficacy and safety of the triple combination GEM/LOHP/5-FU in patients (pts) with advanced or metastatic carcinoma of the gallbladder. Methods: One-stage, multicentre phase II study. Eligibility criteria: chemonaive pts with histologically proven advanced, recurrent or metastatic gallbladder carcinoma (ECOG 0–1; expected survival >3 months; measurable disease; adequate renal, hepatic and bone marrow function). According to the results of our previous phase I-study (Proc ASCO 2003, # 1298), pts were treated with GEM 900mg/m2 as a 30-min infusion, followed by LOHP 65 mg/m2 (2-hr infusion) after a 30 min rest and 5-FU 1500 mg/m2 (24-hr-infusion) on d 1, 8, every 3 weeks. Planned sample size: 35 response evaluable patients. The primary endpoint was tumor response, secondary endpoints were toxicity, median survival, the one-year-survival rate, clinical benefit and quality of life. Results: At time of abstract submission, median follow-up of 35 enrolled pts is 9.8 months. Pt. characteristics: m/f: 11/24, median age 61 (range 42–81), ECOG 0/1: 24/11 (69/31%) pts, locally advanced/metastatic disease 1/32 (3/91%) pts. Analysis of tumor response is still pending. Grade III/IV (NCI-CTC) toxicities occurred in 36/3% of 191 cycles and were: leucopenia 3/1%, neutropenia 4/1%, thrombocytopenia 4/1%, anemia 2/0%, nausea 1/0%, sensory neuropathy 4/0%, asthenia 1/0%, elevated bilirubin 2/0%, AP 4/0%, or elevated SGOT/SGPT 1/0%, edema 1/0%, infection 1/0%, dyspnoe 1/1%. Median survival of all pts is 9.9 months (95% CI: 7.5–11.5), the one-year-survival-rate is 30 % (95% CI: 16–47). Conclusions: GEM/LOHP/5-FU combination therapy is tolerated well in patients with gallbladder cancer. The promising survival data has to be confirmed in a phase III study. (Supported by grants from Eli Lilly and Company, Indianapolis, IN, USA and Sanofi-Synthelabo, Paris, France). [Table: see text]
EXIBIT: An international multicenter phase II trial of gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer
Authors: André T. , Reyes-Vidal J. M. , Fartoux L. , Ross P. , Leslie M. , Rosmorduc O. , Clemens M. R. , Louvet C. , Perez N. , Scheithauer W. 
Published: March 2020

4135 Background: Biliary tract carcinomas (BTC) are often diagnosed at an advanced/metastatic stage and have a poor prognosis. The combination of gemcitabine and oxaliplatin (GEMOX) showed promising activity in a French Phase II study (4 centers) in advanced BTC (André. Ann Oncol 2004;15:1339–1343). The objective of this study is to further evaluate the efficacy and safety of GEMOX as first-line therapy in patients (pts) with advanced BTC. Methods: Eligible pts were >18 years of age with histologically proven and measurable, locally advanced or metastatic BTC, had an ECOG PS ≤ 2, adequate renal and hematologic functions, bilirubin < 2.5 × upper limit of normal, and no prior malignancy or brain metastases. Gemcitabine 1000 mg/m2 (Day 1) and oxaliplatin 100 mg/m2 (Day 2) were administered every 2 weeks. The primary objective was response rate (RR) by RECIST (one dimension); secondary objectives were progression-free survival (PFS), overall survival (OS), and safety. Here we report an interim analysis of OS and safety. Results: A total of 70 pts were enrolled between April 2003 and April 2005. The median age was 62 years (range 30–83), 40.0% of pts were male, 94.3% had ECOG PS 0–1. Tumor sites were intrahepatic bile ducts (37.1%), gallbladder (31.4%), extrahepatic bile ducts (12.9%), ampulla of Vater (1.4%), intra/extrahepatic bile ducts (1.4%), missing data (15.7%); 98.6% of pts had no prior radiotherapy and 50% had no prior surgery for BTC. Median OS is 8.25 months (68% of pts are dead and 32% have censored data). Sixty-seven pts were evaluable for safety. Grade 3/4 (NCI-CTC v. 2) hematologic toxicities (% of pts) included thrombocytopenia 10.4%, anemia 9.0%, and neutropenia 9.0%. One pt had febrile neutropenia. Grade 3/4 nonhematologic toxicities included pain 10.4%, ALT elevation 9.0%, fatigue 9.0%, infection 10.4%, vomiting 9.0%, sensory neuropathy 4.5%, nausea 4.5%, and diarrhea 3.0%. One patient died during treatment (cause unknown). Conclusions: GEMOX has acceptable toxicity in pts with BTC. Updated efficacy data (RR, PFS, and OS for the entire population and also by tumor sites) will be presented at the meeting. [Table: see text]
Current treatments, determinants of use, and survival for patients with hepatoma in the United States from 1998–2002
Authors: Siegel A. B. , McBride R. , Hershman D. , Brown R. S. , Emond J. , Neugut A. I. 
Published: March 2020

4138 Background: Multiple case series have described the use of current therapies for hepatocellular carcinoma (HCC), but recent estimates of treatment utilization in the general population and the impact of various treatments on survival are not known. Methods: We first identified 2898 adults diagnosed with HCC with known tumor size and stage in the Surveillance, Epidemiology, and End-Results Program (SEER), from 1998–2002. Treatment was categorized as transplant, resection, ablation, or none of these. We created a second data set of 1856 HCC patients who were potentially operable, as defined by SEER. We used these patients to construct Kaplan-Meier survival curves and adjusted Cox proportional hazards models. Results: The median age of the larger cohort at HCC diagnosis was 62 (range:18–96). Approximately 42% were white, 32% Asian, 16% Hispanic, and 10% African American. Overall, 10% received a transplant, 18% resection, 8% ablation, and 65% none of these. Only 5% of African Americans with HCC received a transplant, versus 12% of whites, 10% of Hispanics, and 8% of Asians. Asians were most likely to receive resection (24%) and ablation (9%), and least likely to have non-surgical treatment (60%). Using the restricted cohort, improved survival in the multivariate analysis was seen with later year of diagnosis, younger age, female sex, Asian race, smaller tumor size, lower tumor grade, and localized disease. Treatment was highly correlated with survival. This was greatest in the transplanted group (1, 3, and 5-year survivals 93%, 79%, and 71%), followed by resection (70%, 45%, and 29%), and ablation (71%, 33%, and 18%). The non-surgical group had poor survival (33%, 9%, and 0%). Conclusions: Transplantation yields excellent survival on a population scale, similar to reported series, and resection gives relatively good outcomes as well. Asians are more likely to be resected and ablated than other groups. They also had better survival than other groups, perhaps due to underlying etiology of HCC (hepatitis B) and better preserved liver function. No significant financial relationships to disclose.