bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of first line treatment in the 5 (5yS) and 10-year (10yS) survival outcomes of patients with gastroenteropancreatic neuroendocrine tumors (GNETs): 2001–2005 Spanish task force GNET group
Authors: Vilar E. , Martinez M. , Alonso V. , Sevilla M. , Sastre J. , Castellano D. , Marazuela M. , Diaz J. , Villabona C. , Salazar R. 
Published: March 2020

14058 Background: Data on incidence, morbidity and mortality of GNETs is limited due to the low frequency of these tumors. However this survival data is critical to design studies with new agents. Methods: Data was obtained from medical records of 262 patients with GNETs and centralized in an online registry at www.retegep.net . Among the study parameters were histology, localization, stage, diagnostic workup, 1st line and subsequent treatments, 5yS and 10yS for the whole dataset and for different stages, tumor types and 1st line systemic treatment. Results: Mean age 58, 58% male. Primary tumors: 49% Carcinoids (C), 19% non-functioning pancreatic tumors (PT), 9% insulinomas, 6% gastrinomas and 8% unknown primary. Localizations: midgut (36%), head (17%) and body of pancreas (10%). Functioning symptoms led to diagnosis in 38% of cases. 4% were associated to MEN1. Stage at diagnosis was advanced (Adv) in 46%, localised (L) in 30% and locorregional (LR) in 13% (unknown in 11%). Diagnostic workup were CT Scan (84%), Octreoscan (52%) and US (52%) and serum hormone tests (65%). Treatments for Adv disease included somatostatin analogues (SA) (47%), surgery (S) (43%), chemotherapy (CT) (35%) and interferon (IFN) (34%), embolization (7%) and radiofrequency ablation (3%). 5yS and 10yS for the whole group was 61.6% (SD: 5.2%) and 49.8% (SD: 7.7%) respectively. 5yS and 10yS for the L/LR and Adv stages were 78.1% (SD: 7.3%) and 71% (SD: 10%), and 48.9% (SD: 7.7%) and 29% (SD: 12.4%), respectively. LR PT and C had similar 5 and 10yS but Adv PT did worse than Adv C (5yS of 36.2% and 61.1%, respectively). 1st line systemic treatment for LR and Adv disease (n=90) included SA (39%), CT (34.4%), IFN (5.6%), combinations of SA+IFN (13.3%), A+CT (4.4%) and other combinations (3.3%), with a 10yS rate of 69%, 79%, 50%, 89%, 66% and 50%, respectively. Adv PT perform worse than C regardless of treatment choice. As second line systemic treatment (n=43) 30% received SA, 30% CT, 26% inmunotherapy and 14% combinations. Conclusions: An extensive use of systemic therapy and a scarce use of non-surgical LR treatments is observed in the Adv stages. Choice of 1st line systemic treatment does not seem to influence survival outcomes. No significant financial relationships to disclose.
Phase I/II trial of continuous hepatic arterial infusion (HAI) of Irinotecan in patients with hepatocellular carcinoma (HCC). Preliminary results
Authors: Pantaleo M. , Derenzini E. , Piscaglia F. , Golfieri R. , Bolondi L. , Mirarchi M. G. , Danesi R. , Biasco G. , Brandi G. 
Published: March 2020

14061 Background: No standard therapies are available for HCC patients (pts) who are not eligible for curative treatments (surgery, RF, TACE or PEI). Methods: This dose finding phase I/II study investigates the tolerability of increasing doses of continuous HAI of CPT-11 (during days 1–5 every 21) in pts with histologically confirmed Child A/B HCC, confined to the liver, not eligible for curative treatments. Secondary endpoints are pharmacokinetics and efficacy. To date, 5 dose levels (DL) of CPT-11 have been investigated (from 7,5 to 17,5 mg/m2/die) and the 6th (20 mg/m2/die) being evaluated. An arterial port-a-cath was placed in the hepatic artery by percutaneous catheterization of the femoral or axillary artery. Before each cycle an angiography was performed to define the optimal liver perfusion. DLT was defined as one G4 hematogical and/or two G3 nonhematological toxicities or liver function impairment (Child C). AEs were graded using NCI-CTC. Responses were evaluated after the 3rd cycle with ultrasonography or CT scan (WHO criteria). Results: To date 16 pts have been enrolled and evaluated for tolerability. Median age is 63, 8 years (range 41–80), M/F 11/5, median ECOG 1 (0–2), Child-Pugh A/B 10/6 . Total n° of courses was 41 (median 2, range 1–10). DLT was not reached. Two grade 3 toxicities were reported at DL 4: diarrhea in 1 pt and anemia in another pt. There were no G4 toxicities. Most common G1–2 toxicities at any DL were: neutropenia 5 pts (31%), nausea/vomiting 4 pts (25%), diarrhea 3 pts (18%), thrombocytopenia 2 pts (12.5%). In two pts (DL3 and DL4) treatment was discontinued because of chemotherapy induced arteritis after 1 and 3 courses respectively. 12 pts were assessable for response: 3 PR, 6 SD, 3 PD. α-fetoprotein levels decreased significantly in 6 pts (50%). Pharmacokinetics data will be presented later. Conclusions: To date MTD hasn’t been reached. At DL 1–5 this schedule shows little and manageable toxicity - without impairment of liver function - and promising activity (PR+SD=75%). No significant financial relationships to disclose.
Radiochemotherapy followed by gemcitabine and capecitabine in extrahepatic bile duct cancer (EBDC): A phase I/II-trial
Authors: Schoppmeyer K. , Wiedmann M. W. , Liebmann A. , Miethe S. , Mossner J. , Caca K. , Witzigmann H. , Hildebrandt G. 
Published: March 2020

14087 Background: The 5-year survival rate of patients with resected EBDC is less than 30%. Phase II trials demonstrated that advanced EBDC responds to both chemotherapy with gemcitabine and capecitabine and to radiotherapy. Our objective was to define a feasible and effective postoperative therapy in patients with EBDC. Methods: Patients were eligible after surgery for EBDC. Surgery included resection of lymph node positive cancer, incomplete resections and diagnostic laparotomy in unresectable tumors. Patients received a fractionated radiotherapy with 49.6 Gy accompanied by gemcitabine 100 mg/m2 weekly × 5. After a two week rest patients were treated with gemcitabine (1000 mg/m2 IV D1+8 q3w) and capecitabine (1500 mg/m2 PO D1–14 q3w) on a 3-week cycle. Treatment continued for 6 cycles in nonmeasurable disease or until disease progression or intolerable toxicity. Primary endpoint was toxicity; secondary endpoints were response rate in measurable disease and overall survival. Results: 18 Patients (resectable/unresectable disease 7/11) were enrolled. Radiotherapy was completed in all patients and a total of 66 cycles of chemotherapy were applied. Anemia, fatigue, and nausea were the most common mild adverse events in 16, 14, and 16 patients, respectively. Grade 3 and 4 toxicity was rare after resection but frequent in unresectable disease and consisted of fatigue, nausea, duodenal ulcer, cachexia and cholangitis in 1, 2, 2, 4, and 4 patients, respectively. We observed a 50% disease stabilization rate in patients with measurable disease. Median overall survival was 7.9 months in patients with unresectable tumors. Median overall survival in patients after resection has not been reached after a median follow-up of 19.5 months. Conclusions: Radiochemotherapy with gemcitabine followed by gemcitabine and capecitabine is an active regimen with manageable toxicity after resection of EBDC but has significant toxicity in unresectable disease. No significant financial relationships to disclose.
Irinotecan with 5-FU/FA in advanced biliary tract adenocarcinomas—A two-center phase II trial (GBFiri)
Authors: Feisthammel J. , Schoppmeyer K. , Wiedmann M. , Mossner J. , Schulze M. , Caca K. 
Published: March 2020

14088 Background: The majority of patients with biliary tract cancer present with advanced, unresectable tumors. Irinotecan and 5-Fluorouracil/folinic acid (FOLFIRI) have synergistic activity in gastrointestinal cancers. The aim of this study was to determine the tolerability and activity of systemic chemotherapy with FOLFIRI in patients with intrahepatic cholangiocarcinoma (CCC) or gallbladder cancer (GBC). Methods: This was a prospective, multicenter, non-randomised, open-label, phase II trial. Eligibility criteria: Inoperable adenocarcinoma of the biliary tract, measurable disease, age 18–80 years, ECOG PS 0–2. Patients received irinotecan 80 mg/m2 as a 30 min infusion, followed by folinic acid 500 mg/m2 over 2 h and 5-FU 2000 mg/m2 over 24h weekly × 6 followed by a 2 week rest. Treatment was continued until progression or limiting toxicity. Response to therapy was assessed after every other cycle according to RECIST criteria. Primary end point was response rate, secondary end points were overall survival, progression free survival and toxicity. Results: 30 pts (CCC 17, GBC 13) were enrolled. A total of 387 doses (Median 12.9; 1 to 36) were administered with an overall relative dose intensity of 98%. 30 patients are evaluable for safety. WHO grade 3/4 drug related adverse events occured in 7 patients (23%): Leukopenias in 2, anemia in 1, and diarrhea in 4 patients. 14 patients completed 2 cycles and were evaluable for response. Response rates: CR 0/30, PR 3/30 (10%) and SD 3/30 (10%). 8 patients presented with disease progression at restaging. Median overall survival: CCC 166 days, GBC 327 days. Progression-free-survival: CCC 84 days, GBC 159 days. Conclusions: FOLFIRI is a well tolerated regimen in patients with biliary cancer that can be safely administered on an outpatient basis. FOLFIRI has no substantial activity in CCC and moderate activity in GBC. Further studies are required to define a standard palliative chemotherapy for treatment of biliary cancer. No significant financial relationships to disclose.
Pancreatic cancer survivorship: Intrathecal drug delivery system for pain management
Authors: Stearns L. J. , Poling W. H. , Kiser J. , Nasternak J. , Berryman E. 
Published: March 2020

14100 Background: Pancreatic cancer is predominantly unresectable at diagnosis and is most frequently fatal. Nationally the average survivorship is 10 months. Among pancreatic cancer patients, pain is associated with decreased survival rates. Quality of life and survivorship are the principal outcome measures for these patients. Successful pain management may be a significant predictor of prolonged survivorship. No study has demonstrated an impact on survivorship secondary to the treatment of pancreatic cancer pain and the use of Intrathecal Drug Delivery Systems (IDDS). Methods: A retrospective chart review identified all pancreatic cancer patients treated at a cancer pain treatment center between January 2002 and June 2005. 43 patients had known dates of diagnosis and known dates of death. The Arizona Department of Health Services Cancer Registry provided similar information for pancreatic cancer patients residing in Maricopa County for that time period. 713 Maricopa county residents had known dates of diagnosis and known dates of death. Results: Among the Maricopa County pancreatic cancer patients, the mean survivorship was 5 months. Among the treatement center patients who did not receive the IDDS for pain, 10 (23.3%), the mean survivorship was 10.8 months. Among the pancreatic cancer patients receiving IDDS for pain management, 33 (76.7%), the mean survivorship was 14.2 months. Mean survivorship among the treatment center patients receiving IDDS for pain management is nearly 3 times greater than the general survivorship of pancreatic cancer patients in Maricopa County. Among the treatement center patients the mean survivorship is nearly 50% greater for patients receiving IDDS versus those that did not. Conclusions: The implantable IDDS for pain management among pancreatic cancer patients may be a significant predictor of increased survivorship. A larger sample size may be needed to detect significant differences in survivorship. Controlled studies examining survivorship as the primary outcome for patients with unresectable pancreatic cancer by evaluating the implantable IDDS as compared to usual care modalities such as comprehensive medical management (CMM) or neurolytic celiac plexus block (NCPB) for pain management are warranted. No significant financial relationships to disclose.
Preliminary results of a phase II-study: Vaccination therapy of pancreatic carcinoma patients with autologous, tumor lysate pulsed dendritic cells
Authors: Bauer C. , Dauer M. , Schnurr M. , Junkmann J. , Bauernfeind F. , Conrad C. , Bruns C. , Jauch K. , Emmerich B. , Endres S. , Eigler A. 
Published: March 2020

14102 Background: Vaccination trials in the experimental and in the clinical setting have shown that it is possible to use dendritic cells (DC) to induce a specific antitumoral immune response. In this study, a protocol for the treatment of patients with metastasised pancreatic carcinoma with autologous, tumor-lysate pulsed dendritic cells was established. Methods: Patients with strong suspicion of pancreatic carcinoma receiving abdominal surgery are recruited to the study. Tumor-lysate is derived by freeze-taw-cycles from surgically derived tissue specimens. After recurrence of histologically verified pancreatic carcinoma or in a primarily palliative situation, patients are eligible for DC vaccination. DC are derived from PBMC according to a six-day protocol, loaded with tumor lysate and stimulated with TNF-alpha and PgE2. DC are applicated intracutaneously into the groin region three times in twice weekly cycles, then in monthly cycles. Immune response is controlled by DTH skin testing. Samples of non adherent cells are frozen for future MLR and ELISPOT assays. Main study end point is partial or complete remission four months after the start of vaccination. Alternative end points are adverse effects, quality of life, one-year survival and immuno-monitoring. Results: Tumor material of 49 patients has been worked up to tumor lysate and stored for future vaccinations. Four patients have received dendritic cell vaccination. Two of these patients have received their four months staging CT. In one case local disease was stable. The other patient showed progressive disease. A more pronounced proliferation of specific T cells compared to the control setting could be demonstrated by MLR assay. Discussion: A protocol for vaccination with tumor lysate pulsed dendritic cells of patients with pancreatic carcinoma has been established. Four patients have been vaccinated with dendritic cells according to a phase II study protocol. Vaccination was tolerated well. Because of a severe adverse reaction after the beginning of gemcitabine therapy, vaccination had to be omitted intercurrently with this patient. Results of most immuno monitoring assays are pending. One patient receiving DC vaccination therapy showed stable local disease. No significant financial relationships to disclose.
A phase I study of combination S-1 and weekly docetaxel (TXT) for advanced or recurrent gastric cancer
Authors: Ozaki T. , Satoh T. , Shimizu T. , Miyazaki M. , Kurata T. , Fukuoka M. , Tamura K. 
Published: March 2020

14108 Background: S1, a novel oral fluoropyrimidine derivative, and docetaxel (TXT) have both been identified as active against the treatment of gastric cancer. The two drugs have incompletely overlapping principal toxicities, no cross resistance and have reported synergistic anti-tumor effect in vivo. Response rate of S1 and TXT for advanced gastric cancer were 46.5% and 17.1%, respectively. One report showed that full dose of S1: 80 mg/m2 daily for 2 weeks and TXT: 40 mg/m2 intravenously on day1, every 3 weeks was recommend dose (RD), however, dose of TXT has been limited low by neutropenia and allergic reactions. Weekly administration schedule of TXT has been reported as safe and effective treatment for advanced gastric cancer. The primary objective of this study was to determine the maximum tolerated dose (MTD) of combination with S-1 and weekly administration schedule of TXT, the toxicity profile and RD for phase II. Methods: Eligibility criteria includes histologically diagnosed metastatic or recurrent, or unresectable locally advanced gastric cancer, 2 prior regimens were permitted, ECOG PS 0–1, age>20, adequate organ function and written informed consent. Fixed full dose of S1: 80 mg/m2 daily was administrated orally for 3 weeks. TXT was infused intravenously over 60 minutes (Level 1: 15mg/m2; Level 2: 20mg/m2; Level 3: 25mg/m2) on day1, 8 and 15. This schedule was repeated every 5 weeks. Pharmacokinetic study was performed of S1 on day 7, 8 and of TXT on day1, 8 in order to evaluate the drug interactions. Results: Total 14 patients were registered in this study. Three patients were enrolled at the dose level 1, 6 patients at level 2 and 5 patients at level 3, respectively. No DLTs (dose-limiting toxicities) occurred at both level 1. One out of 6 patients developed DLT of Grade 3 diarrhea at Level 2. DLTs were observed in 3 out of 5 patients at level 3. There are febrile neutropenia, Grade3 stomatitis and continuous Grade 4 neutropenia. Pharmacokinetic study suggested no drug interactions between S1 and TXT. Conclusions: MTD was level 3. RD for multi-center phase II trial was Level 2 (S1 80 mg/m2 for 3 weeks and TXT: 20 mg/m2 day1, 8 and 15, every 5 weeks). This combination was active and well tolerated for advanced gastric cancer. No significant financial relationships to disclose.
Combination irinotecan, capecitabine and celecoxib in patients with advanced biliary cancers
Authors: Lee F. , Roach M. , Parasher G. , Hunt C. , Heywood G. 
Published: March 2020

14126 Background: Patients with metastatic biliary cancers continue to face a very grim prognosis with no effective chemotherapy. Median survival is around 6–9 months. Irinotecan and capecitabine have modest activity against cholangiocarcinoma. Cyclooxygenase-2 (COX-2) enzyme expression is reported in many human cholangiocarcinoma cell line studies and is linked to tumor cell resistance to chemotherapy-induced apoptosis. We hypothesized that adding a COX-2 inhibitor would improve the therapeutic benefits in patients with biliary tumors. Methods: From 9/2003 to 2/2005, a total of 12 patients were treated with a combination regimen, delivered at a cycle interval of 21 days, that consisted of 120 mg/m2 irinotecan given intravenously over 60 minutes on day 1, 1500 mg/m2/day capecitabine taken orally in divided doses on days 1–14 and 400 mg/day celecoxib taken orally in divided doses on days 1–21. Results: A total of 117 treatments were administered to the 12 patients (9 females and 3 males; median age, 56 years; 10 cholangiocarcinoma and 2 gallbladder cancer). Based on the tumor marker CA19–9, 7 of the patients had a partial response (7/12, 58%). Of the seven patients for which sequential CT evaluation was available, the partial response rate was 43% (3/7) and two additional patients had stable disease. The median progression-free survival was 13 months and the median overall survival was 17 months. We encountered grade II neutropenia and anemia (2/12 each, 17%) and grade I diarrhea and hand-foot syndrome (33% and 7%, respectively). Conclusions: These data suggest that the combination of irinotecan, capecitabine and celecoxib is an effective palliative regimen for patients with metastatic biliary cancers. Further development of this regimen is severely hindered by the potential cardiovascular risk associated with long-term use of COX-2 inhibitor. No significant financial relationships to disclose.
Results of a prospective study with FOLFOX and Ca/Mg infusions for treatment of advanced and metastatic gastric carcinoma
Authors: Des Guetz G. , Assouad S. , Spano J. , Chouahnia K. , Gil-Delgado M. , Wind P. , Morere J. , Breau J. 
Published: March 2020

14131 Background: Gastric cancer is often diagnosed in locally advanced or metastatic stages and prognostic is particularly bad. Results of a Phase II study of oxaliplatin, fluorouracil, and folinic acid was previously published (Louvet et al, J Clin Oncol. 20:4543–8, 2002). Grade 3 peripheral neuropathy occurred in 21% of patients (oxaliplatin-specific scale). Seven patients withdrew because of treatment-related toxicity. For these patients, tolerance of chemotherapy must be considered. Ca/Mg infusions seem to reduce incidence and intensity of acute oxaliplatin-induced symptoms and might delay cumulative neuropathy (Gamelin et al, Clin Cancer Res 15: 4055–61, 2004). Methods: In this study, in our medical Oncology department, we treated a first group of patients with FOLFOX 4 and a second group with FOLFOX S (FOLFOX S: LV5FU2 Simplified (Folonic acid 200 mg/m2, 2h, 5FU 400 mg/m2,bolus, 5FU infusion 1200 mg/m2, 44h) + oxaliplatin: 85 mg/m2, 2h, d1-d15) combined with infusions of Ca gluconate and Mg sulfate (1 g) before and after oxaliplatin and then we evaluated efficacy and toxicity. Results: Of the seventeen patients with advanced and/or metastatic stomach carcinoma enrolled between August 2000 and December 2004: Median age was 59 range (26;73) years, 12 were male, 5 female with a WHO performance status (PS) <3. There were 7 patients with objective response. Of the 13 evaluable patients for neurotoxicity, 6 were treated with FOLFOX 4 and 7 with FOLFOX S combined with Ca/Mg infusions. Neurotoxicity gr II was noted for 3/6 patients of the FOLFOX 4 group but for 1/7 patients also treated with Ca/Mg infusions. No grade 3/4 leukopenia, or thrombocytopenia were observed. Conclusions: This oxaliplatin-containing regimen is effective in the treatment of advanced gastric cancer. This regimen combining FOLFOX and Ca/Mg infusions seems to have a more favourable toxicity profile. No significant financial relationships to disclose.
Phase II clinical trial of curcumin in patients with advanced pancreatic cancer
Authors: Dhillon N. , Wolff R. A. , Abbruzzese J. L. , Hong D. S. , Camacho L. H. , Li L. , Braiteh F. S. , Kurzrock R. 
Published: March 2020

14151 Background: Pancreatic cancer is virtually always lethal, and the only FDA-approved therapies- gemcitabine and erlotinib- produce objective responses in less than 10% of patients. Curcumin (diferuloyl methane) is a plant- derived compound that inhibits the nuclear factor-kappa B (NF-kappa B) transcription factor (central to pancreatic cancer growth) and has substantial antitumor activity in preclinical models. We evaluated the toxicity and anti-tumor activity of curcumin, and its impact on survival and biologic correlates. Methods: Patients received 8 grams of curcumin (Sabinsa Corp.) by mouth daily for two months. Maintenance therapy was continued at the same dose and schedule until disease progression. Results: Seventeen patients were enrolled as of the date of analysis. Six were inevaluable: noncompliance (n = 1), never dosed (n = 1), noted to have gastric obstruction after one dose (n = 1), and too early (n = 3). Eleven patients were evaluable for response and 15 were evaluable for toxicity. To date, four patients have stable disease (2+, 2+, 3+ and 7 months) and one patient had a brief partial remission (73% reduction in tumor size by RECIST) that lasted one month. No toxicities have been observed. Serum was available for evaluation of pre-and post-dose cytokine levels in thirteen patients. Interestingly, the patient with the partial remission had marked increases (4–35 fold) in serum IL-1 receptor antagonist, IL-6, IL-10 and IL-8 levels. One to three other patients also had post-treatment increases in one or more of the above cytokines, albeit to a lesser extent (2–6 fold). Conclusions: We conclude that curcumin is well tolerated and our preliminary results suggest biologic activity in pancreatic cancer. Supported in part by the National Cancer Institute grant R21 CA 104337–01, The Topfer Fund for Pancreatic Cancer and Pancreatic SPORE grant 1 P20 CA10193–03. No significant financial relationships to disclose.