bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II study of gemcitabine (GEM) given at fixed-dose rate (FDR) infusion, low-dose cisplatin (CDDP), and bevacizumab (BEV) for metastatic adenocarcinoma of the pancreas (PanCa): Update with completion of study accrual
Authors: Ko A. H. , Dito E. , Schillinger B. , Venook A. P. , Bergsland E. K. , Wong D. , Allen J. , Tempero M. A. 
Published: March 2020

4548 Background: The objectives of this study are to determine safety and efficacy in pts with metastatic PanCa treated with a novel combination consisting of FDR GEM, low-dose CDDP, and BEV. We present here updated results on the full 53-pt study cohort. Methods: Chemotherapy-naive pts with histologically confirmed PanCa and documented extrapancreatic metastases received GEM 1,000 mg/m2 at FDR infusion (10 mg/m2/min), CDDP 20 mg/m2, and BEV 10 mg/kg, all administered on dd 1 and 15 of a 28-dd cycle. Pts were monitored by CT scans every 2 cycles and monthly serum CA19–9 measurements. Results: 53 pts (24M,29F; median age 60 y.o. [range 39–85]; ECOG PS 0–1) were enrolled betw 6/2004 and 9/2006 (med f/u, 513 dd; range, 93–885). 16 pts remain alive, with 9 still undergoing study rx. Pts received a median of 4.75 cycles of rx (range, 0.5–20). 29 pts discontinued study rx 2o to progressive dz (med # of cycles, 5; range, 0.5–20); 9 pts 2o to rx-assoc toxicity; 4 pts 2o to plateau in response with cumulative asthenia (after 8–12 cycles); and 2 pts 2o to prolonged rx delay from bowel obstruction. Major events include 2 bowel perforations, one associated with placement of a duodenal stent; 4 major GI bleeds; 7 DVT/PE; 1 stroke-like sxs; and 3 cardiac events (MI x 1, arrhythmias x 2). 4 pts (7.5%) developed grade 3/4 HTN. Gr 3/4 hematologic toxicities inc. neutropenia in 4 pts (7.5%) and thrombocytopenia in 1 pt (2.9%). 16 pts (20%) required dose reduction in gemcitabine during study rx and 4 required holding of cisplatin. There were 3 deaths potentially assoc with rx. 12 pts (22.6%) have had an unconfirmed response (1 CR, 11 PR) and 26 pts (49.1%) have had stable dz for >2 cycles, for an overall dz control rate of 71.7%. 20 of 35 pts (57.1%) with elev baseline CA19–9 levels (>2X ULN) had >50% biomarker decline during rx. Median TTP is 6.2 months. Median overall survival is 8.0 months with an est. 1-yr survival rate of 40%. Conclusions: The addition of BEV to FDR GEM/low-dose CDDP shows promising efficacy, particularly in TTP and 1-yr survival rate, with manageable toxicity. Further efforts are ongoing to identify which pts are most likely to benefit from BEV-based rx. [Table: see text]
Final results from cohort 1 of a phase II study of volociximab, an anti-α5β1 integrin antibody, in combination with gemcitabine (GEM) in patients (pts) with metastatic pancreatic cancer (MPC)
Authors: Evans T. , Ramanathan R. K. , Yazji S. , Glynne-Jones R. , Anthoney A. , Berlin J. , Valle J. W. 
Published: March 2020

4549 Background: A critical survival step for proliferating endothelial cells is the ligation of fibronectin in the extracellular matrix to integrin a5β1. Volociximab, a chimeric monoclonal antibody, blocks fibronectin binding to a5β1, and induces apoptosis of proliferating endothelial cells. Volociximab activity is independent of growth factor stimuli, suggesting that a5β1 signalling occurs downstream of growth factor signalling, and is possibly a final common pathway for the development of neovasculature. The efficacy and safety of volociximab in combination with GEM was determined in pts with MPC. Methods: This is a multi-center, open-label, 2-cohort, single-arm Phase II study. Eligible pts had confirmed MPC, no prior chemotherapy for MPC, adequate hematologic, renal and hepatic function, and had measurable disease. Pts received volociximab 10mg/kg iv every 2 weeks (days 1 and 15) with GEM (1,000 mg/m2 iv) on days 1, 8, 15 of a 4- week cycle until disease progression (PD). Radiologic assessments of measurable disease were performed every 8 weeks. The primary endpoint was objective tumor response (RECIST criteria). Sample size was 20 pts per cohort. At least 1 confirmed response at 4 months (mo) or SD ≥ 4 mo was necessary in cohort 1 (n=20) before expansion to the second cohort. Results: 20 pts (male=11, female=9), median age = 59.8 years (range 34–74), were treated in cohort 1 and were evaluable for safety and efficacy. PS (ECOG) was 0–1 (n=19; 95%) or 2 (n=1; 5%). Pts received a median of 8 weeks’ (range 2–58) treatment. Most frequent toxicities included nausea in 14 (70%) pts, vomiting (12; 60%) and constipation (10; 50%). Overall response included 1 confirmed PR (5%), and stable disease in 10 (50%) pts. Median time to progression was 4.3 mo; 41% had not progressed at 6 mo. Overall survival was 5.4 mo, and at 6 and 8 mo was 45%, and 37% at 12 mo. 12 pts died in the study due to PD (10 pts), GI perforation (1), pulmonary embolism (1). Conclusions: Volociximab is well tolerated at 10mg/kg 2-weekly with GEM. Cohort 2 is currently recruiting at a higher dose of volociximab (15 mg/kg) administered weekly. [Table: see text]
A randomized phase II study of axitinib (AG-013736) and gemcitabine versus gemcitabine in advanced pancreatic cancer, preceded by a phase I component
Authors: Spano J. , Chodkiewicz C. , Maurel J. , Wong R. P. , Wasan H. S. , Pithavala Y. K. , Bycott P. W. , Liau K. , Kim S. , Rixe O. 
Published: March 2020

4551 Background: The current standard of care for patients (pts) with advanced pancreatic cancer (APC) is gemcitabine (GEM)- based chemotherapy. Axitinib (AG) is a potent inhibitor of vascular endothelial growth factor receptors. A phase I study of AG in solid tumors identified 5 mg BID as the therapeutic starting dose. The main objectives of this trial are to determine whether the overall survival (OS) of the combination of AG and GEM is superior to that of GEM alone as first-line therapy in pts with APC, and to determine doses of AG and GEM that can be safely administered together. Methods: 8 pts were treated on the phase 1 (P1) portion of this trial. For the phase 2 (P2) portion of the trial, 103 pts with locally advanced or metastatic disease, no prior GEM or VEGF/VEGFR inhibitors, PS 0–2 were randomized (2:1) to GEM 1,000 mg/m2 over 30 minutes on days (D) 1, 8, 15 every 28 D with or without AG at a starting dose of 5 mg po BID between Jan 06 and Aug 06. CT scans were performed every 2 cycles. Results: Data from the evaluable P1 pts (n=5) indicated that PK of GEM and AG appeared to be unchanged in combination. The GEM mean plasma exposure (AUC) was 11,348 alone vs 12,840 ng.h/mL with AG; similarly mean steady-state AG AUC was 250 alone vs 270 ng.h/mL with GEM. 3 of 8 pts had a PR. The median number of days on study drug was 158 days (range: 57–330 days) with 2 pts ongoing. Data from the randomized P2 pts: male 48%; median age 62 (36- 81); PS 0/1 vs 2: 91% vs 9%; 41% with locally advanced disease; 59% with metastatic disease. The most commonly reported adverse events are anemia (48%), alk phos elevations (48%), leukopenia (45%), neutropenia (42%), LFT elevations (39%), and thrombocytopenia (27%). The most common non-hematologic adverse events are nausea (24%), vomiting (20%), fatigue (19%), diarrhea (18%), anorexia (18%), constipation (13%), dyspnea (12%), and pyrexia (12%). 55 events have been reported in the 103 P2 pts. The pooled median OS is 203 days with a 95% CI of (158, not estimable). The median follow-up time is currently 223 days. Conclusions: AG can be safely administered at a starting dose of 5 mg BID in combination with standard dose GEM in patients with APC. Final safety and OS results by treatment arm will be presented. [Table: see text]
Impact of gene expression of orotate phosphoribosyl transferase for complete response to chemoradiotherapy in patients with squamous cell carcinoma of the esophagus
Authors: Kajiwara T. , Nishina T. , Hyodo I. , Moriwaki T. , Endo S. , Nasu J. , Hori S. , Iguchi H. , Hiasa Y. , Onji M. 
Published: March 2020

4566 Background: Chemoradiotherapy (CRT) is a potential alternative to surgery in patients with squamous cell carcinoma of the esophagus. Complete response (CR) to CRT is essential for a good prognosis and there is a need for a predictive method of CR in CRT. Methods: The pretreatment formalin-fixed, paraffin-embedded endoscopic tumor biopsy material was obtained from 41 patients treated with a definitive concurrent CRT (5-FU/CDDP and 60 Gy) for esophageal cancer (cStage II or III). cDNA was derived from tumor cells of biopsy specimens by the laser capture microdissection and analyzed to determine mRNA expression relative to an internal reference gene (β-actin) using fluorescence-based, real-time reverse transcription PCR. Gene expression levels of thymidylate synthase, thymidine phosphorylase, dihydropyrimidine dehydrogenase, orotate phosphoribosyl transferase (OPRT), metylenetetrahydrofolate reductase, dihydrofolate reductase (DHFR), excision repair cross-complementing gene 1, vascular endothelial growth factor, epidermal growth factor receptor and matrix metalloproteinase 9 (MMP-9) were measured. Results: Median gene expression levels of OPRT and DHFR were significantly higher in CR patients (p=0.0206 and 0.0191, respectively). MMP-9 was significantly lower in CR patients (p=0.0436). When the median values of the gene expression levels were selected as the cutoff values, CR rate was significantly higher in the high OPRT group and high DHFR group (p=0.0104 and 0.0104, respectively). However, there was no statistical difference in CR rate between the low MMP-9 group and the high MMP-9 group. Multivariate analysis, including clinical stage and biomarkers, revealed that high OPRT gene expression was an independent predictive factor of CR (p=0.0329, relative risk=6.65, 95% confidence interval, 1.17–37.89%). Conclusions: The measurement of OPRT gene expression in tumor biopsies may be a predictive factor of CR to CRT in patients with squamous cell carcinoma of the esophagus. No significant financial relationships to disclose.
Bevacizumab in patients (pts) with advanced hepatocellular carcinoma (HCC): Preliminary results of a phase II study with circulating endothelial cell (CEC) monitoring
Authors: Malka D. , Dromain C. , Farace F. , Horn S. , Pignon J. , Ducreux M. , Boige V. 
Published: March 2020

4570 Background: Effective therapy for pts with advanced HCC is still lacking. This phase II trial was designed to define efficacy of bevacizumab in HCC pts. Methods: Pts with unresectable HCC received bevacizumab at 5–10 mg/kg bimonthly. Prior treatment for HCC was allowed. Main ineligibility criteria included Child-Pugh score > 7; CLIP score > 3; recent (< 6 months) thromboembolic event; and anticoagulation or anti-platelet therapy. Propranolol had to be prescribed in case of large esogastric varices. CEC, identified by a CD45- CD31+CD146+7AAD- phenotype by four-color flow cytometry, were measured at day (D) 1,3,15 and 46 after start of treatment. Results: Overall, 30 pts (27 men; median age, 65.5 years [range, 23–84]; histologically proven cirrhosis, 20 pts [Child-Pugh A5/A6/B7: 12/15/3; CLIP 0/1/2/3/4: 1/6/14/6/3] received a median of 6 cycles (range, 2–25; total, 234). As progressive disease (PD) was observed within 16 weeks in 12 pts after inclusion of the first 23 pts treated at 5mg/kg, subsequent pts (n=7) were treated at 10 mg/kg as planned by the protocol design. Of the 30 pts treated at either dose, 6 (20%) discontinued bevacizumab because of variceal hemorrhage (variceal banding successful in every case) (n=3); grade 3 transient ischemic attack (n=1); grade 3 hemorrhagic ascites (n=1); and grade 3 proteinuria (n=1). Grade 1–2 toxicities included fatigue, epistaxis, hypertension, and proteinuria. Among the 24 pts evaluable for efficacy, 3 (12.5%) had partial response (PR), and 13 (54%) had stable disease (SD) (> 16 weeks in 7 pts) (disease control rate (DCR), 67%). Median baseline CEC level (n=21) was 14/ml (range, 0- 71), as compared to 5.5/ml (range, 0–15) in healthy subjects (n=20) and 16/ml (range, 0–179) in pts with various metastatic cancers (n=80). CEC levels increased more than two-fold at D3 in 11 (52%) among 21 pts; a dramatic drop was observed in all PR pts, as well as in a fraction (25%) of SD pts. Conclusions: Bevacizumab is relatively safe and provides an encouraging DCR in patients with HCC and compensated cirrhosis. Accrual is ongoing at the dose of 10 mg/kg. The predictive value of CEC will be presented at the meeting. [Table: see text]
Randomised prospective phase II study of combination chemotherapy epidoxorubicin, cisplatin, 5-FU (ECF) versus epidoxorubicin, cisplatin, capecitabin (ECX) in patients with advanced or metastatic gastric cancer
Authors: Ocvirk J. , Rebersek M. , Skof E. 
Published: March 2020

4571 Background: In phase II studies ECF with 5- FU inf. resulted in response rates (RR) > 50 %. Despite high responses the potential drawback of ECF may be the poor patient’s (pts) acceptability of the indwelling catheter and external infusion pump and related complications: sepsis, catheter-related infections, shoulder pain, thrombosis and pneumothorax. Capecitabin can maintain a constant level of 5- FU without complications and inconvenience associated with central venous access. The aim was to compare the efficacy and safety ECF versus ECX. Secondary endpoint was overall survival. Methods: Pts with histological proven, previously untreated advanced or metastatic gastric cancer, >18 years, ECOG performance status 0- 2 and adequate organ and hematological function were randomized to ECF or ECX. In ECF epidoxorubicin 50 mg/m2 and cisplatin 60 mg/m2 were administrated on day 1 by i.v., 5- FU 200 mg/m2/day was administrated by cont. inf. day 1- 14 of each cycle. Cycle was repeated every 3 weeks. In ECX epidoxorubicin 50 mg/m2 and cisplatin 60 mg/m2 were administrated on day 1 by i.v., capecitabin 825 mg/m2 twd was administrated orally day 1- 14. Cycle was repeated every 3 weeks. Results: Seventy- one pts were enrolled in this study between Jan 03 to Dec 05. Male 80 %, median age 56 yrs (40- 77). Thirty pts received ECF and 41 pts received ECX . All pts were assessable for responses and toxicity. The overall clinical RR were 45 % including 12.9 % partial responses (PR) and 6.4 % complete responses (CR) in ECF group and 69 % including 21.4 % PR and 4.7 % CR in ECX group. Median OS and TTP were 8.8 months (mos) ± 7.8 and 6.0 mos ± 4.4 in ECF group and 10.5 mos ± 7.2 and 7.0 mos ± 4.6 in ECX group respectively. The most frequent grade ¾ side effects graded according to CTCAE - 3 were fatigue - 20 % in ECF group and 19.5 % in ECX group, hematological (neutropenia) - 16 % in ECF group and 4.8 % in ECX group, nausea - 10 % in ECF group and 7.3 % in ECX group, diarrhea - 2.4 % in ECX group, hand- foot syndrome - 2.4 % in ECX group. Conclusions: ECX is at least effective as ECF with less toxic pattern and more convenient for pts and could replace ECF in first- line therapy in pts with advanced or metastatic gastric cancer. No significant financial relationships to disclose.
Immunological and clinical response after vaccination therapy of pancreatic carcinoma patients with autologous, tumor-lysate pulsed dendritic cells: Results of a phase II-study
Authors: Bauer C. , Dauer M. , Saraj S. , Schnurr M. , Jauch K. , Rüttinger D. , Bruns C. , Emmerich B. , Endres S. , Eigler A. 
Published: March 2020

4579 Background: Multiple studies in the experimental and in the clinical setting have shown that vaccine therapy using dendritic cells can induce antitumor immunity. Here, we report about the results of a phase II-study using autologous, tumor-lysate pulsed dendritic cells for the treatment of patients with advanced pancreatic carcinoma. Methods: Pancreatic carcinoma patients receiving abdominal surgery were included into to the study protocol. Tumor-lysate was derived by freeze-taw-cycles from surgically derived tissue specimens. Patients were eligible for DC vaccination after recurrence of pancreatic carcinoma or in a primarily palliative situation. DC were derived from PBMC according to a six-day protocol, loaded with tumor lysate and stimulated with TNF-a and PgE2. DC were applicated intracutaneously into the groin region every other week for three cycles, then monthly. All patients received standard chemotherapy with gemcitabine concomitantly. Immune response was controlled by DTH skin testing. Samples of non adherent cells were frozen for MLR and ELISPOT assays to monitor immune response ex vivo. Main study end point was partial or complete remission. Results: Ten patients have received dendritic cell vaccination so far. Of these, one patient developed a partial remission after a four-months course of vaccination therapy. Another patient showed stable disease after having received five vaccinations. Both patients showed immunological response. The patient with stable disease had a mean of 56 IFN-γ positive spots per 50E3 DC-stimulated non adherent cells prior to vaccination. After vaccination, this number increased to 191 spots per 50E3 cells (negative control: 5; positive control: 315). Both patients are alive 13 and 7 months after the start of vaccination therapy, respectively. Conclusions: Vaccination therapy with dendritic cells can be of clinical benefit in the setting of advanced pancreatic carcinoma. Clinical responses were associated with the induction of a stable immunological response. No significant financial relationships to disclose.
First-line simplified GEMOX (D1-D1) versus classical GEMOX (D1-D2) in metastatic pancreatic adenocarcinoma (MPA). A GERCOR randomized phase II study
Authors: Andre T. , Afchain P. , Lledo G. , Nguyen S. , Paitel J. , Mineur L. , Artru P. , Selle F. , de Gramont A. , Louvet C. 
Published: March 2020

4592 Background: GEMOX was defined as a D1-D2 schedule, based on preclinical data. In order to improve convenience for patients, we evaluated a simplified D1-D1GEMOX regimen (S-GEMOX) in MPA. Methods: Patients (pts) with MPA were 2:1 randomly assigned for first-line treatment to S-GEMOX (arm A : gemcitabine 1,000mg/m2, 100 min infusion D1 immediately followed by oxaliplatin 100 mg/m2, 120 min infusion) or to GEMOX (arm B : gem D1 and ox D2). Treatment was repeated in each arm every 2 weeks until disease progression. Stratification was performed on centre and PS. Results: Fifty-seven pts were enrolled, A = 37 (PS 2 : 22%), B = 20 (PS 2 : 20%). Populations were well balanced for age (64.9 yrs vs 66.6), gender (57% male vs 65), location of primary tumor (pancreas head 49% vs 50), and metastasic sites (liver 76% vs 85; peritoneum 24% vs 20; lung 16% vs 10; lymph nodes 14% vs 15; other 5% vs 5). Tumor differentiation significantly differed among the 2 groups (A : 8% poorly differentiated vs B : 36%). Response rate was 27% (95% CI : 12–42) in arm A and 10% (95% CI : 0 - 23) in arm B. Median PFS was 4.0 and 2.5 months in arm A and B, respectively. Median OS was 7.6 and 3.2 months in arm A and B, respectively. S-GEMOX was more toxic than GEMOX for gr 3–4 neutropenia (20% vs 0%) and thrombocytopenia (16% vs 10%). Other toxicities were comparable. However, since more cycles were administered in arm A (8.5 (1–29) vs 5.8 (2–12)), gr 3 oxaliplatin- induced neuropathy was higher in arm A (21.6% vs 0%). Conclusions: S-GEMOX is active in MPA. This activity is in the same range as compared to our previous experiences of GEMOX. The very bad outcome of pts randomized in arm B could be in part explained by the high rate of poorly differentiated tumors. This study emphazises one more time the limit of studies with small sample size of pts in MPA. No significant financial relationships to disclose.
Gemcitabine, oxaliplatin (GEMOX) and cetuximab for treatment of hepatocellular carcinoma (HCC): Results of the phase II study ERGO
Authors: Louafi S. , Hebbar M. , Rosmorduc O. , Tesmoingt C. , Asnacios A. , Romano O. , Fartoux L. , Artru P. , Poynard T. , Taieb J. 
Published: March 2020

4594 Background: A promising efficacy of the GEMOX combination was previously reported in HCC. Moreover, the EGFR signalling pathway is involved in hepatic carcinogenesis and tumor progression. This phase II study of GEMOX plus cetuximab was therefore undertaken in patients with unresectable HCC. Methods: 44 patients were included in the study between November 2005 and October 2006. All patients received cetuximab (initial dose 400 mg/m2 BSA then 250 mg/m2 weekly) combined with GEMOX (gemcitabine 1000 mg/m2, Day 1 and oxaliplatin 100 mg/m2, Day 2), repeated every 14 days until disease progression or limiting toxicity. Inclusion criteria were: histologically proven HCC or morphologically typical hepatic tumor with alpha-feto protein (AFP) level >250 ng/mL, ECOG performance status (PS) 0–2, age =18, measurable lesion, platelets >100.109 G/L, PNN >1.5.109 G/L, creatinine <120 μmol/L, non decompensated Child A or B cirrhosis, documented tumor progression (RECIST), informed consent. Results: 43 patients, including 22 with baseline AFP >400, were evaluable for safety and 35 for efficacy. Patients’ characteristics, toxicity and efficacy are summarized in the table below; 26% of patients received prior intra-arterial chemotherapy. Only one grade 4 toxicity was reported (thrombocytopenia). Grade 3 toxicities were: thrombocytopenia (21%) neutropenia (19%), acneiform rash (19%), asthenia (7%). Grade 2 and 3 neurotoxicity (specific scale) occurred in 16% and 5% of patients, respectively. No toxic death or other severe toxicity was reported. Conclusion: GEMOX plus cetuximab was well tolerated and induced a satisfactory control of disease in progressive HCC. Final results will be presented at the meeting. [Table: see text] No significant financial relationships to disclose.
A phase II open-label study of cetuximab in unresectable hepatocellular carcinoma: Final results
Authors: Gruenwald V. , Wilkens L. , Gebel M. , Greten T. F. , Kubicka S. , Ganser A. , Manns M. P. , Malek N. P. 
Published: March 2020

4598 Background: Hepatocellular carcinoma (HCC) express the epidermal growth factor receptor (EGFR), and EGFR-targeting therapies are known to block tumor growth. We tested the activity of cetuximab (CET) in HCC and evaluated serial tumor biopsies for biomarker analyses. Methods: Patients (pts) with advanced or metastatic HCC with ECOG = 2 and adequate organ function were eligible. Prior therapy was permitted. CET was given iv weekly (400 mg/m2 loading dose, 250 mg/m2 thereafter). The primary endpoint was the rate of progression-free survival (PFS) at 24 wks. Serial tumor biopsies were performed prior to treatment, after 4 wks and at time of progression. 32 pts were enrolled. 27 pts are evaluable for tumor response. Results: Stable disease (SD) was achieved in 44.4% (12 pts) for at least 8 weeks of treatment. 55.6% failed to respond to CET (15 pts). The median time to progression (TTP) for all pts was 8.0 wks. Pts, which were stable for more than 8 wks achieved a median TTP of 22.5 wks (11–48 wks) compared to a median TTP of 6.0 wks (3–8 wks) in progressive pts. No treatment-related severe adverse events were noted throughout the study. Preliminary evaluation of surrogate markers showed no correlation with cytogenetic abnormalities based on FISH analyses for chromosome 1 and 8. Furthermore, only 5 of 21 tumor specimens were positive for EGFR expression without gene amplification, evaluated by FISH analyses. Serial tumor specimens are available in 5 responding and in 7 non-responding pts for changes of p27 and p21 expression. p27 and p21 were upregulated simultaneously in 60% (3/5 pts) of responding pts, whereas in pts with treatment failure p27 and p21 expression was detectable in 14% (1/7 pts) only. Conclusions: Cytogenetic aberrations of chromosome 1 and 8 failed to predict response to CET. In a subgroup of pts with SD >8 weeks, induction of p21 and p27 were associated with prolonged TTP >20 wks. Further evaluation of p21 and p27 as early molecular tumor response is warranted to identify pts, which benefit from anti-EGFR therapies. [Table: see text] No significant financial relationships to disclose.