bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II trial of the proteasome inhibitor bortezomib in patients with recurrent or metastatic adenocarcinoma of the bile duct or gallbladder (NCI #6135)
Authors: Costello M. R. , Meropol N. J. , Denlinger C. S. , Engstrom P. F. , Wright J. J. , Li T. , Mclaughlin S. , Beard M. , Cimildoro R. , Cohen S. J. 
Published: August 2020

e15605 Background: There is currently no standard therapy for recurrent or metastatic cancers of the bile duct or gallbladder and available chemotherapy is of uncertain benefit. As activation of NF-κB has been described in these tumors, we initiated a phase II trial of the proteasome inhibitor bortezomib in patients with recurrent or metastatic disease. Methods: Patients with measurable metastatic or unresectable adenocarcinoma of the bile duct or gallbladder who had received up to 2 prior chemotherapy regimens were eligible. Other eligibility criteria included ECOG PS 0–2, total bilirubin ≤1.5X ULN, and ALT/AST ≤2.5 X ULN. Patients with baseline neuropathy ≥grade 2 were excluded. Bortezomib was administered at a dose of 1.3 mg/m2 as an intravenous bolus on days 1, 4, 8, and 11 of 21 day cycles with CT evaluation every 6 weeks. The primary endpoint was response rate. Null hypothesis: PR/CR≤5%. Alternative hypothesis: PR/CR ≥20%. 35 patients were required for 90% power with an early stopping rule at 20. Results: 20 patients were enrolled: 11M/9F, PS 0/1 (7/13), 6 gallbladder /14 bile duct. There was one patient with an unconfirmed partial response, 9 patients with stable disease, and 10 patients with progressive disease. Accrual was halted after 20 patients were enrolled as the early stopping rule for futility was met. Median PFS was 48 days (95% CI [32,124]) and median OS was 284 days (95% CI [155, 513]). Grade 3/4 toxicities were observed in 13 patients (65%), most commonly fatigue (4 patients), thrombocytopenia (3 patients), hyperbilirubinemia (3 patients), and hypotension (2 patients). Other SAEs at least possibly related to bortezomib included grade 3 vasculitis (1 patient) and grade 2 meningitis (1 patient). Conclusions: Bortezomib is not an active agent in the treatment of metastatic gallbladder or biliary tract cancer. No significant financial relationships to disclose.
Phase II study of postoperative chemoradiotherapy for esophageal carcinoma
Authors: Wu S. , Deng X. , Zhang P. , Xie C. , Zhang X. , Jin Z. 
Published: August 2020

e15606 Background: Esophageal squamous cell carcinoma is still a virulent disease diagnosed at late stage and remains a major cause of carcinoma mortality in China. The preoperative chemoradiotherapy had been applied to patients with esophageal carcinoma in an effort to reduce the relapse and improve survival. However, randomized controlled trails have shown conflicting results. Intergroup study 0116 demonstrated that postoperative chemoradiotherapy significantly improved overall survival in gastric carcinoma patients. The question remains whether postoperative chemoradiotherapy can improve overall survival in patients with esophageal carcinoma. Our planning study was to investigate the role of postoperative chemoradiotherapy in the multimodality treatment for locally advanced esophageal carcinoma. Methods: From October 2000 to October 2007, Fifty-two patients who underwent esophagectomy with stage II-III esophageal carcinoma were enrolled. All patients received 50Gy of postoperative radiotherapy over 25 fractions in 5 weeks. Two cycles of chemotherapy (Paclitaxel 135mg/m2 d1,cisplatin 20mg/m2d1–3) were administered concurrently on days 1–3 and days 29–31 of radiotherapy. Results: Of the total 52 patients, 28 (54%) developed grade 3 or 4 toxicity.At the time of analysis, 23 patients died. The median follow-up for surviving patients was 23.5 months. The median survival time was 37.2 months. Incidences of tumor recurrence were 53.8 % (28/52) of patients. As expected, distant metastasis was predominant. The 2-year local-regional control survival, distant metastasis-free survival and relapse-free survival were 60.01%, 71.38% and 42.01%, respectively. 1-year and 3-year overall survival were 82.19% and 47.13%, respectively. Conclusions: This novel postoperative chemoradiation regimen for treatment of patients with stage II-III esophageal cancer has a tolerable toxicity and promising 3-year overall survival. No significant financial relationships to disclose.
COX-2 inhibition in combination with preoperative chemoradiation for CA esophagus
Authors: Kwong D. L. , Law S. Y. , Tong D. K. , Wong K. H. , Nicholls J. 
Published: August 2020

e15607 Background: Squamous cell carcinoma of the thoracic esophagus (ESCC) is often diagnosed in advanced stage. Pre-operative chemoradiation is employed to downstage the disease before operation. Pathological complete response (pCR) was observed in around 20–40% of patients and was associated with improved survival. Cyclooxygenase 2 (COX-2) is overexpressed in ESCC and may contribute to chemo- and radio-resistance. This pilot study evaluates if COX-2 inhibition in combination with pre-operative chemoradiation will improve the response rate in ESCC. Methods: Patients with histologically confirmed ESCC undergo endoscopic ultrasound, ultrasound of neck and PET/ thoracic, abdominal CT for staging. Patients with disease which is considered potentially resectable are eligible. The primary and involved lymph nodes are irradiated to 40Gy in 20 fractions over 4 weeks with 2 cycles of concurrent cisplatin (100mg/sqm, D1, D22) and 5 fluorouracil (500mg/sqm, D1–5, D22–26). Celecoxib, a specific COX-2 inhibitor, 400mg bid, is started for 2 weeks before chemoradiation, continued throughout chemoradiation and for 4 more weeks after completion of chemoradiation. Patients are re-evaluated and esophagectomy is performed 6–8 weeks after completion of chemoradiation. Results: From 2004 to 2008, 32 patients were recruited. Pre-operative staging was stage II in 4, stage III in 25 and stage IVA in 3 patients. Celecoxib was well tolerated. 3 patients did not have full course of celecoxib: 1 complained of epigastric pain, 1 died early of disease, 1 had renal impairment after chemotherapy. 29 patients had esophagectomy performed after chemoradiation. Median follow-up after completion of chemoradiation was 11 months (range: 3 to 43 months). 23 patients (79.3%) had downstaging of the primary compared with pre-operative staging. The pCR rate in primary tumor was 51.7% (15/29 patients) and pCR rate in lymph nodes was 65.4% (17/26 patients). 3 years overall survival of patients who had esophagectomy was 79.3%. Conclusions: COX-2 inhibition in combination with pre-operative chemoradiation is well tolerated. Preliminary results of the pCR rates and survival are encouraging. Incorporation of COX-2 inhibition into multi-modality treatment of ESCC should be further investigated in a randomized trial. No significant financial relationships to disclose.
Phase II study with preoperative oxaliplatin (O), cisplatin (P), 5-fluorouracil (F) (OPF) and radiation (XRT) in patients with esophageal (ES), gastroesophageal (GE), and gastric (G) cancer
Authors: Pera M. , Gallego R. , Martin-Richard M. , Montagut C. , Iglesias M. , Conill C. , Balaguer C. , Petriz L. , Momblan D. , Maurel J. 
Published: August 2020

e15612 Background: A phase I study showed the feasibility of the triplet combination (OPF) with XRT in ES and GE cancer (Maurel et al, IJRBOP, 2005). We conducted a phase II study to evaluate the efficacy of the regimen. Methods: Enrolled pts had resectable, high-risk (HR) based on endoscopic ultrasonography (EUS) (uT3, uN1 or uT4 if deemed resectable) ES, GE and G cancer. The primary objective was to determine the pathologic complete response (pCR). If 2 or more pCR were reported in the first 18 pts treated, enrollment continues with 23 additional pts. Eligibility criteria: squamous cell or adenocarcinoma of the ES, GE or G cancer and ECOG Performance status (PS) 0–1. Staging was done with EUS and computed spiral tomography. Laparoscopic staging was mandatory for pts with ES, GE and G adenocarcinoma. Pts received 2 cycles of O 85 mg/m2, P 55 mg/m2, F (3 g/m2 in 96h CI) q4w, with concomitant 45 Gy XRT in 25 fractions; surgery was planned 5–8 weeks after XRT. All pathological specimens were reviewed by a unique pathologist and regression analysis was recorded using Cologne (C) and M.D.Anderson (MDA) classification for ES and European Journal of Surgical Oncology (EJSO) for GE and G. Results: Between 5/04 to 12/07, 41 pts were enrolled in 5 Spanish Institutions. Median age 62 yrs (39–75 yrs); Male/female 83%/17%; PS 0/1 27%/73%; ES/GE/G 39%/32%/29%; EUS stageT3N0 (20%), T2–3N1 (65%) and T4 (10%). G3/4 adverse events included asthenia (27%), infection (7%), diarrhea (7%) and stomatitis (5%). There were 2 toxic deaths. Of the 31 pts who underwent surgery, there were R0=94%/R1=3%/R2= 3%. 7/41 pts (17%) achieved pCR. Using C and MDA classification, 9/14 (61%) and 12/14 (85%) ES achieved grade IV/III and P0/P1 regression, respectively. With EJSO classification 3/17 (18%) GE and G tumors achieved pCR. Median time to progression or death (PFS) was 16.2 (CI:12.2-NR) months (mo). Median overall survival (OS) was 28.9 mo. (CI: 22.5-NR). Conclusions: Although in the whole group pCR, PFS and OS does not appear superior to results achieved in other trials with preoperative P/F/XRT in HR pts, the OPF regimen seems specially active in ES cancer. No significant financial relationships to disclose.
Preliminary results of a multicenter phase II study of imatinib and fluorourcail/leucovorin (FU/LV) in patients with unresectable or metastatic gallbladder or biliary tract cancer
Authors: Schuette K. , Moehler M. , Kettner E. , Al-Batran S. , Hegewisch-Becker S. , Steffens C. , Pustowka A. , Goekkurt E. , Ehninger G. , Stoehlmacher J. 
Published: August 2020

e15622 Background: There are no standard chemotherapeutic regimens for incurable biliary adenocarcinomas. Monotherapies with gemcitabine or FU/LV achieve occasional responses and a median overall survival of about 6 months. By blocking PDGFR a decreased intrastromal pressure may increase therapy effects of chemotherapy. The combination of imatinib and FU/LV has been shown to be safe and feasible in a previous Phase I trial. This multicenter phase II trial was designed to investigate the disease control rate (DCR) of FU/LV and imatinib. Methods: Eligibility criteria included unresectable or metastatic measurable biliary tract cancer (BTC)/gallbladder cancer (GBC), performance status < 2, adequate organ function and no clinically significant cardiovascular disease. Enrolment of 44 chemonaive patients (pts.) was planned. Pts. received LV 200 mg/m2 followed by FU 2000 mg/m2 as a 24-hour infusion on days 1 and 2 combined with 600mg imatinib on days -4 to 4 (8 days). Cycles were repeated every 2 weeks up to 12 cycles. Radiological assessments were performed every 4 cycles. Results: 41 pts (19 GBC; 22 BTC) were enrolled in this phase II study since May 2007. Median age was 62 years (range 33–77), male/female=24/17, ECOG 0/1/2=13/23/5. 35 pts. showed metastatic disease at baseline. Treatment was well tolerated. Treatment related grade 3/4 toxicities included (number of pts): diarrhea (2), edema (1), neutropenia (2), nausea (2), transient SGPT elevation (4). The DCR of 26 pts. available for response assessment at time of analysis 1 was 58% (15 pts) (1 CR, 1 PR,13 SD of at least 4 cycles). 11 pts. showed progressive disease (PD) per RECIST criteria. 3 pts. had disease stabilization after 12 cycles and continue on treatment. We present these preliminary data as they represent a large patient number in this entity and response data are promising. Conclusions: This preliminary analysis suggests that the combination of FU/LV and imatinib can be safely administrated in pts. with GBC/BTC. Early evidence of antitumor activity was seen with some pts. achieving long term stabilization of the disease. [Table: see text]
Biweekly cetuximab and irinotecan as second-line therapy to patients with platinium-resistant gastroesophageal cancer
Authors: Bjerregaard J. K. , Schønnemann K. R. , Jensen H. A. , Vestermark L. W. , Hansen T. P. , Pfeiffer P. 
Published: August 2020

e15624 Background: There is no established 2nd line therapy for patients (pts) with advanced gastroesophageal (GE) cancer. In 2004, the Danish government initiated a national health programme for pts with advanced cancer. Non- proven therapy may be offered after approval by an expert panel appointed by the National Board of Health that subsequently finances the cost of treatment. This programme has had a major impact on the management of cancer pts in Denmark and has accelerated the introduction and implementation of new therapies. Inspired by the excellent results in colorectal cancer a combination of cetuximab and irinotecan (CetIri) was chosen for platinum-resistant GE cancer. While awaiting approval of a phase II protocol CetIri was offered at a single institution. We report our preliminary experience with biweekly CetIri as 2nd line therapy in pts with GE cancer. Methods: All pts had histologically confirmed GE cancer (adeno- or squamous cell carcinoma) and all pts had previously received first line platinum based therapy. Pts received CetIri (cetuximab 500 mg/m2and irinotecan 180 mg/m2day 1) every 2nd week until progression or unacceptable toxicity. Response rate was evaluated by the investigator according to RECIST every 8th week. Toxicity was prospectively evaluated according to NCIC-CTC 3.0. Results: From December 2007 to August 2008, 31 consecutive pts was treated with CetIri. Median age was 62 years (33–76). Median performance status was 1 (0–2). Localisation of primary was: Esophagus 10%, GE junction 64%, gastric 26%. Twenty-seven pts (87%) had adenocarcimona. Median number of cycles were 6 (1–21). Most important grade 2–4 toxicities were non-haematological toxicity as diarrhea (25%), nausea (21%) and vomiting (11%). Three pts (11%) had grade 3 leukopenia, 1 had febrile neutropenia. Two pts had PR. Median PFS was 3.2 months. Fourteen pts (45%) received at least 6 courses (3 month of therapy). After a median follow-up of 6 month 5 pts continue CetIri without sign of PD. Conclusions: Biweekly CetIri is a convenient and well-tolerated 2nd line regimen in pts with GE cancer. Predictive factors are needed to select which pts will benefit from therapy. A confirmatory phase II study is ongoing. [Table: see text]
A phase II study of IMGN242 (huC242-DM4) in patients with CanAg-positive gastric or gastroesophageal (GE) junction cancer
Authors: Goff L. W. , Papadopoulos K. , Posey J. A. , Phan A. T. , Patnaik A. , Miller J. G. , Zildjian S. , O'Leary J. J. , Qin A. , Tolcher A. 
Published: August 2020

e15625 Background: IMGN242 is a conjugate of the cytotoxic maytansinoid DM4 and the monoclonal antibody huC242, which binds to CanAg. In a Phase I study, the maximum tolerated dose for IMGN242 was determined to be 168 mg/m2, with ocular changes the primary dose-limiting toxicity. This Phase II study was initiated to assess IMGN242 for the treatment of gastric cancer. Methods: In this open-label, multi-center study, IMGN242 is given as a single IV infusion every three weeks to patients with CanAg-expressing metastatic or locally-advanced gastric or GE junction cancer. Patients must have been treated with at least one prior therapy to qualify for enrollment. The study has a 2-step design: If ≥1 objective response is achieved among the first 23 patients (Step 1), a total of 39 response-evaluable patients will be enrolled (Step 2). Results: Overall, 9 patients have received IMGN242. The first 6 were treated with 168 mg/m2, and 1 of these patients showed a marked biologic response by the FDG-PET scan in Cycle 1 followed by an unconfirmed partial response based on CT scan in Cycle 2. However, 3 of these 6 patients developed ocular toxicities assessed to be study drug related. Only patients with low plasma CanAg levels (<1000 U/ml) developed ocular toxicities, and clinical pharmacokinetic and pharmacodynamic (PK/PD) analyses revealed that plasma CanAg affects study drug exposures. The study was amended to differentiate the IMGN242 doses (126 mg/m2 or 168 mg/m2) administered based on the patient's plasma CanAg levels (< or >1000 U/mL). To date, 3 patients have received IMGN242 with this dosing strategy and no ocular toxicities have been reported. Conclusions: IMGN242 showed preliminary evidence of activity in this patient population. A novel Phase II dosing strategy is being used that should enhance tolerability. Patient enrollment is ongoing and updated results will be reported. [Table: see text]
Phase II study of darinaparsin in patients with advanced hepatocellular carcinoma
Authors: Wu J. , Muggia F. , Henderson C. , Feun L. , Veldhuizen P. V. , Gold P. , Zheng H. , Abbadessa 66201 G. , Lewis J. , Zhu A. X. 
Published: August 2020

e15630 Background: Inorganic arsenic has reported activity in advanced hepatocellular carcinoma (HCC) in Asia, yet its efficacy is limited by liver toxicity. Darinaparsin is a novel organic arsenic that is capable of reaching higher intracellular concentration in cells with decreased toxicity compared to inorganic arsenic. It is highly active as a single agent in HCC cell lines and animal tumor models. We conducted a multi-center phase II study with darinaparsin in patients with advanced HCC. Methods: Eligibility criteria included unresectable or metastatic measurable HCC, up to two prior systemic treatments, ECOG performance status ≤2, Child Pugh Class A or B and adequate organ functions. Darinaparsin was given at 420 mg/m2 intravenously administered over 60 minutes through a central line, twice weekly at least 72 hours apart for three weeks followed by one-week rest in a four-week cycle. The primary end point of the study was response rate. A Simon two-stage design was used to assess the efficacy of darinaparsin and the study would be terminated if no responses were observed after the first stage. Results: The planned 15 patients of the first stage were enrolled: median age = 60 (35 - 79). M/F = 14/1, ECOG performance status 0/1= 4/11, Child Pugh class A/B = 11/4. Seven patients received prior systemic chemotherapies. No objective responses were observed. Three patients had stable disease. The median number of cycles on study per patient was 2 (1–6). The median progression free survival and overall survival were 55 days (95% confidence interval: 50 - 59) and 190 days (95% confidence interval: 93–227), respectively. Treatment was well tolerated. No treatment related hospitalizations or deaths occurred. Treatment related grade 1–2 toxicities included nausea/vomiting (31%), fatigue (23%), anorexia (15%) and diarrhea (15%). Grade 3 anorexia, wheezing, agitation, right upper quadrant pain and SGPT were observed in 1 patient each (8%), 1 patient experienced grade 4 hypoglycemia (8%). Conclusions: Darinaparsin was safely administered with tolerable toxicity profiles in HCC patients. However, it has shown no objective responses in HCC and this trial was terminated as planned after the first stage of efficacy analysis. [Table: see text]
Palliative systemic chemotherapy with gemcitabine (GEM) and 5-fluorouracil (5-FU) as 24h-infusion in patients with advanced inoperable biliary tract cancer (UICC stage IV)
Authors: Kersten S. , Wein A. , Albrecht H. , Reulbach U. , Maennlein G. , Wolff K. , Ostermeier N. , Hohenberger W. , Hahn E. G. , Boxberger F. 
Published: August 2020

e15633 Background: Due to the late diagnosis of biliary tract carcinomas in an advanced tumor stage, the application of palliative chemotherapy frequently remains as a possible treatment option. The aim of this study is to evaluate the efficacy and toxic side effects of a chemotherapy schedule consisting of GEM combined with 5-FU in patients (pts.) with metastatic biliary tract cancer. Methods: Evaluation of 35 pts. based on our prospective tumor registry data; essential inclusion criteria: histologically proven adeno-carcinoma, UICC stage IV, chemonaivity; all the pts. were presented in the interdisciplinary tumorboard of Erlangen University and were primarily non-curatively-resectable (n = 35); evaluation period: 11/1998 - 09/2008; treatment schedule: 1.000 mg/m2 of GEM as a 0.5h-infusion (inf.) combined with 2.000 mg/m2 of 5-FU as a 24h-inf. via port catheter on day 1, 8, 15 qd 22. Results: Median age: 64 years; men/women: n=18/17; ECOG 0/1/2: n=10/21/4; localisation: intrahepatic bile ducts: n=19, extrahepatic bile ducts: n=11; gall bladder: n=4; metastases: liver: 91.4%, lymph nodes: 51.4%, peritoneum: 28.8%, bones: 8.6%, intestine: 8.6%, skin: 2.9%, lungs: 2.9%; chemotherapy applications: total number: 486, average value/patient: 13.9; CA 19–9 elevated yes/no: n=13/22 (37.1%/62.9%); CEA elevated yes/no: n=15/9 (42.9%/25.7%, not evaluable: 11); higher grade toxicity (III or IV): leukocytopenia III: 14.3%, thrombocytopenia III: 2.9%, weariness III: 2.9%, diarrhea III: 5.7%, diarrhea IV: 2.9%, vomiting IV: 2.9%, pain III: 5.7%, ascites III: 5.7%, infections III: 2.9%, thromboembolia IV: 2.9%, elevated bilirubin value III: 1.7%, grade IV: 8.3%; deep leg vein thrombosis: 15%; median TTP: 5.1 months (95% CI: 2.9 - 7.2); median overall survival: 10.4 months (95% CI: 7.9 - 12.9); 6-months-/1-year-/2-year-survival rate: 65.7%/45.7%/17.1%; response rate: PR: n=5 (14.3%), SD: n=18 (51.4%), PD: n=7 (20%), not evaluable: n=5 (14.3%); tumor control (PR/SD): n=23 (65.7%); median follow-up: 10.4 months. Conclusions: Combination chemotherapy with weekly GEM as a 0.5h-inf. and 5-FU as a 24h-inf. on an out-patient basis is an effective palliative treatment schedule with solely low grade toxicity. No significant financial relationships to disclose.
Phase IIb trial of fluorouracil, leucovorin, oxaliplatin, and paclitaxel (POF) compared with fluorouracil, feucovorin, and irinotecan (IF) as first-line treatment for advanced gastric cancer (AGC)
Authors: Lin R. , Chen Q. , Fan N. , Ye Y. , Guo Z. , Wang X. , Liu J. , Chen L. 
Published: August 2020

e15642 Background: Primary results of POF as 1st and 2nd line treatment for AGC have been presented at ASCO 2007 and 2008. We report here data on the feasibility and the toxicity of POF versus IF(Dank, et al, ASCO 2005) in 1st line treatment of AGC. Methods: Patients with previously untreated, advanced, unresectable, and histologically confirmed adenocarcinoma of the gastric or gastroesophageal junction were randomly assigned to POF or IF regiment. Treatment was continued until disease progressed, unacceptable toxicity, or patient choice. Results: 25 patients were entered in this study between March 2007 and July 2007: 13 in the POF group and 12 in the IF group. The median patient age was 55 years (range, 36 to 67 years), 18 were males and 7 were females. No complete response was observed. The response rate was 62.5% (POF) and 33.3% (IF) respectively. At a median follow-up of 285 days, 7(POF) versus 6(IF) patients were still alive. Hematological toxicity was the most frequent toxicity in both groups. Grade 3 to 4 neutropenia were 38.5% (POF) versus 8.3% (IF). Diarrhea was found 0% and 8.3% in POF and IF group respectively. No grade 3 peripheral neurotoxicity was observed. Conclusions: Compared with IF regiment, POF could also be used as first-line treatment for AGC with acceptable safety profile, good efficacy, and more encouraging results. No significant financial relationships to disclose.