bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of oxaliplatin and sorafenib in advanced gastric cancer after failure of cisplatin-fluoropyrimidine-based (PF) treatment.
Authors: Gallego Rosa , Martin-Richard Marta , Pericay Carles , Garcia-Foncillas Jesus , Queralt Bernardo , Casado Esther , Feliu Jaime , Vega Iranzazu , Juez Ignacio , Visa Laura , Saigí Eugeni , Garcia-Albeniz Xabier , Barnadas Agust , Maurel Joan ,   GEMCAD
Published: March 2020

4079 Background: PF-based chemotherapy is the standard first line treatment in advanced GC. Although some drugs as taxanes or oxaliplatin (Ox) have shown efficacy in combination with P or F, no established second line exists. RAF/MEK/ERK pathway activation as well as VEGF expression have been related with more advanced GC. Sorafenib (S) is a potent Raf and VEGFR inhibitor and Ox has demonstrated non-cross resistance with P. Methods: A multicenter phase II to evaluate the efficacy of OX- S combination in gastric or GEJ adenocarcinoma (pts) with progressive disease after CF based first line chemotherapy, was planned. Other inclusion criteria: ECOG 0-2, measurable disease and adequate organ function. Treatment doses were Ox 130mg/m2/3 weeks and S 800 mg/bid/d until progression or toxicity. CT scan evaluation every 3 cycles. The study followed a A-Hern single-stage design (HR = 1.67, median expected PFS of 4.3m if treatment ineffective, sample size: 43). The study was closed with the inclusion of 40 pts, maintaining a power > 87%. Ten pts would have to be alive and free of progression at 12m to consider the study positive. Results: Forty pts were included and evaluable for PFS. Thirty-six pts were evaluable for response. Median age was 63 ( range 39 - 76) years, ECOG 0/1/2 in 36/59/5 % of pts. PFS to 1st line was > 6m in 59% of pts. One CR and, 47.2% of SD were observed. Gr ¾ toxicity (%) was: neutropenia (9.8), thrombocitopenia (7.3), neurotoxicity (4.9) and diarrhea (4.9). Median PFS was 3 (95 %CI: 2.3-4.1 )m and median OS was 6.5 ( 95% CI: 5.2-9.6)m. PFS at 12 m was 0%. Median OS in pts with PFS to 1º line > 6m/ <6m was 9.7m and 5.6m respectively (p0.04). Conclusions: The combination of Oxaliplatin-Sorafenib in advanced GC patients previously treated with CF shows a safe profile but these results do not support the implementation of a phase III trial. Our results show that PFS under a CP-based first line therapy determine subgroups of GC patients with different clinical behaviors.
Feasibility of perioperative chemotherapy with infusional 5-FU, leucovorin, and oxaliplatin with or without docetaxel, in elderly patients with locally advanced esophagogastric cancer.
Authors: Lorenzen Sylvie , Pauligk Claudia , Homann Nils , Schmalenberg Harald , Tauchert Felix , Jäger Elke , Al-Batran Salah-Eddin 
Published: March 2020

4080 Background: The aim of this study was to determine feasibility and efficacy of perioperative chemotherapy in elderly, potentially operable esophagogastric cancer patients. Methods: Patients aged 65 or older with locally advanced esophagogastric adenocarcinoma were randomized to perioperative chemotherapy consisting of four preoperative and four postoperative cycles of infusional 5-FU, leucovorin, and oxaliplatin (FLO) with or without docetaxel 50mg/m² (FLOT), every 2 weeks. Results: 44 patients with a median age of 70 years were randomized to either FLO (22) or FLOT (22) chemotherapy. In the FLO and FLOT group, 20 and 18 patients completed four cycles of preoperative chemotherapy and 17(77.3%) and 15(68.2%) patients proceeded to surgery, with 88.2% and 93.3% R0 resections, respectively. FLOT was associated with significantly more treatment-related NCI-CTC grade 3/4 adverse events, including neutropenia (p<.0001), leukopenia (p<.0001), stomatitis (p=0.02) and nausea (p=0.02) and a higher rate of patients experiencing a ≥10-points deterioration of EORTC QoL global health status scores (FLOT, 54%; FLO 23.1%) at 8 weeks. No perioperative mortality was observed, however postoperative morbidity was nearly doubled with the FLOT regimen (60% versus 35.3% for FLO), mostly due to wound infections in the FLOT group (20%). 11 (64.7%) and 9 (60.0%) of patients in the FLO/FLOT group were able to undergo postoperative chemotherapy. Compared with the FLO group, the FLOT group had a better response rate (61.9% vs. 18.2%) and a trend towards an improved median disease free survival (21.1 vs. 12.0 months; p=0.09). Conclusions: Age alone is not a contra-indication for the selection of patients for three-drug regimens in the multimodal treatment approach. FLOT seems to be more effective than FLO, but is associated with an increased toxicity and higher postoperative morbidity. Therefore, careful patient selection is warranted.
Lenalidomide for second-line treatment of advanced hepatocellular cancer (HCC): A Brown University Oncology Group phase II study.
Authors: Safran Howard , Charpentier Kevin , Kaubisch Andreas , Dubel Gregory , Perez Kimberly , Faricy-Anderson Katherine E. , Miner Thomas J. , Victor Joel , Taber Angela Marie , Bakalarski Pamela , Wingate Patti , Mantripragada Kalyan C , Luppe Denise , Rosati Kayla , Espat Joseph , Isdale Debora , Eng Yoko , Martel Diane , Berz David , Wands Jack 
Published: March 2020

4098 Background: Lenalidomide inhibits fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF) and multiple tumor growth pathways. There is no standard of care for patients who progress after sorafenib. Therefore, we performed a phase II study to determine the activity of lenalidomide in second-line HCC therapy. Methods: Patients with advanced HCC who progressed on or were intolerant to sorafenib were eligible. Prior chemoembolization, RFA, or surgery were allowed. Eligibility criteria also included bilirubin <4 mg/dL, AST and ALT <5 times upper limit of normal, ECOG performance status 0-2, platelet count >60,000/mm3, absolute neutrophil count >1000/mm3, and creatinine <2mg/dL. Patients were treated with lenalidomide 25mg orally days 1-21 of a 28 day cycle until disease progression or unacceptable toxicities. The planned original sample size was 25 patients but when early activity was demonstrated the study was expanded to 40 patients. Results: The study has completed accrual of 40 patients. The median age was 60.5 years (17-88 years). Nineteen patients were Child-Pugh A, 16 patients were B, and 5 patients were C. Twenty four patients had extrahepatic disease. Preliminary data is available on the first 37 patients. One patient had grade 4 neutropenia. Grade 3 toxicities included ANC (n=2), fatigue (n=4), rash (n=2), arthritis (n=1), diarrhea (n=1), dehydration (n=2). One patient developed variceal bleeding which precipitated encephalopathy and death. Of the 32 patients with elevated baseline AFP, nine (28%) had a >50% reduction including one patient with a reduction in AFP from 56,900ng/ml to 5 ng/ml. Six of the first 37 patients (16%) had a radiographic partial response. Two patients achieved a complete response and have not progressed at 36 and 32 months. Conclusions: Lenalidomide can be administered to patients with advanced HCC and significant hepatic dysfunction. Promising, and in a small percentage of patients, dramatic and durable activity has been demonstrated. Investigations are underway to explore the mechanism of action of lenalidomide in HCC.
A phase II trial of temsirolimus (TEM) and bevacizumab (BEV) in patients with advanced hepatocellular carcinoma (HCC).
Authors: Knox Jennifer J. , Qin Rui , Strosberg Jonathan R. , Kaubisch Andreas , El-Khoueiry Anthony B. , Bekaii-Saab Tanios B , Erlichman Charles 
Published: March 2020

4099 Background: There is strong rationale to combine an m-TOR inhibitor (TEM) with a VEGF inhibitor (BEV) as a potentially active and well tolerated treatment for HCC. Both agents have shown modest single agent activity in HCC and so evaluated here in a phase II trial. Methods: A modified 2-stage Simon design planned 25 or 50 patients (pts) to test the null hypothesis that true tumor response rate is at most 10% andtrue 6-mo progression-free survival rate (PFS) (by RECIST) is at most 65%, or no better than single agent BEV (6 mo PR >2 pts or PFS 6 mo >18 out of 25.) Toxicity, TTP, PFS and survival were 2nd endpoints. Eligible pts had confirmed HCC with disease unresectable or amenable to other localised therapies, Child Pugh A liver status and no prior systemic therapy involving the VEGF or m-TOR class of agents. TEM was administered at starting dose 25 mg IV d1,8,15,22 with BEV at 10mg/kg IV d 1, 15, all q 28 days (1 cycle). Imaging was q 8 wks. Results: From 09/09 to 09/11, 27 eligible pts were enrolled with 25 evaluable for toxicity and efficacy. Med age 59 yrs, 85% male, PS 0/1: 35/65, 58% metastatic, >85% BCLC stage C. With med 6 cycles (range 1-14) delivered, most pts (88%) experienced a grade 3+ adverse event (a/e.) Common grade 3 a/es related to treatment included thrombocytopenia (40%), neutropenia (20%), leucopenia (12%), fatigue (8%), anemia, mucositis, dyspnea, diarrhea, bleeds, fistula, infections (4% each). There was one possible treatment related death. Per protocol dose reductions/discontinuation for TEM-related a/es were most common. There were 2 confirmed PRs and 16 pts progression-free by 6 mos. A third pt developed a late PR at cycle 13. Median TTP on study was 6 mos, median PFS was 7.4 mos and median survival was 8.3 mos, with 13 pts still alive. Accrual closed at end of stage 1 as neither the number of responses nor the PFS at 6 mos passed the futility stopping rule set for this combination. Conclusions: This multicenter study is the first HCC trial evaluating the BEV/TEM doublet. Despite manageable toxicity, the ORR and 6 mo PFS did not surpass assumptions based on single agent BEV in HCC. Further study of BEV/TEM combination in this advanced HCC population is not recommended.
A phase II trial of MEK inhibitor BAY 86-9766 in combination with sorafenib as first-line systemic treatment for patients with unresectable hepatocellular carcinoma (HCC).
Authors: Lim Ho Yeong , Yen Chia-Jui , Tak Won-Young , Heo Jeong , Choi Hye Jin , Lin Cheng-Yao , Yoon Jung-Hwan , Hsu Chiun , Rau Kun-Ming , Poon Ronnie Tung Ping , Yeo Winnie , Park Joong-Won , Tay Miah Hiang , Hsieh Wen Son , Kappeler Christian , Rajagopalan Prabhu , Krissel Heiko 
Published: March 2020

4103 Background: Sorafenib (S) is the only approved systemic treatment for unresectable HCC. Nevertheless, there remains an unmet medical need for more effective treatment options for this disease. BAY 86-9766 (B) is an oral, allosteric inhibitor of MEK, a key component of the MAP kinase pathway. This study evaluated the efficacy and safety of a combination therapy with B plus S in patients (pts) with HCC. Methods: This is a single arm, open-label, phase 2 study. Eligible were pts with unresectable HCC, Child-Pugh Class A, performance status (PS) 0-1, and no prior systemic anticancer therapy for HCC. Pts started Cycle 1 (21 days) with B 50 mg bid orally plus S 600 mg daily (200 mg AM, 400 mg PM) orally. If there was no hand-foot skin reaction, fatigue, or gastrointestinal toxicity ≥ grade 2, S was escalated to 400 mg bid from Cycle 2 on. Treatment continued until progression or withdrawal criteria were met. Tumor assessment was performed every 6 weeks during treatment. Safety was evaluated every week for the first 6 weeks and every 3 weeks thereafter. Results: Seventy pts from Asia started study treatment. Pts were predominantly male (86%); median age was 56 years; 54% had PS of 0 and 46% PS of 1. The vast majority had liver cirrhosis (83%) and infection with HBV (76%) or HCV (17%). Sixty-five were evaluable for efficacy per protocol. Three pts (5%) had confirmed partial response and 25 pts (38%) had prolonged stable disease (≥10 weeks), with a disease control rate of 43%. Median time-to-progression was 4.1 months. Survival data are not mature, yet. The most frequent drug-related adverse events (AEs) were rash (60%), diarrhea (59%), AST elevation (43%), vomiting (30%), nausea (29%), ALT elevation (26%), and anorexia (26%). There were 4 Grade 5 related AEs (hepatic failure, sepsis/hepatic encephalopathy, tumor lysis syndrome, and unknown cause, respectively). Dose modifications due to AEs were necessary in almost all pts. The median daily dose was 64.2 mg for B and 443.3 mg for S, respectively. Conclusions: B in combination with S showed antitumor activity in pts with HCC. However, frequent dose modifications due to AEs might have limited the treatment effect of this combination.
Adjuvant chemotherapy following curative intent hepatectomy for intrahepatic cholangiocarcinoma: Results from a multi-institutional analysis of 575 patients.
Authors: Ribero Dario , Pinna Antonio Daniele , Nuzzo Gennaro , Guglielmi Alfredo , Aldrighetti Luca , Giulini Stefano Maria , Gerunda Giorgio Enrico , Ponti Antonio , Tomatis Mariano , Leone Francesco , Aglietta Massimo , Berloco Pasquale , Calise Fulvio , Opocher Enrico , Gruttadauria Salvatore , Torzilli Guido , Capussotti Lorenzo 
Published: March 2020

4110 Background: Surgical resection alone is the standard of care for patients with resectable intrahepatic cholangiocarcinoma (IHC). This study evaluates the benefit of adjuvant chemotherapy (AdjCTx) following curative intent hepatectomy for IHC. Methods: Clinicopathologic and long-term outcome data of 575 consecutive patients treated with curative intent hepatectomy for IHC (1995-2011) were extracted from a multi-institutional registry. After excluding operative mortality and M1 (n=46), Cox regression analysis was used to identify independent determinants of early recurrence (i.e., within 3 years). Propensity scores, which are used in observational studies to reduce selection bias by equating groups on the basis of relevant covariates, were calculated and utilized to match patients who had or had not AdjCTx (one-to-one match). Cases whose propensity score deviated more than 0.10 were considered unmatched and excluded from the analysis. Primary end-point was recurrence-free survival (RFS) at 3-years. Results: At a median FU of 42 months, 247 patients had recurred. Predictors of recurrence were LN metastases (HR 1.83 [1.36-2.44]), radical resection (HR 0.64 [0.45-0.9]), an elevated preoperative CA19.9 (HR 1.54 [1.15-2.07]), vascular invasion (HR 1.97 [1.49-2.61]), multiple tumors (HR 2.21 [1.71-2.86]), and size (analysed as continuous variable) (HR 1.01 [1.01-1.01]). After matching, no difference was observed between patients who had or had not AdjCTx (n=155 per group; 3-yrs RFS 28.3% vs. 38.0%, respectively; p=NS). When the analysis was restricted to patients who had gemcitabine, GEMOX or FOLFOX for 3 or more cycles (n=64 per group) again no difference emerged between patients who had or had not AdjCTx (3-yrs RFS 27.7% vs. 40.0% respectively, p=NS ). Conclusions: Our data suggest that AdjCTx following resection of IHC does not increase 3-years RFS.
A phase II trial of gemcitabine, irinotecan, and panitumumab in advanced cholangiocarcinoma, with correlative analysis of EGFR, KRAS, and BRAF: An interim report.
Authors: Sohal Davendra , Teitelbaum Ursina R. , Uehara Takeshi , Mykulowycz Kristine , Watt Christopher D. , Damjanov Nevena , Giantonio Bruce J. , Carberry Mary , Wissel Paul Stephen , Jacobs-Small Mona , O'Dwyer Peter J. , Sepulveda Antonia , Sun Weijing 
Published: March 2020

4111 Background: Cholangiocarcinoma is an aggressive neoplasm. Current chemotherapy approaches achieve modest results. The epidermal growth factor receptor (EGFR) pathway appears to be associated with tumor stage, prognosis and response to therapy. This trial was designed to evaluate the tolerability and efficacy of the combination of panitumumab, a monoclonal anti-EGFR antibody, with gemcitabine and irinotecan, in patients with advanced cholangiocarcinoma. Molecular analysis of EGFR pathway genes was planned as well. Methods: Patients with advanced (unresectable or metastatic) cholangiocarcinoma, ECOG PS 0-2, and adequate liver, kidney and bone marrow function were treated with panitumumab (9 mg/kg) on day 1, and gemcitabine (1000 mg/m2) and irinotecan (100 mg/m2) on days 1 and 8 of a 21-day cycle. Tissue specimens were collected at diagnosis for correlative molecular analyses. Primary objective is to evaluate the 5-month progression-free survival (PFS) rate. Secondary objectives include overall response rate (ORR), overall survival (OS) and toxicity of the combination. Mutational analysis of EGFR (del 19; 858), KRAS (codons 12, 13) and BRAF (V600E) was done on samples with adequate material for testing. Results: There have been 26 (of planned 42) patients recruited to the study. A median of 6 (0-30) cycles were administered. There were no treatment related deaths. The most common gr 3 or higher toxicities were neutropenia (10 pts, 38%), thrombocytopenia (10 pts, 38%), skin rash (10 pts, 38%) and diarrhea (3 pts, 12%). During the study, there were 3 CR, 6 PR, 10 SD (disease control rate of 90%), and 2 PD (by RECIST) in 21 evaluable pts. Two pts went on to have surgical resection. Median OS is 12.7 months. Of 13 testable samples, no EGFR or BRAF mutations were identified; however, there were 7 KRAS mutations. Retrospective analysis showed no difference in OS by KRAS mutation status. Conclusions: Interim evaluation of this ongoing study showed encouraging tolerability and efficacy of this regimen. Several patients have KRAS mutations; there appears to be no association with response, however. The pre-specified efficacy criteria to continue enrollment were met.
SWOG 0941: A phase II study of sorafenib and erlotinib in patients (pts) with advanced gallbladder cancer or cholangiocarcinoma.
Authors: El-Khoueiry Anthony B. , Rankin Cathryn J , Iqbal Syma , Micetich Kenneth C. , Kayaleh Omar , Lenz Heinz-Josef , Blanke C. D. 
Published: March 2020

4113 Background: The treatment of pts with advanced biliary cancers represents a therapeutic challenge. The vascular endothelial growth factor and epidermal growth factor receptor pathways play an important role in biliary carcinogenesis, as evidenced by their up-regulation and prognostic impact. Methods: The primary objective was progression free survival (PFS) (improvement in PFS from 4 to 8 months); secondary endpoints included overall survival (OS), objective response rate, and toxicity. A two-stage design was used; if 13 or more eligible pts of the 25 initially accrued were alive without progression at 4 months, an additional 25 were to be accrued. Eligibility criteria included no prior treatment for advanced or metastatic disease, histologic diagnosis of gallbladder cancer or cholangiocarcinoma, presence of measurable disease, Zubrod performance status 0-1, AST/ALT ≤ 5 IULN, total bilirubin ≤1.5 IULN, adequate hematologic function. Pts were treated with sorafenib 400 mg PO BID and erlotinib 100 mg PO q daily continuously. Restaging scans were performed every 8 weeks. Results: 32 eligible pts were accrued. 30 pts were evaluable for response. 2 patients (7 %) had an unconfirmed partial response (95% CI:1%-23%), and 8 pts (27%) had stable disease. Median PFS was 2 months (95% CI: 2-3 months). 22/32 patients progressed or died within 4 months of registration. Median OS was 6 months (95% CI: 3 -7 months). The study failed to meet its primary endpoint to proceed to the second stage of accrual. There were 3 deaths on study, 1 of which was possibly related to treatment. 19 patients (59%) had grade 3 or 4 toxicities: AST/ALT (22%), bilirubin (16%), alkaline phosphatase (16%), hypertension (16%), diarrhea (9%), hepatic infection (6%). Conclusions: This multicenter study was the first to evaluate the combination of sorafenib and erlotinib in pts with advanced biliary cancers. Despite manageable toxicity, the study failed to meet its primary endpoint. Correlative studies on collected tissue and blood are ongoing; improved pt selection based on tumor biology and molecular markers is necessary for future evaluation of targeted therapies in this disease.
Multiparametric quantitative functional MRI for assessing early changes in volumetric functional tumor burden in hepatocellular carcinoma treated by intra-arterial therapies.
Authors: Gowdra Halappa Vivek , Bonekamp Susanne , Corona Villalobos Celia Pamela , Cosgrove David , Diaz Luis A. , Pawlik Timothy M , Geschwind Jean-Francois , Kamel Ihab R. 
Published: March 2020

4114 Background: Hepatocellular carcinoma (HCC) is the most common primary malignant disease of the liver. Intra-arterial therapy (IAT) has been shown to improve survival and is commonly used in unresectable HCC. Assessing response to IAT as early as possible using objective criteria is paramount for clinical care. The purpose of this study was to evaluate volumetric diffusion weighted (DWI) and contrast Enhanced MR imaging (CE-MRI) changes for assessing early treatment response to IAT in hepatocellular carcinoma. Methods: This study included 177 lesions of HCC in 107 patients (85 Male, mean age 64 years) with BCLC A (19) B (44) C (36) D (8) treated by IAT. All patients had pre-IAT and 3-4 weeks follow up MRI with DWI and CE-MR. Tumors were segmented using semi automated software to provide volumetric functional analysis of DWI and CE- MRI as well as percent tumor burden. Statistical analyses include paired t-test, Kaplan-Meier curves, log rank test and multivariate analysis with cox model. Results: There was significant increase in volumetric ADC and significant decrease in volumetric arterial (AE) and venous (VE) enhancement after IAT. Patients with tumor burden of < 10% had improved survival compared to patients with high tumor burden of >10% (log rank p <.008 ) This survival benefit was larger among patients with tumor burden of < 10% who demonstrated an increase in volumetric ADC (>20%. Overall survival (OS) 33.5 mo) and decrease in volumetric VE (>50% OS 35.2 mo) compared to patients with high tumor burden >10% who no favorable response in ADC ( OS 14.1 mo) or VE (OS 16.5 mo) (Log rank p < .001) . In multivariate analysis factors associated with favorable prognosis were: increased ADC, (Hazard Ratio (HR) = 0.44, 95% CI =0.24 - 0.80) decreased VE, (HR = 0.43, 95% CI = 0.22 - 0.84) and BCLC A and B (HR = 0.31, 95% CI =0.18 - 0.54). Conclusions: Volumetric functional analysis of DWI and CE-MR are reliable imaging biomarkers of treatment response and tumor necrosis were able to differentiate responders and non responders. Early assessment of treatment response by volumetric functional MRI predicts prognosis in patients undergoing IAT in HCC.