bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized, double-blind, multi-center phase III study evaluating paclitaxel with and without RAD001 in patients with gastric or esophagogastric junction carcinoma who have progressed after therapy with a fluoropyrimidine/platinum-containing regimen (RADPAC).
Authors: Lorenzen Sylvie , Riera Knorrenschild Jorge , Pauligk Claudia , Goetze Thorsten Oliver , Hegewisch-Becker Susanna , Seraphin Jörg , Thuss-Patience Peter C. , Kopp Hans-Georg , Dechow Tobias Nicolaas , Vogel Arndt , Luley Kim Barbara , Pink Daniel , Stahl Michael , Kullmann Frank , Hebart Holger Frithjof , Siveke Jens T. , Egger Matthias , Homann Nils , Probst Stephan , Al-Batran Salah-Eddin 
Published: September 2018

4027 Background: There is a need for effective treatments in the second- or further line setting in advanced gastric cancer, especially for new agents. In the current trial we evaluated paclitaxel with RAD001 (everolimus) in patients with gastric carcinoma who have progressed after therapy with a fluoropyrimidine/platinum-containing regimen. Methods: This is a randomized, double-blind, multi-center phase III study. Patients with gastric carcinoma or adenocarcinoma of the esophagogastric junction (EGJ) who have progressed after treatment with a fluoropyrimidine/platinum-containing regimen were randomly assigned to receive Paclitaxel (80 mg/m2) on day 1, 8 and 15 plus placebo (arm A) or RAD001 (10mg daily, arm B) d1-d28, repeated every 28 days as 2nd, 3rd or 4th line therapy. Primary end point was overall survival (OS), secondary endpoints were best overall response, disease control rate, progression free survival (PFS) and toxicity. Results: 300 patients (median age: 62 years; median lines prior therapy: 2; 47.7% of patients had prior taxane therapy) were randomly assigned (Arm A, 150, Arm B, 150). In the intention to treat population, there was no significant difference in median PFS (placebo, 2.07 vs. RAD001, 2.2 months, HR 0.88, p = 0.3) or median OS (placebo, 5.0 vs. RAD001, 6.1 months, HR 0.93, p = 0.54). For patients with prior taxane use, RAD001 improved PFS (placebo 1.8 vs. RAD001, 2.7 months, HR 0.69, p = 0.03) and OS (placebo 3.9 vs. RAD001, 5.8 months, HR 0.73, p = 0.07). Combination of paclitaxel and RAD001 was tolerable, but the RAD001 arm was associated with significantly more grade 3-5 mucositis (13.3% vs. 0.7%; p < 0.001). Conclusions: The addition of RAD001 to paclitaxel/RAD001 did not improve outcomes in pretreated metastatic gastric/EGJ cancer. Of note, activity was seen in the taxane pretreated group. Additional biomarker studies are planned to look for subgroups that may have a benefit. Clinical trial information: 2009-018092-14.
Current trends and survival in patients with esophageal squamous cell carcinoma: An analysis of the National Cancer Database from 2007 to 2013.
Authors: Chapman Brandon C. , Weyant Michael J. , Hosokawa Patrick W , Overbey Douglas M , Hilton Sarah , McCarter Martin , Gleisner Ana , Edil Barish H. , Gajdos Csaba 
Published: September 2018

4032 Background: Although surgical resection is the treatment of choice for patients with esophageal squamous cell carcinoma (ESCC), some evidence suggests that definitive chemoradiation (CR) may have equivalent survival compared to surgery alone. The objective of this study was to evaluate current trends in the treatment of ESCC and its impact on overall survival (OS). Methods: Using the NCDB (2004-2013), patients with non-metastatic/loco-regional ESCC were categorized into definitive CR, neoadjuvant CR/surgery, surgery alone, and surgery/adjuvant therapy. Multivariate Cox proportional hazard models by stepwise selection were applied to estimate hazard ratios (HR) of predictors of OS. Results: We identified 11,229 patients with ESCC undergoing definitive CR (n = 8855, 78.9%), neoadjuvant therapy/surgery (n = 953, 8.5%), surgery alone (n = 1130, 10.1%), and surgery/adjuvant therapy (n = 291, 2.6%). The distance of primary tumor from incisors was comparable for all four groups. On multivariable analysis, treatment modality had the largest impact on OS followed by AJCC stage, age and annual surgical volume. Compared to neoadjuvant therapy/surgery, both surgery only (HR 1.17, 95% CI 1.04-1.32) and definitive CR (HR 1.51, 95% CI 1.37-1.66) were associated with increased long-term mortality. However, there was no difference in mortality in the surgery/adjuvant therapy group (HR 1.10, 95% CI 0.94-1.30) compared to the neoadjuvant therapy/surgery group. Patients treated at facilities performing more than 20 esophagectomies per year, regardless of whether they underwent surgical resection, had improved OS compared to facilities performing 10-19 per year (HR 1.47, 95% CI 1.29-1.68), 5-9 per year (HR 1.44, 95% CI 1.29-1.62), and < 5 per year (HR 1.53, 95% CI 1.38-1.70). Conclusions: Patients receiving either neoadjuvant therapy or adjuvant therapy and esophagectomy for ESCC have improved OS compared to patients undergoing esophagectomy alone and definitive CR. These findings suggest that patients with ESCC should be considered for multimodality treatment at high-volume centers and surgery should be included in the treatment plan whenever possible.
How many lymph nodes is enough? Defining the optimal lymph node dissection in stage I-III gastric cancer using the National Cancer Database.
Authors: Sura Karna Tushar , Ye Hong , Vu Charles C , Robertson John M. , Kabolizadeh Peyman 
Published: September 2018

4034 Background: Gastric cancer is one of the most causes of cancer-related death worldwide. Surgical resection with lymph node dissection is the primary therapeutic modality. However, the appropriate extent of lymph node dissection remains controversial. Herein, the National Cancer Database (NCDB) was used to determine the optimal number of lymph nodes (LNs) to be dissected for resectable gastric cancer. Methods: The NCDB was queried from 2004-2013 for patients with invasive gastric cancer who underwent surgical resection with negative margins. The optimal number of LNs dissected was determined using a univariate χ2 cut-point analysis. Actuarial survival was determined using the Kaplan Meier method, and comparisons of survival estimates were completed with log-rank tests. Multiple sensitivity analyses were utilized to decrease bias. Results: 17,851 patients were included. The mean (±SD) number of LNs examined was 16 ± 11. For all patients, the optimal number of LNs needed to be examined was 20+ nodes. When correcting for stage migration ( < 7 LNs removed), the optimal cut-off value was 20+ LNs. When stratifying by pathologic nodal stage, the cutpoint was 10+ LNs for pN1 and pN2. The 5-year survival was 30.6 ± 1.6% for 0-9 removed LNs compared to 48.2 ± 1.2% for 10+ removed LNs (p < 0.001) in pN1 disease and 18.3 ± 1.7% for 0-9 removed LNs compared to 32.6 ± 1.2% for 10+ removed LNs (p < 0.001) in pN2 disease. For pN3 disease, the optimal cut-off point was 20+ LNs; the 5-year survival was 17.2 ± 1.3% for 0-19 removed LNs compared to 28.5 ± 1.7% for 20+ removed LNs (p < 0.001). Moreover, the outcome was inferior among patients who had > 10% positive dissected LNs (p < 0.05). Conclusions: The optimal number of dissected LNs of 20+ LNs was associated with superior survival. Extended LN dissection is to be considered especially in patients with > 10% positive dissected LNs.
Comparison of chemoradiotherapy (CRT) using carboplatin/paclitaxel (CP) versus cisplatin/5-FU (CF) for esophageal or gastroesophageal junctional (GEJ) cancer.
Authors: Sim Hao-Wen , Chan Bryan Anthony , Natori Akina , Lim Charles Henry , Jiang Di Maria , Moignard Stephanie , Chen Eric Xueyu , Liu Geoffrey , Darling Gail Elizabeth , Swallow Carol Jane , Brar Savtaj Singh , Brierley James D. , Ringash Jolie , Wong Rebecca , Kim John , Rogalla Patrik , Hafezi-Bakhtiari Sara , Knox Jennifer J. , Jang Raymond Woo-Jun , Elimova Elena 
Published: September 2018

4053 Background: For resectable esophageal or GEJ cancer, trimodality therapy improves survival compared to surgery alone and represents the current standard of care. The optimal CRT regimen for neoadjuvant or definitive treatment of locoregional esophageal or GEJ cancer remains uncertain. Methods: A retrospective comparison of CF and CP for locoregional esophageal or GEJ cancer (2011-2015) was performed. Overall survival (OS) and disease-free survival (DFS) were assessed using multivariable Cox proportional hazards regression, controlling for age, performance status and Charlson comorbidity index. Results: 101 patients (pts) were identified (61 CF, 40 CP). 75% were male. Median age was 62 years (range 30-84). Primary sites were esophageal (52%, with 65% squamous histology) and GEJ (48%). Surgery was undertaken in 34 (56%) CF and 27 (68%) CP pts. Median follow-up was 43 months. Overall, there was a non-significant trend for improved OS with CF compared to CP (HR 0.61, 95% CI 0.33-1.14, p = 0.12). In the subgroup having surgery (N = 61), we found no significant difference in OS (HR 0.99, 95% CI 0.39-2.55, p = 0.99). In the subgroup without surgery (N = 40), CF was significantly superior to CP (HR 0.21, 95% CI 0.08-0.53, p < 0.001). Comparing only pts in this subgroup who received equitable radiation doses (N = 33), CF was still significantly superior to CP (HR 0.09, 95% CI 0.03-0.32, p < 0.001). OS was similar by histology (adenocarcinoma/squamous) in all-comers (p = 0.54), and in CF (p = 0.90) and CP subgroups (p = 0.63). DFS results corresponded with OS. There was a non-significant numerical difference in pCR rates between CF (31%) and CP (18%) (p = 0.35), which were lower than previously reported. Conclusions: Survival is similar for CF and CP CRT regimens in pts undergoing trimodality therapy, but for those who do not proceed to surgery, it appears that CF is more effective than CP. Clinicians may prefer CP for surgical candidates given its favourable toxicity profile. However, when treating with definitive CRT, CF may be preferable to CP as a standard regimen.
Safety results of a phase 3 study of comparing paclitaxel plus 5-fluorouracil versus cisplatin plus 5-fluorouracil in chemoradiotherapy for locally advanced esophageal carcinoma (ESO-Shanghai 1).
Authors: Chen Yun , Zhao Kuaile , Ye Jingjun , Zhu Zhengfei , Zhao Weixin , Li Ling , Zhou Jialiang , Wu Chaoyang , Tang Huarong , Xu Gang , Lin Qin , Li Jiancheng , Xia Yi , Li Yunhai , Zhang Zhen 
Published: September 2018

4066 Background: Concurrent chemoradiotherapy (CCR) with cisplatin plus 5-Fu (PF) regimen is the standard modality for inoperable locally advanced esophageal squamous cell carcinoma (ESCC) patients. In this phase 3 trial, we aimed to assess the efficacy and safety of the paclitaxel plus 5-Fu (TF) regimen versus PF regimen in CCR for ESCC patients. Methods: ESCC patients presented with stage IIa to IVa were enrolled in a prospective multicenter phase 3 study. Patients were randomized to either PF group or TF group. Patients in PF group were treated with 2 cycles of CCR followed by 2 cycles of consolidation chemotherapy with PF (cisplatin 25 mg/m2/d, d1-3, plus 5-Fu 1800 mg/m2, civ 72h, q28d). Patients in TF group were treated with 5 cycles of weekly TF (5-Fu 300 mg/m2, civ 96h plus paclitaxel 50 mg/m2, d1) in CCR followed by 2 cycles of monthly TF (5-FU 1800 mg/m2, civ 72h, plus paclitaxel 175 mg/m2 d1) in consolidation chemotherapy. The radiotherapy dose in both groups was 61.2 Gy delivered in 34 fractions. Adverse events (AE) defined according to CTCAE 4.0. The primary end-point was 3-yr OS. The number and grade of participants with AE was analyzed by intention to treat. Results: Between April 2012 and July 2015, 436 ESCC patients in 7 centers were enrolled. TF group had a significant higher incidence of acute Grade 3/4 leukopenia (31.3% vs. 18.9%), hiccup (0.9% vs. 0.0%), dermatitis (17.5% vs. 7.5%), pneumonitis (9.8% vs. 2.3%), and esophagitis (6.0% vs. 3.2%), and lower incidence of anemia (0.5% vs. 1.9%), thrombocytopenia (0.5% vs. 13.8%), fatigue (5.6% vs. 17.3%), anorexia (0.5% vs. 14.1%), nausea (0.5% vs. 14.1%), and vomiting (0.9% vs. 17.7%) than PF group (P < 0.05). There were 3(1.4%) patients in TF group died of acute pneumonitis. For long-term AE, 1(0.5%) patient in each group died of pneumonitis. There was no significant difference in total numbers of incidence of ≥ Grade 3 AE between two groups. Until Jan 2017, the median survival has not reached. Conclusions: The safety results of this trial were acceptable. TF regimen showed a different AE profile compared with PF regimen used in CCR in ESCC patients. Clinical trial information: NCT01591135.
Predicting survival in gastric cancer patients randomized to docetaxel with mass spectrometric quantitation of TUBB3.
Authors: Cecchi Fabiola , Catenacci Daniel V.T. , Schwartz Sarit , Sellappan Shankar , Tian Yuan , Miceli Rosalba , Pietrantonio Filippo , Pellegrinelli Alessandro , Martinetti Antonia , Di Bartolomeo Maria , Hembrough Todd A. 
Published: September 2018

4068 Background: No predictive biomarker for chemotherapy has been validated for clinical use. A relationship between resistance to taxanes and expression of class III β-tubulin (TUBB3) protein has been suggested by small clinical studies, but not confirmed in randomized trials. Immunohistochemical definitions of “TUBB3 positive” vary widely between studies and depend on subjective measures of strong vs weak staining. We retrospectively evaluated the relationship between survival and TUBB3 protein quantitated by mass spectrometry in the tumor samples of 247 patients from the Intergroup Trial of Adenocarcinoma of the Stomach (ITACA-S). Patients had been randomized to a docetaxel-containing adjuvant regimen or to monotherapy with fluorouracil and leucovorin (5-FU/LV). Methods: Archived tumor tissues were microdissected and solubilized for proteomic analysis. TUBB3 and 44 other protein biomarkers were quantified with a mass spectrometry-based assay. A TUBB3 protein cutoff of 750 amol/ug was predetermined based on the assay’s limit of detection. The Mantel-Cox log-rank test was used for survival comparisons. Results: Among gastric cancer (GC) patients treated with docetaxel-containing chemotherapy (n = 125), those with TUBB3 levels below the cutoff (750 amol/µg of total protein) had a longer median overall survival (mOS) than patients with TUBB3 levels above the cutoff (1563 vs 886 days, p = 0.04). TUBB3 level made no difference in survival among patients who received 5-FU/LV. Of note, among patients with high TUBB3 levels ( > 750 amol), those treated with 5-FU/LV survived 3 years longer than patients in the docetaxel arm (mOS = 1991 vs 886 days, p = 0.048). Conclusions: Quantitative proteomic analysis of TUBB3 identified a subset of GC patients who benefitted from the addition of docetaxel to adjuvant chemotherapy. GC patients with TUBB3-expressing tumors had worse outcomes on a docetaxel-containing regimen than on 5-FU/LV. An ongoing study of triple-negative breast cancer patients treated with docetaxel suggests that proteomic TUBB3 may be predictive in other cancer indications. Personalized chemotherapy based on quantitated TUBB3 is promising and warrants broader evaluation.
Comparison of efficacy and safety of first-line palliative chemotherapy with TX and XELOX regimens in patients with metastatic gastric adenocarcinoma: A randomized phase II trial.
Authors: Zhu Xiaodong , Li Jin , Xiaoying Zhao , Guo Weijian , Liu Xin , Zhang Wen , Chen Zhiyu , Qiu Lixin , Li Wenhua , Huang Mingzhu , Zhang Xiaowei 
Published: September 2018

4070 Background: Docetaxel has shown antitumor activity in the treatment of MGC as a single or combination chemotherapy. This study was designed to compare the clinical outcome of docetaxel based and platinum based doublet regimen as first-line treatment in MGC patients. Methods: In an open, randomized, single center phase II trial, 134 pts were randomly assigned and treated with either TX (capecitabine 1g/m2/twice daily/ 1-14 days and docetaxel 75mg/m2 in 1st day) or XELOX (capecitabine 1g/m2/twice daily/ 1-14 days and oxaliplatin 130 mg/m2 in 1st day) as first-line chemotherapy. The primary endpoint is finding potential predictive factors, secondary endpoint is ORR, PFS, OS and safety. After progression, patients were switched into the other group. Results: Now, the potential predictive factors are testing in genomics and proteomics. In 134 randomly assigned and treated pts (TX = 69; XELOX = 65). Most pts were male (87pts).Overall survival was longer with TX versus XELOX (13.1m vs. 9.6m, p = 0.173), but no statistical differences. Progression free survival was similar with TX versus XELOX (4.57m vs. 5.27m, p = 0.297). Overall response rate was equal with TX versus XELOX (50.8% vs. 47.6%, p = 0.72). G3-4 treatment-related AE occurred in 60.6% (TX) v 55.4% (XELOX) of patients. Frequent G3-4 toxicities for TX v XELOX were: neutropenia (60.6% v 15.4%), febrile granulocyte deficiency (17.4% v 1.5%), anemia (10.1% v 10.8%), thrombocytopenia (1.4% v 15.4%), and all grade peripheral neurotoxicity (11.6% v 38.5%).After first-line treatment failure, 35 patients in the TX group switched to XELOX, and 27 patients in the XELOX group switched to TX, and there is also no significant difference in survival time from the first-line treatment between the two groups (p = 0.129). Conclusions: Although TX led to more neutropenia, first-line palliative chemotherapy with docetaxel based doublet regimens provides a new choice and can gain almost the same response rate and survival time as frequently-used fluorouracil and platinum based regimen. And potential predictive factors will indicate who will get more benefit from taxanes or platinums. Clinical trial information: NCT01963702.
PrE0204: A multi-institutional, single arm, two-stage phase II trial of nab-paclitaxel and gemcitabine for first-line treatment of patients with advanced or metastatic cholangiocarcinoma—A PrECOG LLC study.
Authors: Sahai Vaibhav , Catalano Paul J. , Lubner Sam Joseph , Menge Mark R. , Munshi Hidayatullah G. , Nimeiri Halla Sayed , Benson Al Bowen , O'Dwyer Peter J. 
Published: September 2018

4072 Background: Pts with advanced or metastatic cholangiocarcinoma (CCA) have limited response to current chemotherapy regimens and poor overall survival (OS). Nab-Paclitaxel (nabPAC) can increase the intra-cellular concentration of gemcitabine (GEM) through depletion of its metabolizing enzyme, cytidine deaminase (CDA). We investigated the nabPAC+GEM combination in a ph II single arm trial in advanced or metastatic CCA pts with exploratory biomarker evaluation, including CDA, hENT1, SPARC and circulating tumor cells (CTCs). Methods: Key eligibility criteria: advanced or metastatic CCA with no prior systemic chemotherapy, age > 18, ECOG PS 0-1 and Child-Pugh < 8. Pts received nabPAC (125 mg/m2 IV) and GEM (1000 mg/m2 IV) days 1, 8 and 15 Q4 weeks until progression. Primary endpoint: progression-free survival (PFS) rate at 6 months. Secondary endpoints: safety, time to progression (TTP), objective response (ORR) and disease control rates (DCR), median PFS and OS, as well as correlation of change in CA 19-9 to clinical efficacy. The study required > 43 of 67 evaluable patients alive and progression-free at 6 months to conclude the 6-month PFS rate is at least 70% against a null hypothesis of 55% based on historical data. Results: 73 eligible patients (41.1% male, 91.8% Caucasian, 45.2% ECOG PS 0) were enrolled across 22 sites with a median age of 62 (range 36-87) years and received a median of 6 (range 1-18) cycles. The primary endpoint of PFS rate at 6 months was 54.7% on intention to treat analysis. Response evaluation is underway and will be reported at the meeting. The median PFS and OS were 6.5 (95% CI, 5.1-7.7) and 10.3 (95% CI, 9.1-14.6) months, respectively. The safety profile of nabPAC+GEM was similar to that reported in ph III MPACT trial. The most common treatment-related G3/4 toxicities were neutropenia (24.3%), fatigue (13.5%) and anemia (12.2%). Five patients remain on the trial. Exploratory analyses are pending. Conclusions: The observed PFS rate at 6 months with nabPAC+GEM in CCA is insufficient to reject the null hypothesis of 55% PFS at 6 months, and appears to be as effective as the historical control. Clinical trial information: NCT02181634.
BBI608-503-103HCC: A phase Ib/II clinical study of napabucasin (BBI608) in combination with sorafenib or amcasertib (BBI503) in combination with sorafenib (Sor) in adult patients with hepatocellular carcinoma (HCC).
Authors: El-Rayes Bassel F. , Richards Donald A. , Cohn Allen Lee , Richey Stephen Lane , Feinstein Trevor , Kundranda Madappa N. , El-Khoueiry Anthony B. , Melear Jason M. , Braiteh Fadi S. , Hitron Matthew , Ortuzar Waldo Feliu , Khan Waheed , Xu Bo , Li Wei , Li Youzhi , Li C J 
Published: September 2018

4077 Background: Napabucasin, a first-in-class cancer stemness inhibitor in clinical development, suppresses cancer stemness by targeting STAT3-driven gene transcription. Amcasertib targets multiple serine threonine stemness kinases and inhibits Nanog and other cancer stemness pathways. Preclinically, potent and broad-spectrum anti-cancer activity was observed in vitro and in vivo, alone and in combination with sorafenib. Methods: A phase Ib/II open-label, multi-center study in adult patients with advanced HCC who have not received prior systemic chemotherapy was performed to determine the safety, tolerability, and recommended Phase II dose (RP2D) ,according to the criteria for DLT and for dose-escalation of Napabucasin (Arm 1), administered at 160 mg BID (dose level I) and at 240 mg BID (dose level II) in combination with sorafenib and of Amcasertib (Arm 2), administered at 100 mg QD (dose level I) and at 200 mg QD (dose level II) in combination with sorafenib. Results: 20 pts were enrolled, 10 in Arm 1 and 10 in Arm 2. 12 patients were evaluable for DLT determination; 2 pts d/c prior to starting protocol treatment; 11 pts received evaluation by RECIST, 6 pts in Arm 1 and 5 pts in Arm 2. The safety profile was consistent with that of each agent as monotherapy and most common AEs were attributed to (Sor) and included rash, PPE, grade 1/2 diarrhea, nausea, abdominal cramps, and vomiting. No signs of drug-drug interactions were observed in pharmacokinetics. Among all patients who received RECIST evaluation, Disease Control Rate (DCR=CR+PR+SD) for Arm 1 was 100% (6/6pts) and 100% (5/5pts) for Arm 2. DCR in ITT Arm 1 population was 67% and 50% in Arm 2. Median OS is not yet reached. Conclusions: In this phase Ib study, RP2D were determined for napabucasin and amcasertib to be safely combined with sorafenib at full dose, showing encouraging anti-tumor activity in patients with HCC who have not received prior systemic chemotherapy. A randomized phase II is schedule to start. Clinical trial information: NCD02279719. [Table: see text]