bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survivorship care plans: Is there buy-in from oncology providers?
Authors: Salz Talya , Onstad Erin , McCabe Mary S. , Baxi Shrujal S. , Deming Richard L. , Franco Regina A , Glenn Lyn A. , Harper Gregory R. , Jumonville Alcee , Payne Roxanne m , Peters Elissa A , Salner Andrew L. , Schallenkamp John M , Williams Sheron R. , Yiee Kevin , Oeffinger Kevin C. 
Published: February 2017

8 Background: The Institute of Medicine advised that cancer survivors and their primary care providers receive survivorship care plans (SCPs) to summarize cancer treatment and plan ongoing care. However, the use of SCPs remains limited. Methods: Oncology providers at 14 National Cancer Institute Community Cancer Centers Program (NCCCP) hospitals completed a survey regarding their perceptions of SCPs, including barriers to implementation, strategies for implementation, the role of oncology providers, and the importance of topics in SCPs (diagnosis, treatment, recommended ongoing care, and the aspects of ongoing care that the oncology practice will provide). Results: Among 245 providers (70% response rate), a minority reported ever providing an SCP or any of its components to patients. The most widely reported barriers were personnel to creating SCPs and time (69% and 64% of respondents, respectively). The most widely endorsed strategy among those using SCPs was the use of a template with pre-specified fields; 94% of those who used templates found them helpful. For each topic of an SCP, while 87%-89% of oncology providers felt it was very important for primary care providers to receive the information, only 58%-65% of respondents felt it was very important for patients to receive the information. Further, 33%-38% of respondents had mixed feelings about whether it was oncology providers’ responsibility to provide SCPs. Conclusions: Practices need additional resources to overcome barriers to implementing SCPs. We found resistance toward SCPs, particularly the perceived value for the survivor and the idea that oncology providers are responsible for SCP dissemination.
Pattern of chemotherapy use at end of life (EOL) in patients with solid tumors (ST).
Authors: Burke Thomas W. , DeJesus Yvette A , Cheng Lee , Buzdar Aman , Rodriguez Maria Alma 
Published: February 2017

93 Background: Quality performance measures for cancer care, including use of chemotherapy in the last two-weeks of life, will be required for reporting. In this study, we evaluated the pattern and frequency of chemotherapy use for ST patients in the last two-weeks of life, and whether such treatment included standard or investigational drugs. Methods: We conducted a retrospective study of 5,607 adult cancer patients (≥18 years) who received their care at The University of Texas MD Anderson Cancer Center and died between December 01, 2010 through May 31, 2012. Data on patients’ demographics, and chemotherapy agents dispensed (excluded: hormones) were obtained from the institution’s administrative databases. Type of treatment (research versus standard) was obtained from our chemotherapy dispensed database. Chi-square test and Fisher's exact test were used to determine the association between categorical variables.All statistically significant levels were determined with p values < 0.05. Results: Only 3.9% (216/5,607) of ST patients who died had received chemotherapy within 14 days EOL. For those 216 patients who received chemothapy: median age 64 years; 48% female; 89% metastatic disease. The distribution by chemotherapy treatment route: intravenous (IV) 85%; IV plus oral 6%; oral 6%; other 3%. The distribution of patients by number of chemotherapy agents: one 56%; two 31%, and three or more 13%. Among those who received chemotherapy, 98.6% (213/216) of the chemotherapy administered were standard agents. There were no differences in frequency distribution for chemotherapy treatment route (p>0.05), number of chemotherapy agents (p>0.05) between patients with metastatic and non-metastatic disease, or between men and women (p>0.05). Conclusions: Our results indicate EOL chemotherapy use was infrequent in our patients with STs, and most of those treated received standard chemotherapy, with simple one or two drug regimens. We need more research to determine factors that influence chemotherapy use at EOL, and if it palliates physical symptoms and/or emotional distress in advanced stages of disease.
A retrospective comparison study of docetaxel and paclitaxel for patients with advanced or recurrent esophageal cancer who previously received fluoropyrimidine and platinum-based chemotherapy.
Authors: Shirakawa Tsuyoshi , Kato Ken , Takahashi Naoki , Shoji Hirokazu , Terazawa Tetsuji , Honma Yoshitaka , Iwasa Satoru , Takashima Atsuo , Okita Natsuko , Hamaguchi Tetsuya , Yamada Yasuhide , Shimada Yasuhiro 
Published: February 2017

112 Background: Fluoropyrimidine plus platinum (FP)-based chemotherapy has been widely used as a first-line regimen for advanced or recurrent esophageal cancer (EC). Although the taxanes have shown efficacy in esophageal cancer after FP-based chemotherapy, there is no standard regimen for second-line chemotherapy (SLC). We conducted a retrospective study to investigate the clinical features of taxane therapy in SLC of EC. Methods: The selection criteria were pathologically proven EC; advanced or recurrent disease that had previously been treated with FP at our hospital; performance status 0-2; and adequate organ functions. The FP regimens used included 5-FU or S-1 and cisplatin or nedaplatin. Docetaxel (DTX) was administerd at 70mg/m2 triweekly for 6 weeks with 1 week’s rest. Paclitaxel (PTX) was administered at 100mg/m2 weekly with the same schedule. Overall survival of PTX was compared to DTX with baseline prognostic factors adjusted, using Cox proportional hazard model. Results: The analysis covered 110 patients over the period from August 2006 to June 2012. The median age was 64 years (range 39-83); 97 males and 13 females; 108 squamous cell carcinomas and 2 adenocarcinomas; 34 advanced and 76 recurrent; cStage I/II/III/IV at diagnosis 8/21/49/32; PS 0/1/2 score 20/81/9; DTX treatment 82 patients and PTX treatment 28. Progression-free survival and overall survival were 2.3 & 6.1 months with PTX and 2.8 and 6.9 months with DTX (no significant difference). The response rates were PTX/DTX/Total 11.1%/3.7%/5.5%. Hazard ratio of overall survival between DTX and PTX was 1.054 with adjusted by PS, sex and number of metastasis. The rate of grade 3-4 neutropenia was higher with DTX (28%) than with PTX (7%). Grade 3 febrile neutropenia was seen in 3.7% of DTX-treated patients but in no PTX patients. Grade 2 or more fatigue was seen in 16% of DTX patients and 10% of PTX ones, and grade 2 or more neuropathy was seen in 1.2% of DTX patients and 32% of PTX ones. Conclusions: PTX and DTX were both effective in SLC of EC, but the toxicity profiles of the two regimens differed. In terms of febrile neutropenia or fatigue, PTX seems more appropriate for SLC of EC.
A phase I/II study of ABT-888 in combination with 5-fluorouracil (5-FU) and oxaliplatin (Ox) in patients with metastatic pancreatic cancer (MPC).
Authors: Pishvaian Michael J. , Wang Hongkun , Zhuang Tingting , He Aiwu Ruth , Hwang Jimmy J. , Hankin Amy , Ley Lisa , White Keisha , Littman Susan Joy , Weiner Louis M. , Marshall John , Brody Jonathan Robert 
Published: February 2017

147 Background: The PARP inhibitor, ABT-888 is a potent sensitizing agent for, and has been safely combined with DNA-damaging chemotherapies. The sensitizing effects of ABT-888 are magnified when cancer cells harbor underlying defects in DNA repair mechanisms, such as BRCA2 mutations. Methods: We have initiated a Phase I/II trial, and we present here the data from the Phase I portion. Patients (pts) with MPC who had any number of prior therapies were eligible. A standard 3+3 dose escalation of ABT-888 was employed, in cohorts of 40, 60, 80, 100, 150, 200, 250, and 300mg orally twice a day, days 1-7 of a 14 day cycle. Pts also received 85mg/m2 of Ox, 400mg/m2 of 5-FU, and 400mg/m2 of leucovorin on Day 1, and 2400mg/m2 of 5-FU continuous infusion Days 1-3. Restaging studies were performed every 4 cycles. The primary objective was to determine the Recommended Phase II Dose (RP2D) of ABT-888 combined with 5-FU and Ox. Secondary clinical objectives included an assessment of the pharmacokinetics (PKs) of ABT-888 metabolism, as well as response rate (RR), progression-free survival (PFS), and overall survival (OS). Results: Between 01-2011 and 09-2012, 22 pts received treatment. 55% were male; median age = 64, most with an ECOG PS of 1. 55% were previously untreated. The first 6 pts experienced persistent ≤Grade 2 myelosuppression, primarily thrombocytopenia, prompting an amendment to drop the 5-FU bolus. In the latter 16 pts, the combination of ABT-888 plus 5-FU and Ox was well tolerated, with no DLTs. The RP2D is expected to be 300mg BID of ABT-888, with the final analysis including ABT-888 PKs to be presented. For the 22 pts, the RR was 14%, and the PFS and OS were 2.9 and 5.4 months, respectively. Of the 11 previously untreated pts, the RR was 18%, and the PFS and OS were 4.3 and 7.7 months, respectively. 2 pts with deleterious mutations in BRCA2 were included: Pt 6 had a PR and remains on study after 17 months; Pt 14 had a CR and a normalization of CA 19-9, and is still on treatment after 10 months. Conclusions: The combination of ABT-888, 5-FU, and Ox is safe and well tolerated. The combination has demonstrated promising efficacy in MPC, particularly in pts with BRCA2 gene mutations. Clinical trial information: NCT01489865.
Promotion of gemcitabine resistance in pancreatic cancer cells by three-dimensional collagen I through HMGA2-dependent histone acetyltransferase expression.
Authors: Sahai Vaibhav , Dangi-Garimella Surabhi , Ebine Kazumi , Kumar Krishan , Munshi Hidayatullah G. 
Published: February 2017

172 Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with a pronounced stromal reaction that has been shown to contribute to chemo-resistance. We have previously shown that PDAC cells are resistant to gemcitabine chemotherapy in the collagen microenvironment due to increased expression of the chromatin remodeling protein high mobility group A2 (HMGA2). Methods: Pancreatic TMAs were stained with trichrome and for histone H3K9, H3K27 acetylation (Ac), and histone acetyltransferase (HAT) expression. PDAC cells were plated onto tissue culture plastic or in three-dimensional (3D) collagen gels and protein expression assessed by Western blotting. DNA damage response was assessed by comet and clonogenic assays. Results: PDAC tumors display higher levels of H3K9Ac and H3K27Ac in fibrotic regions. Moreover, PDAC cells upregulate H3K9Ac and H3K27Ac along with GCN5, PCAF and p300 HATs in 3D collagen compared to tissue culture plastic. Knocking down HMGA2 attenuates the effect of collagen on H3K9Ac, H3K27Ac and p300, PCAF and GCN5 expression. We also show that human PDAC tumors with HMGA2 expression demonstrate increased H3K9Ac and H3K27Ac. Additionally, we show that cells in 3D collagen gels demonstrate reduced tailing with the comet assay, increased clonogenic potential and increased γH2AX following gemcitabine treatment, suggesting an increased response and repair to damaged DNA in the 3D collagen microenvironment. Significantly, down-regulation of HMGA2 or p300, PCAF and GCN5 HATs decreases gemcitabine-induced γH2AX detected and attenuates clonogenic potential. Conclusions: Collagen microenvironment limits the effectiveness of gemcitabine through HMGA2-dependent HAT expression. HMGA2 expression is associated with histone acetylation and HAT expression in human PDAC tumors, particularly in area of fibrosis, suggesting that fibrosis may contribute to chemo-resistance through increased HMGA2-HAT signaling. Overall, our results increase our understanding of how the collagen microenvironment contributes to chemo-resistance and identify HATs as potential therapeutic targets against this deadly cancer.
A phase I study of ASG-5ME, a novel antibody-drug conjugate, in pancreatic ductal adenocarcinoma.
Authors: Coveler Andrew L. , Von Hoff Daniel D. , Ko Andrew H. , Whiting Nancy Cherry , Zhao Baiteng , Wolpin Brian M. 
Published: February 2017

176 Background: ASG-5ME is an antibody-drug conjugate (ADC) targeting SLC44A4, an ion transporter expressed on >90% of pancreatic ductal adenocarcinoma (PDA). ASG-5ME comprises a fully human antibody covalently linked, with a protease-cleavable linker, to the microtubule-disrupting agent monomethylauristatin E (MMAE). Upon binding to SLC44A4 and internalization, MMAE is released by proteolytic cleavage, binds to tubulin, and subsequently induces cell cycle arrest and apoptosis. Selective targeting of tumor cells by an ADC represents a novel therapeutic approach for patients (pts) with PDA. Methods: This phase I, dose-escalation, multicenter study investigated the safety, PK, and antitumor activity of ASG-5ME in pts with metastatic PDA. Patients received ASG‑5ME IV in cohort-specific doses on Days 1, 8, and 15 of 28-day cycles until disease progression or unacceptable toxicity. Results: Thirty-five pts (median age 63 yrs, range 32-73) were treated at doses of 0.3 to 1.5 mg/kg. All pts had metastatic PDA and ECOG status 0-1. Thirty-three pts (94%) had previously received chemotherapy for metastatic disease or in the perioperative setting; the median number of prior therapies for metastatic PDA was 3 (range 1-6; n=27). The maximum tolerated dose (MTD) was exceeded at the 1.5 mg/kg dose level, with 1 DLT of Grade 4 GI hemorrhage and 4 pts experiencing non-DLT Grade 3 or 4 neutropenia. Thus, 1.2 mg/kg was identified as the MTD and expanded (N=18). The most common AEs observed at the MTD were fatigue (50%), vomiting (44%), decreased appetite (39%), nausea (33%), and abdominal pain (33%); Grade 3 or 4 toxicities at the MTD included fatigue (28%), abdominal pain (22%), vomiting (17%), and neutropenia (17%). Antitumor activity was observed: 1 pt achieved an unconfirmed PR and 12 pts achieved SD. Five patients (14%) had reductions in CA19-9. Serum ASG-5ME exposures were approximately dose proportional. Of 23 pts with archived biopsies available for IHC analysis, 100% expressed SLC44A4 and 15 pts (65%) had high expression. Conclusions: ASG-5ME treatment was generally well tolerated in metastatic PDA pts, with preliminary evidence of antitumor activity. Further study of ASG-5ME in SLC44A4-expressing malignancies is warranted. Clinical trial information: NCT01166490.
Comparative benefits of nab-paclitaxel over gemcitabine or polysorbate-based docetaxel in experimental pancreatic cancer.
Authors: Awasthi Niranjan , Ostapoff Katherine T , Zhang Changhua , Schwarz Margaret A. , Schwarz Roderich 
Published: February 2017

192 Background: Gemcitabine (Gem), a standard cytotoxic therapy for pancreatic cancer, has shown limited clinical benefits. Nanoparticle albumin-bound (nab) paclitaxel (NPT), an approved treatment for breast cancer, has shown efficacy as mono- and combination therapy in multiple tumor types including pancreatic, lung and ovarian cancer. We evaluated the NPT treatment benefits compared with Gem or solvent-based taxane docetaxel (DT) in experimental pancreatic cancer. Methods: In vitro cell proliferation and protein expression were measured by WST-1 assay and immunoblotting. Tumor growth and animal survival studies were performed in murine xenografts. Intratumoral proliferative activity was measured using Ki67 nuclear antigen staining. Results: For AsPC-1, BxPC-3, MIA PaCa-2 and Panc-1 cells in vitro, Gem IC50 levels were 23.9 mM, 506 nM, 332 nM and 14.5 nM; DT IC50 levels were 30 nM, 4.6 nM, 37.5 nM and 27 nM; and NPT IC50 levels were 7.6 mM, 208 nM, 519 nM and 526 nM. NPT addition decreased Gem IC50 to 1.7 mM, 189 nM, 123 nM and 913 nM; DT addition decreased Gem IC50 to 436 nM, 470 nM, 124 nM and 0.2 nM in AsPC-1, BxPC-3, MIA PaCa-2 and Panc-1 cells, respectively. NPT and DT treatment increased stathmin phosphorylation and decreased tubulin expression in vitro. In a heterotopic in vivo model, net tumor growth inhibition after Gem, DT and NPT was 67, 31 and 72 percent, while intratumoral proliferative index inhibition was 41, 53 and 68 percent, respectively. In an intraperitoneal model, median animal survival was significantly longer in the NPT treatment group (41 days, p<0.002 vs. control and Gem) compared to Gem (32 days, p=0.005 vs. control), DT (32 days, p=0.005 vs. control) and controls (20 days). Animal survival in NPT-Gem and DT-Gem sequential treatment groups was 43 and 40 days, and thus not superior to NPT alone. Conclusions: Nab-paclitaxel has significantly superior antitumor activity as a single agent in experimental pancreatic cancer compared with gemcitabine or docetaxel. These findings provide a strong rationale for considering nab-paclitaxel as first-line monotherapy in patients with pancreatic cancer.
The clinical significance of S100A10 in pancreatic cancer.
Authors: Yamamoto Naoto , Nakamura Yoshiyasu , Morinaga Soichiro , Numata Koji , Sawazaki Sho , Watanabe Takuo , Numata Masakatsu , Tamagawa Hiroshi , Godai Teni , Shiozawa Manabu , Akaike Makoto , Yoichi Kameda , Ueno Makoto , Ohkawa Shinichi , Oshima Takashi , Yukawa Norio , Rino Yasushi , Masuda Munetaka , Miyagi Yohei 
Published: February 2017

194 Background: S100A10 is a member of the S100 family of proteins containing two EF-hand calcium-binding motifs. They regulate a number of cellular processes such as cell cycle progression and differentiation. The objective of this study is to clarify the clinical significance of S100A10 in patients with pancreatic cancer. Methods: A total of 48 pancreatic adenocarcinoma tissues from patients underwent curative surgery were enrolled. Double 2-mm core tissue microarrays were made from paraffin-embedded pancreatic cancer samples and examined by immunohistochemistry for S100A10 protein. The correlations of expression level and clinicopathological outcome including recurrence free survival (DFS) were analyzed. Results: Expression level of the S100A10 protein in cytoplasm was categorized as overexpressed or others according to the baseline expression level in normal pancreatic duct. Overexpression of S100A10 protein was found in 9 of 48 (16.7%) cases. Statistical analysis revealed that related factor was distant lymph node metastasis. Univariate and multivariate Cox proportional hazard analysis showed S100A10 overexpression was significant independent predictors of DFS in patients with R0/1 resected pancreatic cancer (p=0.003). Although univariate Cox analysis showed overall survival in patient with S100A10 overexpression was significantly shorter (p=0.04), it didn’t show significance in multivariate analysis. Conclusions: S100A10 overexpression is considered to be useful predictor of post-operative recurrences in patients with pancreatic cancer.
Phase III trial of linifanib versus sorafenib in patients with advanced hepatocellular carcinoma (HCC).
Authors: Cainap Calin , Qin Shukui , Huang Wen-Tsung , Chung Ik-Joo , Pan Hongming , Cheng Ying , Kudo Masatoshi , Kang Yoon-Koo , Chen Pei-Jer , Toh Han Chong , Gorbunova Vera , Eskens Ferry , Qian Jiang , McKee Mark D. , Ricker Justin L. , Carlson Dawn M. , El Nowiem Saied 
Published: February 2017

249 Background: Linifanib (ABT-869; Lin) is a potent and selective inhibitor of the vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptor tyrosine kinase families. In a phase II trial in patients (pts) with advanced HCC, Lin showed clinical activity (objective response rate [ORR] 10.5% in Child-Pugh A [CPA] pts). This open-label, global phase 3 trial evaluated Lin versus sorafenib (Sor) as first-line therapy in pts with advanced CPA HCC (NCT01009593). Methods: Pts were randomized 1:1 to Lin 17.5 mg QD or Sor 400 mg BID and stratified by region (non-Asia/Japan/rest of Asia), ECOG performance status (0/1), vascular invasion or extrahepatic spread (yes/no) and HBV infection (yes/no). The primary efficacy endpoint was overall survival (OS); both non-inferiority (margin 1.0491) and superiority hypotheses were to be tested. Secondary efficacy endpoints included time to progression (TTP) and ORR, using RECIST v1.1. AE severity was graded using NCI-CTCAE v4.0. Results: 1035 pts (median age 60 y, 68% Asian, 65% ECOG 0, 49% HBV, 70% vascular invasion or extrahepatic spread) were randomized at 149 sites in 26 countries. Hazard ratio (HR) for OS was 1.046 (95% CI: 0.896, 1.221). Median OS (95% CI) was 9.1 months (m) (8.1, 10.2) on Lin and 9.8 m (8.3, 11.0) on Sor. For all pre-specifed subgroup analyses, OS HRs ranged from 0.793-1.119, and the 95% CI contained 1.0. TTP HR was 0.759 (95% CI: 0.643, 0.895; p=0.001) favoring Lin. Median TTP (95% CI) was 5.4 m (4.2, 5.6) on Lin and 4.0 m (2.8. 4.2) on Sor. ORR was 13.0% on Lin and 6.9% on Sor. Grade 3/4 AEs, serious AEs and AEs leading to discontinuations, dose interruptions and reductions were more frequent on Lin versus Sor (all p<0.001). Conclusions: Lin and Sor resulted in similar OS in advanced HCC. Predefined superiority and non-inferiority OS boundaries were not met for Lin. Secondary endpoints (TTP and ORR) favored Lin while safety results favored Sor. Clinical trial information: NCT01009593.
A phase I study of ganetespib in advanced hepatocellular carcinoma (HCC).
Authors: Goyal Lipika , Wadlow Raymond Couric , Blaszkowsky Lawrence Scott , Wolpin Brian M. , Vasudev Eamala , Sheehan Susan , Knowles Michelle , Zhu Andrew X. 
Published: February 2017

259 Background: Ganetespib is an Hsp90 inhibitor that downregulates EGFR, VEGFR, HER2, MET, IGF-IR, and other Hsp90 client proteins involved in hepatocarcinogenesis, thereby making it an attractive therapy for HCC. This multicenter Phase I study was performed to establish the safety, tolerability, recommended Phase 2 dose (RP2D), and preliminary activity of ganetespib in patients with advanced HCC. Methods: Thirteen patients with advanced HCC, Child-Pugh A or B cirrhosis, progression on or intolerance to sorafenib, and ECOG PS ≤ 1 were enrolled in a standard 3x3 dose escalation study at ganetespib doses of 100 mg/m2, 150 mg/m2, and 200 mg/m2 IV given on days 1, 8, and 15 of a 28 day cycle. RECIST 1.1 response was evaluated by CT/MRI every 8 weeks. The primary objective was to determine the RP2D, and secondary objectives included assessments of safety, toxicity, pharmacokinetics, median time to progression (TTP), median progression-free survival (PFS), median overall survival (OS), and objective response rate (ORR). Results: Twelve of the 13 patients enrolled received study drug, and enrollment is ongoing for the 200 mg/m2 cohort. Of the 12 patients: male 66%; median age 57 years; median number of prior treatments 2; Asian 33%; HCC etiology (HBV 41.7%, HCV 41.7%, hemachromatosis 8.3%, unknown 16.7%); median baseline AFP 115.3 ng/mL. Median TTP for the 10 evaluable patients was 49 days (1.6 months). No responses were seen, but 2/10 (20.0%) patients had stable disease at 8 weeks. AFP response, defined as reduction from baseline of >50% in patients with an elevated baseline AFP, was seen in 0% of patients. Most common AEs: diarrhea (100%), AST elevation (58.3%), hyperglycemia (58.3%), and fatigue (58.3%). Most common Gr 3/4 AEs: hyperglycemia (25%), anemia (16.7%), lipasemia (16.7%), and ALKP elevation (16.7%). One (8.3%) patient had a fatal AE, septic shock, within 30 days of receiving the drug. One DLT was observed: Gr 3 lipasemia at the 100mg/m2 dose. Conclusions: Ganetespib had a manageable safety profile and demonstrated limited efficacy in patients with advanced HCC. Determination of the R2PD, further assessment of clinical efficacy, and analysis of molecular markers are still pending, and a follow-up Phase II study will be considered based on this data. Clinical trial information: NCT01665937.