tbuckley/cabot-search huggingface dataset:
The biomarkers of gemcitabine and erlotinib treatment in advanced pancreatic cancer.
Authors: Kuniyasu Irie, Makoto Ueno, Satoshi Kobayashi, Yoshihiro Gouda, Shinichi Ohkawa, Morimoto Manabu
Journal: Journal of Clinical Oncology (2014)

358 Background: A combination of gemcitabine+erlotinib is one of the standard chemotherapies in advanced pancreatic cancer (APC). Since APC patients often take antiulcer drugs to prevent gastritis (e.g., NSAIDs to reduce cancer pain), erlotinib concentration is generally decreased through the mechanism of CYP3A4. Furthermore, unlike lung cancer, the biomarkers for APC are not obvious except rash. Here, we examined biomarkers of gemcitabine+erlotinib treatment in APC patients including the presence of antiulcer drugs. Methods: The subjects were 59 advanced pancreatic cancer patients. They were treated with gemcitabine+erlotinib starting from Nov. 2011 to Apr. 2013. Gemcitabine was administered at 1000 mg/m 2 , on days 1, 8, and 15 for every 4 weeks, and erlotinib was taken 100 mg daily. The progression-free survival (PFS), UICC stage, sex, age, CRP concentration, performance status (PS), rash, and presence of antiulcer drugs were examined. The PFS curve was plotted according to the method of Kaplan and Meier. The difference in the PFS was calculated using the log-rank test, and a multivariate analysis was conducted using Cox hazard model. Results: UICC stages were as follows; i.e., stage II: 1, stage III: 8, and stage IV: 50. There were 36 males and 23 females, and their ages ranged from 41 to 82 years old (median: 65). The CRP concentrations ranged from 0.02 to 11.5 mg/dl (median: 0.57). 37 patients received antiulcer drugs, and 48 patients had rash. The univariate analysis revealed that the CRP concentration and rash were significant (p=0.009 and p=0.005, respectively). Low CRP (&lt;0.57mg/dl) and presence of rash were related to good PFS. The multivariate analysis also revealed that the CRP concentration (HR, 0.34; 95%CI, 0.16-072; p=0.005) and rash (HR, 0.40; 95%CI, 0.16-0.96; p=0.04) were significant. The presence of antiulcer drugs on PFS was insignificant. Conclusions: The CRP concentration and rash were biomarkers of gemcitabine+erlotinib treatment in APC patients.
The prognostic value of seven soluble proteins measured in plasma or serum from patients with colorectal cancer in TNM stages I-III.
Authors: Ib Jarle Christensen, Gunilla Høyer-Hansen, Tine Thurison, Barry Dowell, Julia S. Johansen, Rikke Henriksen, Kristoffer Staal Rohrberg, Nils Brunner, Hans J. Nielsen
Journal: Journal of Clinical Oncology (2012)

35 Background: In colorectal cancer (CRC) several independent blood-borne biomarkers have been proposed as prognostic and/or predictive markers. However only CEA is at present recommended as a serological CRC biomarker. We have identified 6 other biomarkers and the aim of this study is to see if a combination of markers improves the prognostic and/or predictive value. Methods: Two-hundred and twenty-eight patients with CRC have been included in this study, all with TNM stages I-III. Overall survival (OS) was chosen as the primary endpoint with 93 events and the minimum follow-up was 47 months. Seven biomarkers measured in plasma or serum were analysed: CEA, TIMP-1, the 3 soluble uPAR forms suPAR(I-III), suPAR(I-III)+(II-III) and uPAR(I), PAI-1 and YKL-40. Multivariable analyses of OS were done using regression analysis and results presented by 3 and 5 year OS rates with area under the receiver operating characteristic curve (AUC). All biomarker levels were analysed on the log scale (base 2). Results: High levels of each of the included biomarker were significantly associated in a multivariable analysis (adjusted for age, gender, TNM stage, tumor localization, adjuvant chemotherapy,interaction between adjuvant therapy and biomarker) to poor prognosis in patients not receiving adjuvant chemotherapy. The results are shown for those patients (see Table). The uPAR forms were the only biomarkers significantly associated to OS in patients receiving adjuvant chemotherapy. Combining the markers resulted in an enhanced prediction of 3 and 5 year OS. For TNM stage II patients not receiving adjuvant therapy, the AUC was 0.765 for 3 year OS and 0.745 for 5 year OS. The corresponding AUC’s for TNM stage III were 0.859 and 0.861. Conclusions: The presented combination of blood biomarkers are shown to predict OS with higher precision than any single marker for patients not receiving adjuvant chemotherapy and may provide useful information for use in the management of patients with CRC. [Table: see text]
Phase I trial of oral vorinostat in combination with bexarotene in patients with advanced cutaneous T-cell lymphoma
Authors: K. Hymes, R. Dummer, W. Sterry, M. Steinhoff, C. Assaf, H. Kerl, J. Ahern, S. Rizvi, J. L. Ricker, S. Whittaker
Journal: Journal of Clinical Oncology (2008)

8613 Background: The histone deacetylase (HDAC) inhibitor vorinostat and the RXR-selective retinoid bexarotene are each clinically active and safe as monotherapy in the treatment of cutaneous T-cell lymphoma (CTCL). This study was performed to test whether the combination of vorinostat and bexarotene could be safely administered. Methods: A Phase I trial of vorinostat (200, 300, or 400 mg daily) in combination with bexarotene (150, 225, or 300 mg/m2 or 150 mg, daily) was conducted. Cycles were repeated every 28 d for ≤6 cycles until PD or intolerable toxicity. Adult patients (pts) with stage ≥IB progressive, persistent, or recurrent CTCL refractory to ≥1 systemic therapy were eligible. Pts must not have received prior bexarotene within 3 m or prior HDAC inhibitor treatment and must have adequate hematologic, hepatic, and renal function. The primary objective was to determine the maximum tolerated dose (MTD). Activity and safety of the combination regimen were also assessed. Results: 19 pts have been enrolled: median age, 58 years (range 33–77), median number prior systemic therapies, 3 (range 1–14). 18 pts have received ≥1 dose and were evaluable for safety as of 11/1/07. Two pts (Cohort 2) experienced dose-limiting toxicity (DLT, Table). The MTD has not been reached. The most common drug-related toxicities were hypertriglyceridemia (50%), hypercholesterolemia (28%), hypothyroidism (28%), and lethargy/fatigue (28%). Grade 3 drug-related adverse events included hypertryglyceridemia (17%) and neutropenia (11%). Two pts had drug-related serious adverse events (skin necrosis; lymphangitis + lymph node abscess) and both recovered. 12 pts have discontinued treatment: only 2 due to adverse events (skin necrosis, fatigue). Preliminary data indicate that of 18 evaluable pts, 1 had a CR, 3 had a PR, 12 had SD, and 2 had PD. Conclusion: Accrual continues to determine the MTD. The combination of vorinostat and bexarotene is tolerable and active in advanced CTCL pts. Cohort Vorinostat (mg) Bexarotene N CTCL Stage # of Cycles DLTs Best Response 1 200 150* 3 IB, IVA (2) 2, 5, 6 - PD, SD (2) 2 300 150* 5 IIB (3), IVA, IVB 1, 1, 2, 3, 6 Grade 3 fatigue, Grade 3 hypertriglyceridemia (3) PR, SD (4) 2a 200 225* 3 IIB, IVA (2) 3, 4, 6 - CR, SD (2) 2b 200 300* 3 III, IVA (2) 6, 6, 6 - PR, SD (2) 3 400 150† 5 IB, IIB (2), III, IVA 1, 1, 2, 5, 6 - PR, SD (2), PD, NE NE = not evaluable; PD = progressive disease; PR = partial response; SD = stable disease. * mg/m2/d; † mg/d Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Merck Merck Merck Merck
Evaluation of pretransplant variables predicting cardiomyopathy following high-dose melphalan conditioning and autologous peripheral blood stem cell transplantation.
Authors: J. S. Bleeker, M. A. Gertz, P. A. Pellikka, F. Buadi, D. Dingli, A. Dispenzieri, S. R. Hayman, W. J. Hogan, S. Kumar, M. Lacy
Journal: Journal of Clinical Oncology (2011)

8079 Background: Although cardiomyopathy following high dose melphalan (HDM) prior to autologous peripheral blood stem cell transplant (PBSCT) has not been described, there are multiple anecdotal cases of cardiomyopathy following HDM in the Mayo Clinic experience. We reviewed our experience to determine the frequency of cardiomyopathy in this setting as well as pre-transplant variables that may identify patients at highest risk for this complication. Methods: From our database of all patients undergoing HDM conditioning and autologous PBSCT for myeloma or amyloidosis from 1989-2009, those with echocardiograms performed before and within 4 months of PBSCT were reviewed for evidence of cardiomyopathy. Charts of patients experiencing cardiomyopathy were reviewed for mulitple potentially predisposing variables. Age and sex-matched controls who did not suffer cardiomyopathy were then similarly evaluated in a case-control fashion. Results: Of 1,476 patients (1,050 myeloma; 426 amyloidosis) who received HDM conditioning prior to PBSCT, 40 (2.7%) met criteria for cardiomyopathy. After accounting for other factors, HDM was felt to be a probable cause of cardiomyopathy in 16 patients, a possible cause in 18, and an unlikely cause in 6. Cardiomyopathy was noted more frequently in patients undergoing PBSCT for amyloidosis (23/426, 5.4%) than myeloma (17/1050, 1.6%). The mean pre-PBSCT ejection fraction in this cohort was 59% (range 42-70%), which decreased to a mean of 38% (range 15-50%) following PBSCT. The majority of amyloidosis patients with HDM-associated cardiomyopathy had pre-PBSCT evidence of both cardiac (17/23, 73.9%) and renal (16/23, 69.6%) involvement. Evidence of cardiac dysfunction was also common in the amyloidosis population, with 72% of patients having an elevated troponin T and 100% having an elevated NT-proBNP prior to PBSCT. Conclusions: To our knowledge, this is the first series to report cardiomyopathy following HDM conditioning and autologous PBSCT. Ongoing analysis will further define pre-transplant variables which may help identify patients at risk of cardiomyopathy following conditioning with HDM.
Weekly nanoparticle albumin-bound paclitaxel(nab-PTX) as second-or later-line treatment for unresectable or recurrent gastric cancer in practice.
Authors: Masataka Yagisawa, Susumu Sogabe, Ichiro Iwanaga, Tomohiro Oshino, Takahiro Yamamura, Hajime Hirata, Masahito Nakajima, Kazuharu Suzuki, Joji Shimono, Takuma Takasaka, Kazuhiro Takahashi, Yoshimitsu Kobayashi, Taiki Kudo, Kohei Okada, Masayoshi Dazai, Hisashi Oda, Takuto Miyagishima
Journal: Journal of Clinical Oncology (2015)

168 Background: Nanoparticle albumin-bound paclitaxel (nab-PTX) is a novel, solvent polyoxyethylated castor oil-free, biologically interactive form of paclitaxel (PTX). Nab-PTX allows shorter infusion schedules and needs no premedication for hypersensitivity reactions, so nab-PTX will be used as the alternative to PTX for more patients. In Japan, nab-PTX was approved as tri-weekly regimen (210mg/m 2 every 3weeks) for gastric cancer. On the other hands, weekly PTX (80mg/m 2 on day1, 8, and 15, every 4weeks) is mostly used as PTX regimen as 2nd or later line treatment for gastric cancer in Japan. So in practice, nab-PTX would be used by weekly regimen same as weekly PTX. However, the safety and efficacy of weekly nab-PTX for gastric cancer had not been reported yet. Methods: Unresectable or metastatic gastric cancer patients who began receiving weekly nab-PTX as 2nd or later line chemotherapy in our two facilities from February 2013 to August 2014 were retrospectively analyzed for the safety and efficacy. Written informed consent about the treatment of weekly nab-PTX was obtained from all patients before treatment. Results: A total of 32 patients were assessed, retrospectively. The dose and schedule of nab-PTX was 100mg/m 2 on day1, 8, and 15, every 4weeks in all patients. Patients characteristics were as follows: median age 67.5(37-84); Male/female: 24/8; PS 0/1/2/3:15/8/7/2; treatment line 2/3/4/5: 12/14/5/1. The overall response rate was 9.3% (CR/PR/SD/PD/NE: 1/2/12/15/2). The median progression-free survival (mPFS) and median overall survival (mOS) were 2.99 months and 5.95 months, in all patients. In 23 patients whose PS were 0 or 1, mPFS and mOS were 4.14 months and 8.44 months. Most common grade 3/4 hematological toxicities were anemia (46.9%), neutropenia (40.6%), febrile neutropenia (15.6%). About the sensory neuropathy, grade 3 was 9.3%, grade2 was 21.9%, and grade1 was 3.1%. There were no treatment-related deaths. Conclusions: Weekly nab-PTX showed promising efficacy against previously treated unresectable or recurrent gastric cancer especially for good PS patients, The Common toxicities of weekly nab-PTX were well-tolerated.
Biomarker analysis from a phase III trial (GOLD) of dovitinib (Dov) versus sorafenib (Sor) in patients with metastatic renal cell carcinoma after one prior VEGF pathway–targeted therapy and one prior mTOR inhibitor therapy.
Authors: Bernard J. Escudier, Camillo Porta, Matthew Squires, Cezary Szczylik, Christian K. Kollmannsberger, Bohuslav Melichar, Sun Young Rha, Emilio Esteban, Georg A. Bjarnason, Nicholas J. Vogelzang, Cora N. Sternberg, Michael Shi, Mathab Marker, Robert John Motzer
Journal: Journal of Clinical Oncology (2014)

473 Background: In the GOLD trial, Dov did not improve progression-free survival (PFS) or overall survival (OS) over Sor. An exploratory objective of the study was to investigate plasma and tumor biomarkers to predict outcome. Methods: Plasma samples were obtained longitudinally throughout the study, and biomarkers were assessed by immunoassay. Primary archival tumor samples were assessed by immunohistochemistry. Log-rank tests, stratified by baseline MSKCC risk group, for difference in Kaplan-Meier curves between biomarker category (low/high based on &lt;/≥ median baseline values) within treatment arm were performed. Hazard ratios (HRs) were estimated from Cox proportional hazards models. Results: Plasma samples were available from 561 patients (Dov, n = 281; Sor, n = 280), and tumor samples were available from 341 patients (Dov, n = 181; Sor, n = 160). Baseline plasma biomarker levels were not predictive of Dov or Sor PFS or OS. However, strong prognostic effects, particularly for OS, were observed. High baseline cKIT and low baseline FGF2, HGF, PlGF, sVEGFR1, VEGFA, and VEGFD were associated with better OS for both Dov and Sor (Table). Changes from baseline in a number of plasma biomarkers were observed following treatment with Dov and Sor, consistent with VEGFR/FGFR inhibitory effects. Prognostic effects were also observed for low FGFR2 (PFS) and low FGF2 (OS) expression in archival tumors. Conclusions: Baseline plasma biomarkers are prognostic but not predictive in the third-line setting. Clinical trial information: NCT01223027. [Table: see text]
Practice of venous thromboembolism (VTE) prophylaxis in hospitalized cancer patients at a comprehensive cancer center.
Authors: M.Alma Rodriguez, Alma Yvette DeJesus, Lee Cheng, Michael Kroll
Journal: Journal of Clinical Oncology (2014)

149 Background: VTE prophylaxis measures are endorsed by the National Quality Forum in alignment with quality indicators from the Centers for Medicare &amp; Medicaid Services. Accordingly, documentation of VTE risk, prophylaxis measures, and contraindications are recommended for hospitalized patients. To standardize practice we embedded a VTE risk assessment and prophylaxis module into admission and post-surgical order sets (OS), starting August 15, 2011. Methods: A retrospective study of 9,065 cancer patients (≥18 years) admitted to The University of Texas MD Anderson Cancer Center between June 01, 2013 through September 30, 2013. Pharmacological prophylaxis was executed with low-molecular-weight heparin or unfractionated heparin. Mechanical prophylaxis was executed with graduated compression stockings and/or sequential compression devices. Chi-square testing was used to determine the association between categorical variables. All statistically significant levels were determined with P values &lt; 0.05. Results: 7,366 (81%) of all hospital admissions had documented VTE risk assessment and prophylaxis through the standardized VTE module. Before implementation of the new OS, only 40% of eligible patients received an order for VTE prophylaxis. The majority of patients were designated high or moderate risk (91.1%). Patients with high risk were more likely to receive pharmacological prophylaxis than those with moderate risk (74.1% vs. 38.2%, P&lt;0.01). The most frequent contraindications to pharmacological prophylaxis were major surgery with risk of bleeding and thrombocytopenia (Table). Conclusions: Most patients received VTE prophylaxis based on VTE risk levels presented in a standardized OS. There is is limited information in the clinical literature about the impact of VTE prophylaxis on outcomes among cancer patients, we plan to assess anticoagulation-related outcomes in this cohort of patients. [Table: see text]
IL-6 as a prognostic biomarker in patients with metastatic melanoma.
Authors: L. Hoejberg, L. Bastholt, J. S. Johansen, K. Fode, H. Schmidt
Journal: Journal of Clinical Oncology (2011)

8538 Background: Interleukin (IL)-6 is an immunomodulatory cytokine produced by cancer cells and different immune cells. The function of IL-6 in cancer is unknown. Serum IL-6 is elevated in patients with different types of cancer. Methods: IL-6 was measured by ELISA in pretreatment serum samples from 110 patients (46 women and 64 men, median age of 53 years, range 29-74) with metastatic melanoma receiving IL-2 based immunotherapy. Serum concentrations of IL-6 were also determined in 245 healthy subjects. Results: Patients with metastatic melanoma had higher serum IL-6 than healthy subjects (median 3.37 ng/l, range 0.3-93 ng/l vs. median 1.4 ng/l, range 0.25-22.5 ng/l, p<0.000). Pretreatment serum IL-6 was elevated in 43% of the patients (cut-off 4.92 ng/l = upper 95% confidence limit in healthy subjects). Patients with elevated pretreatment serum IL-6 had shorter overall survival compared to patients with normal serum IL-6 (p<0.001). Median overall survival was 10.8 months (95% confidence interval (CI): 8.86-13.46) in patients with normal serum IL-6 compared to 4.5 months (CI: 3.04-7.39) in patients with elevated serum IL-6. Multivariate Cox analysis showed that serum IL-6 (Hazard ratio (HR) = 1.88, p=0.004) and serum LDH (HR = 1.93, p=0.003) were independent prognostic factors for overall survival. A combination variable of elevated serum IL-6 and elevated serum LDH almost quadrupled the risk of early death (HR=3.79, p<0.001) compared to patients with normal serum levels of these two biomarkers (Table). Conclusions: Elevated serum IL-6 is an independent prognostic biomarker of short survival in patients with metastatic melanoma. A larger retrospective study is ongoing to confirm the findings. Multivariate Cox analysis of potential clinical and serologic parameters of survival in patients with metastatic melanoma.* HR 95% CI P value Elevated IL-6 1.88 1.23-2.88 0.004 Elevated LDH 1.93 1.25-2.99 0.003 Elevated IL-6 and elevated LDH 3.79 2.27-6.32 <0.001 * Number of metastatic sites, blood neutrophils, and performance status were not statistically significant.
Implantable sites (IS) in medical oncology: Experience of the Salah Azaiz Tunisian National Cancer Center
Authors: H. Boussen, M. Mtaallah, J. Ben Hassouna, T. Damak, W. Bachouche, K. Rahal, H. Chaaba
Journal: Journal of Clinical Oncology (2008)

20733 Background: To describe and analyse the results within an observational study with epidemiological data concerning our experience concerning the long term use of implantable sites in adults and paediatric cancer patients in medical oncology in Tunisia. Patients and Methods: From April 1992 to January 2008, we indicated the insertion of 1120 IS in adults (1115 patients) and 103 in children (100 patients). Devices were inserted per cutaneously using Seldinger technique in all patients. Device-related events and complications during the follow-up period were assessed. Results: The mean ages were 49 years (range, 18–81years) and 8.5 years (range, 4 months-18 years) for adults and children patients and sex-ratio 1.5 for adults and 1.1 for children. Indications for central venous access were chemotherapy for colorectal (34.6%) and breast cancer (27.1%) in adults, and leukaemia-lymphoma (32.6%) and sarcoma (29.5%) in children. In most cases, cervical veins were used (96.5%). The internal jugular vein (IJV) was the most commonly used (56.2%), particularly after 2002 (83.7%) and especially by the low lateral approach (57.7%). Pneumothorax was the most serious early complication (0.5%). Late complications were represented by device related infection (3.8%) and deep venous thrombosis (1.8%). We observed during the last years a clear reduction in early and late complications of IS. Mean duration of the IS was 384.3 days (3 to 1950 days). Conclusion: Experience of the medical team, echography guided catheter insertion, and use of the IJV instead of subclavian vein appear to have an important role in the success or complications of the catheterisation and long term use of IS. The low lateral approach of the IJV can be considered as first choice technique of veinipuncture and long term central venous access. No significant financial relationships to disclose.
Barriers to goals of care discussions with patients with advanced cancer and their families: A multicenter survey of oncologists.
Authors: Josee-Lyne Ethier, Thivaher Paramsothy, Sonal Gandhi
Journal: Journal of Clinical Oncology (2015)

15 Background: Early documentation of end-of-life (EOL) preferences in patients with advanced cancer is associated with less aggressive EOL care, however, several barriers to having these discussions exist. Evaluating practitioner-level barriers in the ambulatory oncology setting by adapting an existing survey from the critical care and internal medicine contexts was deemed important. Methods: The previously published “DECIDE” survey was modified to the ambulatory oncology setting and pilot tested. Surveys were then distributed to oncologists in Ontario, Canada via paper and secure online methods. The survey asked physicians to rank on a numerical scale the importance of various barriers to having EOL discussions with patients and their families. Trends were established using descriptive statistics. Analysis by respondent demographic was not completed due to small numbers. Results: A total of 30 out of 79 participants responded to the survey, for a response rate of 38%. Respondents generally ranked patient and family related barriers highest. For instance, patient difficulty accepting prognosis or indicating a desire to be “aggressive” was rated by 69% of respondents as an extremely or very important barrier to initiating EOL discussions. Sixty-three percent of respondents also rated patients’ inflated expectations of further cancer treatment benefit as a very or extremely important barrier to discontinuing active cancer-directed therapies. Patient or family refusal for referral was rated by 47% of respondents as a very or extremely important barrier to early palliative care referral. The majority ( &gt; 85%) of respondents were very or extremely willing to initiate, lead, and finalize the EOL discussions with patients and their families. Conclusions: Oncologists in this study ranked patient and family related barriers to having EOL discussions above all other barriers. Further work is required to better understand such perceived barriers, and compare them to patient preferences and perceptions about EOL planning and cancer care at the end of life. Targeted interventions to address these barriers could then be developed.