tbuckley/cabot-search huggingface dataset:
Safety and pharmacokinetics (PK) of T138067 (T67) administered as a weekly 3-hour infusion in subjects with hepatocellular carcinoma (HCC) in a phase 1 study
Authors: A. P. Venook, E. K. Rowinsky, R. C. Donehower, T. Leung, L. C. Floren, M. Levy
Journal: Journal of Clinical Oncology (2004)

4087 Background: T67 is a novel irreversible tubulin inhibitor currently being studied in a pivotal trial for the treatment of unresectable HCC. The safety and PK of T67 were investigated in subjects with HCC in this Phase 1 study. Methods: T67 was administered as a weekly 3-hour infusion in subjects with HCC and other cancers. Results: 13 subjects with HCC received 110, 220, 300 or 330 mg/m2 (1, 3, 7, and 2 subjects, respectively). Dose-limiting toxicities (DLTs) were thrombocytopenia (CTC Grade 1, 2 subjects, 330 mg/m2) and neutropenia (CTC Grade 3, 3 subjects, 300 mg/m2). There were no DLTs at lower doses, and no drug-related serious adverse events were reported. Linear PK were observed and apparent steady-state plasma concentrations were dose-proportional except for the 300 mg/m2 dose due to relatively low total body clearances at this dose level. Mean total body clearances (SD) were 19.2 (3.7) L/h/m2 at 300 mg/m2 versus 48.9 at 110 mg/m2, 33.0 (9.0) at 220 mg/m2 and 34.9 (5.0) at 330 mg/m2. Volume of distribution at steady-state was dose-independent. One subject (110 mg/m2) had a durable (>1 year) partial response per SWOG response criteria. Conclusions: The MTD of T67 administered as a weekly 3-hour infusion in HCC subjects is within the window of 220–300 mg/m2 with dose-limiting neutropenia identified at 300 mg/m2. Results support the T67 dose of 250 mg/m2 administered as a weekly 3-hour infusion in the ongoing registration trial. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Tularik, Inc. Tularik, Inc. Tularik, Inc.
Exposure-response (E-R) and case-control analyses of ramucirumab leading to recommendation for dosing optimization in patients with gastric cancer.
Authors: Runyan Jin, Hongshan Li, Lillian H Zhang, Hong Zhao, Lola Fashoyin-Aje, Steven Lemery, Patricia Keegan, Brian Booth, Nam Atiqur Rahman, Yaning Wang, Vikram Sinha, Liang Zhao
Journal: Journal of Clinical Oncology (2015)

2578 Background: Ramucirumab was approved for the treatment of advanced gastric or gastro-esophageal junction adenocarcinoma in combination with paclitaxel based on an efficacy and safety trial that demonstrated 2.2 months (median) of overall survival (OS) benefit with a hazard ratio of 0.81 (p = 0.02) for patients treated with ramucirumab plus paclitaxel as compared to patients treated with placebo plus paclitaxel. In exploratory Kaplan-Meier survival analyses stratified by model predicted ramucirumab minimum concentration after first dose (Cmin,1), the OS effect was only shown for the patients with Cmin,1 greater than the median value. Further exploratory E-R analyses were conducted. Methods: Data for E-R analyses were obtained from a randomized (1:1), double-blind, placebo-controlled, efficacy and safety trial that randomized 665 patients. Case-control analysis was conducted to match patients in the placebo arm to patients in each Cmin,1 quartile subgroup (Q1-Q4) based on key baseline prognostic factors, which could potentially confound assessment of therapeutic benefit from ramucirumab. The relationship between Cmin,1 and OS based on exposure subgroups and matched placebo controls was re-evaluated by Kaplan-Meier analyses. Results: Four baseline prognostic factors were identified: ECOG performance status (0 vs. 1), tumor differentiation (well, moderately, poorly or unknown), Asian (yes or no), and the total number of target and non-target tumor lesions ( ≤ 4, 4-8 or ≥ 9). These were used for selection of case-controls. Kaplan-Meier curves showed no apparent difference in OS throughout the treatment period for the Q1 and Q2 subgroups and > 4-month difference in estimated median OS for the Q3 and Q4 subgroups as compared to their corresponding controls. Conclusions: An incremental OS benefit was observed with increasing exposure of ramucirumab after case control, suggesting that patients with higher ramucirumab exposure may derive more benefit from the addition of ramucirumab to paclitaxel. These analyses led FDA to recommend a post-marketing clinical trial to explore the benefits and safety of a higher dosing regimen of ramucirumab.
Association of circulating transcriptomic profiles with mortality in sickle cell disease
Authors: Ankit A. Desai, Zhengdeng Lei, Neil Bahroos, Mark Maienschein-Cline, Santosh L. Saraf, Xu Zhang, Binal N. Shah, Seyed M. Nouraie, Taimur Abbasi, Amit R. Patel, Roberto M. Lang, Yves Lussier, Joe G. N. Garcia, Victor R. Gordeuk, Roberto F. Machado
Journal: Blood (2017)
Correlation of 12-weeks decrease of CA19.9 with overall response rate (ORR) and progression-free survival (PFS) in advanced pancreatic cancer (APC) patients (pts) treated with first-line nab-paclitaxel (Nab-P) and gemcitabine (G).
Authors: Guido Giordano, Antonio Febbraro, Michele Orditura, Teresa Troiani, Maria Maddalena Laterza, Alessio Fabozzi, Jole Ventriglia, Beatrice Savastano, Angelica Petrillo, Fortunato Ciardiello, Ferdinando De Vita
Journal: Journal of Clinical Oncology (2014)

e15256 Background: Nab-P and G have shown superiority both in terms of activity and efficacy versus G alone as a first line treatment for APC in a phase III randomised trial. In the same trial CA 19.9 response has been related to a longer Overall Survival (OS). Here we report data on our experience about the correlation between CA 19.9 response, ORR and PFS in a single cohort of pts receiving first line Nab-P + G for APC. Methods: 34 pts receiving combination of nab-P 125 mg/m2 + G 1000 mg/m2 days 1, 8, and 15 every 4 weeks were included in our analysis. CA19.9 was evaluated at baseline and then every 12 weeks. ORR defined as Complete Responses (CR) + Partial Responses (PR) was detected by PET-CT scan every 12-weeks according to RECIST v1.0 criteria. Pearson correlation analysis was performed to evaluate relation between CA19.9 response, ORR and PFS. Results: The median age was 67 years (range 37 - 77) and ECOG PS was 0 (11.7%), 1 (70.6%), 2 (17.7%). Pts had advanced disease with liver metastases (58.8%), multiple metastatic sites (41.2%) and median CA19.9 level of 469 U/I (range 20.7 – 61546 U/I). 23% of pts had biliary stent implantation. 2 pts achieved CR and 8 pts PR with ORR of 37%. Median PFS (mPFS) was 7 months (range 2 - 14). At 12-weeks evaluation, 55% of pts showed > 50% CA19.9 reduction from baseline levels. In this group of pts ORR was 60%, significantly higher than 13.5% ORR obtained in pts with < 50% CA19.9 decrease (p = 0.0001). Moreover CA19.9 > 50% reduction was also related with longer mPFS than pts with < 50% CA19.9 decrease (8 vs 5.5 months respectively; p = 0.004). Conclusions: Nab-P + G represents an active and effective first line regimen for APC treatment. CA 19-9 levels reduction > 50% from baseline at 12-weeks evaluation, seems to be a valid, easily detectable, positive predictor of pts outcome both in terms of ORR and PFS.
Randomized Comparison of Cladribine Plus Cyclophsophamide with Fludarabine Plus Cyclophosphamide in Progressive Chronic Lymphocytic Leukemia: An Updated Report of Prospective PALG-CLL3 Study.
Authors: Tadeusz Robak, Jerzy Z. Blonski, Joanna Gora-Tybor, Krzysztof Jamroziak, Bernadetta Ceglarek, Lech Konopka, Malgorzata Calbecka, Aleksandra Kostyra, Beata Stella-Holowiecka, Janusz Kloczko, Krzysztof Warzocha, Ilona Seferynska, Anna Dmoszynska, Malgorzata Kowal, Krzysztof Lewandowski, Jadwiga Dwilewicz-Trojaczek, Elzbieta Wiater, Stanislaw Potoczek, Andrzej Hellmann, Aleksander Skotnicki, Kazimierz Sulek, Jacek Dybowicz, Krystyna Zawilska
Journal: Blood (2006)
Carboplatin-pemetrexed in treatment of recurrent/metastatic cancers of the head and neck: Outcomes in oropharyngeal primaries.
Authors: Binu Malhotra, Emily Light Bellile, Nghia Pham Trung Nguyen, Vicki Kay Fung, Matthew Slack, Francis P. Worden
Journal: Journal of Clinical Oncology (2014)

e17016 Background: Platinum/5-fluorouracil with cetuximab has shown the best survival in pts with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). The purpose of this study is to evaluate the efficacy and tolerability of carboplatin, pemetrexed and to assess differential outcomes in pts with oropharyngeal primary and HPV related disease Methods: Charts of all pts with R/M SCCHN treated with at least 1 cycle of this combination (carboplatin area under the curve 5 and pemetrexed 500mg/m2) were reviewed for response, safety and survival Results: A total of 63 pts were treated with this regimen between 2008 and 2012, 58%were smokers. 45% had oropharyngeal primary, and of those 50% had HPV positive disease. Median number of cycles administered was 3.5 (range 1-14 cycles) and 50% of the pts received 4 or more cycles. 76% of the pts had been treated with prior chemoradiation. On Kaplan Meier analysis, median progression free survival (PFS) was calculated at 5.1 mos (95% CI 3.2, 6.2) and median overall survival (OS) of 9.4 mos (95% CI 4.3, 13.1). Among pts with oropharyngeal primary (n=26), median PFS was calculated at 6.4 mos (95% CI 2.8, 7.9) and median OS of 16.6 mos (95% CI 9.6, 19.5). Among HPV positive pts (n=13), median PFS was calculated at 7.0 mos (95% CI 4.8, ne) and median OS of 17.1 mos (95% CI 11.2, 21,7). Grade 3 fatigue was seen in 14% of pts and neutropenic fever was reported in 5%. 38% went on to receive another line of therapy after failing carboplatin-pemetrexed Conclusions: Carboplatin-pemetrexed is an effective and well tolerated regimen in treatment of cancers of the head and neck. The survival advantage is likely from the favorable toxicity profile, ability to treat pts for a longer duration and tolerate further lines of therapy. In line with most other published data, pts with oropharyngeal primary and HPV positive disease fared better than those with cancers from other primary sites. Given the retrospective nature of this review and the single institution experience, there is an inherent bias; the results however, are very promising. This regimen allows a good quality of life, limited toxicity while conferring as much benefit as any other combination therapy
Prognostic factors in patients with T-cell non-Hodgkin's lymphoma
Authors: N. S. Liu, M. Escalon, Y. Yang, T. A. Smith, N. H. Dang
Journal: Journal of Clinical Oncology (2004)

6603 Background: T-cell non-Hodgkin's lymphomas (T-NHL) are generally more aggressive and have a poorer prognosis compared to the corresponding B-cell lymphoma. Methods: This retrospective study examines the clinical outcome of 135 previously untreated patients with T-NHL seen at M.D. Anderson Cancer Center between 1996 and 2002. All T-cell histologies with the exception of mycosis fungoides were included. Results: With a minimum follow-up of 13 months, the estimated median overall survival was 46 months. Patients with age > 60, disease stage ≥3, extensive extranodal involvement, performance status ≥3, hemoglobin < 10, beta 2- microglobulin > 3, LDH > normal, and T-cell histologies other than CD30+ T-anaplastic large cell lymphoma (T-ALCL) had significantly worse 3-year overall survival. We then evaluated the overall survival based on the following 3 treatment groups: (1) CHOP therapy, (2) intensive therapy, which includes patients treated with hyperCHOP, hyperCVAD, ATT, and autologous stem cell transplant, (3) “other” therapy, which includes patients treated with any other alternative regimen. Thirty-seven percent of patients received CHOP therapy, 48% received intensive therapy, and 15% received “other” therapy. The 3-year overall survival was 62% in the patients treated with CHOP therapy and 56% in the patients treated with intensive therapy. After exclusion of CD30+ T-ALCL, which is known to have a better prognosis than the other T-cell histologies, the 3-year overall survival was 43% in the patients treated with CHOP therapy and 49% in the patients treated with the intensive therapy. Conclusions: (1) Parameters that may be independent prognostic factors for survival in T-NHL include: age, stage, extranodal involvement, performance status, hemoglobin, beta 2-microglobulin, LDH, and T-cell histology. (2) Consistent with previous findings, CD30+ T-ALCL has a better prognosis than other T cell histologies when treated with standard CHOP therapy. (3) Our data suggests that patients treated with the prior intensive therapies at our institution did not fare better than standard CHOP therapy. New treatment regimens need to be considered for T-NHL. No significant financial relationships to disclose.
Clinical outcomes in a cohort of patients with heparin-induced thrombocytopenia
Authors: David J. Kuter, Barbara A. Konkle, Taye H. Hamza, Lynne Uhl, Susan F. Assmann, Joseph E. Kiss, Richard M. Kaufman, Nigel S. Key, Bruce S. Sachais, John R. Hess, Paul Ness, Keith R. McCrae, Cindy Leissinger, Ronald G. Strauss, Janice G. McFarland, Ellis Neufeld, James B. Bussel, Thomas L. Ortel
Journal: American Journal of Hematology (2017)

Heparin-induced thrombocytopenia (HIT) is a thrombotic disorder usually prompting treatment with non-heparin anticoagulants. The benefits and risks of such treatments have not been fully assessed.We analyzed data for 442 patients having a positive heparin-platelet factor 4 antibody test and recent heparin exposure. The primary outcome was a composite endpoint (death, limb amputation/gangrene, or new thrombosis). Secondary outcomes included bleeding and the effect of anticoagulation.Seventy-one patients (16%) had HIT with thrombosis (HIT-T); 284 (64%) had HIT without thrombosis (isolated HIT); 87 (20%) did not have HIT. An intermediate or high "4T" score was found in 85%, 58%, and 8% of the three respective groups. Non-heparin anticoagulation was begun in 80%, 56%, and 45%. The composite endpoint occurred in 48%, 36%, and 17% (P = .01) of which 61%, 38%, and 40% were receiving non-heparin anticoagulation. Compared with the no HIT group, the composite endpoint was significantly more likely in HIT-T [HR 2.48 (1.35-4.55), P = .003)] and marginally more likely in isolated HIT [HR 1.66 (0.96-2.85), P = .071]. Importantly, risk increased (HR 1.77, P = .02) after platelet transfusion. Major bleeding occurred in 48%, 36%, and 16% of the three groups (P = .005). Non-heparin anticoagulation was not associated with a reduction in composite endpoint events in either HIT group.HIT patients have high risks of death, limb amputation/gangrene, thrombosis, and bleeding. Non-heparin anticoagulant treatment may not benefit all patients and should be considered only after careful assessment of the relative risks of thrombosis and bleeding in individual patients.
QuantiFERON test interpretation in patients receiving immunosuppressive agents: an alert
Authors: Julie Belliere, Antoine Blancher
Journal: European Respiratory Journal (2017)

Latent tuberculosis infection (LTBI) diagnosis in immune-mediated inflammatory diseases is complex because of the patient characteristics and the imperfection of available tests [1]. Functional T-cell assays are exposed to bias at several levels (manufacturing, pre-analytical, analytical and immunological) [2] and, unfortunately, the lack of a gold standard precludes higher diagnostic accuracy. However, the QuantiFERON GOLD In-tube test (QFT; QIAGEN, Hilden, Germany) represents a largely used and modern alternative to the tuberculin skin test. Even if performance specifications of QFT are of great interest (specificity of 99% and sensitivity of 84%) [3], some patients remain with an "indeterminate result" because of failed positive control corresponding to the incapacity of lymphocytes to secrete interferon (IFN)-γ after 24 h of stimulation by phytohemagglutinin A (PHA). Caution to patients with negative QuantiFERON and low mitogen response receiving immunosuppressive agents <http://ow.ly/MKsP308O3jo>
Phase I/II trial of gemcitabine plus treosulfan (GeT) in stage IV uveal melanoma and carcinomas
Authors: A. H. Schmittel, R. Schuster, N. Bechrakis, J. Siehl, M. H. Foerster, E. Thiel, U. Keilholz
Journal: Journal of Clinical Oncology (2004)

7525
Effectiveness, safety, and tolerability of oxymorphone extended release for moderate to severe cancer pain
Authors: N. Slatkin, T. Ma, A. Frailey, H. Ahdieh
Journal: Journal of Clinical Oncology (2004)

8194 Background: Effective management of chronic cancer pain often requires opioid analgesics, but few studies have assessed their long-term use in moderate to severe pain. Methods: This multicenter, 2-year, open-label extension study included patients who completed a phase III, randomized trial. Patients continued with oxymorphone extended release (ER) q12h at their previous dose. Oxymorphone immediate release was available for rescue medication. Effectiveness assessments (at weeks 1, 2, 6, 10, 16, and at 6-week intervals thereafter) measured pain recall scores, current pain intensity, patient global assessment, rescue analgesic use, and daily dosage. Safety was assessed by adverse events, laboratory tests, and vital signs. Results: Forty- four patients enrolled with an estimated median time to discontinuation of 213 days; 16 completed 12 months and 5 completed 24 months. Current pain assessments (visual analog scale of 0–100 mm) remained relatively unchanged with means of 32.1 at week 1 and 31.3 at week 104, and there were no meaningful changes in mean recalled least, worst, or average pain intensity. The mean daily dosage of oxymorphone ER was 125 mg at week 1, 151 mg at week 52, and 197 mg at week 104. Mean use of rescue medication was low (23–30 mg/d). Serious adverse events caused the most withdrawals; the most frequent serious adverse event was concomitant disease progression. At each assessment, more than 90% of patients rated oxymorphone as “excellent,” “very good,” or “good.” Conclusions: Oxymorphone ER q12h is effective for long-term control of moderate to severe cancer pain with minimal dose escalation or need for rescue medication. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Endo Pharmaceuticals
Detecting Bacteremia Pathogens
Authors: Rebecca Voelker
Journal: JAMA (2017)

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Hospital Risk of Data Breaches
Authors: Ge Bai, John (Xuefeng) Jiang, Renee Flasher
Journal: JAMA Internal Medicine (2017)

mended screening to women 40 years or older.Our findings are largely consistent with a 2014 survey of PCPs from 4 clinical networks where similar proportions of physicians recommended screening with higher rates noted among gynecologists. 5 We also found sharp differences in recommendations based on which guidelines physicians trusted most, which may suggest that current practices reflect both varying adherence to guidelines as well as differences in which guidelines are trusted.The results provide an important benchmark as guidelines continue evolving and underscore the need to delineate barriers and facilitators to implementing guidelines in clinical practice.
Cetuximab single-agent activity in refractory metastatic colorectal cancer: Single-center experience
Authors: B. Mirtsching, C. Headlee, S. Beasley, C. Teel, D. Jackson
Journal: Journal of Clinical Oncology (2004)

3703 Background: The response rate (RR) in > 3rd-line therapy salvage therapy after failure of flouropyrimidine(F)-, irinotecan(I)-, and oxaliplatin(O)-containing regimens is low and average time-to-progression (TTP) is short. Methods: At a single research center, 29 consecutive patients refractory to F, I, and O were treated with single-agent weekly Cetuximab (400 mg/m2 wk1, then 250 mg/m2 weekly). All patients who did not progress were treated continuosly until disease progression. Here we report our observations. Results: Baseline characteristics: Mean age: 60, all ECOG PS 0–1, 20 male (69%), 9 female (31%), 25 white (87%), 2 black (7%), 1 Asian (3%) and 1 American Indian (3%). Treatment was 3rd-line in 6 (21%), 4th-line in 11 (38%), 5th-line in 7 (24%) or 6th-line in 5 (17%). Responses: 1/29 has not been assessed for response. CR 0 (0%), PR 3 (11%), SD 13 (46%) and PD 12 (43%). The mean number of doses of Cetuximab was 11 (range: 2–27). TTP ranged from 7–185d (mean 72d). SD duration ranged from 41 to 185d (mean 109d). The patients with protracted non-progression (>4 mos) had the following characteristics: best response: 4 SD 2 PR, 2 females, 4 males, 5 caucasians, 1 black, mean age 67. Toxicities: One G3 rash and one G4 infusion reaction occurred in 328 total weekly doses. Mean weight loss through the duration of therapy was 4 pounds. 28/29 patients had maintenance or improvement of performance status during therapy. Conclusions: Cetuximab for salvage therapy for refractory colorectal cancer delays progression, even though many were heavily pre-treated. Toxicities are minimal and infusions are well-tolerated. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Amgen Bristol-Myers Squibb/ImClone