tbuckley/cabot-search huggingface dataset:
Abandoning oral oncolytic prescriptions at the pharmacy: Patient and health plan factors influencing adherence.
Authors: L. S. Schwartzberg, S. B. Streeter, N. Husain, M. Johnsrud
Journal: Journal of Clinical Oncology (2011)

6036 Background: Oral oncolytic agents are an increasingly important component of cancer therapy. Adherence with therapy begins with filling the prescription in a timely manner. Little is known of the factors associated with abandonment of oral oncolytics at the initial or subsequent prescription. Methods: This cross-sectional study analyzed a nationally representative pharmacy claims database and identified 10,508 Medicare and commercial patients initiating oral oncolytic therapy between 2007 and 2009. We calculated the rate of abandonment of the initial claim, where abandonment was defined as the reversal of an adjudicated pharmacy claim without a subsequent paid claim for any oncolytic (oral or IV) within the subsequent 90 days. The likelihood of abandonment was assessed using bivariate and multivariate logistic regression analyses including patent demographic factors, plan type, drug type, cost-sharing and number of other prescriptions. Results: The abandonment rate of newly initiated oral oncolytic agents was 10.0%. Unadjusted bivariate analyses found that high cost-sharing, larger prescription burden, lower income, and Medicare coverage were associated with a higher abandonment rate (p<0.01). Our logistic regression model found that as both cost-sharing and concurrent prescription use rose, there was a significantly higher likelihood of abandonment. Claims with cost-sharing over $500 were 4 times more likely to be abandoned than claims with cost-sharing of $100 or less (OR=4.46, p<0.001). Medicare patients were more likely to have cost-sharing over $500 than patients with commercial plans (p<0.001). Patients with 5 or more prescriptions in the previous month had 50% higher likelihood to abandon than patients with no prescription burden (OR=1.50, p<0.001). Conclusions: Abandonment of newly prescribed oral oncolytic therapy is not uncommon, and the likelihood increases for patients enrolled in plans with pharmacy benefit designs that require high cost sharing. Higher prescription burden was also associated with a larger abandonment rate. These factors should be taken into account when considering likely adherence to cancer therapy.
Safety and efficacy of extended-duration thromboembolic prophylaxis following radical cystectomy.
Authors: Harras B. Zaid, David Yang, Matthew K. Tollefson, Igor Frank, William P. Parker, Robert Houston Thompson, R. Jeffrey Karnes, Stephen A. Boorjian
Journal: Journal of Clinical Oncology (2016)

389 Background: Venous thromboembolism (VTE) has been reported in approximately 5-7% of patients undergoing radical cystectomy (RC). While extended-duration pharmacologic prophylaxis (EDPP) has been investigated following surgery for a variety of malignancies, limited data exist in bladder cancer. Herein, we evaluated the efficacy and safety of EDPP after RC. Methods: We instituted a change in our clinical practice beginning in May 2014 such that patients undergoing RC were prescribed 30 days of enoxaparin at discharge. We recorded symptomatic VTE and lymphocele rates within 30 days of RC among patients treated from 5/14-6/15, and compared these outcomes to the cohort of all patients who underwent RC at our institution in the year prior to EDPP implementation. Patients in both groups received subcutaneous unfractionated heparin and mechanical prophylaxis during hospitalization. Patients with a history of VTE prior to surgery (n = 24) were excluded from study. Unadjusted descriptive statistics and univariate analyses were performed using the Pearson or Fisher chi-square test for categorical variables and Wilcoxon rank-sum test for continuous variables. Results: In total, 58 patients who received EDPP and 82 patients who had not received EDPP after RC were included for analysis. Baseline clinicopathologic demographics were similar between the cohorts. We found that only 1 patient (1.9%) discharged with EDPP was diagnosed with a VTE within 30 days of RC, compared to 5 (6.1%) who had not received EDPP. Mean time to VTE was 18.0 days after RC (range 9-28 days). Events consisted of DVT alone (n = 2), DVT and PE (n = 2), and PE alone (n = 2). The odds ratio for VTE in the absence of EDPP was 3.31 (95% CI 0.38, 29.2). Overall, 3 patients developed a symptomatic lymphocele within 30 days of RC: 1 (1.9%) who received EDPP and 2 (2.4%) who had not (p = 0.84). No patient in either cohort was rehospitalized for bleeding complications. Conclusions: Our initial experience suggests that EDPP was associated with a lower rate of VTE following RC, and does not increase the risks of bleeding or symptomatic lymphocele. Future evaluation in a larger-scale prospective clinical trial setting is needed to confirm the benefit of EDPP in RC patients.
A multi-institutional phase II study of high-dose hypofractionated proton beam therapy (HF-PBT) for unresectable primary liver cancers: Long-term outcomes in patients (pts) with hepatocellular carcinoma (HCC).
Authors: Theodore S. Hong, Jennifer Yon-Li Wo, Edgar Ben-Josef, Erin McDonnell, Lorraine C. Drapek, Lawrence Scott Blaszkowsky, Eunice Lee Kwak, Jeffrey W. Clark, Lipika Goyal, David P. Ryan, Milind M. Javle, Ronald Arellano, John A. Wolfgang, John Thomas Mullen, Cristina Ferrone, Kenneth Tanabe, Thomas F. DeLaney, Christopher H. Crane, Andrew X. Zhu
Journal: Journal of Clinical Oncology (2016)

376 Background: Retrospective reports of PBT in hepatocellular carcinoma (HCC) demonstrate local control (LC) rates exceeding 85%. We prospectively replicate these findings and explore predictors of overall survival (OS) in pts with unresectable HCC receiving high dose, HF-PBT. Methods: Pts were enrolled on an NCI sponsored, multi-institutional, phase II study (NCT00976898). Key eligibility were unresectable HCC; Child’s A/B; ECOG PS 0-2; no extrahepatic disease; no prior RT. Maximum tumor size was 12 cm if solitary, 10 cm if 2 tumors, and 6 cm if 3. PBT was given in 15 fractions to a maximum total dose of 67.5 GyE. Sample size was calculated to demonstrate &gt; 80% LC at 2 yrs (LC-2). Results: From 2009-2015, 44 patients were treated. Median age was 70 years (53-89) and 37 (84.1%) were male. 35 (79.5%) pts had Child A or no cirrhosis. 32 (72.7%) pts had 1 tumor, 12 (27.2%) had multiple tumors. Median longest tumor dimension was 5.0 cm (range 1.9-12.0). Median baseline AFP was 18.6 ng/mL (range 1.3-66081) and 29 pts (67.4%) had elevated AFP ( &gt; 7.9 ng/mL). Median RT dose delivered was 58.0 GyE (range 40.5-67.5). 1 pt (2%) had grade 3 RT related toxicity (thrombocytopenia). With a median follow up 21.8 mo among 28 survivors, the LC-2 was 94.8% (95% CI 84.5-99.1%). mOS was 49.9 mo (95% CI 17.8 months- upper limit not reached) and mPFS was 13.9 mo (95% CI 8.4-49.9). OS did not differ by CLIP score, PS, prior treatment, vascular thrombus, baseline AFP, size, or dose. Median AFP change from baseline to 3 mo post treatment was a 32.8% reduction. Median time to AFP nadir in pts with elevated baseline levels was 3.9 mo (0-30.5). % decrease in AFP from baseline to 6 mo post-treatment was significantly associated with lower hazard of death. (HR = 0.993, p = 0.016). Conclusions: High dose hypofractionated proton beam therapy demonstrated a high local control rate for HCC with favorable safety profiles, supporting the ongoing evaluation of radiation in HCC in phase III studies. AFP decrease from baseline to 6 months post-radiation is associated with improved overall survival. Clinical trial information: NCT00976898.
Vascular CXCR4 Expression Promotes Vessel Sprouting and Sensitivity to Sorafenib Treatment in Hepatocellular Carcinoma
Authors: Jing Xu, Jing Liang, Ya-Ming Meng, Jing Yan, Xing-Juan Yu, Chao-Qun Liu, Li Xu, Shi-Mei Zhuang, Limin Zheng
Journal: Clinical Cancer Research (2017)

Purpose: C-X-C chemokine receptor type 4 (CXCR4) is known to be involved in both developmental and adult angiogenesis; however, its role in tumor angiogenesis remains largely unknown. Here, the role of vascular CXCR4 in regulating vascular structure in hepatocellular carcinoma (HCC) was assessd, and the clinical value of CXCR4 was explored.Experimental Design: The expression of CXCR4 in HCC was determined by IHC and immunofluorescence. Characteristics of CXCR4+ cells were determined by in vitro and mice experiments. Kaplan-Meier survival analysis was used to determine the correlation of CXCR4 expression with prognosis.Results: We found that CXCR4 is selectively expressed on a fraction of tumor endothelial cells (TECs) in HCC tissues, but not on the hepatic endothelium in peritumoral area. High levels of CXCR4 on TECs tended to develop a sinusoidal vasculature in tumors and predicted poor prognosis for patients with HCC. CXCR4+ endothelial cells (EC) displayed the functional features of tip cells, with increased expression of tip cell-related markers. Functional studies revealed that CXCR4 could directly promote vessel sprouting in vitro and in vivo Interestingly, sorafenib treatment reduced the frequency of CXCR4+ ECs in culture and inhibited the formation of sinusoidal vasculature and growth of CXCR4High xenograft tumors. Moreover, high CXCR4 vascular density in resected tumor tissues before sorafenib treatment was associated with prolonged survival in patients with advanced HCC treated with sorafenib.Conclusions: These data revealed that CXCR4 is a novel HCC vascular marker for vessel sprouting and could serve as a potential therapeutic target and a predictive factor for sorafenib treatment in patients with HCC. Clin Cancer Res; 23(15); 4482-92. ©2017 AACR.
Survival update of a subset of previously treated patients with malignant pleural mesothelioma (MPM) in an expanded access program (eap) of pemetrexed (P) alone or combined with cisplatin (cis)
Authors: M. Orlando, T. F. Wozniak, P. A. Janne, C. P. Belani, M. L. Keohan, H. J. Ross, J. Polikoff, D. M. Mintzer, Z. Ye, C. K. Obasaju
Journal: Journal of Clinical Oncology (2005)

7173 Background: P plus cis demonstrated superiority versus cis alone for pts with MPM. Prior to the approval of the regimen there was an increased demand for patient access to P. To gather additional efficacy and safety data, an Eli Lilly and Company EAP was opened to allow access to all eligible pts. Methods: Pts were treated q 21 days with P 500mg/m2 alone or in combination with cis 75mg/m2 for a maximum of 6 cycles. Chemotherapy-naïve pts received the combination of P plus cis, while pre-treated pts received P alone. All pts received were supplemented with folic acid, vitamin B12, and received steroid prophylaxis. Serious adverse events (SAEs) were reported by investigators and compiled in a pharmacovigilance database for all pts enrolled in the EAP. Results: There were 1056 pts MM that received at least one dose of study drug at 462 sites in the United States. Of these pts, 187 were previously treated pts with MPM. Median age of this subset analysis was 65.9 years (range: 27- 87). The most commonly reported SAEs in the overall EAP regardless of causality were: dehydration (7.2%), nausea (5.2%), vomiting (4.9%), dyspnea (3.8%), and pulmonary embolism (2.4%). Conclusions: The toxicity observed for all pts enrolled in the EAP group is acceptable. The respective disease control rates are provocative in this poor prognostic patient population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Eli Lilly Eli Lilly Eli Lilly Eli Lilly
The Safety of Appropriate Use of Over-the-Counter Proton Pump Inhibitors: An Evidence-Based Review and Delphi Consensus
Authors: David A. Johnson, Philip O. Katz, David Armstrong, Henry Cohen, Brendan C. Delaney, Colin W. Howden, Peter Katelaris, Radu I. Tutuian, Donald O. Castell
Journal: Drugs (2017)

The availability of over-the-counter (OTC) proton pump inhibitors (PPIs) for the short-term (2 weeks) management of frequent heartburn (≥2 days/week) has increased markedly, yet evidence-based recommendations have not been developed. A panel of nine international experts in gastroesophageal reflux disease developed consensus statements regarding the risks and benefits of OTC PPIs using a modified Delphi process. Consensus (based on ≥80% approval) was reached through multiple rounds of remote voting and a final round of live voting. To identify relevant data, the available literature was searched and summarized. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system terminology was used to rate the quality of evidence and strength of recommendations; consensus was based on ≥2/3 agreement. After 4 rounds of review, consensus was achieved for 18 statements. Notably, the available data did not directly reflect OTC use, but instead, prescription use; therefore, extrapolations to the OTC setting were often necessary. This limitation is regrettable, but it justifies performing this exercise to provide evidence-based expert opinion on a widely used class of drugs. The panel determined that using OTC PPIs according to label instructions is unlikely to mask the symptoms of esophageal or gastric cancer or adversely impact the natural history of related precursor conditions. OTC PPIs are not expected to substantially affect micronutrient absorption or bone mineral density or cause community-acquired pneumonia, Clostridium difficile infection, or cardiovascular adverse events. However, OTC PPI use may be associated with slightly increased risks for infectious diarrhea, certain idiosyncratic reactions, and cirrhosis-related spontaneous bacterial peritonitis. The available evidence does not suggest that OTC PPI use consistent with label instructions is associated with substantial health risks. To minimize potential risks, healthcare professionals and consumers must actively participate in decision making when managing reflux-related symptoms in the self-care setting.
Survival outcomes of dose-escalated external beam radiotherapy (DE-EBRT) versus combined brachytherapy for intermediate- and high-risk prostate cancer using the National Cancer Data Base.
Authors: Arya Amini, Matthew Wayne Jackson, Norman Yeh, Timothy V Waxweiler, Bernard Jones, Paul Maroni, Brian D. Kavanagh, David Raben
Journal: Journal of Clinical Oncology (2016)

7 Background: The purpose was to evaluate survival outcomes between dose-escalated external beam radiotherapy (DE-EBRT) versus EBRT plus brachytherapy for intermediate- and high-risk prostate cancer, using the National Cancer Data Base (NCDB). Methods: Patients with cN0M0 prostate cancer treated from 2004-2006, with available data for radiation therapy dose were included. Radiation treatment comparison groups were the following: EBRT alone (75.6-81 Gy) and EBRT (40-50.4 Gy) plus brachytherapy, with EBRT delivered in 1.8-2.0 Gy per fraction. Eligible patients had known T-stage, prostate-specific antigen, Gleason score, and receipt of androgen deprivation therapy. Results: A total of 20,279 patients with intermediate (n = 12,617) and high-risk (n = 7,662) prostate cancer were included; 71.3% (n=14,452) received EBRT alone, 28.7% (n = 5,827) received EBRT plus brachytherapy. Median follow up was 82 months (range, 3-120 months) and median age was 70 years (36-90 years). By multivariate analysis, EBRT plus brachytherapy had a significantly improved survival benefit (hazard ratio [HR], 0.75; p &lt; 0.001) compared to EBRT alone (75.6-81 Gy); this significance remained consistent for both intermediate-risk (HR, 0.73; p &lt; 0.001) and high-risk (HR, 0.76; p &lt; 0.001) when analyzed separately. On subset analysis however, EBRT plus brachytherapy did not have a significant survival improvement (HR, 0.91; p = 0.083) when compared to very high dose EBRT alone (79.2-81 Gy) for all patients combined; this persisted for intermediate-risk (HR, 0.73; p = 0.062) and high-risk (HR, 0.93; p = 0.400) patients when analyzed separately. Conclusions: Patients receiving EBRT plus brachytherapy had improved survival compared to DE-EBRT alone (75.6-81 Gy) for intermediate- and high-risk prostate cancer. When comparing EBRT plus brachytherapy versus very high dose EBRT alone (79.2-81 Gy), this survival advantage disappeared. Given these findings, intermediate- and high-risk prostate cancer patients may benefit from EBRT plus brachytherapy compared with DE-EBRT alone; however, very high doses of EBRT may also be an equivalent option.
A comparison of outcomes for 3D conformal versus intensity modulated radiation therapy in postoperative gastric cancer.
Authors: Emory McTyre, Jessica Freilich, Michael Chuong, William J. Fulp, Khaldoun Almhanna, Kenneth Meredith, Sarah Hoffe, Ravi Shridhar
Journal: Journal of Clinical Oncology (2013)

139 Background: Postoperative radiation therapy (RT) for gastric cancer results in increased survival. Treatment planning studies have demonstrated improved target coverage and normal tissue sparing with intensity modulated RT (IMRT) versus 3D conformal radiotherapy (3DCRT). The purpose of this study was to compare outcomes of gastric cancer patients treated with IMRT vs 3DCRT. Methods: An IRB approved database was queried for all postoperative gastric cancer patients who received adjuvant chemoradiation with either 3DCRT or IMRT between 2000 and 2012. The primary endpoints were survival and toxicity. Overall (OS) and disease-free survival (DFS) were calculated with Kaplan-Meier analysis and multivariate analysis (MVA) was performed using a Cox proportional hazard ratio model. Results: We identified 39 patients (23 3DCRT, 16 IMRT). Median followup for all patients, 3DCRT patients, and IMRT patients was 16.2, 24.6, and 14.4 months, respectively. The only difference between groups noted was the presence of more positive lymph nodes (p=0.015) and higher N stage (0.012) in the 3DCRT group. There was no difference in OS or DFS on univariate or MVA. The median OS was 27.6 for the IMRT patients versus 27.4 months in the 3DCRT patients (p=0.63). In patients treated with IMRT we observed a nonsignificant decrease in grade ≥3 toxicity (25% vs. 39%; p = 0.50), any hospitalization (25% vs. 30%; p = 0.74), and median weight change (7% vs. 9%; p=0.62). On MVA for grade &gt;3 toxicity age, gender, stage, type of surgery, pre-operative chemotherapy, number of lymph nodes removed and radiation technique were all nonsignificant. The hazard ratio for radiation technique was 0.600 (95% CI 0.118-3.042; p value=0.537). Conclusions: Our data did not demonstrate differences in OS or DFS but did show a decrease in toxicity. Caution should be taken given small sample size and short follow up in IMRT patients. Comparative outcomes for these two techniques therefore warrant continued exploration.
Peripheral neuropathy (PN) in patients (pts) with metastatic breast cancer treated with eribulin: Resolution and association with efficacy.
Authors: Peter Kaufman, Martin Olivo, Yi He, Susan McCutcheon, Linda Vahdat
Journal: Journal of Clinical Oncology (2014)

147 Background: PN is a known adverse effect of various antimicrotubule agents, including eribulin. We report here the incidence and resolution of PN in breast cancer pts treated with eribulin in completed phase 2 and 3 studies, and the efficacy of eribulin in pts with PN in the phase 3 EMBRACE and 301 studies. Methods: In EMBRACE, women had received 2-5 lines of chemotherapy for advanced disease. In this ≥ 3rd-line setting, pts randomized to eribulin mesylate received it at 1.4 mg/m 2 iv, days 1 and 8 every 21 days. The dosing schedule was the same in study 301, which involved pts who had received 0-2 prior chemotherapies for advanced disease. Overall survival (OS) and progression-free survival (PFS) were analyzed by stratified log-rank test. Data from EMBRACE and 301 were pooled with data from 2 phase 2 studies to assess time to improvement (a decrease of ≥ 1 grade) and resolution (decrease in grade to 0, 1 or baseline) of grade 3 or 4 PN. Results: In the pooled safety analysis, 7.7% (116/1503) of pts treated with eribulin had grade 3 or 4 PN; 63.8% of these experienced improvement in PN and 50% had resolution. Median time to improvement was 2.1 weeks and to resolution was 7.7 weeks. Characteristics were similar in pts with or without PN in EMBRACE and 301. Those with PN had longer exposure to eribulin vs pts without PN (median exposure [months], study 301: 4.9 vs 3.2; EMBRACE: 4.8 vs 2.9). OS and PFS were significantly longer in pts with PN (Table). Conclusions: Pts who had a favourable therapeutic response to eribulin, received a longer course of treatment and thus had a greater risk of PN. Severity of PN improved in most pts within a short period. Regarding PN, the risk–benefit ratio for eribulin supports treatment. Clinical trial information: NCT00337103, NCT00388726. [Table: see text]
Prognostic effect of angiotensin-converting-enzyme inhibitors (ACEI) and diuretics in patients with pancreatic cancer.
Authors: Humaid Obaid Al-Shamsi, Akram Shalaby, Aneeqa Yousaf Dar, Manal Hassan, Robert A. Wolff, Donghui Li
Journal: Journal of Clinical Oncology (2016)

420 Background: Prior history of chronic medical conditions and medical treatment exposure has been significantly associated with the development and prognosis of different cancers. Population-based studies reported a reduced cancer-related mortality among patients with pancreatic cancer who were Statin or Metformin users as compared with non-users. We aimed to study the effect of antihypertensive medications on the survival outcome of pancreatic cancer. Methods: Under institutional ethical approval, medical records were reviewed and clinical characteristics at baseline (time of diagnosis) were retrieved. Blood pressure and antihypertensive medications use were documented including Angiotensin Converting Enzyme Inhibitor (ACEI), diuretics, Angiotensin Receptor Blockers (ARBs) and Beta-Blockers (BB). Hazard ratios (HRs) and 95% CIs were calculated by using Cox proportional hazard models with a backward stepwise selection procedure to identify independent prognostic factors for overall survival. Results: A total of 1,204 patients with adenocarcinoma of the pancreas were diagnosed at MD Anderson Cancer center between 1999 and 2009 were identified. The mean age value (± SD) is 61.9± 10 where 58.6% (N=705) were men and 87.5% (N=1,054) were white. The majority of patients were Caucasian (87%). 41.9% had metastatic disease. A total of 639 (53%) patients had chemotherapy with or without radiation. ACEI and diuretics use independently reduced all-cause mortality, ACEI by 24% with HR 0.76 (CI 0.63-0.91), and diuretics by 26% with HR 0.73 (CI 0.60- 0.89). Neither ARBs nor beta blockers use was statistically significant in reducing all-cause mortality (HR.80, CI 0.63 -1.0), BB HR 0.85 (CI 0.7-1.0). Conclusions: Our findings indicate a significant impact of anti-hypertensive medications including ACEI and diuretics on pancreatic cancer outcomes with improved survival in users versus non-users, this effect was independent of the cancer treatment received, tumour histology and site of metastasis. The potential antitumor activities of these agents in pancreatic cancer should be studied further.