bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lorazepam as an adjuvant to haloperidol for agitated delirium at the end of life: A double-blind randomized controlled trial.
Authors: Hui David , Frisbee-Hume Susan , Wilson Annie , Dibaj Seyedeh , Nguyen Thuc , De La Cruz Maxine Grace Jaucian , Walker Paul , Delgado-Guay Marvin , Vidal Marieberta , Zhukovsky Donna S. , Epner Daniel E. , Reddy Akhila Sunkepally , Tanco Kimberson , Williams Janet L. , Hall Stacy , Liu Diane D , Hess Kenneth R. , Amin Sapna R. , Breitbart William , Bruera Eduardo 
Published: September 2018

10003 Background: Agitated delirium is a highly distressing neuropsychiatric syndrome common in the last days of life. The use of benzodiazepines for agitated delirium is highly controversial. We compared the effect of lorazepam versus placebo as an adjuvant to haloperidol for persistent agitated delirium. Methods: In this double-blind trial, we randomly assigned patients with advanced cancer admitted to an acute palliative care unit with agitated delirium despite scheduled haloperidol to either lorazepam 3 mg IV or placebo, in addition to haloperidol 2 mg IV upon the onset of agitation. The primary outcome was the Richmond Agitation Sedation Scale (RASS) over the first 8 hours, ranging from -5 (unarousable) to +4 (combative). Secondary endpoints were rescue neuroleptic use, perceived comfort, delirium-related distress, adverse effects and overall survival. 26 patients per arm provided 80% power to detect a between arm difference of 0.5 effect size in mean RASS with a=5%. We used the Wilcoxon Rank Sum test for primary comparison. Results: 52 of 58 (90%) patients who received the medications completed 8 h of observation. RASS decreased significantly within 30 min of treatment in both arms (Table). The lorazepam arm was associated with significantly greater reduction of RASS (Table), less rescue neuroleptics (mean haloperidol equivalent dose 1 mg v. 3 mg, P=0.02), and greater comfort as perceived by blinded caregivers (84% v. 37%, P=0.007) and nurses (77% v. 30%, P=0.005) compared to placebo. We found no significant between-group differences in delirium-related distress, adverse effects and overall survival (median 68 v. 73 h, P=0.56). Conclusions: The combination of lorazepam/haloperidol resulted in rapid and significant reduction of agitation compared to haloperidol alone. Our study supports the judicious use of single dose lorazepam/haloperidol for persistent agitated delirium. Clinical trial information: NCT01670097. [Table: see text]
FDA analysis of enrollment of older adults in clinical trials for cancer drug registration: A 10-year experience by the U.S. Food and Drug Administration.
Authors: Singh Harpreet , Kanapuru Bindu , Smith Che , Fashoyin-Aje Lola A. , Myers Adrian , Kim Geoffrey , Pazdur Richard 
Published: September 2018

10009 Background: Older adults are a growing segment of our oncology population, with an expected increase in cancer incidence of 67% from 2010 to 2030 in people age 65 and older. However, older adults have been proportionally underrepresented in clinical trials. We sought to analyze the age-related enrollment of cancer patients onto trials supporting registration of new drugs or new indications approved by the US Food and Drug Administration from 2005 to 2015. Methods: This study involved retrospective analyses of demographic data of cancer patients enrolled onto trials supporting registration from 2005-2015. The data on 224,766 cancer patients supporting 105 drug applications were analyzed according to age distributions of <65, 65-69, 70-74, 75-79, and ≥80 years. The rates of enrollment were compared with the corresponding rates in the US cancer population. The age distributions of the US cancer population were derived from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute for the year 2013 based on the 2010 US Census. Conclusions: Older adults were under-represented in the registration trials of new cancer therapies, especially those over age 75. Various strategies may be needed to evaluate cancer therapies for older adults in prospective clinical trials and to improve cancer care in adults over age 75. These include re-evaluating what may be considered restrictive eligibility criteria so as not to exclude older adults. Incorporating elements from geriatric assessment tools may help identify older adults most likely to benefit from treatment. More detailed labeling information that reflects the clinical experience with older adults could be considered. The FDA encourages drug sponsors as well as clinical trial cooperative groups to devise strategies to recruit patients that are reflective of their intended population. [Table: see text]
Impact of hearing and visual impairment in older adults with cancer.
Authors: Soto Perez De Celis Enrique , Sun Can-Lan , Tew William P. , Mohile Supriya Gupta , Gajra Ajeet , Klepin Heidi D. , Owusu Cynthia , Gross Cary Philip , Muss Hyman B. , Lichtman Stuart M. , Chapman Andrew E. , Cohen Harvey Jay , Dale William , Kim Heeyoung , Katheria Vani , Hurria Arti 
Published: September 2018

10036 Background: Hearing and visual impairment increase the risk of psychological, functional, and cognitive deficits in older adults. However, little is known about their impact in older patients (pts) with cancer. Methods: This is a cross-sectional analysis of 2 prospective studies of pts ≥65 with cancer (Hurria et al. JCO 2011 & 2016) which identified risk factors for chemotherapy (CT) toxicity. Relationships between self-reported hearing/visual impairment (fair, poor or deaf/blind) and the need for assistance in instrumental activities of daily living (IADL, i.e. shopping), or activities of daily living (ADL, i.e. bathing); anxiety; depression and cognitive deficit (>11 on Blessed OMC test) were assessed (adjusted for age, sex, race, education, cancer type/stage, comorbidity, falls & medication). Results: Among 750 pts (median age 72, range 65-94) with solid tumors (28% lung, 27% GI, 30% breast/GYN; 58% stage IV), 28% (n = 213) reported 1 impairment (61% hearing, 39% visual) and 7% (n = 55) both. On multivariate analysis, impaired hearing was associated with IADL dependency, anxiety and depression. Visual impairment was associated with IADL dependency, ADL limitation and depression. Impairment in both was associated with IADL dependency, anxiety, depression and cognitive deficit. Conclusions: Older pts with cancer and hearing/visual impairment are at higher risk of functional, psychological and cognitive deficits. Interventions aimed at improving vision and hearing of older adults with cancer should be studied. [Table: see text]
Randomized trial of a smartphone mobile app for adherence to oral chemotherapy.
Authors: Greer Joseph , Jacobs Jamie M. , Pensak Nicole , Nisotel Lauren Ellen , Fishbein Joel , MacDonald James , Ream Molly , Fuh Charn-Xin , Buzaglo Joanne S , Muzikansky Alona , Lennes Inga Tolin , Safren Steven , Pirl William F. , Temel Jennifer S. 
Published: September 2018

10055 Background: As patients with cancer are increasingly prescribed oral chemotherapy, they share greater responsibility for ensuring adherence and monitoring side effects. The aim of this study was to test the effect of a smartphone mobile app to improve adherence and symptom management in patients prescribed oral chemotherapy. Methods: From 2/15 to 12/16, 181 patients with diverse cancers prescribed oral chemotherapy were randomized to receive either the smartphone mobile app or standard care. The mobile app included a medication treatment plan with alerts, symptom reporting module, education library, and cancer-specific resources. The primary outcome was adherence, measured by electronic pill cap (MEMS) and self-report (Morisky Medication Adherence Scale; MMAS). To assess symptoms, mood, and satisfaction with care, participants completed the MD Anderson Symptom Inventory, Hospital Anxiety & Depression Scale (HADS); and Functional Assessment of Chronic Illness Therapy-Treatment Satisfaction (FACIT-TS) at baseline and 12 weeks. General linear models were used to assess intervention effects on patient outcomes. Results: Study groups did not differ across outcome measures from baseline to week 12. Secondary analyses showed that baseline adherence (MMAS) and anxiety (HADS) were moderators of intervention effects on adherence and treatment satisfaction. Among patients who reported adherence problems, those assigned to the mobile app had better average MEMS adherence (Mean Diff = 19.30, 95% CI = 0.09-38.51, p = .05) and satisfaction with clinician explanations per the FACIT-TS (Mean Diff = 1.69, 95% CI = 0.25-3.13, p = .02) compared to standard care. Also, among patients with higher anxiety, those in the mobile app group reported better adherence on the 12-week MMAS (95.2% vs. 68.0%, OR = 0.11, 95% CI = 0.01, 0.94, p = .04) and satisfaction with interpersonal treatment per the FACIT-TS (Mean Diff = 0.76, 95% CI = 0.13-1.39, p = .02) compared to standard care. Conclusions: Although potentially not for everyone taking oral chemotherapy, a smartphone mobile app to improve adherence and treatment satisfaction may be useful for patients with certain risk factors, such as those struggling with adherence or anxiety. Clinical trial information: NCT02157519.
Final results of a phase 2 study of talazoparib (TALA) following platinum or multiple cytotoxic regimens in advanced breast cancer patients (pts) with germline BRCA1/2 mutations (ABRAZO).
Authors: Turner Nicholas C. , Telli Melinda L. , Rugo Hope S. , Mailliez Audrey , Ettl Johannes , Grischke Eva-Maria , Mina Lida A. , Balmana Gelpi Judith , Fasching Peter A. , Hurvitz Sara A. , Wardley Andrew M. , Chappey Colombe , Verret Wendy , Hannah Alison L. , Robson Mark E. 
Published: September 2018

1007 Background: TALA is a dual-mechanism PARP inhibitor that traps PARP on DNA. This study was designed to assess the activity of TALA in pts with g BRCA1/2mutation previously exposed to platinum or multiple prior cytotoxic regimens. Methods: ABRAZO (NCT02034916) is a 2-cohort, 2-stage phase 2 study of TALA (1 mg/d) following platinum-based therapy (Cohort 1 [C1]) or ≥ 3 platinum-free cytotoxic-based regimens (Cohort 2 [C2]) in pts with locally advanced or metastatic breast cancer (MBC) and g BRCA1/2mutation. Pts had ECOG PS ≤ 1 and measurable disease by RECIST v1.1. Five responses per cohort were required in ≤ 35 pts to progress to stage 2. The primary endpoint was confirmed ORR by independent radiology facility (IRF). Secondary endpoints: clinical benefit rate ≥ 24 weeks (CBR24), DOR, PFS, and OS. Results: From May 2014 to Feb 2016, 84 pts were enrolled (C1, n = 49; C2, n = 35). At data cutoff (1 Sep 2016), 9 pts continued on treatment. Both cohorts proceeded to stage 2 before enrollment closed. Median age was 50 (range, 31–75) years; 58% of pts had an ECOG PS of 0. TNBC/HR+ incidence in C1 and C2 was 59%/41% and 17%/83%, respectively. Median number of prior cytotoxic regimens administered for advanced disease was 2 in C1 and 4 in C2. ORR by IRF for BRCA1/BRCA2 was 24%/34%, and ORR by IRF for TNBC/HR+ was 26%/29%. Common all grade AEs: anemia (52%), fatigue (45%), nausea (42%), diarrhea (33%), thrombocytopenia (33%), and neutropenia (27%). Grade ≥ 3 AEs: anemia (35%), thrombocytopenia (19%), and neutropenia (15%). Nonhematological AEs grade ≥ 3 did not occur. AEs related to TALA led to drug discontinuation in 3 pts (4%); 4 AEs resulted in death, none related to TALA. Conclusions: TALA was well tolerated in MBC pts with a g BRCA1/2 mutation, exhibiting promising antitumor activity in C1 and C2. TALA vs physician’s choice of treatment in g BRCA1/2-mutated MBC is being evaluated in the phase 3 EMBRACA trial (NCT01945775). Clinical trial information: NCT02034916. [Table: see text]
The contribution of pre-existing cardiovascular (CV) risk factors to the risk of stroke or heart attack among non-Hodgkin lymphoma (NHL) survivors.
Authors: Salz Talya , Zabor Emily Craig , de Nully Brown Peter , Dalton Susanne Oksbjerg , Raghunathan Nirupa Jaya , Matasar Matthew J. , Steingart Richard , Hjalgrim Henrik , Svenssen Munksgaard Peter , Specht Lena , Vickers Andrew J. , Oeffinger Kevin C. , Johansen Christoffer 
Published: September 2018

10082 Background: Increased risk of myocardial infarction (MI) and cerebrovascular accident (CVA) among NHL survivors is commonly attributed to NHL treatment. The extent to which pre-existing CV risk factors also contribute to increased risk is unknown. We investigated this association among an entire national population of NHL survivors who have a full range of important CV risk factors. Methods: Using Danish population-based registries, we identified all adults diagnosed with primary aggressive NHL from 2000-2010 and followed them for MI and CVA from 9 months after diagnosis through 2012. MI and CVA diagnoses were ascertained from the nationwide Hospital Discharge Register and Cause of Death Register. CV risk factors (hypertension, dyslipidemia, and diabetes), vascular disease, and intrinsic heart disease prevalent at NHL diagnosis were ascertained algorithmically using the National Prescription Register and the Hospital Discharge Register. Cumulative anthracycline dose was coded continuously. Receipt of radiation was coded dichotomously for both chest and neck. Controlling for age, sex, treatment, and CV diseases, we used Cox multivariate regression to test the association between pre-existing CV risk factors and subsequent CVA or MI. Results: Among 2604 patients with NHL, median age was 62, and median follow-up time was 2.4 years. Overall, 131 patients were diagnosed with MI or CVA. Before NHL diagnosis, 40% of patients had at ≥1 CV risk factor, 13% had vascular disease, and 6% had intrinsic heart disease. 90% of the patients were treated with anthracyclines, 9% had received chest radiation, and 15% had received neck radiation. Patients with ≥1 CV risk factor had an increased risk of MI or CVA compared to patients with none (HR = 1.5 [95% CI = 1.1-2.2). Prevalent vascular disease, prevalent intrinsic heart disease, and NHL treatment were not associated with MI or CVA (p’s > 0.05). Conclusions: In a large, well-characterized, and nationally representative cohort of NHL survivors, prevalent CV risk factors were associated with later CVA and MI. To prevent MI and CVA among survivors, decisions about post-treatment monitoring should take into account prevalent CV risk.
Abemaciclib for the treatment of brain metastases (BM) secondary to hormone receptor positive (HR+), HER2 negative breast cancer.
Authors: Tolaney Sara M. , Lin Nancy U. , Thornton Donald , Klise Suzanne , Costigan Timothy Michael , Turner P. Kellie , Anders Carey K. 
Published: September 2018

1019 Background: Abemaciclib is an oral selective CDK4 and CDK6 inhibitor administered on a continuous dosing schedule, which has demonstrated clinical activity and an acceptable safety profile in patients (pts) with heavily pre-treated HR+ metastatic breast cancer (MBC). Abemaciclib has been shown preclinically to cross the blood-brain barrier, providing rationale for testing this agent in pts with BM. Furthermore, as previously presented, levels of abemaciclib similar to plasma were detected in resected BM in a subset of pts with HR+, HER2- MBC in this study. Methods: Study I3Y-MC-JPBO is an open-label, Phase 2, Simon 2-Stage trial evaluating the safety and efficacy of abemaciclib 200 mg BID in pts with new or progressive BM secondary to HR+ MBC, NSCLC, or melanoma. Eligible pts in Part B (the focus of this presentation) include pts with HR+, HER2- MBC who have ≥1 measurable brain lesion. The primary objective was objective intracranial (IC) response rate as defined by Response Assessment in Neuro-Oncology BM response criteria. Secondary objectives (IC related) include best overall response, duration of response, disease control rate, and clinical benefit rate. Exploratory objectives include assessment of drug concentrations in resected tumors. Safety, tolerability, and PK of abemaciclib were also assessed. Stage 1 includes 23 pts; if < 2 of the 23 pts respond to abemaciclib, futility is met. However, if ≥2 respond, 33 additional pts are to be enrolled to Stage 2. Results: This Stage 1 efficacy analysis included 23 pts; 32 pts were included in the safety analysis. Although 5 pts were considered nonevaluable, 2 pts (8.7%) had confirmed partial response (PR) (meeting the predefined threshold for advancement to Stage 2); enrollment is ongoing. At the time of the analysis, the 2 pts with PR had completed 14 and 15 cycles each (21d cycles) of therapy. The majority of adverse events were gastrointestinal in nature, consistent with previous studies of abemaciclib. Conclusions: This study has provided preliminary evidence that abemaciclib penetrated BM in pts with HR+, HER2- MBC and had antitumor activity in this population. Final results will be presented following Stage 2 analyses. Clinical trial information: NCT02308020.
Health-related quality of life from a phase 3 randomized trial of fulvestrant 500 mg vs anastrozole for hormone receptor-positive advanced breast cancer (FALCON).
Authors: Robertson John Forsyth Russell , Cheung Kwok-Leung , Noguchi Shinzaburo , Shao Zhimin , Degboe Arnold , Lichfield Jasmine , Thirlwell Jackie , Fazal Mehdi , Ellis Matthew J 
Published: September 2018

1048 Background: The Phase 3 randomized FALCON trial (NCT01602380) demonstrated improved progression-free survival with fulvestrant 500 mg (F) vs anastrozole 1 mg (A) in postmenopausal women with hormone receptor-positive (HR+) locally advanced or metastatic breast cancer (BC) without prior endocrine therapy (hazard ratio [HR] 0.797, 95% confidence interval [CI] 0.637-0.999; p = 0.0486; Robertson et al. Lancet 2016). Overall health-related quality of life (HRQoL) was maintained and similar for F and A. There was no evidence of a detriment with F vs A in time to deterioration for both Trial Outcome Index (TOI; HR 0.90, 95% CI 0.70-1.15; p = 0.4008) and Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B) total score (HR 0.84, 95% CI 0.66-1.07; p = 0.1594). We present additional analyses of patient (pt)-reported HRQoL outcomes from FALCON. Methods: Women with HR+ BC were randomized 1:1 to F (Days 0, 14, 28, then every 28 days) or A (daily) until disease progression or discontinuation. HRQoL was assessed by FACT-B questionnaire (TOI [summary of physical and functional well-being and breast cancer subscale scores] and FACT-B total score) at randomization and every 12 weeks during treatment. HRQoL data post-treatment (with or without progression) were also collected. Results: 462 pts were randomized (F, n = 230; A, n = 232). Compliance to FACT-B during treatment ranged from 84.6-100.0%. Mean change from baseline in TOI (scale range 0-92) and FACT-B total score (scale range 0-144) remained broadly stable (approximately ±3 points to Week 132) and similar between arms during treatment. HRQoL was also maintained in FACT-B subscales. Approximately one third of pts had improved TOI (≥ +6 points) and FACT-B (≥ +8 points) total scores from baseline up to Week 144 of treatment with F (ranges 26.4-45.0%, and 20.0-35.8%, respectively) and A (ranges 18.6-32.9%, and 22.7-37.9%, respectively). Conclusions: Compliance to the FACT-B questionnaire on treatment with F and A for HR+ BC in the FALCON trial was good; mean change from baseline in TOI and FACT-B total score was maintained, and similar proportions of pts had improved TOI and FACT-B total score in both arms. Clinical trial information: NCT01602380.
Effect of chimeric antigen receptor-modified T (CAR-T) cells on responses in children with non-CNS extramedullary relapse of CD19+ acute lymphoblastic leukemia (ALL).
Authors: Talekar Mala Kiran , Maude Shannon L. , Hucks George E , Motley Laura S , Callahan Colleen , White Claire M , Baniewicz Diane , Barrett David Maxwell , Rheingold Susan R. , Lacey Simon F. , Levine Bruce L , Melenhorst Jan J. , Teachey David T. , June Carl H. , Grupp Stephan A. 
Published: September 2018

10507 Background: Anti-CD19 CAR-T cell therapies have shown high efficacy in inducing durable marrow responses in patients with relapsed/refractory CD19+ ALL. We now report on outcome of 10 patients with extramedullary (EM) involvement of ALL treated with CAR-T, including 5 patients who had EM disease at time of infusion. Methods: We identified patients treated on pediatric phase 1/2a trials of murine (CTL019) or humanized (CTL119) anti-CD19 CAR-T cells for isolated EM or BM/EM relapse of ALL. EM relapse was defined as involvement of non-CNS site by imaging +/- pathology within 12 months (mos) of infusion. Post infusion, patients had diagnostic imaging done at 1, 3, 6, 9, and 12 mos. Results: Among 97 patients receiving CAR-T, ten (CTL019, n=6; CTL119, n=4) were identified who had EM involvement on average 2.3 mos (range 0-9 mos) prior to infusion; including 5/10 at time of infusion. Sites of EM relapses included testes, sinus, parotid, bone, uterus, kidney and skin, and 5 patients had multiple sites of EM involvement. Patients ranged from 2-4 relapses of their ALL pre-CAR-T. Two had isolated EM relapse (sites were parotid and multifocal bony lesions in one; testis and sinus in second). All 10 patients had undergone hematopoietic stem cell transplantation prior to EM relapse, 2 had received radiation directed to the EM site prior to CAR-T. Five patients evaluated by serial imaging had objective responses: 2 had resolution of EM disease by day 28; 2 had resolution by 3 mos; 1 had continued decrease in size of uterine mass at 3 and 6 mos and underwent hysterectomy at 8 mos with no evidence of disease on pathology. In the 4 patients with prior history of skin or testicular involvement, there was no evidence by exam at day 28. One patient had progressive EM disease within 2 weeks of CAR-T cell infusion and died at 6 weeks. Three relapsed with CD19+ disease [1 skin/medullary- died at 38 mos post CAR-T; 2 medullary (1 died at 17 mos, 1 alive at 28 mos)]. The remaining 6 are alive and well at median follow-up of 10 mos (range 3-16 mos) without recurrence of disease. Conclusions: Single agent CAR-T immunotherapy can induce potent and durable responses in patients with EM relapse of their ALL. Clinical trial information: NCT01626495, NCT02374333.