bluuebunny/crossref_metadata_2025_split huggingface dataset:
Telotristat Ethyl, a Tryptophan Hydroxylase Inhibitor for the Treatment of Carcinoid Syndrome
Authors: Kulke Matthew H. , Hörsch Dieter , Caplin Martyn E. , Anthony Lowell B. , Bergsland Emily , Öberg Kjell , Welin Staffan , Warner Richard R.P. , Lombard-Bohas Catherine , Kunz Pamela L. , Grande Enrique , Valle Juan W. , Fleming Douglas , Lapuerta Pablo , Banks Phillip , Jackson Shanna , Zambrowicz Brian , Sands Arthur T. , Pavel Marianne 
Published: February 2017

Purpose Preliminary studies suggested that telotristat ethyl, a tryptophan hydroxylase inhibitor, reduces bowel movement (BM) frequency in patients with carcinoid syndrome. This placebo-controlled phase III study evaluated telotristat ethyl in this setting. Patients and Methods Patients (N = 135) experiencing four or more BMs per day despite stable-dose somatostatin analog therapy received (1:1:1) placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg three times per day orally during a 12-week double-blind treatment period. The primary end point was change from baseline in BM frequency. In an open-label extension, 115 patients subsequently received telotristat ethyl 500 mg. Results Estimated differences in BM frequency per day versus placebo averaged over 12 weeks were –0.81 for telotristat ethyl 250 mg ( P < .001) and ‒0.69 for telotristat ethyl 500 mg ( P < .001). At week 12, mean BM frequency reductions per day for placebo, telotristat ethyl 250 mg, and telotristat ethyl 500 mg were –0.9, –1.7, and –2.1, respectively. Responses, predefined as a BM frequency reduction ≥ 30% from baseline for ≥ 50% of the double-blind treatment period, were observed in 20%, 44%, and 42% of patients given placebo, telotristat ethyl 250 mg, and telotristat ethyl 500 mg, respectively. Both telotristat ethyl dosages significantly reduced mean urinary 5-hydroxyindole acetic acid versus placebo at week 12 ( P < .001). Mild nausea and asymptomatic increases in gamma-glutamyl transferase were observed in some patients receiving telotristat ethyl. Follow-up of patients during the open-label extension revealed no new safety signals and suggested sustained BM responses to treatment. Conclusion Among patients with carcinoid syndrome not adequately controlled by somatostatin analogs, treatment with telotristat ethyl was generally safe and well tolerated and resulted in significant reductions in BM frequency and urinary 5-hydroxyindole acetic acid.
Italian, Multicenter, Phase III, Randomized Study of Cisplatin Plus Etoposide With or Without Bevacizumab as First-Line Treatment in Extensive-Disease Small-Cell Lung Cancer: The GOIRC-AIFA FARM6PMFJM Trial
Authors: Tiseo Marcello , Boni Luca , Ambrosio Francesca , Camerini Andrea , Baldini Editta , Cinieri Saverio , Brighenti Matteo , Zanelli Francesca , Defraia Efisio , Chiari Rita , Dazzi Claudio , Tibaldi Carmelo , Turolla Gianni Michele , D’Alessandro Vito , Zilembo Nicoletta , Trolese Anna Rita , Grossi Francesco , Riccardi Ferdinando , Ardizzoni Andrea 
Published: February 2017

Purpose Considering promising results in phase II studies, a randomized phase III trial was designed to assess the efficacy of adding bevacizumab to first-line cisplatin plus etoposide for treatment of extensive-disease (ED) small-cell lung cancer (SCLC). Patients and Methods Treatment-naive patients with ED-SCLC were randomly assigned to receive either cisplatin plus etoposide (arm A) or the same regimen with bevacizumab (arm B) for a maximum of six courses. In the absence of progression, patients in arm B continued bevacizumab alone until disease progression or for a maximum of 18 courses. The primary end point was overall survival (OS). Results Two hundred four patients were randomly assigned and considered in intent-to-treat analyses (103 patients in arm A and 101 patients in arm B). At a median follow-up of 34.9 months in arm A and arm B, median OS times were 8.9 and 9.8 months, and 1-year survival rates were 25% and 37% (hazard ratio, 0.78; 95% CI, 0.58 to 1.06; P = .113), respectively. A statistically significant effect of bevacizumab on OS in patients who received maintenance was seen (hazard ratio, 0.60; 95% CI, 0.40 to 0.91; P = .011). Median progression-free survival times were 5.7 and 6.7 months in arm A and arm B, respectively ( P = .030). Regarding hematologic toxicity, no statistically significant differences were observed; for nonhematologic toxicity, only hypertension was more frequent in arm B (grade 3 or 4, 1.0% v 6.3% in arms A v B, respectively; P = .057). Conclusion The addition of bevacizumab to cisplatin and etoposide in the first-line treatment of ED-SCLC had an acceptable toxicity profile and led to a statistically significant improvement in progression-free survival, which, however, did not translate into a statistically significant increase in OS. Further research with novel antiangiogenic agents, particularly in the maintenance setting, is warranted.
Androgen Deprivation Therapy and the Risk of Dementia in Patients With Prostate Cancer
Authors: Khosrow-Khavar Farzin , Rej Soham , Yin Hui , Aprikian Armen , Azoulay Laurent 
Published: February 2017

Purpose Recent observational studies have associated the use of androgen deprivation therapy (ADT) with an increased risk of dementia and Alzheimer’s disease, but these studies had limitations. The objective of this study was to determine whether the use of ADT is associated with an increased risk of dementia, including Alzheimer’s disease, in patients with prostate cancer. Patients and Methods Using the United Kingdom’s Clinical Practice Research Datalink, we assembled a cohort of 30,903 men newly diagnosed with nonmetastatic prostate cancer between April 1, 1988 and April 30, 2015, and observed them until April 30, 2016. Time-dependent Cox proportional hazards models were used to estimate adjusted hazard ratios with 95% CIs of dementia associated with the use of ADT compared with nonuse. ADT exposure was lagged by 1 year to account for delays associated with the diagnosis of dementia and to minimize reverse causality. Secondary analyses assessed whether the risk varied with cumulative duration of use and by ADT type. Results During a mean (standard deviation) follow-up of 4.3 (3.6) years, 799 patients were newly diagnosed with dementia (incidence, 6.0; 95% CI, 5.6 to 6.4) per 1,000 person-years. Compared with nonuse, ADT use was not associated with an increased risk of dementia (incidence, 7.4 v 4.4 per 1,000 person-years, respectively; adjusted hazard ratio, 1.02; 95% CI, 0.87 to 1.19). In secondary analyses, cumulative duration of use ( P for heterogeneity = .78) and no single type of ADT were associated with an increased risk of dementia. Conclusion In this population-based study, the use of ADT was not associated with an increased risk of dementia. Additional studies in different settings are needed to confirm these findings.
Impact of a Panel of 88 Single Nucleotide Polymorphisms on the Risk of Breast Cancer in High-Risk Women: Results From Two Randomized Tamoxifen Prevention Trials
Authors: Cuzick Jack , Brentnall Adam R. , Segal Corrinne , Byers Helen , Reuter Caroline , Detre Simone , Lopez-Knowles Elena , Sestak Ivana , Howell Anthony , Powles Trevor J. , Newman William G. , Dowsett Mitchell 
Published: February 2017

Purpose At least 94 common single nucleotide polymorphisms (SNPs) are associated with breast cancer. The extent to which an SNP panel can refine risk in women who receive preventive therapy has not been directly assessed previously. Materials and Methods A risk score on the basis of 88 SNPs (SNP88) was investigated in a nested case-control study of women enrolled in the International Breast Intervention Study (IBIS-I) or the Royal Marsden study. A total of 359 women who developed cancer were matched to 636 controls by age, trial, follow-up time, and treatment arm. Genotyping was done using the OncoArray. Conditional logistic regression and matched concordance indices (mC) were used to measure the performance of SNP88 alone and with other breast cancer risk factors assessed using the Tyrer-Cuzick (TC) model. Results SNP88 was predictive of breast cancer risk overall (interquartile range odds ratio [IQ-OR], 1.37; 95% CI, 1.14 to 1.66; mC, 0.55), but mainly for estrogen receptor–positive disease (IQ-OR, 1.44; 95% CI, 1.16 to 1.79; P for heterogeneity = .10) versus estrogen receptor–negative disease. However, the observed risk of SNP88 was only 46% (95% CI, 19% to 74%) of expected. No significant interaction was observed with treatment arm (placebo IQ-OR, 1.46; 95% CI, 1.13 to 1.87; tamoxifen IQ-OR, 1.25; 95% CI, 0.96 to 1.64; P for heterogeneity = .5). The predictive power was similar to the TC model (IQ-OR, 1.45; 95% CI, 1.21 to 1.73; mC, 0.55), but SNP88 was independent of TC (Spearman rank-order correlation, 0.012; P = .7), and when combined multiplicatively, a substantial improvement was seen (IQ-OR, 1.64; 95% CI, 1.36 to 1.97; mC, 0.60). Conclusion A polygenic risk score may be used to refine risk from the TC or similar models in women who are at an elevated risk of breast cancer and considering preventive therapy. Recalibration may be necessary for accurate risk assessment.
Cholesterol, Cholesterol-Lowering Medication Use, and Breast Cancer Outcome in the BIG 1-98 Study
Authors: Borgquist Signe , Giobbie-Hurder Anita , Ahern Thomas P. , Garber Judy E. , Colleoni Marco , Láng István , Debled Marc , Ejlertsen Bent , von Moos Roger , Smith Ian , Coates Alan S. , Goldhirsch Aron , Rabaglio Manuela , Price Karen N. , Gelber Richard D. , Regan Meredith M. , Thürlimann Beat 
Published: February 2017

Purpose Cholesterol-lowering medication (CLM) has been reported to have a role in preventing breast cancer recurrence. CLM may attenuate signaling through the estrogen receptor by reducing levels of the estrogenic cholesterol metabolite 27-hydroxycholesterol. The impact of endocrine treatment on cholesterol levels and hypercholesterolemia per se may counteract the intended effect of aromatase inhibitors. Patients and Methods The Breast International Group (BIG) conducted a randomized, phase III, double-blind trial, BIG 1-98, which enrolled 8,010 postmenopausal women with early-stage, hormone receptor–positive invasive breast cancer from 1998 to 2003. Systemic levels of total cholesterol and use of CLM were measured at study entry and every 6 months up to 5.5 years. Cumulative incidence functions were used to describe the initiation of CLM in the presence of competing risks. Marginal structural Cox proportional hazards modeling investigated the relationships between initiation of CLM during endocrine therapy and outcome. Three time-to-event end points were considered: disease-free-survival, breast cancer–free interval, and distant recurrence–free interval. Results Cholesterol levels were reduced during tamoxifen therapy. Of 789 patients who initiated CLM during endocrine therapy, the majority came from the letrozole monotherapy arm (n = 318), followed by sequential tamoxifen-letrozole (n = 189), letrozole-tamoxifen (n = 176), and tamoxifen monotherapy (n = 106). Initiation of CLM during endocrine therapy was related to improved disease-free-survival (hazard ratio [HR], 0.79; 95% CI, 0.66 to 0.95; P = .01), breast cancer–free interval (HR, 0.76; 95% CI, 0.60 to 0.97; P = .02), and distant recurrence–free interval (HR, 0.74; 95% CI, 0.56 to 0.97; P = .03). Conclusion Cholesterol-lowering medication during adjuvant endocrine therapy may have a role in preventing breast cancer recurrence in hormone receptor–positive early-stage breast cancer. We recommend that these observational results be addressed in prospective randomized trials.
Global Use of Traditional and Complementary Medicine in Childhood Cancer: A Systematic Review
Authors: Diorio Caroline , Lam Catherine G. , Ladas Elena J. , Njuguna Festus , Afungchwi Glenn M. , Taromina Katherine , Marjerrison Stacey 
Published: February 2017

PurposeTraditional and complementary medicine (T&CM) strategies are commonly used in pediatric oncology. Patterns may vary based on country income. We systematically reviewed published studies describing T&CM use among pediatric oncology patients in low-income countries (LIC/LMIC), middle-income countries (UMIC), and high-income countries (HIC). Objectives included describing estimated prevalence of use, reasons for use, perceived effectiveness, modalities used, rates of disclosure, and reporting of delayed or abandoned treatment.MethodsMEDLINE, EMBASE, Global Health, CINAHL, PsycINFO, Allied and Complementary Medicine Database, Cochrane Database of Systematic Reviews, and ProceedingsFirst were searched. Inclusion criteria were primary studies involving children younger than the age of 18 years, undergoing active treatment of cancer, and any T&CM use. Exclusion criteria included no pediatric oncology–specific outcomes and studies involving only children off active treatment. Data were extracted by two reviewers using a systematic data extraction form determined a priori.ResultsSixty-five studies published between 1977 and 2015 were included, representing 61 unique data sets and 7,219 children from 34 countries. The prevalence of T&CM use ranged from 6% to 100%. Median rates of use were significantly different in LIC/LMIC (66.7% ± 19%), UMIC (60% ± 26%), and HIC (47.2% ± 20%; P = .02). Rates of disclosure differed significantly by country income, with higher median rates in HIC. Seven studies reported on treatment abandonment or delays.ConclusionThe use of T&CM in pediatric oncology is common worldwide, with higher median prevalence of use reported in LIC/LMIC. Further research is warranted to examine the impact on treatment abandonment and delay.
Potential Obstacles in the Acquisition of Oral Anticancer Medications
Authors: Niccolai Jennifer L. , Roman Danielle L. , Julius Justin M. , Nadour Rachelle W. 
Published: February 2017

Purpose: To determine the amount of time elapsed between prescriber order and patient receiving oral anticancer medication. Patients and Methods: Adult patients with a diagnosis of cancer were prospectively identified in three outpatient oncology clinics when oral anticancer agents were prescribed during a 4-month observation period. For each patient, time to obtain medication was analyzed by the following time points: date of prescription, date of submission to insurance, date prior authorization was obtained, date financial assistance was received, date prescription was processed by pharmacy, and date patient received medication. Out-of-pocket cost and time spent by clinic staff to facilitate the medication acquisition process were recorded. Results: Thirty-four patients were prescribed oral anticancer medication during the data collection period. For the 27 patients who were eligible for the primary end point, medication acquisition required a median of 10 days (range, 3 to 28 days). Overall, the rate-limiting step for medication acquisition was processing by the pharmacy, with a median of 6 days (range, 1 to 27 days). Most patients’ prescription insurance plan covered a portion of medication cost, and the majority of patients considered their out-of-pocket expense to be affordable. Clinic staff spent a median of 2 hours per prescription to facilitate medication acquisition. Conclusion: Patients may encounter process barriers in acquiring oral therapy, particularly because of pharmacy processing time, as well as high copays. Time to treatment initiation may have implications for patients’ clinical outcomes. Adequate staff with dedicated time to facilitate this process should be used in the ambulatory oncology practice setting.
Drug Interaction Database Sensitivity With Oral Antineoplastics: An Exploratory Analysis
Authors: Bossaer John B. , Thomas Christan M. 
Published: February 2017

Purpose: Drug interactions are a concern in oncology with the shift toward oral antineoplastics (OAs). Using electronic databases to screen for drug interactions with OAs is a common practice. There is little literature to guide clinicians on the reliability of these systems with OAs. The primary objective of this study was to explore the sensitivity of commonly available drug interaction databases in detecting drug interactions with OAs. Methods: A list of 20 drug interactions with OAs was developed by two Board-certified oncology pharmacists. The list included multiple types of drug interactions. The sensitivity in detecting these interactions by MicroMedex, Facts & Comparisons, Lexi-Interact, and Epocrates were evaluated. These databases were chosen based on their local availability and widespread use in practice. Drugs.com was evaluated as a surrogate for a patient-accessible drug interaction database. The Cochran Q test was used to assess the sensitivity distribution across the five groups. Results: Lexi-Interact and Drugs.com had a sensitivity of 95% for the 20 tested drug interaction pairs. Epocrates had a sensitivity of 90%, and both Micromedex and Facts & Comparisons had a sensitivity of 70%. There was a statistically significant difference ( P = .016) in the distribution across the databases in detecting clinically significant drug interactions. Conclusion: Commonly used databases for identifying drug interactions with oral antineoplastics vary significantly in their sensitivity. Clinicians should not rely on a single database and should consider using multiple resources as well as sound clinical judgment. Further work is needed in this area.
Patient Perspectives on the Ethical Implementation of a Rapid Learning System for Oncology Care
Authors: Jones Rochelle D. , Sabolch Aaron N. , Aakhus Erin , Spence Rebecca A. , Bradbury Angela R. , Jagsi Reshma 
Published: February 2017

Introduction: A rapid learning system (RLS) of health care harnesses data generated from routine patient care to create a virtuous cycle of data collection and analysis for quality improvement and research. The success of such systems depends on understanding patient perspectives regarding the ethical issues that arise from the ongoing implementation of this transformative concept. Methods: An interview guide was designed to evaluate patient perspectives to inform the ethical implementation of an oncology RLS. A purposively selected, diverse sample of 32 patients with cancer was recruited from two institutions to participate in semistructured, in-depth interviews for formal qualitative analysis. Results: The extent to which respondents expressed discomfort with more permissive system features (less formal notification/consent, broader uses/users, inclusion of sensitive data) reflected their trust, which in turn seemed to vary by sociodemographic features. It was also influenced by their familiarity with technology and their attitudes and beliefs regarding privacy and the use of electronic medical records more generally. Distrust of insurers and the pharmaceutical industry led subjects to desire greater oversight and restriction of these potential users of the system. Subjects were most comfortable when doctors were the primary users, engaged patients directly in the notification and consent discussion, and oversaw the system. Conclusion: Those actively developing RLSs should recognize the critical importance of trust and the key role that doctors will need to play in order for such systems to be successful and to ensure that their implementation is ethically palatable to the patients whose data are being included.
Qualitative Study of Oncologists’ Views on the CancerLinQ Rapid Learning System
Authors: Mayo Rachel M. , Summey Julie F. , Williams Joel E. , Spence Rebecca A. , Kim Shally , Jagsi Reshma 
Published: February 2017

Introduction: ASCO is actively developing CancerLinQ (CLQ), a rapid learning system for oncology care. The purpose of this study was to explore providers’ opinions and concerns related to implementation of CLQ, including ethical issues. Methods: Twenty key informant oncologists were recruited for individual in-depth interviews through ASCO contacts, purposively selected to represent a wide variety of cancer specialties as well as different levels of familiarity with CLQ (familiar v unfamiliar). Qualitative data analysis was completed by a three-member team using an inductive narrative approach. Themes were examined by participants familiar and unfamiliar with CLQ, and quotations exemplifying each theme are provided. Results: Participants’ opinions centered on three main themes: (1) general attitudes regarding learning health care systems, (2) optimal approach to patient consent, and (3) appropriateness of data use. There was clear support for the use of big data in clinical decision making for patients and in research. Unfamiliar participants expressed concerns regarding system protections against patient identification, and both familiar and unfamiliar participants discussed the dilemma of including genetic information. Respondents were in agreement with notifying patients early; however, there was debate over whether patients should opt in or opt out. Overall, there was great concern regarding sharing data with drug companies and insurers. Conclusion: Understanding oncologists’ perspectives regarding the ethical implications of CLQ implementation is critical to its success. More research is needed on the impact of rapid learning systems on providers, patients, health systems, and the ultimate effect on cancer care.
Transparency of Industry-Sponsored Oncology Patient Financial Assistance Programs Using a Patient-Centered Approach
Authors: Zafar S. Yousuf , Peppercorn Jeffrey , Asabere Akwasi , Bastian Alex 
Published: February 2017

Objective: Pharmaceutical manufacturers sponsor drug-specific patient assistance programs that provide eligible patients with financial assistance, either in the form of providing the drug free of charge or copayment assistance. Describing these programs and determining who receives assistance is an important first step in understanding the impact and role of financial assistance in cancer care. Our objective was to describe eligibility criteria and benefits for cancer-specific, manufacturer-sponsored patient assistance programs. Methods: We conducted a prospective review of patient assistance program Web sites and called patient assistance program telephone hotlines from the perspective of a patient or caregiver requesting program details. Results: We identified 24 manufacturers with patient assistance programs, covering 87% of Food and Drug Administration–approved oncology drugs. For free drug programs, the average maximum annual income for qualification was $86,279. For copayment assistance programs, the average was $104,790. Thirty-five percent of free drug programs and 53% of copayment assistance programs declined to provide details on how financial need was determined. None of the programs shared details on patient usage statistics. Conclusion: Variation exists in the quality and quantity of data available to patients seeking financial assistance for cancer treatment via manufacturer Web sites and hotlines. Greater transparency among patient assistance programs would enhance utility for patients and help to determine the net impact on costs and adherence.