bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of procedures to address health and safety issues in the administration of gene therapy within the clinical setting
Authors: Stoner Nicola S , Gibson Rachel N , Edwards Jeanette 
Published: May 2003

Background. The Cancer Research UK Medical Oncology Unit is a clinical research unit with a 16- bed inpatient facility. Clinical research pharmacists are integral members of the multidisciplinary team. In the last three years, six gene therapy clinical trials have been undertaken, requiring containment level one facilities. The vectors used for gene transfer in these studies included inactivated retrovirus, adenovirus, herpes simplex virus and vaccinia. Purpose. The aim of this paper is to highlight the procedures used throughout the clinical trial process, including storage, handling and disposal of the vectors, to minimize the health and safety risk to staff, patients and the environment. Findings. Little researched evidence is available on the clinical implications of gene therapy, especially with regard to health and safety. Published literature and protocol guidelines were reviewed. Visits were made to other sites administering gene therapy, and national and international symposia were attended. Standard operating procedures for handling containment level one gene therapy vectors were produced to ensure safe practice. These are in accordance with current UK Health and Safety Executive guidelines. Conclusions. The future treatment of the patient with cancer will conceivably involve genetic modification. There is, therefore, an urgent need for further research into the safety of these therapies to patients, clinicians, the general public and the environment. This is a new and exciting area for practice research.
External contamination of vials containing cytotoxic agents supplied by pharmaceutical manufacturers
Authors: Favier Bertrand , Gilles Laurence , Ardiet Claude , Latour Jean François 
Published: May 2003

Objectives. The aim of this report was to study the external contamination of vials of 5-fluorour-acil, cyclophosphamide, ifosfamide, etoposide, doxorubicin and docetaxel. It also investigated the possible contamination of 5-fluorouracil outer packaging. Methods. External contamination was measured on vials containing 5-fluorouracil, etoposide, cyclophosphamide, ifosfamide, doxorubicin and docetaxel. Samples from the outer wall of the vials were obtained by immersing and rotating the stoppered vials for 30 seconds in water for injections. Results. All vials tested were contaminated with quantities varying from 0.5 ng to 2.4 g per vial, depending on the supplier. The outer packaging containing 25 vials of 5-fluorouracil was contaminated with 1.5 g, but no contamination was detected on the plastic packaging of etoposide. Conclusion. These results demonstrate that the environment of operators may be contaminated, even in the absence of any handling error, and that contamination is present even before the cytotoxic reconstitution has begun. This source of exposure to cytotoxics may account for the contamination detected in the urine of operators. We demonstrate the necessity of protecting effectively all skin surfaces that are likely to come into contact with antineoplastic agents when unpacking the vials. Wearing long disposable gloves with adequate thickness (such as surgical gloves) is strongly recommended, from the very moment operators enter the preparation room. In general, the contamination of operators can only be controlled efficiently when all possible sources of contamination are considered, and suitable protection facilities are used (safety cabinet or isolator).
A review of imatinib mesilate in the treatment of patients with gastrointestinal stromal tumours and chronic myeloid leukaemia
Authors: Hole Alison , Blake Denise 
Published: May 2003

Context. Imatinib mesylate (GlivecÒ, GleevecÒ, Novartis) has made a dramatic impact on the treatment available for both chronic myeloid leukaemia (CML) and gastrointestinal stromal tumours (GISTs). Both are rare diseases that have possibly been unfamiliar to many pharmacists until now. Objective. To provide readers with a structured overview of CML and GISTs and the trial data available to support the role imatinib is playing in the treatment of these diseases. Data sources. Published reviews and primary trial results were sourced via Medline to prepare the review. Articles published up to and including August 2002 were considered. Additionally, pertinent books were used to prepare the text and Novartis kindly supplied information currently only available on file at the company. As imatinib has only been available for a short time, all types and sizes of trials were considered for inclusion. The authors made the final decision as to the relevance and therefore subsequent inclusion of data. Conclusions. Imatinib is a new molecularly targeted therapy for the treatment of CML and GISTs. It has provided an efficacious alternative therapy choice for physicians managing the care of patients suffering from these diseases. In the future there is the possibility that imatinib may demonstrate activity in other disease states characterized by the genetic changes targeted by imatinib. The results of randomized controlled trials in new and existing indications are awaited.
Implementation of a telephone callback service for ambulatory oncology patients
Authors: Dobish Roxanne B , Tulloch Karen J , Chambers Carole R 
Published: May 2003

Introduction. A pilot project was established at the Cross Cancer Institute pharmacy to assess the feasibility of implementing a patient callback program to determine which patients would benefit from a callback and the impact a callback service would have on the workload of the pharmacy department. Program description/development/implementation/evaluation. A pharmacy student conducted the pilot project over a 14-week time period. Four categories of patients were selected for inclusion in the pilot. The student approached patients at the time of medication pick-up to receive verbal permission to be included in the callback program. A standardized callback form was utilized to record medication information and any recommendations made. Data were collected on the numbers of patients in each category with questions or concerns as this was felt to be indicative of patients who would most benefit from a callback. The total time spent making the telephone calls was recorded. Over the eight-week period, 530.5 minutes were spent making the telephone calls with the average length of call being 3.27 minutes. Discussion/conclusion. The student researcher proposed that three patient groups would benefit from receiving a callback: new patients or patients on new medications; elderly patients; and patients with specific disease-drug combinations. The project also provided an estimate of pharmacist time required to implement such a service and it was concluded that implementation could occur with minimal disruption to workflow.
Next-day chemotherapy scheduling: a multidisciplinary approach to solving workload issues in a tertiary oncology center
Authors: Dobish Roxanne 
Published: May 2003

Introduction/background information. In 1998, increasing patient volumes and workloads related to ambulatory chemotherapy began to result in delays in the outpatient clinics, laboratory, pharmacy and the chemotherapy administration areas. The various departments that were being impacted met to review the situation and propose a solution. Program description. The team proposed that a next-day chemotherapy schedule be implemented, whereby patients would have their laboratory and physician appointment on one day and their chemotherapy administered on the next day. Originally, this was turned down by senior management, however, a year later the same issues resurfaced and the next-day chemotherapy scheduling was once again proposed and approval received to implement. Program implementation. A timetable was created and chemotherapy administration appointments were scheduled based on the available timeslots. The goal was to have the majority of patients scheduled for chemotherapy administration on the day following their appointment with the physician. Patients who would be exceptions to the next-day scheduling system were identified and education of staff and patients regarding the change was completed. Resistance from patients and staff was encountered and managed through continued education and reinforcement regarding the reasons for the change. Pharmacy issues/evaluation. Pharmacy conducted a follow-up timing study and the results supported that the timetable change was successful in improving pharmacy’s ability to prepare the chemotherapy for the patient’s appointment time. Pharmacy operational issues had to be worked through, however, overall the change was found to be positive. Conclusion. The implementation of a next-day chemotherapy administration schedule has resulted in improved efficiencies for pharmacy and nursing and a decrease in waiting times for patients to receive their chemotherapy.
High circulating levels of cytokines (IL-6 and TNFa), adhesion molecules (VCAM-1 and ICAM-1) and selectins in patients with peripheral arterial disease at rest and after a treadmill test
Authors: Signorelli Salvatore Santo , Mazzarino Maria Clorinda , Pino Luigi Di , Malaponte Grazia , Porto Carmela , Pennisi Giuseppe , Marchese Giuseppe , Costa Maria Pia , Digrandi Daniele , Celotta Gabriella , Virgilio Vittorio 
Published: May 2003

Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis that is associated with systemic inflammation. The aim of our study was to assess whether plasma markers of inflammation increased after exercise in patients with PAD. The study was conducted on two groups of 20 subjects each: one group (mean age 68.4 6 5.09 years) was affected by PAD with claudication, while the other group consisted of healthy controls (66.9 6 6.1 years). Concentrations of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFa) were determined in plasma, in supernatants and in cells stimulated with 1 mg lipopolysaccharide in all patients. E-selectin (ES), L-selectin (LS) and P-selectin (PS) concentrations and plasma concentrations of VCAM-1 and ICAM-I were also determined. All determinations were performed in patients at rest and after the treadmill exercise. Resting values of soluble mediators were greater in PAD patients than in controls. They increased in both groups after the treadmill test, even if post-treadmill concentrations were signifi cantly higher in PAD patients (PAD p < 0.001 or 0.0001, controls p < 0.05 or 0.001). These results confi rm that white blood cell activation is characteristic of systemic atherosclerosis and that these inflammation markers increase in conditions of hemodynamic stress.
Vascular viewpoint
Authors: Prabhakaran Dorairaj , Anand Sonia S 
Published: May 2003

Question: What are the effects of celecoxib, a selective COX-2 inhibitor on endothelial function? Population: Fourteen male patients (46-77 years) with severe coronary artery disease and chronic stable angina who did not have a coronary revascularization procedure three months prior to randomization. All patients were on aspirin and statins. Design and methods: Randomized double-blind, placebo-controlled crossover study. All patients received celecoxib 200 mg twice a day or matching placebo for two weeks. One patient discontinued study medication and was not included in the fi nal analysis. The primary outcome was endothelial function as assessed by flow-mediated and glycerol nitrate-induced vaso-dilation of the brachial artery after each treatment period using a high-resolution ultrasound device (10 MHz linear array transducer; WTS-2, Pie Medical, Indianapolis, IN, USA). Flow-mediated dilatation of the brachial artery was induced by the release of a wrist cuff inflated to suprasystolic blood pressure for 5 min. After release of the cuff pressure the arterial diameter was recorded every 15 s for 3 min. Secondary outcomes included oxidized LDL-cholesterol, high-sensitivity C-reactive protein (CRP) and prostaglandins (prostaglandin E2, 6-keto-prostag-landin-F1a-a stable metabolite of prostaglandin I2) and thromboxane B2 (an immediate and stable metabolite of thromboxane A2). Heart rate and blood pressure were also assessed. Results: Flow-mediated vasodilation signifi cantly increased after celecoxib administration compared with placebo (3.3 6 0.4% versus 2.0 6 0.5%, p = 0.03). Glyceryl trinitrate (GTN)-induced vasodilatation remained unchanged. High-sensitivity CRP and oxidized LDL were signifi cantly lowered by celecoxib as compared with placebo (p = 0.02 and p = 0.03 respectively), and the prostaglandins, including thromboxane B2, were not signifi cantly altered. No changes in clinical parameters such as heart rate and blood pressure were observed. Conclusion: Selective COX-2 inhibition improves endothelium-dependent vasodilation, reduces low-grade chronic inflammation and oxidative LDL in patients with coronary artery disease.
Cancer-Specific Mortality After Surgery or Radiation for Patients With Clinically Localized Prostate Cancer Managed During the Prostate-Specific Antigen Era
Authors: D’Amico Anthony V. , Moul Judd , Carroll Peter R. , Sun Leon , Lubeck Deborah , Chen Ming-Hui 
Published: May 2003

Purpose: To determine whether pretreatment risk groups shown to predict time to prostate cancer–specific mortality (PCSM) after treatment at a single institution retained that ability in a multi-institutional setting. Patients and Methods: From 1988 to 2002, 7,316 patients treated in the United States at 44 institutions with either surgery (n = 4,946) or radiation (n = 2,370) for clinical stage T1c-2, N0 or NX, M0 prostate cancer made up the study cohort. A Cox regression analysis was performed to determine the ability of pretreatment risk groups to predict time to PCSM after treatment. The relative risk (RR) of PCSM and 95% confidence intervals (CIs) were calculated for the intermediate- and high-risk groups relative to the low-risk group. Results: Estimates of non-PCSM 8 years after prostate-specific antigen (PSA) failure were 4% v 15% (surgery versus radiation; Plog rank = .002) compared with 13% v 18% (surgery versus radiation; Plog rank = .35) for patients whose age at the time of PSA failure was less than 70 as compared with ≥ 70 years, respectively. The RR of PCSM after treatment for surgery-managed patients with high- or intermediate-risk disease was 14.2 (95% CI, 5.0 to 23.4; PCox < .0001) and 4.9 (95% CI, 1.7 to 8.1; PCox = .0037), respectively. These values were 14.3 (95% CI, 5.2 to 24.0; PCox < .0001) and 5.6 (95% CI, 2.0 to 9.3; PCox = .0012) for radiation-managed patients. Conclusion: This study provided evidence to support the prediction of time to PCSM after surgery or radiation on the basis of pretreatment risk groups for patients with clinically localized prostate cancer managed during the PSA era.
Groups Potentially at Risk for Making Poorly Informed Decisions About Entry into Clinical Trials for Childhood Cancer
Authors: Simon Christian , Zyzanski Stephen J. , Eder Michelle , Raiz Pauline , Kodish Eric D. , Siminoff Laura A. 
Published: May 2003

Purpose: Some patients may be at greater risk than others of enrolling on a randomized clinical trial (RCT) without fully understanding the implications. To investigate this possibility, this study poses the question, Do non–English-speaking Latino parents of children with leukemia show differences in their discussion of and understanding of an RCT when compared with English-speaking minority parents and with English-speaking majority (ie, white) parents? This research hypothesizes that factors such as social and educational status and the role of language interpreters may account for significant differences in the discussion and understanding of an RCT among the three groups. Patients and Methods: A total of 108 parents are reported on, all of whom were observed, interviewed, and audiotaped during informed-consent discussions about participation in an RCT with their child’s oncologist. Comparisons among the groups were performed using χ2 tests and a one-way analysis of variance. Results: Problems of consent-related communication and understanding were more frequent among parents of low social status who spoke little or no English than they were in the two other groups. Several factors may have contributed to this disparity, including language interpretation, social status, and prevailing cultural norms. Conclusion: Some patients may be at greater risk than others of enrolling on an RCT without fully understanding the implications of their decision to do so. Numerous factors may contribute to this disparity, including language interpretation, social status, and prevailing cultural norms. Some specific strategies are suggested to help address this disparity.
Quality Assessment of Genetic Markers Used for Therapy Stratification
Authors: Ambros I.M. , Benard J. , Boavida M. , Bown N. , Caron H. , Combaret V. , Couturier J. , Darnfors C. , Delattre O. , Freeman-Edward J. , Gambini C. , Gross N. , Hattinger C.M. , Luegmayr A. , Lunec J. , Martinsson T. , Mazzocco K. , Navarro S. , Noguera R. , O’Neill S. , Pötschger U. , Rumpler S. , Speleman F. , Tonini G.P. , Valent A. , Van Roy N. , Amann G. , De Bernardi B. , Kogner P. , Ladenstein R. , Michon J. , Pearson A.D.J. , Ambros P.F. 
Published: May 2003

Purpose: Therapy stratification based on genetic markers is becoming increasingly important, which makes commitment to the highest possible reliability of the involved markers mandatory. In neuroblastic tumors, amplification of the MYCN gene is an unequivocal marker that indicates aggressive tumor behavior and is consequently used for therapy stratification. To guarantee reliable and standardized quality of genetic features, a quality-assessment study was initiated by the European Neuroblastoma Quality Assessment (ENQUA; connected to International Society of Pediatric Oncology) Group. Materials and Methods: One hundred thirty-seven coded specimens from 17 tumors were analyzed in 11 European national/regional reference laboratories using molecular techniques, in situ hybridization, and flow and image cytometry. Tumor samples with divergent results were re-evaluated. Results: Three hundred fifty-two investigations were performed, which resulted in 23 divergent findings, 17 of which were judged as errors after re-evaluation. MYCN analyses determined by Southern blot and in situ hybridization led to 3.7% and 4% of errors, respectively. Tumor cell content was not indicated in 32% of the samples, and 11% of seemingly correct MYCN results were based on the investigation of normal cells (eg, Schwann cells). Thirty-eight investigations were considered nonassessable. Conclusion: This study demonstrated the importance of revealing the difficulties and limitations for each technique and problems in interpreting results, which are crucial for therapeutic decisions. Moreover, it led to the formulation of guidelines that are applicable to all kinds of tumors and that contain the standardization of techniques, including the exact determination of the tumor cell content. Finally, the group has developed a common terminology for molecular-genetic results.
Cyclin D1 Overexpression in Bronchial Epithelia of Patients With Lung Cancer Is Associated With Smoking and Predicts Survival
Authors: Ratschiller D. , Heighway J. , Gugger M. , Kappeler A. , Pirnia F. , Schmid R.A. , Borner M.M. , Betticher D.C. 
Published: May 2003

Purpose: Cyclin D1 is overexpressed in almost 60% of resectable non–small-cell lung cancer (NSCLC). In the absence of cyclin D1 gene amplification, overexpression is characterized by allelic imbalanced transcript levels. Methods: The aims were to study cyclin D1 expression by immunohistochemistry and allelic balance of transcripts in tumor-free bronchial epithelia from patients with resectable NSCLC by using monoclonal antibodies (48 patients and 288 sites), microdissection/reverse transcriptase polymerase chain reaction/restriction fragment length polymorphism analyses (24 patients and 144 sites). Derived data were related to patient characteristics—in particular, smoking habits. Results: In 167 (58%) of 288 sites, cyclin D1 was overexpressed, with cytoplasmic and nuclear sublocalization in 53% and 7% of all sites, respectively. Nuclear overexpression was more frequent in premalignant versus normal or hyperplastic epithelia (55% v 3%; P < .0001). Allele-specific expression imbalances were found in 69 (48%) of 144 sites; in particular, those in which cyclin D1 was overexpressed (P = .004). In 14 (58%) of 24 patients, balanced or imbalanced transcript ratios and degree of expression were consistent at all sites for the same patient, whereas in another 10 patients, transcript balances and cyclin D1 expression patterns varied across the sites. Nuclear cyclin D1 expression in at least one site (14 of 48 patients) was linked to heavy smoking (> 40 pack-years; P = .02) and shorter overall survival (P = .01). Conclusion: Allele-specific, probably damage-driven, deregulation of the cyclin D1 gene may precede and perhaps facilitate the spread of preneoplastic clones across the bronchial epithelial surface in a significant number of patients. Cyclin D1 expression at multiple bronchial sites may identify a subgroup of heavy-smoking patients with poor outcome.
Phase III Study of Letrozole Versus Tamoxifen as First-Line Therapy of Advanced Breast Cancer in Postmenopausal Women: Analysis of Survival and Update of Efficacy From the International Letrozole Breast Cancer Group
Authors: Mouridsen Henning , Gershanovich Mikhail , Sun Yan , Pérez-Carrión Ramón , Boni Corrado , Monnier Alain , Apffelstaedt Justus , Smith Robert , Sleeboom Harm P. , Jaenicke Fritz , Pluzanska Anna , Dank Magdolna , Becquart Dominique , Bapsy Poonamalle P. , Salminen Eeva , Snyder Ray , Chaudri-Ross Hilary , Lang Raquel , Wyld Peter , Bhatnagar Ajay 
Published: May 2003

Purpose: To analyze overall survival (OS) and update efficacy data for letrozole versus tamoxifen as first-line therapy in postmenopausal women with locally advanced or metastatic breast cancer. Patients and Methods: This multicenter phase III trial randomly assigned 916 patients with hormone receptor–positive or unknown tumors letrozole 2.5 mg (n = 458) or tamoxifen 20 mg (n = 458) daily until disease progression. Optional cross-over was permitted at the treating physician’s discretion. This report updates efficacy at a median follow-up of 32 months. Results: The superiority of letrozole to tamoxifen was confirmed for time to progression (median, 9.4 v 6.0 months, respectively; P < .0001), time to treatment failure (median, 9 v 5.7 months, respectively; P < .0001), overall objective response rate (32% v 21%, respectively; P = .0002), and overall clinical benefit. Median OS was slightly prolonged for the randomized letrozole arm (34 v 30 months, respectively). Although this difference in OS is not significant, survival was improved in the randomized letrozole arm over the first 2 years of the study. Approximately one half of the patients in each arm crossed over. Total duration of endocrine therapy (“time to chemotherapy”) was significantly longer (P = .005) for patients initially on letrozole (median, 16 months) than for patients initially on tamoxifen (median, 9 months). Time to worsening of Karnofsky performance score was significantly delayed with letrozole compared with tamoxifen (P = .001). Conclusion: This study documents the superiority of letrozole over tamoxifen in first-line endocrine therapy in postmenopausal women with advanced breast cancer.