Search

7229 Background: A debate exists over the extent to which gemcitabine is associated with potentially fatal pulmonary toxicities, namely interstitial pneumonitis. Methods: Herein, The Research on Ad...

Background One of the most unusual causes of thrombotic thrombocytopenic purpura (TTP), a life-threatening disease, is ticlopidine hydrochloride, an antiplatelet agent used to prevent strokes in high-risk populations or following coronary artery stent placement. Recently, Hoffman-LaRoche Pharmaceuticals, following reports of 20 deaths from ticlopidine-associated TTP, updated the information about the hematologic adverse effects of the drug. Objectives To review our recent findings on ticlopidine-associated hematologic toxic effects, which served as the impetus for the revised warnings, and to discuss the implications of these findings. Methods Data were obtained from the Food and Drug Administration's MedWatch program, published phase 3 clinical trials and case reports, hematologists, and plasmapheresis centers. Results No cases of TTP have been reported in phase 3 ticlopidine trials. In contrast, postmarketing surveillance has identified serious adverse drug reactions to ticlopidine, resulting in 259 deaths, with TTP accounting for 40 of these deaths. Detailed information was available on 98 cases of ticlopidine-associated TTP. Compared with 42 patients in the coronary artery stent setting, 56 patients with ticlopidine-associated TTP in the stroke prevention setting were more likely to be women (62.5% vs 28.6%; P = .01). Before the onset of TTP in patients receiving stroke prevention therapy and patients with stent placement, ticlopidine had been used for less than 2 weeks in 5.4% and 2.4%, between 2 and 3 weeks in 17.9% and 21.4%, between 3 and 4 weeks in 30.4% and 38.1%, and between 4 and 12 weeks in 46.4% and 38.1%, respectively. Death occurred in almost 60% of all patients not receiving plasmapheresis compared with 21.9% of patients receiving plasmapheresis for stroke prevention and 14.3% of patients receiving plasmapheresis in the stent setting. Conclusions Use of ticlopidine requires frequent physician visits and laboratory tests for at least 3 months in the stroke prevention setting, while, with short-term use in the coronary artery stent setting, adverse events are less likely to occur. These factors, as well as competition from clopidogrel bisulfate, a new antiplatelet agent, potentially limit the feasibility of ticlopidine as a stroke prevention agent, while having less impact on its use following coronary artery stent placement.

Background Several short-term, controlled trials have documented the efficacy of vitamin E in treating tardive dyskinesia. However, the persistent nature of the disease prompted us to perform a multicenter, longer-term trial of vitamin E. Methods The study was a prospective, randomized, 9-site trial of up to 2 years of treatment with d -vitamin E (1600 IU/d) vs matching placebo. One hundred fifty-eight subjects with tardive dyskinesia who were receiving neuroleptic medications were enrolled. The blinded assessments performed were clinical (Abnormal Involuntary Movements Scale, Barnes Akathisia Scale, and Modified Simpson-Angus [for Extrapyramidal Symptoms] Scale) and electromechanical assessments of movement disorders, psychiatric status (Brief Psychiatric Rating Scale), and functioning (Global Assessment of Functioning). There were no significant differences in baseline demographic characteristics or in study assessments between the group that received vitamin E and the group that received placebo. Results Vitamin E was well tolerated and subject compliance with medication was good and similar between treatment groups. One hundred seven subjects (70% of those receiving vitamin E and 66% of subjects receiving placebo) completed at least 1 year of treatment. There were no significant effects of vitamin E on total scores or subscale scores for the AIMS, electromechanical measures of dyskinesia, or scores from the other 4 scales. Conclusion This long-term, randomized trial of vitamin E vs placebo found no evidence for efficacy of vitamin E in the treatment of tardive dyskinesia.

OBJECTIVE: To determine if quality of life, as measured by the Short Form-36 (SF-36), improved during the treatment of opiate dependence and to identify which dimensions of the SF-36 were impacted by treatment. METHODS: The SF-36 was administered via computer to 100 patients enrolled in a clinical trial of a new drug for opiate dependence. The trial compared two dosage forms of the drug. The five time points for administration were upon enrollment (T1) and monthly (T2-T5) for the 16-week trial. The study was conducted at a drug abuse treatment clinic in a large metropolitan area. Data were analyzed using paired t-tests. RESULTS: Significant improvement in health-related quality of life (P T1), general health (T2, T3 > T1), mental health (T2, T3, T5 > T1), social function (T2, T3, T4, T5 > T1), and vitality (T3, T4, T5 > T1 and T3 > T2). Changes in measures of physical functioning and role physical dimensions were not affected by addiction treatment. Changes in general health, mental health, and social function occurred between the enrollment assessment and the first month of treatment (T1 versus T2). However, significant improvement in bodily pain and vitality did not occur until the second month and after (T1 versus T3–T5). CONCLUSION: Quality of life measures improved during opiate dependence treatment. Fewer measures of physical dimensions improved than mental dimensions. The SF-36 was sensitive to improvements in quality of life in patients treated for opiate dependence; therefore it was helpful in measuring patient outcomes.

Background On 30 January 2012, the US FDA approved vismodegib (Erivedge®, Genentech, CA, USA) for the management of both metastatic and locally advanced basal cell carcinoma. Objective Our objective was to identify evidence of hepatotoxicity with vismodegib in the FDA Adverse Event Reporting System (FAERS) in treated patients in two National Cancer Institute Comprehensive Cancer Centers. Methods FAERS was searched for reports dated 1 January 2009 through 31 December 2015 using terms including hedgehog pathway and vismodegib and hepatic-related terms such as liver, jaundice, and hepatitis, among others. Disproportionality analyses with estimates of proportional reporting ratio and empirical Bayesian geometric mean were conducted. A comprehensive literature review was conducted, and the clinical databases at the University of Texas MD Anderson Cancer Center and Robert H. Lurie Comprehensive Cancer Center of Northwestern University were searched. Results Two cases of severe liver dysfunction were published (Common Terminology Criteria for Adverse Events [CTCAE] class III), and 94 reports of adverse events (AEs) were detected in FAERS, 35 of which were serious AEs. Safety notifications related to hepatotoxicity have not been issued by the manufacturer or the FDA, although vismodegib is listed in LiverTox and the European Medicines Agency website. Conclusion We identified a detectable safety signal for hepatotoxicity for vismodegib within 4 years of FDA approval. Vismodegib should be used in patients with severe liver disease only after careful consideration, and concomitant hepatotoxic medications should be avoided. Rapid dissemination of such safety concerns is expected to result in fewer serious hepatotoxic AEs and more optimal outcomes for patients with cancer receiving vismodegib. Electronic supplementary material The online version of this article (doi:10.1007/s40268-016-0168-2) contains supplementary material, which is available to authorized users.