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1.
Vinca alkaloids, thalidomide and eribulin-induced peripheral neurotoxicity: From pathogenesis to treatment.
Islam, B, Lustberg, M, Staff, NP, Kolb, N, Alberti, P, Argyriou, AA
Journal of the peripheral nervous system : JPNS. 2019;:S63-S73
Abstract
Vinca alkaloids, thalidomide, and eribulin are widely used to treat patients with childhood acute lymphoblastic leukemia (ALL), adults affected by multiple myeloma and locally invasive or metastatic breast cancer, respectively. However, soon after their introduction into clinical practice, chemotherapy-induced peripheral neurotoxicity (CIPN) emerged as their main non-hematological and among dose-limiting adverse events. It is generally perceived that vinca alkaloids and the antiangiogenic agent thalidomide are more neurotoxic, compared to eribulin. The exposure to these chemotherapeutic agents is associated with an axonal, length-dependent, sensory polyneuropathy of mild to moderate severity, whereas it is considered that the peripheral nerve damage, unless severe, usually resolves soon after treatment discontinuation. Advanced age, high initial and prolonged dosing, coadministration of other neurotoxic chemotherapeutic agents and pre-existing neuropathy are the common risk factors. Pharmacogenetic biomarkers might be used to define patients at increased susceptibility of CIPN. Currently, there is no established therapy for CIPN prevention or treatment; symptomatic treatment for neuropathic pain and dose reduction or withdrawal in severe cases is considered, at the cost of reduced cancer therapeutic efficacy. This review critically examines the pathogenesis, epidemiology, risk factors (both clinical and pharmacogenetic), clinical phenotype and management of CIPN as a result of exposure to vinca alkaloids, thalidomide and its analogue lenalidomide as also eribulin.
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2.
Total knee arthroplasty application of polyetheretherketone and carbon-fiber-reinforced polyetheretherketone: A review.
Koh, YG, Park, KM, Lee, JA, Nam, JH, Lee, HY, Kang, KT
Materials science & engineering. C, Materials for biological applications. 2019;:70-81
Abstract
Polyetheretherketone (PEEK) and carbon-fiber-reinforced PEEK (CFR-PEEK) have been successfully used in the field of orthopedic implants. The polymers PEEK and CFR-PEEK are resistant to fatigue strain and radiologically transparent. These have mechanical properties and are therefore suitable for a range of orthopedic applications. Polymer composites have been proposed for orthopedic applications with the potential of reducing stress-shielding, weight of the implants, wear, and risk of osteolysis. They prevent the release of metal ions by replacing the metal articulating components. The purpose of this review was to investigate the biomechanical effects, technical data, and safety of PEEK and CFR-PEEK biomaterials and evaluate their potential for new innovations in the design of total knee arthroplasty (TKA). This review paper provides an overview with schematics and descriptions, specifically aimed at the development of PEEK and CFR-PEEK for TKA. The appropriate applications for femoral, tibial, and bearing components are highlighted for the optimal design of TKA composite, showing successful biomechanical effects.
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3.
(5Z)-7-Oxozeaenol: A novel and potent resorcylic acid lactone kinase inhibitor with a cis-enone Michael acceptor.
Ellestad, GA
Chirality. 2019;(2):110-117
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4.
Multiple modes of action of eribulin mesylate: Emerging data and clinical implications.
Cortes, J, Schöffski, P, Littlefield, BA
Cancer treatment reviews. 2018;:190-198
Abstract
Eribulin mesylate (eribulin) is a synthetic analogue of the marine-sponge natural product halichondrin B. Eribulin exhibits potent antiproliferative activities against a variety of human cancer cell types in vitro and in vivo, and is used for the treatment of certain patients with advanced breast cancer or liposarcoma who are refractory to other treatments. The antiproliferative effects of eribulin have long been attributed to its antimitotic activities. Unlike other microtubule-targeting agents, eribulin inhibits microtubule polymerization through specific plus end binding, thus interfering with microtubule dynamic instability. Non-mitotic effects of eribulin on tumor biology have also been established in laboratory settings including: tumor vasculature remodeling, increased vascular perfusion, reduced hypoxia, and phenotypic changes involving reversal of epithelial-to-mesenchymal transition (EMT), resulting in reduced capacities for migration, invasion, and seeding lung metastases in experimental models. Preclinical data suggest that increased perfusion following eribulin treatment improves delivery of subsequent drugs. Supporting evidence for eribulin's non-mitotic effects in the clinical setting include increased tumor oxygen saturation, reduced hypoxia, phenotype changes consistent with EMT reversal, and genotype changes consistent with shifts from nonendocrine-responsive, luminal B, to endocrine-responsive, luminal A, breast cancer subtypes. Finally, potential biomarkers for eribulin response have been established based on tumor-phenotype and gene-expression profiles. Overall, preclinical and clinical data support both antimitotic and non-mitotic mechanisms of eribulin that may underlie the survival benefit observed in various clinical trials.
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5.
Incidence and clinical parameters associated with eribulin mesylate-induced peripheral neuropathy.
Zhao, B, Zhao, H, Zhao, J
Critical reviews in oncology/hematology. 2018;:110-117
Abstract
Eribulin mesylate is a microtubule-targeting agent that has been approved for the treatment of breast cancer and liposarcoma. Due to its novel mechanism of action, eribulin therapy induces a distinct profile of adverse events, including peripheral neuropathy. However, the incidence and risk of eribulin-related neurotoxicities are unclear. Here, we conducted a systematic search of PubMed and Embase from their inception to October 2017. Eligible studies included trials in which eribulin was intravenously administered at a standard dose of 1.4 mg/m2 over 2-5 minutes on days 1 and 8 on a 21-day cycle. The events of all-grade and high-grade peripheral neuropathy were collected to calculate the overall incidence and relative risk (RR). A total of thirty-two studies containing 6129 subjects were included in this analysis. The incidences of all-grade and high-grade eribulin monotherapy-related peripheral neuropathy were 28% (95% confidence interval [CI], 24%-32%) and 4% (95% CI, 3%-5%), respectively. Subgroup analysis further revealed that a higher incidence of neurotoxicities was observed in patients with breast cancer and those with longer treatment duration. Moreover, eribulin-treated subjects had a significantly increased risk of all-grade (RR, 2.00; 95% CI, 1.70-2.35; p = 0.008) and high-grade (RR, 3.68; 95% CI, 2.30-5.89; p<0.001) neurotoxicities. Our results suggested that patients treated with eribulin had an increased risk of developing peripheral neuropathy.
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6.
Outcomes following polyetheretherketone (PEEK) cranioplasty: Systematic review and meta-analysis.
Punchak, M, Chung, LK, Lagman, C, Bui, TT, Lazareff, J, Rezzadeh, K, Jarrahy, R, Yang, I
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 2017;:30-35
Abstract
Polyetheretherketone (PEEK) has been used in cranioplasty since the early 2000s. However, there remains limited data that compares its long-term complication rate to autologous grafts and titanium mesh implants. To compare complication and implant failure rates after PEEK, autologous and titanium mesh cranioplasties, the authors of this study conducted a systematic review using the PubMed database. Studies that contained outcome data on complication rates of PEEK cranioplasty patients and studies that compared outcomes of patients who underwent PEEK cranioplasties versus other materials were included in the meta-analysis. Pooled odds ratios using the Mantel-Haenszel method were used for analysis. Fifteen articles, comprised of 183 PEEK cranioplasty patients were included. Of these patients, 15.3% developed post-operative complications and 8.7% experienced implant failure requiring reoperation. Patients who underwent cranioplasties with PEEK implants had 0.130 times the odds of developing post-operative complications (P=0.065) and 0.574 times the odds of implant failure compared to patients with autologous bone graft cranioplasties (P=0.629). Patients who had undergone PEEK cranioplasties had 0.127 times the odds of developing post-op complications (P=0.360) and 0.170 times the odds of implant failure compared to individuals who had undergone titanium mesh cranioplasties (P=0.168). The analysis was severely limited by the paucity in literature. However, there was a trend toward lower post-operative complication rates following PEEK cranioplasty versus autologous grafts, and lower implant failure rates with PEEK versus titanium mesh implants.
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7.
Ketones and Human Performance.
Scott, JM, Deuster, PA
Journal of special operations medicine : a peer reviewed journal for SOF medical professionals. 2017;(2):112-116
Abstract
Everyone is seeking nutritional strategies that might benefit performance. One approach receiving much attention is ketones, or ketosis. Ketones are very simple compounds made of hydrogen, carbon, and oxygen, and ketosis is a metabolic state whereby the body uses predominantly ketones. Ketosis can be achieved by fasting for longer than 72 hours or by following a very lowcarbohydrate, high-fat diet (ketogenic diet) for several days to weeks. Alternatively, ketone supplements purportedly induce ketosis rapidly and do not require strict adherence to any specific type of diet; however, much of the touted benefits are anecdotal. A potential role for ketosis as a performance enhancer was first introduced in 1983 with the idea that chronic ketosis without caloric restriction could preserve submaximal exercise capability by sparing glycogen or conserving the limited carbohydrate stores. Few human studies on the effects of a ketogenic diet on performance have yielded positive results, and most studies have yielded equivocal or null results, and a few negative results. Many questions about ketones relevant to Special Operations Forces (SOF) remain unanswered. At present, a ketogenic diet and/or a ketone supplement do not appear confer performance benefits for SOF. Instead, Operators should engage with their unit dietitian to develop individualized nutritional strategies based on unique mission requirements. The authors review the concept of a ketogenic diet, describe some potential benefits and risks of ketosis, review the performance literature and how to measure ketone status, and then summarize the landscape in 2017.
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8.
Systemic Therapy for Soft Tissue Sarcoma: Proposals for the Optimal Use of Pazopanib, Trabectedin, and Eribulin.
Kawai, A, Yonemori, K, Takahashi, S, Araki, N, Ueda, T
Advances in therapy. 2017;(7):1556-1571
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Abstract
UNLABELLED Soft tissue sarcoma (STS) is a rare tumor with more than 50 histologic subtypes. Although treatment outcomes for patients with STS have improved greatly over the past few decades owing to the adoption of a multidisciplinary approach, patients with advanced disease have a poor prognosis. The development of anticancer drugs has been directed toward improving overall survival (OS). Doxorubicin monotherapy is currently the only standard option for the first-line treatment of STS. However, there is no standard therapy for second-line and later treatment at present. Since 2012, three anticancer drugs-pazopanib, trabectedin, and eribulin-have been approved in Japan for the second-line or later treatment of patients with advanced STS of any histologic subtype. However, the chemosensitivity of STS to each of these drugs varies by histologic subtype and their safety profiles differ; thus, histologic subtype and patient characteristics must be considered when determining optimal treatment. In this article, we review data from clinical studies related to the efficacy of all three drugs, including their effect on OS, and propose optimal treatment strategies for advanced STS by histologic subtype. In addition, with regard to the safety profiles, we highlight the key issues to be considered when selecting patients for treatment with pazopanib, trabectedin, or eribulin and ensuring their appropriate use, based on our combined clinical experience as specialists in the treatment of patients with STS. The proposed treatment strategies as well as treatment precautions based on clinical experience would benefit patients by maximizing the therapeutic effects and enhancing the proper use of these drugs. FUNDING Eisai Co., Ltd.
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Review on the clinical use of eribulin mesylate for the treatment of breast cancer.
Aseyev, O, Ribeiro, JM, Cardoso, F
Expert opinion on pharmacotherapy. 2016;(4):589-600
Abstract
INTRODUCTION Breast cancer is the second leading cause of cancer death among women and the median survival of metastatic breast cancer (MBC) has remained, for many decades, at two to three years after diagnosis. Eribulin mesylate is a nontaxane inhibitor of microtubule dynamics and the only cytotoxic agent in the last decade to improve overall survival in heavily pretreated patients with MBC. Eribulin was approved for the treatment of MBC in 2010 by the FDA in patients that received at least two prior chemotherapy regimens and as second-line treatment in 2011 by EMA. In both cases prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting. AREAS COVERED This manuscript reviews the current available data on the use of this important cytotoxic agent including its pharmacology, pharmacokinetics, clinical efficacy, safety, and potential economic factors as well as ongoing clinical trials and main areas of research. EXPERT OPINION Eribulin mesylate is a novel microtubule dynamics inhibitor compound important for the management of MBC and can be used for the treatment of patients who have previously received one/two chemotherapeutic regimens for metastatic disease and whose prior therapy included an anthracycline and a taxane. It's toxicity profile is acceptable and presents several favorable features namely a low probability of drug-drug interactions in the clinical setting, easy administration as bolus, low hypersensitivity chances and full tolerability in renal dysfunction patients. Eribulin is currently being evaluated as first-line treatment for MBC, in the adjuvant/neoadjuvant setting alone and in combination with a variety of agents, particularly biologic treatments. Future research is needed to optimize the role of eribulin in the treatment of MBC.
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[Maintenance of Long-Term Stable Disease(SD)in Metastatic Breast Cancer with Eribulin - A Case Report of Long-Term SD in Japan].
Nitta, T, Kimura, K, Tominaga, T, Fujii, K, Sato, N, Ikari, A, Miyoshi, K, Tanaka, S, Ishibashi, T, Iwamoto, M
Gan to kagaku ryoho. Cancer & chemotherapy. 2016;(13):2543-2546
Abstract
This case report discusses a 48-year-old woman with metastatic breast cancer: T4c(10.5 cm)N2bM1,(OSS, LYM), stage IV, estrogen receptor(ER)(+), progesterone receptor(PgR)(+), human epidermal growth factor receptor-2(HER2) (-), and Ki-67 17.2%. Administration of eribulin was initiated after treatment with anthracycline and taxane. Thereafter, 28 courses of eribulin maintained a SD state for over a year and improved the quality of life(QOL). Eribulin is effective for both prolonging life and improving QOL, which are the main goals in the treatment of metastatic or recurrent cancer. Therefore, this evidence suggests that eribulin can be effective in various clinical situations.