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- Volume 4, Issue 2, 2017
Clinical Cancer Drugs - Volume 4, Issue 2, 2017
Volume 4, Issue 2, 2017
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Upfront DPD Deficiency Detection to Secure 5-FU Administration: Part 1 - Where Do We Stand?
Background: 5-Fluoro-Uracil (5-FU) ranks among the most widely prescribed anticancer agents worldwide. Fluoropyrimidines are a mainstay in the treatment of numerous solid tumors, mostly used in combination with other cytotoxics, targeted therapies or biologics. Because most of the administered 5-FU dose will undergo extensive catabolism driven by dihydropyrimidine dehydrogenase (DPD), a liver enzyme that conve Read More
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Pharmacokinetic Markers of 5-Fluorouracil Toxicity in Clinical Trials and Real World
Background: Fluoropyrimidines remain the cornerstone of several regimens for solid malignancies, despite their administration may result in severe or fatal toxicities. Objective: To review pharmacokinetic markers predictive of fluoropyrimidine- associated toxicities. Shifting from i.v. boluses to both continuous infusions of 5-fluorouracil (5-FU) and oral prodrugs, as well as capecitabine, significantly increased the treatment tolera Read More
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Fluoropyrimidine-associated Toxicities in Colorectal Cancer Patients: The Epigenetic Point of View
Authors: Laura Bertolaso and Milena GusellaBackground: Fluoropyrimidines (FPs) have been used for a long time as first-line treatment for colorectal cancer and continue to represent the backbone of combination chemotherapy in both the adjuvant and metastatic disease settings. In a consistent percentage of patients (10-40%) FPs induce severe to life-threatening toxicity. On this basis, markers of tolerance to treatment need to be found. Dihydropyrimidine dehydro Read More
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Dermatological, Cardiovascular and Neurological Morphohistopathological Effects of Fluoropyrimidine-based Chemotherapy in Humans
Authors: Gianfranco Natale, Antonello Di Paolo and Guido BocciBackground: Fluoropyrimidines are anticancer drugs used for the treatment of solid tumours. Apart from general side effects common to other anticancer drugs, the intravenously administered 5-fluorouracil (5-FU) and the recently developed oral prodrugs can induce toxicity at cardiovascular, neurologic and dermatologic level, which is reversed by treatment interruption, discontinuation, dose reduction and sup Read More
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Prevention of Capecitabine Toxicity Using a 5-FU Test Dose
Background and Objective: The extensive clinical use of capecitabine may be associated with important adverse drug reactions. The aim of this study was to prevent the risk of toxicities in patients who are candidates to capecitabine treatment. Methods: Pharmacokinetic parameters of 5-fluorouracil (5-FU)/ 5-fluoro-5,6-dihydrouracil (5-FDHU) were examined in 133 cancer patients given a test dose of 5-FU (250 mg/m2) 2 Read More
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Upfront DPD Deficiency Detection to Secure 5-FU Administration: Part 2- Application to Head-and-Neck Cancer Patients
Background: Upfront screening for dihydropyrimidine dehydrogenase (DPD) deficiency in patients scheduled for 5-FU should help to reduce the risk of toxicities by preventive adaptive dosing. Our group has developed a simple functional testing categorizing patients upon their DPD status, i.e. extensive metabolizer (EM) or poor metabolizer (PM) patients, using UH2/U ratio measurement in plasma as a surrogate for DPD activity Read More
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Progress and Obstacles in the Application of Precision Medicine in the Management of Hepatocellular Carcinoma
Authors: Ping Wang and Xueying SunBackground: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. HCC patients have a poor prognosis due to shortage of effective therapies though a small proportion of patients are eligible for curative treatments. Precision medicine, a recently emerging medicinal model, has provided more avenues in the management of HCC. Methods: Published literatures related to HCC and p Read More
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Intra-arterial Temozolomide, Osmotic Blood-brain Barrier Disruption and Radiotherapy in a Rat F98-Glioma Model
Authors: Annie I. Drapeau, Marie-Belle Poirier, Guru-Swamy Madugundu, J. R. Wagner and David FortinBackground: The blood-brain barrier (BBB) is a major obstacle in the treatment of brain tumors. Intra-arterial (IA) administration with osmotic BBB disruption (BBBD) allows greater drug delivery to the central nervous system (CNS). Its use with temozolomide (TMZ), the first-line agent in the treatment of glioblastoma, has never been reported in an animal glioma model. Objective: This study was designed to investigate wheth Read More
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Salvage Hypofractionated Radiotherapy in Combination with Bevacizumab in Patients with Recurrent High Grade Glioma: A Mono-institutional Experience
Background: After the detection of recurrent high-grade glioma, there are no standard approaches; salvage surgery, chemotherapy and radiotherapy are often used despite the fact that no real clinical benefit has been confirmed and the combination of these approaches has not yet been fully investigated. Objective: In the present retrospective study, we reported the results of a mono-institutional experience studyin Read More
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