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Gastrointestinal cancer
Published in Michael JG Farthing, Anne B Ballinger, Drug Therapy for Gastrointestinal and Liver Diseases, 2019
Justin S Waters, David Cunningham
Drug therapy may have an adjuvant role in the management of operable hepatocellular carcinoma, although there is conflicting evidence from randomized studies. Two trials have reported negative results, one using postoperative adjuvant epirubicin plus chemoembolization with iodized oil and cisplatin,71 and the second using a combination of IHA epirubicin, intravenous epirubicin and oral carmofur.72 In contrast, positive results have been reported for adjuvant IHA doxorubicin and lipiodol,73 for a complex pre- and postoperative regimen of tumour-targeted IHA therapy containing a cocktail of lipiodol, urographin, mitomycin C, carboplatin, epirubicin, leucovorin, 5-fluorouracil, γ-interferon, and interleukin-2,74 and for a single postoperative IHA dose of 131I-labelled lipiodol.75
Development of palliative medicine in the United Kingdom and Ireland
Published in Eduardo Bruera, Irene Higginson, Charles F von Gunten, Tatsuya Morita, Textbook of Palliative Medicine and Supportive Care, 2015
Anticancer drugs cause a wide variety of neurotoxicities. The occurrence of neurotoxicity due to anticancer drugs is affected not only by the mode of action of the drugs but also by the method of administration, dose, presence/absence of concomitant therapies, etc. In particular, leukoencephalopathy is an acute neurotoxicity known to occur in the central nervous system. Leukoencephalopathy is a syndrome that presents with gait disorder, autonomic nerve symptoms, and psychoneurological symptoms including memory disturbance after the administration of anticancer drugs. In addition, the disease can cause disturbance of consciousness. Although the frequency is rare, once the disease develops, the symptoms become serious and can cause irreversible neuropathy. Neurotoxicity occurs after treatment with 5-fluorouracil, methotrexate, cyclophosphamide, carmofur, tegafur, etc.
Malignant Neoplasms of the Rectum
Published in Philip H. Gordon, Santhat Nivatvongs, Lee E. Smith, Scott Thorn Barrows, Carla Gunn, Gregory Blew, David Ehlert, Craig Kiefer, Kim Martens, Neoplasms of the Colon, Rectum, and Anus, 2007
Nagawa et al. (378) evaluated the effectiveness of preoperative radiation therapy for advanced lower rectal carcinoma to preserve the function of pelvic organs and reduce local recurrences in a prospective randomized, controlled study. The patients were randomly allocated to complete autonomic nerve preserving surgery without lateral node dissection, or surgery with dissection of the lateral lymph nodes including autonomic nerves followed by oral administration of carmofur for one year. No difference was observed in either survival or disease-free survival between groups. There was no difference between the two groups in terms of recurrence rate. A significant difference was observed in urinary and sexual function one year after surgery. Their study suggests that lateral node dissection is not necessary in terms of curability for patients with advanced carcinoma of the lower rectum who undergo preoperative radiotherapy.
Promising strategies for improving oral bioavailability of poor water-soluble drugs
Published in Expert Opinion on Drug Discovery, 2023
Bruna Rocha, Letícia Aparecida de Morais, Mateus Costa Viana, Guilherme Carneiro
Several emerging strategies have been proposed to increase the bioavailability of poorly water-soluble antineoplastic drugs. For example, reverse cross-linking strategies have been used to prolong drug circulation in the bloodstream and increase accumulation in tumor tissue through different systems, such as micelles, liposomes, and nanoparticles [96,97]. Cross-linked small molecule micelles carrying gemcitabine and dandelion flower-like micelles loaded with carmofur achieved high tumor inhibition effects [97,98]. (R)-(+)-lipoic acid nanoparticles cross-linked with a camptothecin prodrug and a two-component bioorthogonal nanosystem based on cross-linked lipoic acid nanocapsules also promoted high anticancer activity [99,100]. Water-soluble reticulated reverse vesicles, carriers of paclitaxel, camptothecin, and carmofur also showed promising results [96].
High-throughput discovery of novel small-molecule inhibitors of acid Ceramidase
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Mazen Aseeri, José Luis Abad, Antonio Delgado, Gemma Fabriàs, Gemma Triola, Josefina Casas
AC is one of the better-characterized ceramidases and its role in cancer initiation and progression has been largely studied. Abnormally elevated AC expression has been reported in various type of cancer including prostate cancer13, colon adenocarcinoma14, head and neck cancer15, glioblastoma16 and melanoma17. Moreover, whereas AC overexpression renders the cells more resistant to chemo and radiotherapy18, inhibition of the enzyme sensitises the cell to treatment19, thereby suggesting a role of AC in drug resistance associated to therapy. As a result, AC inhibition has emerged as an attractive target to improve the efficacy and lower the resistance to cancer treatments, and the identification of novel and selective AC inhibitors has gained increasing interest. Tremendous efforts have been done during the last two decades to develop AC modulators. However, most of the reported inhibitors are structurally related to ceramide, which has a negative impact on their selectivity, potency and drug-like properties20. Thus, the discovery of ceramide-unrelated hits would be highly desirable. Some potent and structurally unrelated inhibitors of AC have already been described. Representative examples of this class of compounds are carmofur, identified after the screening of a commercial library using a LC/MS-based assay14, and the related dioxypyrimidine and benzoxazolone carboxamides21–23. Despite these relevant examples, there is still a great need for the identification of novel molecules that can expand the toolbox for AC inhibitors.
Drug delivery to tumours using a novel 5-FU derivative encapsulated into lipid nanocapsules
Published in Journal of Drug Targeting, 2019
Giovanna Lollo, Kevin Matha, Martina Bocchiardo, Jérôme Bejaud, Ilaria Marigo, Angelique Virgone-Carlotta, Thomas Dehoux, Charlotte Rivière, Jean-Paul Rieu, Stephanie Briançon, Thomas Perrier, Olivier Meyer, Jean-Pierre Benoit
In this respect, to improve toxicity/efficacy balance [6], numerous modifications of the 5-FU structure have been performed and novel derivatives of 5-FU have been reported [7,8]. Among them, tegafur, carmofur and floxuridine, 5-FU prodrugs, have proven their clinical efficacy with low toxicity and enhanced metabolic stability [9]. Also, capecitabine (Xeloda®), an oral fluoropyrimidine carbamate that is activated selectively by the thymidine phosphorylase (TP) to form 5-FU, has been developed to increase tumour selectivity [10]. However, the results obtained using these derivatives are still marginal and 5-FU biodistribution and toxicity remain a challenging issue in oncology.