Browsing by Author "Cavaletti, Guido"

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    Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: ASCO Guideline Update
    (ASCO, 2020-10) Loprinzi, Charles L.; Lacchetti, Christina; Bleeker, Jonathan; Cavaletti, Guido; Chauhan, Cynthia; Hertz, Daniel L.; Kelley, Mark R.; Lavino, Antoinette; Lustberg, Maryam B.; Paice, Judith A.; Schneider, Bryan P.; Lavoie Smith, Ellen M.; Smith, Mary Lou; Smith, Thomas J.; Wagner Johnston, Nina; Hershman, Dawn L.; Pediatrics, School of Medicine
    PURPOSE To update the ASCO guideline on the recommended prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathy (CIPN) in adult cancer survivors. METHODS An Expert Panel conducted targeted systematic literature reviews to identify new studies. RESULTS The search strategy identified 257 new references, which led to a full-text review of 87 manuscripts. A total of 3 systematic reviews, 2 with meta-analyses, and 28 primary trials for prevention of CIPN in addition to 14 primary trials related to treatment of established CIPN, are included in this update. RECOMMENDATIONS The identified data reconfirmed that no agents are recommended for the prevention of CIPN. The use of acetyl-l-carnitine for the prevention of CIPN in patients with cancer should be discouraged. Furthermore, clinicians should assess the appropriateness of dose delaying, dose reduction, substitutions, or stopping chemotherapy in patients who develop intolerable neuropathy and/or functional impairment. Duloxetine is the only agent that has appropriate evidence to support its use for patients with established painful CIPN. Nonetheless, the amount of benefit from duloxetine is limited.
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    Systems Pharmacology Modeling Identifies a Novel Treatment Strategy for Bortezomib-Induced Neuropathic Pain
    (Frontiers Media, 2022-01-19) Bloomingdale, Peter; Meregalli, Cristina; Pollard, Kevin; Canta, Annalisa; Chiorazzi, Alessia; Fumagalli, Giulia; Monza, Laura; Pozzi, Eleonora; Alberti, Paola; Ballarini, Elisa; Oggioni, Norberto; Carlson, Louise; Liu, Wensheng; Ghandili, Mehrnoosh; Ignatowski, Tracey A.; Lee, Kelvin P.; Moore, Michael J.; Cavaletti, Guido; Mager, Donald E.; Medicine, School of Medicine
    Chemotherapy-induced peripheral neurotoxicity is a common dose-limiting side effect of several cancer chemotherapeutic agents, and no effective therapies exist. Here we constructed a systems pharmacology model of intracellular signaling in peripheral neurons to identify novel drug targets for preventing peripheral neuropathy associated with proteasome inhibitors. Model predictions suggested the combinatorial inhibition of TNFα, NMDA receptors, and reactive oxygen species should prevent proteasome inhibitor-induced neuronal apoptosis. Dexanabinol, an inhibitor of all three targets, partially restored bortezomib-induced reduction of proximal action potential amplitude and distal nerve conduction velocity in vitro and prevented bortezomib-induced mechanical allodynia and thermal hyperalgesia in rats, including a partial recovery of intraepidermal nerve fiber density. Dexanabinol failed to restore bortezomib-induced decreases in electrophysiological endpoints in rats, and it did not compromise bortezomib anti-cancer effects in U266 multiple myeloma cells and a murine xenograft model. Owing to its favorable safety profile in humans and preclinical efficacy, dexanabinol might represent a treatment option for bortezomib-induced neuropathic pain.