2026-04-17T06:47:55Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/2241442025-11-19T22:14:23Zcom_2072_1057col_2072_478916col_2072_478917

Efficacy of a Novel Sigma-1 Receptor Antagonist for Oxaliplatin-Induced Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Phase IIa Clinical Trial Bruna, Jordi Videla, Sebastià Argyriou, Andreas A. Velasco, Roser Villoria, Jesús Santos, Cristina Nadal, Cristina Cavaletti, Guido Alberti, Paola Briani, Chiara Kalofonos, Haralabos P. Cortinovis, Diego Sust, Mariano Vaqué, Anna Klein, Thomas Plata Salamán, Carlos Medicaments d'alliberament retardat Farmacologia molecular Dolor oncològic Delayed-action drugs Molecular pharmacology Cancer pain This trial assessed the efficacy of MR309 (a novel selective sigma-1 receptor ligand previously developed as E-52862) in ameliorating oxaliplatin-induced peripheral neuropathy (oxaipn). A discontinuous regimen of MR309 (400 mg/day, 5 days per ycle) was tested in patients with colorectal cancer receiving FOLFOX in a phase II, randomized, doubleblind, placebo-controlled, multicenter clinical trial. Outcome measures included changes in 24-week quantitative measures of thermal sensitivity and total neuropathy score. In total, 124 patients were randomized (1:1) to MR309 or placebo. Sixtythree (50.8%) patients withdrew prematurely before completing 12 planned oxaliplatin cycles. Premature withdrawal because of cancer progression was less frequent in the MR309 group (7.4% vs 25.0% with placebo; p = 0.054). MR309 significantly reduced cold pain threshold temperature [mean treatment effect difference (SE) vs placebo: 5.29 (1.60)°C; p = 0.001] and suprathreshold cold stimulus-evoked pain intensity [mean treatment effect difference: 1.24 (0.57) points; p = 0.032]. Total neuropathy score, health-related quality-of-life measures, and nerve-conduction parameters changed similarly in both arms, whereas the proportion of patients with severe chronic neuropathy (National Cancer Institute Common Terminology Criteria for Adverse Events ≥ 3) was significantly lower in the MR309 group (3.0% vs 18.2% with placebo; p = 0.046). The total amount of oxaliplatin delivered was greater in the active arm (1618.9 mg vs 1453.8 mg with placebo; p = 0.049). Overall, 19.0% of patients experienced at least 1treatment-related adverse event (25.8% and 11.9% with MR309 and placebo, respectively). Intermittent treatment with MR309 was associated with reduced acute oxaipn and higher oxaliplatin posure, and showed a potential neuroprotective role for chronic cumulative oxaipn. Furthermore,MR309 showed an acceptable safety rofile. 2025-11-19T22:14:23Z 2025-11-19T22:14:23Z 2025-11-19T22:14:23Z 2025-11-06T09:08:22Z 2025-11-06T09:08:22Z 2017-09-18 2025-11-04T11:17:43Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/2445/224144 Reproducció del document publicat a: https://doi.org/10.1007/s13311-017-0572-5 Neurotherapeutics, 2017, vol. 15, num. 1, 178-189 https://doi.org/10.1007/s13311-017-0572-5 cc-by (c) Bruna, Jordi et al., 2017 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Elsevier Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))