2026-04-13T03:01:53Zhttps://recercat.cat/oai/request
oai:recercat.cat:2445/2241442025-11-19T22:14:23Zcom_2072_1057col_2072_478916col_2072_478917
RECERCAT author Bruna, Jordi author Videla, Sebastià author Argyriou, Andreas A. author Velasco, Roser author Villoria, Jesús author Santos, Cristina author Nadal, Cristina author Cavaletti, Guido author Alberti, Paola author Briani, Chiara author Kalofonos, Haralabos P. author Cortinovis, Diego author Sust, Mariano author Vaqué, Anna author Klein, Thomas author Plata Salamán, Carlos 2025-11-19T22:14:23Z 2025-11-19T22:14:23Z 2025-11-06T09:08:22Z2025-11-06T09:08:22Z2017-09-182025-11-04T11:17:43Z http://hdl.handle.net/2445/224144 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. cc-by (c) Bruna, Jordi et al., 2017 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Medicaments d'alliberament retardat Farmacologia molecular Dolor oncològic Delayed-action drugs Molecular pharmacology Cancer pain Efficacy of a Novel Sigma-1 Receptor Antagonist for Oxaliplatin-Induced Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Phase IIa Clinical Trial info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion