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Efficacy of a Novel Sigma-1 Receptor Ant.pdf (1.87 MB)

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2017-09-18

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cc-by (c) Bruna, Jordi et al., 2017
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/224144

Efficacy of a Novel Sigma-1 Receptor Antagonist for Oxaliplatin-Induced Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Phase IIa Clinical Trial

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https://doi.org/10.1007/s13311-017-0572-5

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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.

Matèries

Medicaments d'alliberament retardat, Farmacologia molecular, Dolor oncològic

Matèries (anglès)

Delayed-action drugs, Molecular pharmacology, Cancer pain

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Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

BRUNA, Jordi, et al. Efficacy of a Novel Sigma-1 Receptor Antagonist for Oxaliplatin-Induced Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Phase IIa Clinical Trial. Neurotherapeutics. 2017. Vol. 15, num. 1, pags. 178-189. ISSN 1933-7213. [consulted: 26 of June of 2026]. Available at: https://hdl.handle.net/2445/224144

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