Efficacy of a Novel Sigma-1 Receptor Antagonist for Oxaliplatin-Induced Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Phase IIa Clinical Trial
Abstract 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 cycle) was tested in patients with colorectal ca...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Bruna, Jordi [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2017 |
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| Schlagwörter: |
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| Anmerkung: |
© The Author(s) 2017 |
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| Übergeordnetes Werk: |
Enthalten in: NeuroRX - Springer-Verlag, 2006, 15(2017), 1 vom: 18. Sept., Seite 178-189 |
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| Übergeordnetes Werk: |
volume:15 ; year:2017 ; number:1 ; day:18 ; month:09 ; pages:178-189 |
| Links: |
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| DOI / URN: |
10.1007/s13311-017-0572-5 |
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| Katalog-ID: |
SPR031272339 |
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| 245 | 1 | 0 | |a 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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| 520 | |a Abstract 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 cycle) was tested in patients with colorectal cancer receiving FOLFOX in a phase II, randomized, double-blind, 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. Sixty-three (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 1 treatment-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 exposure, and showed a potential neuroprotective role for chronic cumulative oxaipn. Furthermore, MR309 showed an acceptable safety profile. | ||
| 650 | 4 | |a Neurotoxicity |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Neuropathic pain |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Adverse effects |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Chemotherapy |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Colorectal cancer |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a MR309/E-52862 |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Videla, Sebastián |4 aut | |
| 700 | 1 | |a Argyriou, Andreas A. |4 aut | |
| 700 | 1 | |a Velasco, Roser |4 aut | |
| 700 | 1 | |a Villoria, Jesús |4 aut | |
| 700 | 1 | |a Santos, Cristina |4 aut | |
| 700 | 1 | |a Nadal, Cristina |4 aut | |
| 700 | 1 | |a Cavaletti, Guido |4 aut | |
| 700 | 1 | |a Alberti, Paola |4 aut | |
| 700 | 1 | |a Briani, Chiara |4 aut | |
| 700 | 1 | |a Kalofonos, Haralabos P. |4 aut | |
| 700 | 1 | |a Cortinovis, Diego |4 aut | |
| 700 | 1 | |a Sust, Mariano |4 aut | |
| 700 | 1 | |a Vaqué, Anna |4 aut | |
| 700 | 1 | |a Klein, Thomas |4 aut | |
| 700 | 1 | |a Plata-Salamán, Carlos |4 aut | |
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10.1007/s13311-017-0572-5 doi (DE-627)SPR031272339 (SPR)s13311-017-0572-5-e DE-627 ger DE-627 rakwb eng Bruna, Jordi verfasserin aut Efficacy of a Novel Sigma-1 Receptor Antagonist for Oxaliplatin-Induced Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Phase IIa Clinical Trial 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2017 Abstract 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 cycle) was tested in patients with colorectal cancer receiving FOLFOX in a phase II, randomized, double-blind, 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. Sixty-three (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 1 treatment-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 exposure, and showed a potential neuroprotective role for chronic cumulative oxaipn. Furthermore, MR309 showed an acceptable safety profile. Neurotoxicity (dpeaa)DE-He213 Neuropathic pain (dpeaa)DE-He213 Adverse effects (dpeaa)DE-He213 Chemotherapy (dpeaa)DE-He213 Colorectal cancer (dpeaa)DE-He213 MR309/E-52862 (dpeaa)DE-He213 Videla, Sebastián aut Argyriou, Andreas A. aut Velasco, Roser aut Villoria, Jesús aut Santos, Cristina aut Nadal, Cristina aut Cavaletti, Guido aut Alberti, Paola aut Briani, Chiara aut Kalofonos, Haralabos P. aut Cortinovis, Diego aut Sust, Mariano aut Vaqué, Anna aut Klein, Thomas aut Plata-Salamán, Carlos aut Enthalten in NeuroRX Springer-Verlag, 2006 15(2017), 1 vom: 18. Sept., Seite 178-189 (DE-627)SPR031264964 nnns volume:15 year:2017 number:1 day:18 month:09 pages:178-189 https://dx.doi.org/10.1007/s13311-017-0572-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER AR 15 2017 1 18 09 178-189 |
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10.1007/s13311-017-0572-5 doi (DE-627)SPR031272339 (SPR)s13311-017-0572-5-e DE-627 ger DE-627 rakwb eng Bruna, Jordi verfasserin aut Efficacy of a Novel Sigma-1 Receptor Antagonist for Oxaliplatin-Induced Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Phase IIa Clinical Trial 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2017 Abstract 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 cycle) was tested in patients with colorectal cancer receiving FOLFOX in a phase II, randomized, double-blind, 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. Sixty-three (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 1 treatment-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 exposure, and showed a potential neuroprotective role for chronic cumulative oxaipn. Furthermore, MR309 showed an acceptable safety profile. Neurotoxicity (dpeaa)DE-He213 Neuropathic pain (dpeaa)DE-He213 Adverse effects (dpeaa)DE-He213 Chemotherapy (dpeaa)DE-He213 Colorectal cancer (dpeaa)DE-He213 MR309/E-52862 (dpeaa)DE-He213 Videla, Sebastián aut Argyriou, Andreas A. aut Velasco, Roser aut Villoria, Jesús aut Santos, Cristina aut Nadal, Cristina aut Cavaletti, Guido aut Alberti, Paola aut Briani, Chiara aut Kalofonos, Haralabos P. aut Cortinovis, Diego aut Sust, Mariano aut Vaqué, Anna aut Klein, Thomas aut Plata-Salamán, Carlos aut Enthalten in NeuroRX Springer-Verlag, 2006 15(2017), 1 vom: 18. Sept., Seite 178-189 (DE-627)SPR031264964 nnns volume:15 year:2017 number:1 day:18 month:09 pages:178-189 https://dx.doi.org/10.1007/s13311-017-0572-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER AR 15 2017 1 18 09 178-189 |
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10.1007/s13311-017-0572-5 doi (DE-627)SPR031272339 (SPR)s13311-017-0572-5-e DE-627 ger DE-627 rakwb eng Bruna, Jordi verfasserin aut Efficacy of a Novel Sigma-1 Receptor Antagonist for Oxaliplatin-Induced Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Phase IIa Clinical Trial 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2017 Abstract 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 cycle) was tested in patients with colorectal cancer receiving FOLFOX in a phase II, randomized, double-blind, 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. Sixty-three (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 1 treatment-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 exposure, and showed a potential neuroprotective role for chronic cumulative oxaipn. Furthermore, MR309 showed an acceptable safety profile. Neurotoxicity (dpeaa)DE-He213 Neuropathic pain (dpeaa)DE-He213 Adverse effects (dpeaa)DE-He213 Chemotherapy (dpeaa)DE-He213 Colorectal cancer (dpeaa)DE-He213 MR309/E-52862 (dpeaa)DE-He213 Videla, Sebastián aut Argyriou, Andreas A. aut Velasco, Roser aut Villoria, Jesús aut Santos, Cristina aut Nadal, Cristina aut Cavaletti, Guido aut Alberti, Paola aut Briani, Chiara aut Kalofonos, Haralabos P. aut Cortinovis, Diego aut Sust, Mariano aut Vaqué, Anna aut Klein, Thomas aut Plata-Salamán, Carlos aut Enthalten in NeuroRX Springer-Verlag, 2006 15(2017), 1 vom: 18. Sept., Seite 178-189 (DE-627)SPR031264964 nnns volume:15 year:2017 number:1 day:18 month:09 pages:178-189 https://dx.doi.org/10.1007/s13311-017-0572-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER AR 15 2017 1 18 09 178-189 |
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10.1007/s13311-017-0572-5 doi (DE-627)SPR031272339 (SPR)s13311-017-0572-5-e DE-627 ger DE-627 rakwb eng Bruna, Jordi verfasserin aut Efficacy of a Novel Sigma-1 Receptor Antagonist for Oxaliplatin-Induced Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Phase IIa Clinical Trial 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2017 Abstract 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 cycle) was tested in patients with colorectal cancer receiving FOLFOX in a phase II, randomized, double-blind, 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. Sixty-three (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 1 treatment-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 exposure, and showed a potential neuroprotective role for chronic cumulative oxaipn. Furthermore, MR309 showed an acceptable safety profile. Neurotoxicity (dpeaa)DE-He213 Neuropathic pain (dpeaa)DE-He213 Adverse effects (dpeaa)DE-He213 Chemotherapy (dpeaa)DE-He213 Colorectal cancer (dpeaa)DE-He213 MR309/E-52862 (dpeaa)DE-He213 Videla, Sebastián aut Argyriou, Andreas A. aut Velasco, Roser aut Villoria, Jesús aut Santos, Cristina aut Nadal, Cristina aut Cavaletti, Guido aut Alberti, Paola aut Briani, Chiara aut Kalofonos, Haralabos P. aut Cortinovis, Diego aut Sust, Mariano aut Vaqué, Anna aut Klein, Thomas aut Plata-Salamán, Carlos aut Enthalten in NeuroRX Springer-Verlag, 2006 15(2017), 1 vom: 18. Sept., Seite 178-189 (DE-627)SPR031264964 nnns volume:15 year:2017 number:1 day:18 month:09 pages:178-189 https://dx.doi.org/10.1007/s13311-017-0572-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER AR 15 2017 1 18 09 178-189 |
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10.1007/s13311-017-0572-5 doi (DE-627)SPR031272339 (SPR)s13311-017-0572-5-e DE-627 ger DE-627 rakwb eng Bruna, Jordi verfasserin aut Efficacy of a Novel Sigma-1 Receptor Antagonist for Oxaliplatin-Induced Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Phase IIa Clinical Trial 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2017 Abstract 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 cycle) was tested in patients with colorectal cancer receiving FOLFOX in a phase II, randomized, double-blind, 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. Sixty-three (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 1 treatment-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 exposure, and showed a potential neuroprotective role for chronic cumulative oxaipn. Furthermore, MR309 showed an acceptable safety profile. Neurotoxicity (dpeaa)DE-He213 Neuropathic pain (dpeaa)DE-He213 Adverse effects (dpeaa)DE-He213 Chemotherapy (dpeaa)DE-He213 Colorectal cancer (dpeaa)DE-He213 MR309/E-52862 (dpeaa)DE-He213 Videla, Sebastián aut Argyriou, Andreas A. aut Velasco, Roser aut Villoria, Jesús aut Santos, Cristina aut Nadal, Cristina aut Cavaletti, Guido aut Alberti, Paola aut Briani, Chiara aut Kalofonos, Haralabos P. aut Cortinovis, Diego aut Sust, Mariano aut Vaqué, Anna aut Klein, Thomas aut Plata-Salamán, Carlos aut Enthalten in NeuroRX Springer-Verlag, 2006 15(2017), 1 vom: 18. Sept., Seite 178-189 (DE-627)SPR031264964 nnns volume:15 year:2017 number:1 day:18 month:09 pages:178-189 https://dx.doi.org/10.1007/s13311-017-0572-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER AR 15 2017 1 18 09 178-189 |
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Bruna, Jordi @@aut@@ Videla, Sebastián @@aut@@ Argyriou, Andreas A. @@aut@@ Velasco, Roser @@aut@@ Villoria, Jesús @@aut@@ Santos, Cristina @@aut@@ Nadal, Cristina @@aut@@ Cavaletti, Guido @@aut@@ Alberti, Paola @@aut@@ Briani, Chiara @@aut@@ Kalofonos, Haralabos P. @@aut@@ Cortinovis, Diego @@aut@@ Sust, Mariano @@aut@@ Vaqué, Anna @@aut@@ Klein, Thomas @@aut@@ Plata-Salamán, Carlos @@aut@@ |
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Efficacy of a Novel Sigma-1 Receptor Antagonist for Oxaliplatin-Induced Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Phase IIa Clinical Trial Neurotoxicity (dpeaa)DE-He213 Neuropathic pain (dpeaa)DE-He213 Adverse effects (dpeaa)DE-He213 Chemotherapy (dpeaa)DE-He213 Colorectal cancer (dpeaa)DE-He213 MR309/E-52862 (dpeaa)DE-He213 |
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Bruna, Jordi Videla, Sebastián 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 |
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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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Efficacy of a Novel Sigma-1 Receptor Antagonist for Oxaliplatin-Induced Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Phase IIa Clinical Trial |
| abstract |
Abstract 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 cycle) was tested in patients with colorectal cancer receiving FOLFOX in a phase II, randomized, double-blind, 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. Sixty-three (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 1 treatment-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 exposure, and showed a potential neuroprotective role for chronic cumulative oxaipn. Furthermore, MR309 showed an acceptable safety profile. © The Author(s) 2017 |
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Abstract 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 cycle) was tested in patients with colorectal cancer receiving FOLFOX in a phase II, randomized, double-blind, 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. Sixty-three (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 1 treatment-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 exposure, and showed a potential neuroprotective role for chronic cumulative oxaipn. Furthermore, MR309 showed an acceptable safety profile. © The Author(s) 2017 |
| abstract_unstemmed |
Abstract 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 cycle) was tested in patients with colorectal cancer receiving FOLFOX in a phase II, randomized, double-blind, 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. Sixty-three (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 1 treatment-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 exposure, and showed a potential neuroprotective role for chronic cumulative oxaipn. Furthermore, MR309 showed an acceptable safety profile. © The Author(s) 2017 |
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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 1 treatment-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 exposure, and showed a potential neuroprotective role for chronic cumulative oxaipn. 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