MilliporeSigma
  • Treatment of oxaliplatin-induced peripheral neuropathy by intravenous mangafodipir.

Treatment of oxaliplatin-induced peripheral neuropathy by intravenous mangafodipir.

The Journal of clinical investigation (2013-12-21)
Romain Coriat, Jérôme Alexandre, Carole Nicco, Laurent Quinquis, Evelyne Benoit, Christiane Chéreau, Hervé Lemaréchal, Olivier Mir, Didier Borderie, Jean-Marc Tréluyer, Bernard Weill, Joel Coste, François Goldwasser, Frédéric Batteux
ABSTRACT

The majority of patients receiving the platinum-based chemotherapy drug oxaliplatin develop peripheral neurotoxicity. Because this neurotoxicity involves ROS production, we investigated the efficacy of mangafodipir, a molecule that has antioxidant properties and is approved for use as an MRI contrast enhancer. The effects of mangafodipir were examined in mice following treatment with oxaliplatin. Neurotoxicity, axon myelination, and advanced oxidized protein products (AOPPs) were monitored. In addition, we enrolled 23 cancer patients with grade ≥ 2 oxaliplatin-induced neuropathy in a phase II study, with 22 patients receiving i.v. mangafodipir following oxaliplatin. Neuropathic effects were monitored for up to 8 cycles of oxaliplatin and mangafodipir. Mangafodipir prevented motor and sensory dysfunction and demyelinating lesion formation. In mice, serum AOPPs decreased after 4 weeks of mangafodipir treatment. In 77% of patients treated with oxaliplatin and mangafodipir, neuropathy improved or stabilized after 4 cycles. After 8 cycles, neurotoxicity was downgraded to grade ≥ 2 in 6 of 7 patients. Prior to enrollment, patients received an average of 880 ± 239 mg/m2 oxaliplatin. Patients treated with mangafodipir tolerated an additional dose of 458 ± 207 mg/m2 oxaliplatin despite preexisting neuropathy. Mangafodipir responders managed a cumulative dose of 1,426 ± 204 mg/m2 oxaliplatin. Serum AOPPs were lower in responders compared with those in nonresponders. Our study suggests that mangafodipir can prevent and/or relieve oxaliplatin-induced neuropathy in cancer patients. Trial registration. Clinicaltrials.gov NCT00727922. Funding. Université Paris Descartes, Ministère de la Recherche et de l'Enseignement Supérieur, and Assistance Publique-Hôpitaux de Paris.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Ethylenediaminetetraacetic acid disodium salt dihydrate, meets analytical specification of Ph. Eur., BP, USP, FCC, 99.0-101.0%
Sigma-Aldrich
Ethylenediaminetetraacetic acid disodium salt dihydrate, BioUltra, for molecular biology, ≥99.0% (T)
Sigma-Aldrich
Ethylenediaminetetraacetic acid disodium salt dihydrate, ACS reagent, 99.0-101.0%
Sigma-Aldrich
Ethylenediaminetetraacetic acid solution, 0.02% in DPBS (0.5 mM), sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
Ethylenediaminetetraacetic acid disodium salt dihydrate, BioUltra, 98.5-101.5%
Sigma-Aldrich
Ethylenediaminetetraacetic acid disodium salt dihydrate, reagent grade, 98.5-101.5% (titration)
Sigma-Aldrich
Ethylenediaminetetraacetic acid disodium salt dihydrate, Sigma Grade, suitable for plant cell culture, 98.5-101.5%
Sigma-Aldrich
Ethylenediaminetetraacetic acid disodium salt dihydrate, suitable for electrophoresis, for molecular biology, 99.0-101.0% (titration)
Sigma-Aldrich
Ethylenediaminetetraacetic acid calcium disodium salt hydrate
Sigma-Aldrich
Ethylenediaminetetraacetic acid disodium salt dihydrate, ≥97.0% (KT)
Supelco
Ethylenediaminetetraacetic acid disodium salt dihydrate, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Ethylenediaminetetraacetic acid disodium salt solution, for molecular biology, 0.5 M in H2O, DNase, RNase, NICKase and protease, none detected
Sigma-Aldrich
Oxaliplatin, powder
Sigma-Aldrich
Ethylenediaminetetraacetic acid, BioUltra, anhydrous, ≥99% (titration)
Sigma-Aldrich
Ethylenediaminetetraacetic acid, ACS reagent, 99.4-100.6%, powder
Sigma-Aldrich
Ethylenediaminetetraacetic acid disodium salt solution, 2%, solution
Sigma-Aldrich
Ethylenediaminetetraacetic acid, anhydrous, crystalline, BioReagent, suitable for cell culture
Sigma-Aldrich
Ethylenediaminetetraacetic acid, purified grade, ≥98.5%, powder
Sigma-Aldrich
Ethylenediaminetetraacetic acid disodium salt solution, BioUltra, for molecular biology, pH 8.0, ~0.5 M in H2O
Sigma-Aldrich
Ethylenediaminetetraacetic acid, 99.995% trace metals basis
Sigma-Aldrich
Ethylenediaminetetraacetic acid, BioUltra, ≥99.0% (KT)
Sigma-Aldrich
Ethylenediaminetetraacetic acid, ≥98.0% (KT)
Oxaliplatin, European Pharmacopoeia (EP) Reference Standard