Treatment of oxaliplatin-induced peripheral neuropathy by intravenous mangafodipir

Coriat, Romain; Alexandre, Jérôme; Nicco, Carole; Quinquis, Laurent; Benoit, Évelyne; Chéreau, Christiane; Lemaréchal, Hervé; Mir, Olivier; Borderie, Didier; Tréluyer, Jean‐Marc; Weill, Bernard; Coste, Joël; Goldwasser, François; Batteux, Frédéric

doi:10.1172/jci68730

Cited by 66 publications

(108 citation statements)

References 48 publications

(45 reference statements)

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“…It was initially approved for use as a MRI contrast agent but was found to have protective antioxidant properties. In patients receiving FOLFOX for colon cancer, mangafodipir pretreatment decreased myelosuppression and protected against the neurotoxic effects of oxaliplatin [63,64]. The therapeutic effects of mangafodipir are dependent on an intact manganese (Mn 2+ ) complex, an effect that is compromised by free or loosely bound zinc in the plasma.…”

Section: Cell Metabolism Pathwaysmentioning

confidence: 99%

Investigational cancer drugs targeting cell metabolism in clinical development

Sborov¹,

Haverkos²,

Harris³

2014

Expert Opinion on Investigational Drugs

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Introduction Malignant cell transformation and tumor progression are associated with alterations in glycolysis, fatty acid synthesis, amino acid delivery and production of reactive oxygen species. With increased understanding of the role of metabolism in tumors, there has been interest in developing agents that target tumor specific metabolic pathways. Numerous promising agents targeting altered metabolic pathways are currently in Phase I – III clinical trials. Areas covered This paper reviews the early phase clinical trial development of these agents and provides perspective on the future direction of this emerging field. Specifically, the authors describe novel and repurposed therapies, focusing on the effects of each agent on tumor metabolism and results from relevant Phase I and II clinical trials. Expert opinion Metabolism modulating agents, alone and in combinations with other classes of agents, have shown efficacy in the treatment of neoplasm, which, the authors believe, will bear positive results in future studies. Because of the significant crosstalk between metabolic pathways and oncogenic signaling pathways, the authors also believe that combining metabolic modifiers with targeted agents will be an important strategy. An increased understanding of cancer metabolism, in addition to the continued study of metabolic modulators, should lead to further advances in this nascent therapeutic field in the future.

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Section: Cell Metabolism Pathwaysmentioning

confidence: 99%

Investigational cancer drugs targeting cell metabolism in clinical development

Sborov¹,

Haverkos²,

Harris³

2014

Expert Opinion on Investigational Drugs

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“…Oxaliplatin was the first platinum-based chemotherapeutic approved for advanced CRC and has been commonly used to treat CRC in combination with folinic acid and 5-fluorouracil known as FOLFOX [4, 5]. The cytotoxic activity of oxaliplatin is attributed to the formation of DNA adducts resulting from the intra- and inter-strand DNA crosslinks which inhibit DNA replication and transcription, followed by the generation of reactive oxygen species (ROS) and the ensuing DNA lesions and reduced glutathione depletion [6, 7]. Along with its pharmaceutical values in oncology, however, oxaliplatin is also known to induce adverse side effects which are related to its hematopoietic, gastrointestinal, and neuronal toxicities [4, 8, 9].…”

Section: Introductionmentioning

confidence: 99%

Aqueous extract of Lithospermi radix attenuates oxaliplatin-induced neurotoxicity in both in vitro and in vivo models

Cho

Park

et al. 2016

BMC Complement Altern Med

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BackgroundOxaliplatin can induce peripheral neuropathy (OXIPN) as an adverse side effect in cancer patients. Until now, no effective preventive or therapeutic drug has been developed; therefore, the dose-limiting factor of OXIPN is still an obstacle in the use of oxaliplatin to treat cancer patients. In the present study, we report for the first time that the aqueous extract of Lithospermi radix (WLR) can attenuate the OXIPN in both in vitro and in vivo neuropathic models.MethodsThe protective effect of WLR on OXIPN was evaluated in vitro by quantifying nerve growth factor (NGF)-stimulated neurite outgrowth in PC12 cells treated with a combination of oxaliplatin and WLR. The neuroprotective potential of WLR was further confirmed by measuring the changes in nociceptive sensitivities to external mechanical stimuli in neuropathic animals induced by oxaliplatin. Histological and immunohistochemical studies were further done to examine the effect of WLR in mouse spinal cords and footpads.ResultsOxaliplatin-induced neurotoxicity in NGF-stimulated PC12 cells. It could reduce the lengths and branching numbers of neuritis in NGF-stimulated PC12 cells. Co-treatment of WLR rescued the differentiated PC12 cells from the neurotoxicity of oxaliplatin. In a chronic OXIPN animal model, administration of oxaliplatin i.p. induced enhanced nociceptive sensitivity to mechanical stimuli (25.0 to 72.5 % of response rate) along with spinal activation of microglias and astrocytes and loss of intraepidermal nerve fibers in footpads, which is remarkably suppressed by oral administration of WLR (67.5 to 35 % of response rate at the end of experiment). Cytotoxicity of oxaliplatin determined in human cancer cells was not affected irrespective of the presence of WLR.ConclusionsIn conclusion, we demonstrated that WLR can attenuate OXIPN in both in vitro and in vivo experimental models, which may be in part attributed to its anti-inflammatory activity in the spinal cord and its neuroprotective potential in the peripheral nerve system without affecting the anti-tumor potential of oxaliplatin. Therefore, WLR could be considered as a good starting material to develop a novel therapeutic agent targeting OXIPN. However, further studies should be done to elucidate the underlying mechanism such as molecular targets and active constituent(s) in WLR with neuroprotective potential.

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“…In fact, oxaliplatin can cause both acute neuropathy (transient, distal paresthesia during or shortly after the first minutes of infusion) and chronic sensory neuropathy (distal paresthesia and numbness which can lead to functional disability, in the case of grade 3 toxicity). These neurosensory symptoms increase in intensity with cumulative doses, persist between cycles and affect the quality of life in the majority of patients (Coriat et al, 2014;Piccolo & Kolesar, 2014).…”

Section: Introductionmentioning

confidence: 99%

Antitumor activity of electrospun polylactide nanofibers loaded with 5-fluorouracil and oxaliplatin against colorectal cancer

et al. 2014

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The purpose of this study was to evaluate both in vitro and in vivo anticancer activities against colorectal cancer (CRC) of electrospun polylactide (PLA) nanofibers loaded with 5-fluorouracil (5-Flu) and oxaliplatin. For in vitro evaluation, human CRC HCT8 cells were directly exposed to the drug-loaded fiber mats, followed with MTT and flow cytometry (FCM) assay. For in vivo evaluation, the drug-loaded fiber mats were locally implanted into mouse colorectal CT26 tumor-bearing mice, followed with histological analysis and detection of survival rate. The results showed that the drug-loaded fiber mats was similar to that of the combination of free 5-Flu and oxaliplatin in vitro cytotoxicity but was much superior to intravenous injection of free drug in vivo anticancer activities, presenting with suppressed tumor growth rate and prolonged survival time of mice. In conclusion, anticancer activities of 5-Flu and oxaliplatin against CRC can be significantly improved by using PLA electrospun nanofibers as local drug delivery system.

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Treatment of oxaliplatin-induced peripheral neuropathy by intravenous mangafodipir

Cited by 66 publications

References 48 publications

Investigational cancer drugs targeting cell metabolism in clinical development

Investigational cancer drugs targeting cell metabolism in clinical development

Aqueous extract of Lithospermi radix attenuates oxaliplatin-induced neurotoxicity in both in vitro and in vivo models

Antitumor activity of electrospun polylactide nanofibers loaded with 5-fluorouracil and oxaliplatin against colorectal cancer

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