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Mangafodipir a Selective Cytoprotectant - with Special Reference to Oxaliplatin and Its Association to Chemotherapy-Induced Peripheral Neuropathy (CIPN)
Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
2017 (English)In: Translational Oncology, ISSN 1944-7124, E-ISSN 1936-5233, Vol. 10, no 4, 641-649 p.Article, review/survey (Refereed) Published
Abstract [en]

Oxaliplatin, in combination with 5-fluorouracil plus folinate (or capecitabine), has increased survival substantially in stage III colorectal cancer and prolonged life in stage IV patients, but its use is compromised because of severe toxicity. Chemotherapy-induced peripheral neuropathy (CIPN) is the most problematic dose-limiting toxicity of oxaliplatin. Oncologists included for years calciumand magnesium infusion as part of clinical practice for preventing CIPN. Results from a phase III prospective study published in 2014, however, overturned this practice. No other treatments have been clinically proven to prevent this toxicity. There is a body of evidence that CIPN is caused by cellular oxidative stress. Clinical and preclinical data suggest that the manganese chelate and superoxide dismutase mimetic mangafodipir (MnDPDP) is an efficacious inhibitor of CIPN and other conditions caused by cellular oxidative stress, without interfering negatively with the tumoricidal activity of chemotherapy. MnPLED, the metabolite of MnDPDP, attacks cellular oxidative stress at several critical levels. Firstly, MnPLED catalyzes dismutation of superoxide (O-2(center dot-) ), and secondly, having a tremendous high affinity for iron (and copper), PLED binds and disarms redox active iron/copper, which is involved in several detrimental oxidative steps. A case report from 2009 and a recent feasibility study suggest that MnDPDP may prevent or even cure oxaliplatin-induced CIPN. Preliminary results from a phase II study (PLIANT) suggest efficacy also of calmangafodipir, but these results are according to available data obscured by a surprisingly low number of adverse events and a seemingly lower than expected efficacy of FOLFOX.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC , 2017. Vol. 10, no 4, 641-649 p.
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-140523DOI: 10.1016/j.tranon.2017.04.012ISI: 000407707700020PubMedID: 28668762OAI: oai:DiVA.org:liu-140523DiVA: diva2:1140102
Note

Funding Agencies|Medical Research Council of Southeast Sweden [FORSS-85191]

Available from: 2017-09-11 Created: 2017-09-11 Last updated: 2017-09-11

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Karlsson, Jan OlofAndersson, RolfJynge, Per
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