Mangafodipir as a cytoprotective adjunct to chemotherapy – a case report

Yri, Olav Erich; Vig, Jens; Hegstad, Elisabeth; Hovde, Øistein; Pignon, Ingrid; Jynge, Per

doi:10.1080/02841860802680427

Cited by 18 publications

(21 citation statements)

References 8 publications

(4 reference statements)

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“…Findings from a case report [54] and a feasibility study [55] reported to the Swedish Medical Product Agency in 2010 (Table 1) suggested that MnDPDP, through its SOD mimetic activity, protects blood, nervous, and mucous tissues in patients during chemotherapy with FOLFOX. Other important properties of DPDP and its metabolite PLED are their high affinities for iron and copper.…”

Section: The Sod Mimetics Mndpdp and Calmangafodipir [Ca4mn(dpdp)5] Amentioning

confidence: 99%

“…Findings from a case report [54] and the above-mentioned feasibility/translational study in stage III colon cancer patients [55] suggest that MnDPDP, through its SOD mimetic activity, protects blood, nervous, and mucous tissues in patients during chemotherapy with Nordic FLOX/FOLFOX (oxaliplatin + 5-FU) (Table 1). Coriat and coworkers [29] have also published promising results with MnDPDP in patients with preexisting oxaliplatin-associated CIPN.…”

Section: Clinical Evidence That Mndpdp Protects Against Oxidative Strmentioning

confidence: 99%

“…The case report of Yri et al [54] described a patient who received 15 palliative cycles of oxaliplatin plus 5-FU/LV (Nordic FLOX regimen). It suggested that MnDPDP protects against oxaliplatin-associated CIPN.…”

Section: Clinical Evidence That Mndpdp Protects Against Oxidative Strmentioning

confidence: 99%

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Mangafodipir a Selective Cytoprotectant — with Special Reference to Oxaliplatin and Its Association to Chemotherapy-Induced Peripheral Neuropathy (CIPN)

Karlsson

Andersson

Jynge

2017

Translational Oncology

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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 calcium and 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 (O2•−), 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.

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Section: The Sod Mimetics Mndpdp and Calmangafodipir [Ca4mn(dpdp)5] Amentioning

confidence: 99%

Section: Clinical Evidence That Mndpdp Protects Against Oxidative Strmentioning

confidence: 99%

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Mangafodipir a Selective Cytoprotectant — with Special Reference to Oxaliplatin and Its Association to Chemotherapy-Induced Peripheral Neuropathy (CIPN)

Karlsson

Andersson

Jynge

2017

Translational Oncology

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“…[8] one precursor N-acetylcysteine (NAC), which can functiondirectlyinthedetoxificationofH 2 O 2 andas athioldonortoprotectcriticalsulfhydrylgroupsin cell proteins, also prevented the hematological toxicityofpaclitaxel.Ontheotherhand,mangafodipir, butnotNACappearstoimprovethetherapeuticactivity of this chemotherapeutic agent against CT26 mouse colon cancer cells in vivo. These chemical compounds also protected normal leukocytes from the toxic effects of oxaliplatin and 5-fluorouracil in vitro.Becausemangafodipiriswidelyused,thisdrug mightbeappropriateforstudyasachemoprotective compoundinhumantrials [12,69,70]. On the other hand, hydrogen peroxide is also knownasastrongoxidantthatinducesapoptosisof tumorcellsin vitro [3,71].PerhapsH 2 O 2 aloneisrelativeunstableandisasmallwater-solublemolecule.…”

Section: Ros-mediated Treatment Of Cancer As a Therapeutic Strategymentioning

confidence: 99%

Significance of selected antioxidant enzymes in cancer cell progression

Bułdak¹,

Bułdak²,

Kukla³

et al. 2014

pjp

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Antioxidantenzymes(AOEs),includingsuperoxidedismutaseisoenzymes(SOD), catalase(CAT),glutathioneperoxidase(GSH-Px)alongwithglutathionereductase (GR),reducedglutathione(GSH)andglutathionetransferase(GST),arethought tobenecessaryforlifeprocessesinalloxygen-metabolizingcellsbyremovingreactiveoxygenspecies(ROS).ThebiologicalsignificanceofAOEsintransformedcells isstillunclear,buttheircapacitytosurvivemaybeaffectedbychangesincellular processessuchasproliferation,invasiveness,migration,apoptosisanddrugresistance.Thisreviewsummarizesthesignificanceofantioxidantenzymesincancer cellprogressionmainlyinanin vitrocontext.

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“…Concerning future brain Mn uptake studies, we find it relevant to address a patient who received MnDPDP in a total dose of 140 mmol/kg during 8 months. 3 In this patient with terminal cancer of the colon, MnDPDP (10 mmol/kg) was administered for the protection of normal tissue during 14 cycles of chemotherapy with anticancer agents (oxaliplatin and 5-fluorouracil). The regimen was well-tolerated without the adverse effects of chemotherapy, and there was a notable relief of pain.…”

mentioning

confidence: 99%