An this is a series of cases supporting this hypothesis

Article Hypomagnesemia as a possible explanation behind episodes of ...

We tried magnesium supplementation following oxaloplatin chemotherapy for colorectal cancer and noticed reduction in the incidence of neuropathy secondary to this chemotherapy

This is interesting and if proven will be quite helpful

I'd say that the first place to look at, regarding Neurotoxicity of Anti-Cancer agents would be the medical equivalent of the package insert for patients, here we call it 'Technical file', if the agent is connected to Neurotoxicty, the information from the drug producer must contain data about the incidence and type of Nerotoxicity, and many times also the drug dose modifcations needed in front od Neurotoxicty, and even therapy choices available.

Early and late neurotoxicity have different mechanisms of origin and different approaches, probably patients always deserve a therapy attempt with group B Vitamin supplements, and also some minerals PO, it will never harm, and sometimes you get results from this, and there are several drugs useful for neuropathic pain, from the good old Tricyclic antidepressants, that have the problem of some specific cardiac, genitourinary, pulmonary and other toxicities, to modern drugs such as Pregabalin, having also an anxiolitic effect, and Venlafaxine.

Some say Opioids are not that good in neuropathic pain, combined pain killer therapy is needed many times, and as usual, attempts should be made to retrieve as much info about the origin an nature of pain as possible, it's not the same a neuropathy by OxaliPlatin or Taxanes, than a compression neuropathy, that may improve just with a surgical procedure, or a Diabetic neuropathy.

A recent RCT stated that Ca and Mg infusions are not useful as a preventive measure for OxaliPlatin neurotoxicity, but it probably would be good never infusing Ca and Mg salts simultaneously, as pKa issues may induce the production of hardly soluble Calcium salts, negating all the preventive effects of Ca and Mg.

Paclitaxel neurotoxicty is due to a big extent to the Cremophor (a Castor Oil derivative) added to make taxane stable in solution, but nabPaclitaxel also has neurotoxicity, lesser in incidence and degree, and the Cremophor acts as a MDR efflux pump inhibitor, thus contributing to the Taxane activity. Hope your patient does fine! Salut †

Dear Colleagues,

Magnesium inhibits calcium entry via blockade of the N‐methyl‐d‐aspartate (NMDA) receptor which has been proposed as a mechanism for its action as a pain "medication". Best evidence for its ability to stop neuralgic pain is in post-herpatic neuralgia where it can be used with or without steroids (published dose: Mg Sulfate 30 mg/kg as an iv infusion). It is also effective in severe migraine. It has also been tried for prevention of pain post anesthesia but it was not found to be consistently effective. One has to remember that Mg infusions have been used for patients with severe hypocalcemia and potential side effects are well established. One should avoid rapid injections/infusions as they can trigger Ventricular tachycardias, CNS depression, and hypotension.

In the context of oxaliplain neuropathy, UptoDate provides a nice summary of the experience that can be summarized as LACK OF ACTIVITY:

"Calcium and magnesium infusions — Based upon an early report suggesting benefit for intravenous calcium and magnesium (IV Ca/Mg) prior to oxaliplatin infusion in patients with advanced disease [123], placebo-controlled phase III trials were initiated in patients receiving oxaliplatin for metastatic colorectal cancer (the CONcePT trial [132]) and in the adjuvant setting (the N04C7 trial [133]). However, a planned interim analysis of the first 180 patients enrolled in the CONcePT trial found significantly lower response rates in patients treated with IV Ca/Mg compared to the control group [125], and the trial was closed by an independent data monitoring committee; enrollment in the N04C7 trial was also suspended. The lower response rate in patients with metastatic CRC who were receiving IV Ca/Mg in conjunction with oxaliplatin was not subsequently confirmed [132,134].

Data on the neuroprotective benefit of IV Ca/Mg from these trials has been mixed. The N04C7 trial [133] suggested significantly less acute muscle spasms with the use of Ca/Mg supplementation and fewer patients with grade 2 or worse chronic neurotoxicity, while a preliminary report of the prematurely discontinued, small CONcePT trial suggested no difference in physician-assessed neurotoxicity outcomes [132].

The issue of neuroprotection with IV Ca/Mg was directly addressed in United States Intergroup trial N08CB, in which 353 patients with resected colon cancer undergoing adjuvant therapy with FOLFOX were randomly assigned to one of three arms: IV CaMg (1 g calcium gluconate, 1 g magnesium sulfate) before and after oxaliplatin, IV CaMg before and placebo after, or placebo before and after oxaliplatin [135]. The primary endpoint was cumulative sensory neurotoxicity as assessed by the sensory subscale of the EORTC QLQ-CIPN20; secondary endpoints included the NCI Common Terminology Criteria for Adverse Events (CTCAE) for neurotoxicity, v4.0 (table 4), and an oxaliplatin-specific neurotoxicity scale; acute neuropathy data were also collected for five days after each oxaliplatin dose. In a preliminary report presented at the 2013 American Society of Clinical Oncology (ASCO) annual meeting, there was no benefit for IV CaMg in preventing or diminishing the severity of acute or chronic neurotoxicity, and supplementation did not allow for higher delivered doses of oxaliplatin or a lower chemotherapy discontinuation rate" (reference: http://www.uptodate.com/contents/neurologic-complications-of-platinum-based-chemotherapy).

There are several options for management of neuropathic pain in cancer patients: http://www.uptodate.com/contents/cancer-pain-management-adjuvant-analgesics-coanalgesics?source=see_link&anchor=H18#H18. In addition to general strategies of pain management, including the use of dexamethasone, the following information can be found about neuropathic pain:

europathic pain — Any of the drugs classified as multipurpose adjuvant analgesics could be considered for a clinical trial in patients with opioid-refractory neuropathic cancer pain. The following reflects our general approach to these patients:

If neuropathic pain refractory to an opioid is associated with significant depressed mood, we suggest first-line therapy with an antidepressant (Grade 2B). Options include a serotonin-norepinephrine reuptake inhibitor (SNRI) such as duloxetine, a secondary tricyclic drug such as desipramine, or possibly bupropion, if the pain is complicated by fatigue or somnolence. (See 'Analgesic antidepressants' above.)

For patients with neuropathic pain that is not associated with a depressed mood, we suggest first line therapy with gabapentin or pregabalin (Grade 2C). We generally prefer pregabalin because of simplified dosing. (See 'Gabapentin and pregabalin' above.)

The positive placebo-controlled trial of duloxetine [50] for painful chemotherapy-induced neuropathy suggests that in this setting, duloxetine is an appropriate first-line agent. However, additional data will be needed to establish the superiority of duloxetine or any other antidepressant over an alpha-2-delta modulator in these patients. (See 'Antidepressants' above.)

For refractory cases, we suggest second-line therapy with the alternative agent, an antidepressant or an anticonvulsant, depending on which drug was used initially.

A trial of another anticonvulsant, a cannabinoid (eg, dronabinol), or an alpha-2 adrenergic agonist (eg, tizanidine) could be considered in patients with neuropathic pain that is refractory to opioids and other appropriate adjuvant analgesics. (See 'Alpha-2 adrenergic agonists' above and 'Cannabinoids' above and 'Other anticonvulsants' above.)

A trial of a transdermal lidocaine patch could be considered in patients who have focal, peripherally-generated pain.

REFERENCES:

Dworkin RH, O'Connor AB, Backonja M, et al. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain 2007; 132:237.

Serpell MG, Neuropathic pain study group. Gabapentin in neuropathic pain syndromes: a randomised, double-blind, placebo-controlled trial. Pain 2002; 99:557.

Caraceni A, Zecca E, Bonezzi C, et al. Gabapentin for neuropathic cancer pain: a randomized controlled trial from the Gabapentin Cancer Pain Study Group. J Clin Oncol 2004; 22:2909.

Frampton JE, Foster RH. Pregabalin: in the treatment of postherpetic neuralgia. Drugs 2005; 65:111.

http://bja.oxfordjournals.org/content/89/5/711.short

I saw a Young girl with a Dysgerminoma suffering sound-triggered seizures that are well explained by hypomagnesemia caused by CisPlatin, and also Torsades de Pointes Ventricular Tachycardia,a potentially lethal arrythmia, may resuklt from acute hypomagnesemia.

Is the neuropathic pain a posible consequence of hypomagnesemia? I'll have to check this, but the degree of hypomagnesemia to produce neuropathy sounds as so high, that other symptoms would appear before, and it must be remarked that both in pre-eclampsia and Miocardial Infarction, the continued dosing of Magnesium products is noxious; in looking for hypomagnesemia, it probably has some importance the fact that there may be differences in extracelular and intracelular magnesium content, around 1980 this was measured by intra-erythrocite Magnesium, and the whole issue is very complex.

I'd say that measuring serum Magnesium may be worth doing before any chemotherapy, to eventually correct deficits, and that, besides acute hypomagnesemia in the frame of a Platin compound administration, you'll get more safe and positive results from B group Vitamin supplements tan from other Mg including products, and it always remains misterious to me the reason why many multivitamins supplements contain more tan 100% the daily allowance for Manganese, when manganese has been linked to Parkinson Disease in IV drug users that employed Permanganate to prepare the drug, and a clear definiton of carential symptomps for Manganese exists. Or yes?

We would need more clinical evidence to support routine determination of magnesium in patients receiving quimo

Thanks, but probably, Mg determination won't be a 'Routine' determination ever, just in patients under some specific risks, or having some symptoms, e.g. heart rhythm changes or any type of nurological/neuromuscular symptom or finding may Mg concentrations assessment be useful.

Doubt: how often the extracellular and intracellular -these last measured for example in RBCs- Mg concentrations differ with clinical signification? 

Salut †