A review of the literature on hypomagnesemia in cancer patients

Abstract
Background
Causes and Prevalence of Magnesium Deficiency in Oncology Patients
Routes of Magnesium Deficiency | Conditions and Medications |
Gastrointestinal | Diarrhea, pancreatitis, irritable bowel disease, bowel resection, protein-calorie malnutrition, total parenteral nutrition, bowel fistula1 |
Renal | Postobstructive diuresis, postacute tubular necrosis, renal transplantation, interstitial nephropathy, Bartter syndrome, Gitelman’s syndrome1 |
Medications | Proton pump inhibitors, corticosteroids, laxatives, loop and thiazide diuretics, foscarnet, digoxin, amphotericin B, colchicines, theophylline, macrolide antibiotics, petamidine, tobramycin, amikacin1; tacrolimus1,2 |
Chemotherapeutic agents | Aminoglycosides (gentamicin, streptomycin)1; cyclosporine, cisplatin3; carboplatin4; cetuximab5; panitumumab6 |
Other | Burns1; alcoholism, diabetes7 |
Prevalence of Magnesium Deficiency With Platinum-based Chemotherapy
Laboratory Testing for Magnesium
Clinical Symptoms of Magnesium Deficiency
Mild | Muscle cramps, constipation, fatigue, anxiety, restless legs, insomnia, irritability, insulin resistance1; loss of appetite, nausea, vomiting, headache, weakness, numbness, tingling23; depression24 |
Major | Refractory hypocalcemia and hypokalemia7; high blood pressure, tremor, prolonged QT interval, cardiac arrhythmias, hyperreflexia, ataxia, carpopedal spasms14; migraine headache, asthma, hypoparathyroidism25; tetany and/or convulsions14,26 |
Severe | Seizures, metabolic alkylosis, psychiatric disturbances27; cortical blindness28 |
Magnesium and Carcinogenesis
Intervention Studies Involving Magnesium and Platinum-based Chemotherapy
Patients | Randomized | Intervention | Control | Outcome |
40 patients with ovarian cancer receiving paclitaxel and cisplatin | Yes (double- blind) | 20.3 mmol IV Mg sulphate (5 g) every 3 wk plus oral Mg carbonate 500 mg 3x/d during the treatment intervals | Placebo | Serum Mg varied significantly between supplemented and placebo groups (P<0.0001). Control group showed significantly greater decrease of GFR assessed by serum levels of creatinine (P=0.0069), Cockroft-Gault (P=0.0077), and Modification Diet of Renal Disease (P=0.032)54 |
32 patients with upper GI malignancies receiving cisplatin/5-fluorouracil | Yes |
12 mmol IV Mg sulfate (2.96 g) prehydration and 16 mmol IV Mg sulfate (3.94 g) posthydration |
Mg only when the serum Mg below normal | Mg supplements necessary in 50% of control group’s cycles, several instances of symptomatic hypomagnesemia requiring further IV supplements in midcycle55 |
201 patients with cervical cancer receiving cisplatin and radiation | Yes |
Group 2: 8.12 mmol IV Mg sulphate (2 g) pre- and posthydration Group 3: 8.12 mmol IV Mg sulphate (2 g) pre- and posthydration and then 12.18 mmol (3 g) pre- and posthydration after cycle 3 |
Group 1: 4.06 mmol IV Mg sulphate (1 g) pre- and posthydration | 62.8% (44/70) control vs 32.6% (22/70) group 2 patients with episodes of hypomagnesemia (P=0.007). Group 3 had a 49.6% decrease in the total number of episodes compared to control. Patients in the second intervention group showed a 100% improvement incidence of persistent hypomagnesemia over the 2 other cohorts (P=0.001)56 |
16 patients with testicular cancer and 1 with ovarian dysgerminoma receiving cisplatin | Yes | 8 mmol IV Mg sulphate followed by oral 246 mg Mg citrate 3x/d | No treatment or placebo | Significantly greater renal tubular damage (as assessed by urine N-acetyl-B-D-glucosaminidase) and lower serum Mg in controls. Trend towards reduced treatment delays in the supplemented group20 |
23 patients with advanced head and neck cancer receiving cisplatin | Yes | 123 mg oral MgAHa 3x/d continuously for 3-4 mo. If fell below <1.4 mg dL serum mg, dose doubled to 246 mg 3x/d
|
123 mg oral MgAH 3x/d as needed | Most controls required continuous Mg supplementation. 20% of continuous MgAH developed hypomagnesemia in a given cycle57 |
41 patients treated with cisplatin, mixed tumor types | Yes | 12.18 mmol IV Mg (3 g) before cisplatin or oral Mg pidolate, 2 g every 8 h on days 2 to 21 of cisplatin | No treatment | Patients in both supplementation arms showed significantly higher Mg levels than controls from the second course on oral or from the third course on IV; 3 of 9 patients (33%) in the IV Mg arm and 4 of 9 (44%) in the oral Mg arm developed hypomagnesemia after the fourth course of cisplatin, compared with 9 of 10 (90%) patients in the control group17 |
33 metastatic patients with colon cancer receiving folinic acid, fluorouracil, and oxaliplatin-6 | Yes | Infusions with Ca gluconate 850 mg and Mg sulfate 720 mg | Placebo | No reduction in neurotoxicity with Ca/Mg infusions. No change in platinum concentrations52 |
401 patients receiving high dose (>60 mkg/m2) of cisplatin in firstline setting, mixed tumor types | No | 20 mEq Mg sulfate with 500 mL of one-quarter isotonic saline over 1 h after cisplatin administration | No treatment | Reduced risk of cisplatin nephrotoxicity (RR:0.175, P=0.0004) and reduced severity of renal toxicity (P=0.012) in Mg-supplemented group58 |
37 patients with NSCLC receiving cisplatin/ irinotecan; matched with 32 controls | No, case-control study | Days 1 through 4 after irinotecan, orally administered alkalinizations with sodium bicarbonate, Mg oxide, basic water, and ursodeoxycholic acid. Controlled defecation with up to 4.0 g/d of Mg oxide and 2 L/d of excess basic water | Matched controls taking cisplatin/ irinotecan |
Use of oral administration and controlled defecation reduced the incidence of delayed diarrhea (> or = grade 2: P=0.005), nausea (P=0.0001), vomiting (P=0.001), granulocytopenia (P=0.03), and lymphocytopenia (P=0.034). Dose intensification was well tolerated in patients receiving oral administration and controlled defecation, allowing dose escalation from 35.6±6.0 to 39.9±5.6 mg/m2/wk (P<0.001)52 |
8 patients with metastatic germ cell cancer and 8 matched controls taking high-dose cisplatin | No | 12.18 mmol IV Mg sulphate (3 g), 12 mmol prehydration, IV and oral as needed | Matched controls received no treatment with Mg or placebo | Mean serum Mg levels higher in supplemented patients (P<0.01)59 |
17 patients with cervical cancer receiving cisplatin | No | 20 mmol if Mg<0.62 mmol/L (4.9 g) | N/A | Incidence of serum hypomagnesemia reduced from 65% to 17.6%60 |
28 children receiving cisplatin, mixed tumor types | No | Unreported | 16 given Mg after cisplatin, 12 pre- and postcisplatin | Mg levels higher in pre- and postcisplatin group than postcisplatin only (P<0.01)61 |
10 patients with metastatic testicular cancer receiving cisplatin | No | 0.3 mmol Mg chloride/kg/day and 0.4 mmol potassium chloride/kg/day | 5 given 0.4 mmol potassium chloride/kg/d only | Mean serum Mg levels higher in supplemented patients (P<0.001)62 |
22 patients with upper GI cancer receiving epirubicin, cisplatin, and fluorouracil | No | IV Mg 25 mmol (6.15 g) pre- and posthydration | IV Mg 12.5 mmol (3 g) pre- and posthydration | No significant difference69 |
214 consecutive patients with mixed tumor types receiving cisplatin | No | Bleomycin, etoposide, cisplatin chemotherapy and 60 mmol IV Mg/cycle (14.78 g), POMBeACE chemotherapy received 20 mmol IV Mg/cycle (4.9 g) | N/A |
60 mmol IV Mg per cycle of 33 mg/m2/wk cisplatin sufficient to prevent hypomagnesemia; 20 mmol IV Mg per cycle of 40 mg/m2/wk cisplatin was insufficient to prevent hypomagnesemia14
|
23 patients with esophageal or hypopharyngeal cancer receiving fluorouracil and cisplatin; 10 patients received Mg supplementation | No | Mg sulphate (20 mEq) administered before fluorouracil (800mg/m2/24 h per days 1-5) and Cisplatin (80mg/m2/d) | 13 patients did not receive Mg supplementation | Mg supplementation successfully reduced the incidence of nephrotoxicity (P=0.038).64 |
Abbreviations: Ca, calcium; GFR, glomerular filtration rate; GI, gastrointestinal; IV, intravenous; Mg, magnesium; MgAH, Mg aspartate hydrochloride; NA, not available; NSCLC, non-small-cell lung carcinoma; RR, relative risk.
Oral Magnesium Cautions and Nutrient/Drug Interactions
Oral Magnesium Cautions and Nutrient/Drug Interactions
Contraindicated | Patients with high grade atrioventricular blocks, bifascicular blocks1 |
Cautions and requires monitoring |
Patients with kidney failure, concomitant use with calcium channel blockers, neuromuscular blocking agents, antidiabetic agents1 |
Drug interactions requiring dose separation |
Tetracycline antibiotics (eg, demeclocycline, doxycycline) and aquinolone antibiotics (eg, ciprofloxacin, levofloxacin): 2 h before Mg or 4-6 h after Mg65 Warfarin: 2 h before Mg or 4-6 h after Mg65 Bisphosphanates: 30 min before Mg or 2 h after Mg1 (Note: Zometa and Aredia do not appear to have the interaction65) Zinc: 1-2 h apart65 |
Synergistic | Adrenergic bronchodilators |
Abbreviation: Mg, magnesium.
Signs of Excess Magnesium
Oral Magnesium: Rationale, Forms, and Dosing
Form of Mg |
Percentage Elemental Mg25,73 | Elemental Mg per Standard Pill | Common Commercial Name and Dosing | Laxative Effect |
Mg citrate | 16.2% | 80 mg or 500 mg tablet | NA; 1-2 2x/d | Yes, mild |
Mg glycinate | 50.0% | 100 mg-150 mg capsule | Chelated Mg; 1-2 2x/d | No |
Mg oxide | 60.3% | 288 mg or 500 mg tablet | NA; 1 2x/d-3x/d | Yes |
Mg chloride | 12.0% | 64 mg or 535 mg tablet | Topical sprays, gels, “Slow Mag”; 1/d | Yes |
Mg taurate | 9.0% | 100 mg-125 mg tablet | NA; 1 2x/d | No |
Mg L threonate | Unknown | 50 mg-75 mg capsule | “Neuro Mag” or “Magtein”; 2x/d-4x/d | Yes, mild |
Abbreviations: Mg, magnesium; NA, not available.
Pain and Hypomagnesemia
Conclusions
References
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