Prevention of Oxaliplatin-Related Neurotoxicity by Calcium and Magnesium Infusions

Abstract

Purpose: Oxaliplatin is active in colorectal cancer. Sensory neurotoxicity is its dose-limiting toxicity. It may come from an effect on neuronal voltage-gated Na channels, via the liberation one its metabolite, oxalate. We decided to use Ca and Mg as oxalate chelators.Experimental Design: A retrospective cohort of 161 patients treated with oxaliplatin ؉ 5-fluorouracil and leucovorin for advanced colorectal cancer, with three regimens of oxaliplatin (85 mg/m 2 /2w, 100/2w, 130/3w) was identified. Ninety-six patients received infusions of Ca gluconate and Mg sulfate (1 g) before and after oxaliplatin (Ca/Mg group) and 65 did not.Results: Only 4% of patients withdrew for neurotoxicity in the Ca/Mg group versus 31% in the control group (P ‫؍‬ 0.000003). The tumor response rate was similar in both groups. The percentage of patients with grade 3 distal paresthesia was lower in Ca/Mg group (7 versus 26%, P ‫؍‬ 0.001). Acute symptoms such as distal and lingual paresthesia were much less frequent and severe (P ‫؍‬ 10 -7 ), and pseudolaryngospasm was never reported in Ca/Mg group. At the end of the treatment, 20% of patients in Ca/Mg group had neuropathy versus 45% (P ‫؍‬ 0.003). Patients with grade 2 and 3 at the end of the treatment in the 85 mg/m 2 oxaliplatin group recovered significantly more rapidly from neuropathy than patients without Ca/Mg. Conclusions: Ca/Mg infusions seem to reduce incidence and intensity of acute oxaliplatin-induced symptoms and might delay cumulative neuropathy, especially in 85 mg/m 2 oxaliplatin dosage.

Pregabalin for the Prevention of Oxaliplatin-Induced Painful Neuropathy: A Randomized, Double-Blind Trial

“…The bulk of evidence is negative for both scenarios [12], [14], [19], [20], with rare exceptions [17], [21]. Importantly, the large majority of studies have not used validated pain measurement tools [10], [11], [13], [14], [16], [19], [22], [23], while most have used the common terminology criteria (CTC) adverse events grading system as the primary outcome measurement. While this choice is sound and supported by robust evidence [24], it must be kept in mind that most patients with OXAIPN have small‐fiber‐predominant polyneuropathy [1], which has as its main symptom neuropathic pain.…”

A pilot clinical trial assessing the efficacy and safety of supplementation with a B complex vitamin to reduce the incidence of chemotherapy induced peripheral neuropathy in patients diagnosed with a malignancy

“…Retrospective study [250] Level III-2 161 3 cycles of FOLFOX every 2 weeks Grade 3 or 4 CIPN in Ca/Mg group recovered significantly quicker DBRCT [251] Level …”

“…Magnesium and calcium infusions with oxaliplatin also showed initial positive results in a retrospective study [250]. Three clinical trials [251][252][253] reported that efficacy was not enhanced with one trial (n=174) being terminated due to the treatment group reporting a significant lower response rate compared to placebo [251].…”

“…There was also a major confounding factor with this study as each patient (either on vitamin E or placebo) also received infusions of calcium and magnesium with each administration of chemotherapy. This may have played a key factor with possible interactions occurring with the vitamin E and could explain why the placebo (68% vs 83%) [256], experienced less CIPN considering previous trials on magnesium/calcium infusion and oxaliplatin [250].…”

“…Limitations identified in the retrospective study [250] include no randomisation of patients, no blinding and patients, medical and nursing staff may have been biased in their reporting or assessment of signs and symptoms. All studies that did not include a placebo noted the limitation of not having a placebo-effect.…”