The serum calcium and potassium levels were within the normal range at the onset of hypomagnesaemia. The cumulative dose, median duration, and number of cycles of Cmab at the onset of hypomagnesaemia were 1400 mg/m2 (900-1650), 6 days (29-42), and 5 cycles (4)-(6), respectively. Among the six patients with hypomagnesaemia, five were treated with 1 mEq/mL of magnesium sulfate. Table 1 Characteristics of six patients

who were treated with oxaliplatin-fluoropyrimidine Inhibitors,research,lifescience,medical combination therapy for metastatic colorectal cancer followed by a combination of Cmab-irinotecan as a secondary treatment All patients experienced mFOLFOX6 regimen-induced peripheral CDK inhibitor neuropathy at the beginning of Cmab therapy, with grade 1 neuropathy in five patients and grade 2 neuropathy in one patient. After Cmab administration, PSN worsened in all six patients, and three patients progressed to grade 3. Among the three patients

with grade 3 PSN, two required a dose reduction and one had to discontinue treatment. Inhibitors,research,lifescience,medical The cumulative dose, median duration, and the number of cycles of Cmab at the time of PSN exacerbation were 2150 mg/m2 (1150-3150), 59.5 days (29-105), and 8 cycles (4)-(12), respectively. Five of the six patients (83%) developed Inhibitors,research,lifescience,medical hypomagnesaemia prior to PSN progression. Among these five patients, one had hypokalemia but none had abnormal calcium and potassium levels. One patient (17%) whose PSN was exacerbated before the onset of hypomagnesaemia had normal calcium and potassium levels. Discussion In the MOSAIC study, 90% of the neurotoxic effects occurred during active L-OHP therapy and the incidence decreased over time after discontinuation. Up to 70% and 80% improvement was Inhibitors,research,lifescience,medical noted after one and two years of discontinuation, respectively, which means that 20-30% did not even have improvement (1). Although precise mechanisms underlying

the development of PSN have not been fully clarified, PSN has been attributed to the accumulation of platinum in the dorsal root ganglion based on the results from animal experiments (8). Gamelin et al. suggested that a possible mechanism may Inhibitors,research,lifescience,medical be the effect of oxalate, a one of the breakdown products Ribonucleotide reductase of L-OHP, on neuronal sodium channels (11). Based on this hypothesis, chelation of oxalate can be a possible candidate for improvement of PSN. For this reason, L-OHP therapy is proactively supplemented with calcium and magnesium for chelation of oxalate. Therefore, administering hypomagnesaemia-inducing Cmab to patients who have been treated with L-OHP over a long period is thought to aggravate PSN by depleting magnesium that is necessary to chelate the breakdown the products of accumulated L-OHP. Furthermore, long-term Cmab therapy has been reported to inf luence not only magnesium levels but also the levels of calcium, potassium, and other electrolytes (9),(14)-(16). These results suggest that hypomagnesaemia may not be the only causative etiology.