3.1 Patient characteristics and treatment details
Fig. 1 shows a flowchart of the patient selection procedure. A total of 113 patients received cetuximab during the study period. Forty-eight patients whose serum magnesium, calcium, or albumin levels were not measured during cetuximab treatment were excluded. Additionally, we excluded six patients who had only one administration of cetuximab and seven patients whose regimen was not completed. Table 1 shows the patient backgrounds. We identified 52 patients (40 males and 12 females) who received cetuximab during the study period. The mean age of the patients was 67.9 ± 10.3 years. Cetuximab was administrated for the treatment of colorectal cancer and head and neck cancer in 11 and 41 patients, respectively. The proportion of patients who had a history of anti-cancer therapy before cetuximab administration was 53.8% (28/52). The mean laboratory data were within the normal range. Table 2 shows the patient treatment details. The average treatment period was 50.5 ± 30.9 d. Regarding the list of regimens, the proportion of patients who received monotherapy and combination therapy group was 67.3% (35/52) and 32.7% (17/52), respectively. Patients were administered one of the following regimens: cetuximab monotherapy; CDDP+5-FU+cetuximab, which included cisplatin, 5-fluorouracil, and cetuximab; PCE therapy, which included paclitaxel, carboplatin, and cetuximab; CPT-11+cetuximab, which included irinotecan and cetuximab; high-dose DTX+cetuximab, which included docetaxel and cetuximab; CBDCA+5-FU+cetuximab, which included carboplatin, 5-fluorouracil, and cetuximab; SOX+cetuximab therapy, which included S-1, oxaliplatin, and cetuximab; and sLV5FU2+cetuximab, which included levofolinate, 5-FU, and cetuximab. Platinum-containing drugs were administered to 12 patients and eight patients received CDDP+5-FU+cetuximab, which were the most frequent regimens. The proportion of patients who additionally received MgO tablet and MgSO4 injection was 57.7% (30/52) and 15.4% (8/52), respectively.
3.2 Effect of patient factors on the serum magnesium levels in patients
Table 3 shows relationships between the onset of hypomagnesemia and patient characteristics during cetuximab administration. The onset of hypomagnesemia was associated with the baseline serum sodium levels [odds ratio (OR): 0.741, 95% CI: 0.588–0.934, p = 0.003], and a combination of MgO tablet (OR: 0.997, 95% CI: 0.995–0.999, p = 0.002). However, the onset of hypomagnesemia was not associated with the baseline serum potassium, magnesium, or calcium levels because these electrolyte levels in the most of patients were within the normal range. Furthermore, no significant difference was observed between the onset of hypomagnesemia and the combined of platinum-containing drugs (OR: 2.333, 95% CI: 0.624–8.719, p = 0.209) and MgSO4 injection (OR: 3.974, 95% CI: 0.826–19.123, p = 0.079). Table 4 shows the multivariable logistic regression analysis of relationships between the onset of hypomagnesemia and patient characteristics or treatment details. The multivariate logistic regression analysis revealed that the baseline serum sodium levels (OR: 0.729, 95% CI: 0.552–0.963, p = 0.017) and the combination of magnesium oxide tablet (OR: 0.997, 95% CI: 0.995–0.999, p = 0.026) were one of the independent factors for hypomagnesemia, and the model of p-value was <0.001. Additionally, the ROC curves of these multiple models were analyzed to assess the predictive abilities. Fig.2 shows the ROC curves of patient characteristics and treatment details to detect the onset of hypomagnesemia. The predictive ability of a ROC curve may be assessed as follows: 0.50–0.70, low; 0.70–0.90, moderate; and 0.90–1.00, high. The AUC value of the model was 0.801, indicating fair predictive performances.
Fig. 3 shows the effects of cetuximab administration on the serum magnesium level in all patients, patients with hypomagnesemia among study period, patients administered MgO tablet, and patients with pre-hyponatremia. Serum magnesium levels tended to decline with an increasing number of administrations. Serum magnesium levels were significantly reduced in the hypomagnesemia group than in the non-hypomagnesemia group (least-square (LS) mean, 95% confidence interval (CI): 1.7 mg/dL, 1.6–1.8 mg/dL vs. 2.1 mg/dL, 2.1–2.2 mg/dL, p < 0.001). The serum magnesium level before administration was not significantly different between the hypomagnesemia group and the non-hypomagnesemia group (LS mean, 95% CI: 2.0 mg/dL, 1.9–2.2 mg/dL vs. 2.2 mg/dL, 2.1–2.3 mg/dL). However, the serum magnesium level after the two administrations was significantly different between the two groups (LS mean, 95% CI: 1.8 mg/dL, 1.7–1.9 mg/dL vs. 2.2 mg/dL, 2.1–2.3 mg/dL). The serum magnesium level was significantly lower in the patient who had pre-hyponatremia (LS mean, 95% CI: 1.8, 1.7–1.9 mg/dL vs. 2.1, 2.0–2.1 mg/dL, p = 0.003). In the patient who developed pre-hyponatremia, the LS mean of serum magnesium level was less than 1.8 mg/dL after the five administrations. Additionally, the serum magnesium levels were significantly higher in the patients receiving combined MgO tablets (LS mean, 95% CI: 2.0, 1.9–2.1 mg/dL vs. 1.9, 1.8–2.0 mg/dL, p = 0.041).