Chemotherapy-Induced Changes in Plasma Amino Acids and Lipid Oxidation of Resected Patients with Colorectal Cancer: A Background for Future Studies

Abstract

Previous studies have documented that FOLFOX and XELOX therapies negatively impact the metabolism of skeletal muscle and extra-muscle districts. This pilot study tested whether three-month FOLFOX or XELOX therapy produced changes in plasma amino acid levels (PAAL) (an estimation of whole-body amino acid metabolism) and in plasma levels of malondialdehyde (MDA), a marker of lipid hyper oxidation. Fourteen ambulatory, resected patients with colorectal cancer scheduled to receive FOLFOX (n = 9) or XELOX (n = 5) therapy, after overnight fasting, underwent peripheral venous blood sampling, to determine PAAL and MDA before, during, and at the end of three-month therapy. Fifteen healthy matched subjects (controls) only underwent measures of PAAL at baseline. The results showed changes in 87.5% of plasma essential amino acids (EAAs) and 38.4% of non-EAAs in patients treated with FOLFOX or XELOX. These changes in EAAs occurred in two opposite directions: EAAs decreased with FOLFOX and increased or did not decrease with XELOX (interactions: from p = 0.034 to p = 0.003). Baseline plasma MDA levels in both FOLFOX and XELOX patients were above the normal range of values, and increased, albeit not significantly, during therapy. In conclusion, three-month FOLFOX or XELOX therapy affected plasma EAAs differently but not the baseline MDA levels, which were already high.

Keywords: FOLFOX and XELOX therapy; colorectal cancer; plasma amino acid changes; plasma malondialdehyde changes; potential clinical implications; primary tumor location.

Figure 1

Percentage change from baseline (TA) of total amino acids in XELOXs and FOLFOXs at TB and TC. Data reported as mean (95% confidence interval). †: p = 0.03 for the comparison XELOX vs. FOLFOX at TB (Mann–Whitney U-test). Abbreviations: AAs, amino acids; TA, Time A; TB, Time B; TC, Time C.

Figure 2

Percentage change from baseline (TA) of essential amino acids in XELOXs and FOLFOXs at TB and TC. Data reported as mean (95% confidence interval). †: p = 0.03 for the comparison XELOX vs. FOLFOX at TB (Mann–Whitney U-test). ‡: p = 0.003 for the comparison XELOX vs. FOLFOX at TC (Mann–Whitney U-test). *: p = 0.008 for the comparison FOLFOX TC vs. TA (Wilcoxon signed rank test). Abbreviations: AAs, amino acids; TA, Time A; TB, Time B; TC, Time C.

Figure 3

Percentage change from baseline (TA) of branched-chain amino acids in XELOXs and FOLFOXs at TB and TC. Data reported as mean (95% confidence interval). †: p = 0.04 for the comparison XELOX vs. FOLFOX at TB (Mann–Whitney U-test). ‡: p = 0.002 for the comparison XELOX vs. FOLFOX at TC (Mann–Whitney U-test). *: p = 0.008 for the comparison FOLFOX TC vs. TA (Wilcoxon signed rank test). Abbreviations: AAs, amino acids; TA, Time A; TB, Time B; TC, Time C.

Figure 4

Scatterplot showing the relationship between isoleucine and lymphocyte count in XELOXs and FOLFOXs at TA. The linear regression line is also shown (red dash-dotted line). Abbreviations: TA, Time A.

Figure 5

Scatterplot showing the relationship between tryptophan and lymphocytes (% of TWBC) in XELOX and FOLFOX patients at TA. The linear regression line is also shown (red dash-dotted line). Abbreviations: TA, Time A; TWBC, total white blood cells.

Figure 6

Scatterplot showing the relationship between tryptophan and neutrophil/lymphocyte ratio in XELOX and FOLFOX patients at TA. The linear regression line is also shown (red dash-dotted line). Abbreviations: TA, Time A.