Many patients with cancer take antioxidant nutritional supplements during cancer treatment to alleviate treatment toxicities and to improve long-term outcomes, but little is known about the efficacy and safety of antioxidant use during cancer treatment [14
Despite the considerable debate about the role of antioxidant status in cancer outcomes, very few studies have assessed changes in antioxidant status and oxidative stress. Among children undergoing treatment for cancer there was only one study, to our knowledge, that measured exposure and treatment outcome in pediatric oncology [15
]. They found that children with ALL have altered antioxidant and micronutrient status at diagnosis and during treatment. Our results support this study; oxidative stress has been found to be increased during treatment and antioxidant status decreased as being measured by serum Glu.Px and MDA in the group of children with ALL who did not receive antioxidants. Antioxidant status was associated with treatment-related oxidative stress (febrile neutropenia and elevated liver enzymes). We observed a significant increase of serum Glu.Px in ALL patients receiving vitamin E and NAC after phase II of therapy in comparison to those who received chemotherapy alone without any supplementation. Although MDA decreased after phase II of therapy in group I of ALL patients, this decrease is not statistically significant; this could be explained, in part, by the relatively small sample size. Comparison of serum level of TNF-α
did not show any difference between both groups of patients. These findings are consistent with the results of Portakal et al. [16
], Ray et al. [17
], and Mantovani et al. [18
] who found an increase of oxidative stress during treatment in cancer patients as compared with control. Thus we may conclude that vitamin E and NAC supplementation had significantly decreased the level of free radicals resulting from oxidation as evidenced by increasing the level of GLu.Px and lowering level of MAD in ALL patients who took the supplementation.
The intensity of chemotherapy taken during induction phase and CNS intensification (vincristine, doxorubicin, cytosine arabinoside, cyclophosphamide, and 6-mercaptopurine) in addition to the prophylactic cranial irradiation which is proven to elicit 10 times more free radicals than chemotherapy alone leads to the increased incidence of toxic hepatitis as evidenced by increased serum levels of liver enzymes (SGOT and SGPT) and serum bilirubin. Occurrence of toxic hepatitis necessitates the interruption of treatment and prolongation of the period of hospital stay. Our study revealed significant decrease in the incidence of toxic hepatitis in group I compared to group II after induction chemotherapy (P
= .02). Furthermore this difference increased more after CNS intensification phase of therapy (P
< .001). Similar results had also been achieved as regard to the serum level of SGOT and SGPT in both groups of patients after the induction and CNS intensification phases of therapy (P
= .007, .004, .022, and < .003, resp.). These results support the findings of Mantovani et al. [19
] who concluded the effective role of some antioxidants in reducing reactive oxygen species, proinflammatory cytokines levels, and increasing Glu.Px levels in cancer patients. The effective in vivo use of NAC as antioxidant to counteract chemotherapy and radiotherapy toxicity in cancer patients concomitantly with vitamin E confirmed the beneficial effect of its in vitro use in advanced stage cancer [21
Hematological complications including bone marrow hypoplasia and febrile neutropenia as well as frequencies of blood and platelet transfusion were found to be significantly lower in group I compared to group II throughout the studied period (P < .001 for all differences).
Oxidative stress increases during treatment and antioxidant status decreases as measured by MDA and serum Glu.Px. With the combined use of NAC and vitamin E, some improvement in oxidative status had occurred; this could be considered as an encouraging result which paves the way for early combined use of these antioxidants as an adjuvant therapy for cancer chemotherapy. However further studies should be contemplated to assess the long term benefit of this adjuvant therapy during the maintenance chemotherapy, taking in consideration survival outcomes including disease-free and overall survival, and total chemo-/radiotherapy doses as basic parameters for evaluating the relative benefits and hazard ratios. This plan is of utmost importance, especially because of the feasible practical application of this adjuvant therapy being of low cost.