Has been found that NAC can be otoprotective when it is administered up to 4 hours after cisplatin [138]. It was also found that the best route of administration of NAC, in order to improve protection against the renal damage caused by cisplatin, is the intra-arterial (compared to the oral, intravenous, and intraperitoneal routes) [212]. According to these trials, it 6-Methoxybaicalein side effects appears that both the timing and the route of administration of the LOR-253 biological activity antioxidant may be important factors to provide some nutritional recommendations associated with cancer treatment. In addition to NAC, other antioxidants have been evaluated to reduce the toxicity of cisplatin, such as lycopene, which has demonstrated its capability of reducing the renal toxicity induced by this drug [139]. The effect of NAC has also been evaluated in patients treated with combinations of chemotherapy agents plus radiotherapy. A clinical trial, in which 40 children with acute lymphoblastic leukemia (ALL) took part, was intended to assess whether the intake of NAC and vitamin E (400 IU/day)11 orally would counteract the high toxicity from chemotherapy (vincristine, doxorubicin, cytosine arabinoside, cyclophosphamide, and 6-mercaptopurine) and the prophylactic cranial irradiation during the first two months of treatment. After analyzing blood levels of GPx, malondialdehyde (MDA), tumor necrosis factor- (TNF-), and liver enzymes, the results indicated that children who received antioxidants showed lower incidence of toxic hepatitis and less probabilities of requirement of blood and platelet transfusions during treatment [121]. As mentioned earlier, melatonin has a great antioxidant capacity through different mechanisms of action. Therefore, we have referred to its role as adjuvant in chemotherapy to treat various cancers. In a clinical trial conducted by Lissoni, the effect of administration of 20 mg/day of oral melatonin was evaluated in patients with NSCLC treated with cisplatin plus etoposide or cisplatin plus gemcitabine, or gastrointestinal cancer treated with oxaliplatin and 5-FU. In both cases, patients who received melatonin had a higher rate of tumor regression and a greater two-year survival rate [122]. And more recently, Sookprasert et al. revealed the results of the MIRCIT trial, which concluded that advanced NSCLC patients receiving melatonin in combination with chemotherapy did not get better levels of survival, though the side effects were fewer [123]. It would be necessary to continue further studies to clarify the role of melatonin and to be able to compare these two clinical trials. This would allow us to establish the similarities and differences between the advanced and nonadvanced NSCLC patient, their appropriate treatment, and their basal serum levels of antioxidants, in order to compare the results of both studies.8. Conclusions and Future PerspectivesConsidering all the results exposed above, we conclude that antioxidant intake seems to influence the effectiveness of antitumor therapy and its adverse effects. However, we believe that at the moment it cannot be possible to give a general recommendation on whether or not to take antioxidants during treatment. This is because the final effect will depend on the type of cancer, the mechanism of action of the drug or drugs used in the treatment, and the type of antioxidants. More studies are needed to clarify the results of the clinical trials, which sometimes are contradictory to each other. It is necessary to define the mo.Has been found that NAC can be otoprotective when it is administered up to 4 hours after cisplatin [138]. It was also found that the best route of administration of NAC, in order to improve protection against the renal damage caused by cisplatin, is the intra-arterial (compared to the oral, intravenous, and intraperitoneal routes) [212]. According to these trials, it appears that both the timing and the route of administration of the antioxidant may be important factors to provide some nutritional recommendations associated with cancer treatment. In addition to NAC, other antioxidants have been evaluated to reduce the toxicity of cisplatin, such as lycopene, which has demonstrated its capability of reducing the renal toxicity induced by this drug [139]. The effect of NAC has also been evaluated in patients treated with combinations of chemotherapy agents plus radiotherapy. A clinical trial, in which 40 children with acute lymphoblastic leukemia (ALL) took part, was intended to assess whether the intake of NAC and vitamin E (400 IU/day)11 orally would counteract the high toxicity from chemotherapy (vincristine, doxorubicin, cytosine arabinoside, cyclophosphamide, and 6-mercaptopurine) and the prophylactic cranial irradiation during the first two months of treatment. After analyzing blood levels of GPx, malondialdehyde (MDA), tumor necrosis factor- (TNF-), and liver enzymes, the results indicated that children who received antioxidants showed lower incidence of toxic hepatitis and less probabilities of requirement of blood and platelet transfusions during treatment [121]. As mentioned earlier, melatonin has a great antioxidant capacity through different mechanisms of action. Therefore, we have referred to its role as adjuvant in chemotherapy to treat various cancers. In a clinical trial conducted by Lissoni, the effect of administration of 20 mg/day of oral melatonin was evaluated in patients with NSCLC treated with cisplatin plus etoposide or cisplatin plus gemcitabine, or gastrointestinal cancer treated with oxaliplatin and 5-FU. In both cases, patients who received melatonin had a higher rate of tumor regression and a greater two-year survival rate [122]. And more recently, Sookprasert et al. revealed the results of the MIRCIT trial, which concluded that advanced NSCLC patients receiving melatonin in combination with chemotherapy did not get better levels of survival, though the side effects were fewer [123]. It would be necessary to continue further studies to clarify the role of melatonin and to be able to compare these two clinical trials. This would allow us to establish the similarities and differences between the advanced and nonadvanced NSCLC patient, their appropriate treatment, and their basal serum levels of antioxidants, in order to compare the results of both studies.8. Conclusions and Future PerspectivesConsidering all the results exposed above, we conclude that antioxidant intake seems to influence the effectiveness of antitumor therapy and its adverse effects. However, we believe that at the moment it cannot be possible to give a general recommendation on whether or not to take antioxidants during treatment. This is because the final effect will depend on the type of cancer, the mechanism of action of the drug or drugs used in the treatment, and the type of antioxidants. More studies are needed to clarify the results of the clinical trials, which sometimes are contradictory to each other. It is necessary to define the mo.