Chemotherapy

Cancer is a worldwide problem, affecting many people across the world in different parts of the body. It is the process of uncontrollable cell division, resulting in an extra mass of tissue being produced, called a tumour [Ref]. There are many effective treatments used to try and combat cancer such as chemotherapy, radiation therapy, surgery and specific anticancer drugs [Ref]. Combining these methods can help reduce the toxicity and side effects, resulting in a less painful treatment. In this essay, I will look further into one of the most common treatments; chemotherapy and outline how it works. Then I will discuss if concurrently taking antioxidants, can enhance the efficacy of chemotherapy or not, by considering the arguments for and against this view.

In order to understand how any treatment can be enhanced, firstly I need to consider how cancer is developed and how it affects our body cells. Cancer has many symptoms that are common to “less serious diseases” and can be caused by a combination of many carcinogens [ref]. Cancer can occur in many of our body cells, which are constantly undergoing the normal cell cycle of growth and division. When cells become damaged, apoptosis occurs and new cells are formed [ref]. This is a controlled process and helps maintain the bodies normal functioning. However, mutation in cell DNA can occur, resulting in inappropriate uncontrolled cell division, known as cancer [ref]. This can cause a tumour to be formed, which can be non-cancer causing (benign) or cancer causing (malignant). Benign tumours are less harmful and can normally be removed, where as malignant tumours are more dangerous and can cause metastasis, which allows the cancer to spread and form tumours in other parts of the body. Different treatments are available and are dependent from patient to patient.

Chemotherapy is used in x% of cancer patients and it involves cytotoxic drugs being administered into the blood stream [ref]. It is available in many different pharmaceutical formulations and works by “damaging the DNA inside the nucleus of dividing cells” [ref]. As our body develops, many normal cells stop dividing and form resting cells. However, cells in our hair, skin and nails for example, continue to grow and divide. As a result, chemotherapy is effective in most cancer situations but has many side effects such as loss of hair, low blood cell count, tiredness, nausea and diarrhoea, as the treatment also acts upon normal cells. However, many of these side effects are reversible, as your body will adequately replace the normal cells, after chemotherapy has been stopped [ref]. Depending on factors such as “how far the cancer has spread, age of patient and the general health of patient”, [ref] the type of treatment recommended, varies from patient to patient. Therefore, chemotherapy might be more effective in one patient, but not in another.

Chemotherapy can also produce harmful oxygen compounds in our body, known as free radicals [ref]. Free radicals are very unstable and react with other compounds to become more stable, creating a chain reaction throughout the body [ref]. They can act on proteins found in DNA or cell membranes, causing their structure to change and mutation to occur [ref]. However, our body can produce free radicals naturally via metabolism, as a result of a poor diet. Nevertheless, our body can handle the natural production of free radicals whereas excessive production is dangerous [ref]. Antioxidants can be given to reduce the dangerous effects of free radicals. They act by chemically binding to the free radical compound, stabilizing and stopping them from reacting with other compounds, thus why they are also known as “free radical scavengers” [ref]. They are found in many natural foods, such as fruits and vegetables but can also be given as a supplement via tablets and capsules [ref]. Therefore, the use of antioxidants combined with chemotherapy should theorectically be successful. However, many studies have been conducted and the results have varied.

Lissoni et al conducted two experiments, firstly consisting of 100 patients with

There are many studies to support the use of ant with chem....

However there is much evidence against the use of antioxidants, as it is argued that antioxidants affect the efficacy of chemotherapy. Bairati et al (DATE) conducted an experiment which was based on 540 cancer patients some of which were taking antioxidants whilst undergoing chemotherapy and others were treated with a placebo. The findings showed that the patients who were taking the antioxidants had reduced side effects which were caused by the chemotherapy. He also stated that those patients, who smoked compared to those who didn't, had reduced chemotherapy side effect improvements. On the other hand, the patients' mortality had decreased due to the severe interaction between the antioxidants and the chemotherapy. This may be due to the fact that instead of destroying the cancerous cells, the use of the antioxidants was protecting the cells and therefore stopping the cells from dying.

In conclusion

Antioxidants are phytochemicals

http://caonline.amcancersoc.org/cgi/content/full/55/5/319 There are considerable in vitro and animal data showing that vitamin C and other antioxidants can protect cells against radiation and chemotherapy. This goes against the use of antioxidants.

Bairati et al. (5,37) reported that among 540 head and neck cancer patients who were randomly assigned to receive either {alpha}-tocopherol with or without β-carotene vs placebo concurrent with their radiation therapy, those who received both antioxidants had a statistically significant 38% reduction in severe, acute side effects. However, this benefit appeared to be offset by reductions of 29% and 56% in the local tumor control rates for {alpha}-tocopherol and {alpha}-tocopherol plus β-carotene, respectively. It is interesting to note that in a recently reported subgroup analysis of these patients (38), the interactions between antioxidant supplementation and cigarette smoking during radiation therapy were associated with an increase in both disease recurrence (hazard ratio [HR] = 2.41, 95% confidence interval [CI] = 1.25 to 4.64) and cancer-specific mortality (HR = 3.38, 95% CI = 1.11 to 10.34). There was no increase in either of these outcome measures for the nonsmokers. The most concerning data are presented in a subsequent publication by Bairati et al. (17) on the same cohort of patients. In this article, they demonstrate that the patients who received antioxidants had statistically significant poorer overall survival. http://jnci.oxfordjournals.org/cgi/content/full/100/11/773

Lissoni et al. (66) observed improved tumor response rates in 100 patients with metastatic non-small-cell lung cancer. The same group of investigators (67) also observed similar results with melatonin in a study of 250 patients with various metastatic solid tumors who received several different chemotherapy regimens. These intriguing results should now be independently confirmed in larger trials.

Several other studies have provided evidence that antioxidants can decrease the effectiveness of radiation therapy. For example, Ferreira et al. (6) randomly assigned 54 head and neck cancer patients who were undergoing radiation therapy to receive an oil-based oral rinse that contained either vitamin E or placebo before and after each daily dose of radiation. Although the vitamin E supplementation was associated with a 36% reduction in symptomatic mucositis, the authors also reported a decrease in 2-year overall survival (32% with supplemental vitamin E vs 63% with placebo; P = .13). This concerning decrease in overall survival, albeit not statistically significant, may have been confounded by the greater percentage of patients with stage 3 and 4 tumors found in the vitamin E group. In another study, Lesperance et al. (14) investigated a historical cohort of 90 patients with nonmetastatic breast cancer who received convential treatment (eg, surgery, chemotherapy, radiation therapy, and hormonal therapy) either alone or in combination with high doses of β-carotene, vitamin C, niacin, selenium, coenzyme Q10, and/or zinc. Breast cancer-specific survival (ie, patients censored only at death from breast cancer) and disease-free survival were shorter in the nutrient-supplemented group than in the nonsupplemented group, but the differences were not statistically significant (hazard ratio of breast cancer death = 1.75, 95% CI = 0.83 to 2.69, and hazard ratio of relapse = 1.55, 95% CI = 0.94 to 2.54, respectively). Despite the substantial limitations of these studies (6,14), it is troubling that both reported results suggesting poorer survival with concurrent administration of antioxidants and cytotoxic therapy, even though these results are at odds with other studies. For example, two randomized trials—Misirlioglu et al. (39), testing pentoxifylline and {alpha}-tocopherol in patients with non-small cell lung cancer, and Lissoni et al. (41), testing melatonin in patients with brain glioblastomas—found that radiotherapy combined with {alpha}-tocopherol or melatonin supplementation increased survival. However, this suggestion of radiosensitization of tumors was not confirmed by Berk et al. (42) in a randomized trial of radiation therapy and high-dose melatonin in brain metastases.

“This review demonstrates that there is no scientific support for the blanket objection to using antioxidants during chemotherapy. In addition, it also appears that these supplements may help mitigate the side effects of chemotherapy,” said Keith I. Block, MD, lead author of the study and Medical Director of the Block Center for Integrative Cancer Treatment. “This is significant because it increases the likelihood that patients will be able to complete their treatment.”

Co-author Dr. Robert Newman, Professor of Cancer Medicine at M. D. Anderson Cancer Center said, “This study, along with the evolving understanding of antioxidant-chemotherapy interactions, suggests that the previously held beliefs about interference do not pertain to clinical treatment.”

The analysis, titled “Impact of Antioxidant Supplementation on Chemotherapeutic Efficacy: A Systematic Review of the Evidence from Randomized Controlled Trials,” evaluated 845 articles from five scientific databases that examined the effects of taking natural antioxidant supplements concurrent with chemotherapy.

Out of the 845 studies that were analyzed, 19 met all evaluation criteria. These included the use of randomized trials with a control group, and the reporting of treatment response (tumor shrinkage) and survival data. The 1,554 patients represented had a variety of cancer types, and most had advanced or relapsed disease. Some of the antioxidants used in the trials included glutathione, vitamin A, vitamin C, vitamin E, ellagic acid, selenium and beta carotene.

Among the findings:

* All of the studies that included survival data showed similar or better survival rates for the antioxidant group than the control group.

* None of the trials supported the theory that antioxidant supplements diminish the effectiveness of chemotherapy treatments.

* All but one of the studies that reported treatment response showed similar or better response in the antioxidant group than in the control group.

* 15 of 17 trials that assessed chemotherapy toxicities, including diarrhea, weight loss, nerve damage and low blood counts, concluded that the antioxidant group suffered similar or lower rates of these side effects than the control group.

The authors noted that reducing side effects may help patients avoid having to cut back on their chemotherapy dosing, interrupt scheduled treatments, or abandon treatment altogether. This in turn, is likely to favorably impact treatment outcomes. A recent study of a group of colon cancer patients indicated that those who completed their full prescribed schedules of chemotherapy had survival rates nearly double those of patients who abandoned their chemotherapy treatment prematurely.

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