Should Supplemental Antioxidant Administration Be Avoided During Chemotherapy and Radiation Therapy?

Radiation Oncology Division, Breast Health Center, Naval Medical Center San Diego, San Diego, CA, USA.
Journal of the National Cancer Institute (Impact Factor: 12.58). 07/2008; 100(11):773-83. DOI: 10.1093/jnci/djn148
Source: PubMed


Despite nearly two decades of research investigating the use of dietary antioxidant supplementation during conventional chemotherapy and radiation therapy, controversy remains about the efficacy and safety of this complementary treatment. Several randomized clinical trials have demonstrated that the concurrent administration of antioxidants with chemotherapy or radiation therapy reduces treatment-related side effects. Some data indicate that antioxidants may protect tumor cells as well as healthy cells from oxidative damage generated by radiation therapy and some chemotherapeutic agents. However, other data suggest that antioxidants can protect normal tissues from chemotherapy- or radiation-induced damage without decreasing tumor control. We review some of the data regarding the putative benefits and potential risks of antioxidant supplementation concurrent with cytotoxic therapy. On the basis of our review of the published randomized clinical trials, we conclude that the use of supplemental antioxidants during chemotherapy and radiation therapy should be discouraged because of the possibility of tumor protection and reduced survival.

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    • "ALDH activity can be inhibited pharmacologically by 4-diethylaminobenzaldehyde (DEAB) (Fig. 1). Because chemotherapy is known to induce oxidative stress [44], it is possible that inhibition of ALDH activity using DEAB may sensitize ALDH hi CSC to therapy through enhanced exposure to ROS and induction of apoptosis [41]. We were able to increase susceptibility of colorectal cancer cells (HT-29) to chemotherapy after incubation with DEAB in our preliminary study. "
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    ABSTRACT: Malignant tumours consist of heterogeneous populations of tumour cells. Cancer stem cells (CSC) represent a population of cells within a tumour with highly tumorigenic and chemoresistant properties. These cells may be identified by the expression of CSC markers. There are several key stem cells markers specified for colon cancer: CD133, CD44, ALDH1, ALCAM. These days, a major obstacle to effective cancer management is development of a multidrug resistance (MDR). The principal mechanism responsible for development of MDR phenotype is the over-expression of ABC transporters. Tumours and relapsing tumours after therapy are drived by subpopulations of tumour cells with aggressive phenotype resistant to chemotherapeutics. These cells are called CSC or tumour-initiating cells (TIC). Here we outline recent information about MDR of colon cancer and CSC markers. We have focused on novel therapeutic strategies which have been developed to prevent or overcome MDR. One such strategy is a combination of chemotherapy and modulators of MDR pumps or chemotherapy and monoclonal antibodies against vascular endothelial growth factor VEGF. Colon cancer is characterized by the presence of colon CSC expressing specific stem cell markers. The divergent presence of these markers can help to adjust personalized therapy. The review provides a detailed overview of resistance of colon cancer cells and discusses how the presence of CSC markers can influence therapy and prognosis of patients.
    Biomedecine [?] Pharmacotherapy 10/2014; 68(8). DOI:10.1016/j.biopha.2014.10.019 · 2.02 Impact Factor
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    • "With regard to sulforaphane, its modus operandi is believed to be as an indirect antioxidant that helps to protect healthy cells from oxidative damage and reduce the short- and long-term harmful effects of cancer treatment [42]. However, concern has been raised that antioxidant supplements may also protect tumor cells during chemotherapy, thereby compromising treatment efficacy [42,43]. "
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    ABSTRACT: Background Pancreatic ductal adenocarcinoma (PDA) is one of the most aggressive malignancies with marked resistance to chemo- and radiotherapy. PDA-cancer stem cells (CSCs) are not targeted by current therapies and may be a reason for poor prognosis. Studies indicate that diets rich in cabbage, broccoli, and cauliflower offer cancer preventative and therapeutic benefits. Recent experimental studies have confirmed these findings and demonstrated that isothiocyanate, sulforaphane, and the polyphenol, quercetin, effectively reduced tumor growth and enhanced the sensitivity of the cancer cells to current chemotherapeutics. The aim of the present study is to test the feasibility of a randomized controlled trial on the application of freeze-dried broccoli sprouts in patients with advanced PDA. Methods and study design The study is designed as a prospective randomized, double-blinded pilot trial with a treatment and a placebo-controlled arm in a single center setting. A total number of forty patients (18 years or older) in two parallel groups with advanced, surgically non-resectable PDA under palliative chemotherapy are planned for recruitment. Patients in the treatment group will receive fifteen capsules of the study substance per day (90 mg of active sulforaphane) during the chemotherapy treatment course. Patients in the placebo group will receive the same capsule size and portion distribution with inactive substances (mainly methylcellulose). The follow-up duration is one year. Feasibility of the study substance, adverse effects, and patient compliance, as well as levels of serum tumor markers (CEA, CA 19-9), quality of life, and patient overall survival rates will be assessed at defined points of time. Discussion The POUDER trial is expected to transfer promising experimental and epidemiological data into a clinical pilot study to assess the effectiveness of broccoli sprout extracts in the treatment of advanced PDA. The study objectives will provide data on the clinical feasibility and acceptability of a supportive treatment option accompanying palliative chemotherapy. Based on these results, future clinical studies to create further evidence in this field are possible. Trial registration The POUDER trial has been registered at with an ID NCT01879878 and WHO with an ID U1111-1144-2013 on June 13th 2013.
    Trials 06/2014; 15(1):204. DOI:10.1186/1745-6215-15-204 · 1.73 Impact Factor
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    • "However, the evidence from observational epidemiologic studies on vitamin C intake and survival following breast cancer diagnosis is not consistent, with dietary vitamin C intake reported to reduce the risk of mortality in some studies (Rohan et al, 1993; Ingram, 1994; Jain et al, 1994; Fleischauer et al, 2003; McEligot et al, 2006) and no association in other studies (Zhang et al, 1995; Hebert et al, 1998; Holmes et al, 1999; Saxe et al, 1999; Saquib et al, 2011). In addition, the safety of oral vitamin C supplements following cancer diagnosis is not clear (Lawenda et al, 2008) and few studies have examined vitamin C supplements in relation to breast cancer survival (Greenlee et al, 2009; Nechuta et al, 2011; Greenlee et al, 2012). The aim of this study was to investigate whether pre-diagnosis dietary vitamin C intake was associated with total and breast cancer-specific mortality among women diagnosed with invasive breast cancer in the Swedish Mammography Cohort (SMC). "
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    ABSTRACT: Background: Vitamin C may influence cancer progression through its antioxidant properties. However, the evidence from observational epidemiologic studies on vitamin C intake and survival following breast cancer diagnosis is not consistent, and the safety of vitamin C supplements following breast cancer diagnosis has not been extensively studied. Methods: Using a food-frequency questionnaire we investigated whether vitamin C intake was associated with survival among 3405 women diagnosed with invasive breast cancer in the Swedish Mammography Cohort. Results: From 1987–2010, there were 1055 total deaths with 416 deaths from breast cancer. Women in the highest quartile of pre-diagnosis vitamin C intake had an adjusted HR (95% CI) of breast cancer death of 0.75 (0.57–0.99) compared with those in the lowest quartile (Ptrend=0.03). There was a borderline significant association between vitamin C intake and total mortality (HR=0.84; 95% CI=0.71–1.00; Ptrend=0.08). Among 717 breast cancer cases for whom post-diagnosis supplement use was available, there was no association between vitamin C supplement use (≈1000 mg) and breast cancer-specific mortality (HR=1.06; 95% CI=0.52–2.17). Conclusion: Our findings suggest that dietary vitamin C intake before breast cancer diagnosis may be associated with breast cancer survival. In addition, post-diagnosis vitamin C supplementation at the level observed in our population was not associated with survival.
    British Journal of Cancer 06/2013; 109(1). DOI:10.1038/bjc.2013.269 · 4.84 Impact Factor
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