Stephen Sagar

Should Supplemental Antioxidant Administration Be Avoided During Chemotherapy and Radiation Therapy

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.

Evidence-based clinical practice guidelines for integrative oncology: complementary therapies and botanicals.

In recent years, the term integrative medicine has gained acceptance in medical academia. The Consortium of Academic Health Centers for Integrative Medicine defi nes this term as “the practice of medicine that reaffi rms the importance of the relationship between practitioner and patient, focuses on the whole person, is informed by evidence, and makes use of all appropriate therapeutic approaches, healthcare professionals, and disciplines to achieve optimal health and healing.” 1 Integrative oncology has been specifi cally described as both a science and a philosophy that focuses on the complex health of people with cancer and proposes an array of approaches to accompany the conventional therapies of surgery, chemotherapy, molecular therapeutics, and radiotherapy to facilitate health. 2 The SIO and its Medline -indexed journal ( Journal of the Society of Integrative Oncology ), founded by leading oncologists and oncology professionals from major cancer centers and organizations, promote quality research and appropriate application of useful, adjunctive complementary modalities T he Society for Integrative Oncology (SIO) is an international organization dedicated to encouraging scientifi c evaluation, dissemination of evidence-based information, and appropriate clinical integration of complementary therapies. Practice guidelines have been developed by the authors and endorsed by the Executive Committee of the SIO. Guidelines are a work in progress; they will be updated as needed and are available on the SIO Web site ().

A Phase I–II study in the use of acupuncture-like transcutaneous nerve stimulation in the treatment of radiation-induced xerostomia in head-and-neck cancer patients treated with radical radiotherapy

PURPOSE Recent studies have suggested that acupuncture may improve radiation-induced xerostomia with an increase in the median salivary flow rate and sustained symptom relief. An acupuncture-like transcutaneous nerve stimulation method (Codetron) without invasive needles was developed to mimic acupuncture treatment. This Phase I-II study examined the effectiveness of Codetron in treating radiation-induced xerostomia. METHODS AND MATERIALS Patients with symptomatic xerostomia after radical radiotherapy for head-and-neck cancer but with evidence of residual salivary function were recruited into the study. Two 6-week courses of Codetron treatment of acupuncture points preselected according to traditional Chinese medicine principles were given with a 2-week break between each course. Basal and citric acid-primed whole saliva production were measured at baseline and up to 1 year after treatment completion. Xerostomia symptoms were assessed by a five-item xerostomia symptom questionnaire with a visual analog scale and quality of life was evaluated using the Head and Neck Radiotherapy Questionnaire. RESULTS We enrolled 46 patients in the study. All patients had received radiotherapy doses of >or=50 Gy to bilateral head-and-neck fields, including the parotid glands. Of the 46 patients, 37 completed the follow-up assessments at 3 and 6 months after treatment completion. No Codetron treatment-related complications occurred. Improvement in xerostomia symptoms was noted, with a mean increase in the visual analog scale score of 86 (p < 0.0005) and 77 (p < 0.0001) at 3 and 6 months after treatment completion, respectively. For all patients, the increase in the mean basal and citric acid-primed whole saliva production at 3 and 6 months after treatment completion was also statistically significant (p < 0.001 and p < 0.0001, respectively). No statistically significant change in the quality-of-life evaluation compared with baseline was observed. CONCLUSION The results suggest that Codetron treatment improves whole saliva production and related symptoms in patients with radiation-induced xerostomia. The treatment effects were sustained for at least 6 months after Codetron treatment completion. A prospective randomized Phase III trial with appropriate controls is being planned.

Acupuncture treatment for chemotherapy-induced peripheral neuropathy – a case series

Chemotherapy induced peripheral neuropathy (CIPN) occurs in 10 to 20% of cancer patients treated with neurotoxic chemotherapy. A mixture of sensory, sensorimotor and autonomic nervous system dysfunction can occur, resulting in deterioration in function and worsened quality of life. A major feature is discomfort and pain. Early termination of treatment and dose reduction of chemotherapy may be necessary. The clinical course is variable and depends on the chemotherapy agents and their cumulative dose. Although symptoms can resolve completely, in most patients CIPN is either only partially reversible or completely irreversible. Current management for CIPN is symptomatic using membrane stabilising medications and antidepressants. The use of nerve growth factors is still experimental. Dysaesthesia and pain involving the feet and hands are described in both traditional Chinese medicine (TCM) and Western biomedicine. In TCM, the pathogenesis is related to the inability to direct Qi and Blood to the extremities, and is associated with Qi, Blood, Yang and Kidney deficiencies. Acupuncture is moderately effective in treating diabetic neuropathy. However, to date, there is no report of the usefulness of acupuncture for CIPN. We report the result of a pilot prospective case series of five patients treated with an acupuncture protocol that aims to correct Qi, Blood and Yang deficiencies and directs Qi and Blood to the extremities, with the goal of improving the symptoms of CIPN. The responses were encouraging, and cannot be easily explained by the known neurophysiological mechanisms of acupuncture.

Soy, Red Clover, and Isoflavones and Breast Cancer: A Systematic Review

Background Soy and red clover isoflavones are controversial due to purported estrogenic activity and possible effects on breast cancer. We conducted a systematic review of soy and red clover for efficacy in improving menopausal symptoms in women with breast cancer, and for potential impact on risk of breast cancer incidence or recurrence. Methods We searched MEDLINE, Embase, the Cochrane Library, and AMED from inception to March 2013 for human interventional or observational data pertaining to the safety and efficacy of soy and red clover isoflavones in patients with or at risk of breast cancer. Results Of 4179 records, we included a total of 131 articles: 40 RCTs, 11 uncontrolled trials, and 80 observational studies. Five RCTs reported on the efficacy of soy for hot flashes, showing no significant reductions in hot flashes compared to placebo. There is lack of evidence showing harm from use of soy with respect to risk of breast cancer or recurrence, based on long term observational data. Soy intake consistent with that of a traditional Japanese diet (2-3 servings daily, containing 25-50mg isoflavones) may be protective against breast cancer and recurrence. Human trials show that soy does not increase circulating estradiol or affect estrogen-responsive target tissues. Prospective data of soy use in women taking tamoxifen does not indicate increased risk of recurrence. Evidence on red clover is limited, however existing studies suggest that it may not possess breast cancer-promoting effects. Conclusion Soy consumption may be associated with reduced risk of breast cancer incidence, recurrence, and mortality. Soy does not have estrogenic effects in humans. Soy intake consistent with a traditional Japanese diet appears safe for breast cancer survivors. While there is no clear evidence of harm, better evidence confirming safety is required before use of high dose (≥100mg) isoflavones can be recommended for breast cancer patients.

Integrative Oncology Practice Guidelines

Integrative Oncology Practice Guidelines Yuan-Sheng Liu, Jong-Hoon Lee, Yeon-Weol Lee, Chong-Kwan Cho, Hwa-Seung Yoo East-West Cancer Center, College of Oriental Medicine, Daejeon University The Society for Integrative Oncology (SIO) is an international organization established to encourage scientific evaluation, dissemination of evidence-based information, and appropriate clinical integration of complementary therapies (http://www.Integrativeonc.org.). Practice Guidelines were developed by the authors listed below and by the Executive Committee of the Society for Integrative Oncology, which approved this document. Guidelines are a work in progress; they will be updated as needed and are available on the SIO Web site as well: www.IntegrativeOnc.org.

Selenium and Lung Cancer: A Systematic Review and Meta Analysis

Background Selenium is a natural health product widely used in the treatment and prevention of lung cancers, but large chemoprevention trials have yielded conflicting results. We conducted a systematic review of selenium for lung cancers, and assessed potential interactions with conventional therapies. Methods and Findings Two independent reviewers searched six databases from inception to March 2009 for evidence pertaining to the safety and efficacy of selenium for lung cancers. Pubmed and EMBASE were searched to October 2009 for evidence on interactions with chemo- or radiation-therapy. In the efficacy analysis there were nine reports of five RCTs and two biomarker-based studies, 29 reports of 26 observational studies, and 41 preclinical studies. Fifteen human studies, one case report, and 36 preclinical studies were included in the interactions analysis. Based on available evidence, there appears to be a different chemopreventive effect dependent on baseline selenium status, such that selenium supplementation may reduce risk of lung cancers in populations with lower baseline selenium status (serum<106 ng/mL), but increase risk of lung cancers in those with higher selenium (≥121.6 ng/mL). Pooling data from two trials yielded no impact to odds of lung cancer, OR 0.93 (95% confidence interval 0.61–1.43); other cancers that were the primary endpoints of these trials, OR 1.51 (95%CI 0.70–3.24); and all-cause-death, OR 0.93 (95%CI 0.79–1.10). In the treatment of lung cancers, selenium may reduce cisplatin-induced nephrotoxicity and side effects associated with radiation therapy. Conclusions Selenium may be effective for lung cancer prevention among individuals with lower selenium status, but at present should not be used as a general strategy for lung cancer prevention. Although promising, more evidence on the ability of selenium to reduce cisplatin and radiation therapy toxicity is required to ensure that therapeutic efficacy is maintained before any broad clinical recommendations can be made in this context.

Vitamin A and Retinoid Derivatives for Lung Cancer: A Systematic Review and Meta Analysis

Background Despite reported antiproliferative activity of vitamin A and its common use for cancer, there is no comprehensive synthesis of its safety and efficacy in lung cancers. To address this issue we conducted a systematic review of the safety and efficacy of vitamin A for the treatment and prevention of lung cancers. Methods and Findings Two independent reviewers searched six electronic databases from inception to July 2009 for clinical, observational, and preclinical evidence pertaining to the safety and efficacy of vitamin A and related retinoids for lung cancers. 248 studies were included for full review and analysis. Five RCTs assessed treatment of lung cancers, three assessed primary prevention, and three looked at secondary prevention of lung cancers. Five surrogate studies, 26 phase I/II, 32 observational, and 67 preclinical studies were also included. 107 studies were included for interactions between vitamin A and chemo- or radiation- therapy. Although some studies demonstrated benefits, there was insufficient evidence overall to support the use of vitamin A or related retinoids for the treatment or prevention of lung cancers. Retinyl palmitate combined with beta carotene increased risk of lung cancer in smokers in the large CARET trial. Pooling of three studies pertaining to treatment and three studies on secondary prevention revealed no significant effects on response rate, second primary tumor, recurrence, 5-year survival, and mortality. There was a small improvement in event free survival associated with vitamin A compared to controls, RR 1.24 (95% CI 1.13–1.35). The synthetic rexinoid bexarotene increased survival significantly among a subset of patients in two RCTs (p<0.014, <0.087). Conclusions There is a lack of evidence to support the use of naturally occuring retinoids for the treatment and prevention of lung cancers. The rexinoid bexarotene may hold promise for use among a subset of patients, and deserves further study.

Acupuncture as an Evidence-Based Option for Symptom Control in Cancer Patients

Opinion statementCurrent technology suggests that acupuncture modulates neurological processes within the central nervous system, especially the spinal cord gating mechanisms, cerebral subcortical nuclei, and the hypothalamic-endocrine axis. Many single arm clinical studies report the effectiveness of acupuncture for controlling symptoms in cancer patients. However, the challenge has been to separate the nonspecific effects of the practitioner, as well as regression to the mean, from the neurophysiological effects of needle penetration. Recently, randomized controlled trials have attempted to answer this question, with mixed results. For example, needle penetration (or equivalent stimulation) is effective for nausea and vomiting, whereas it does not appear to be a major factor in reducing hot flashes. Safety and quality are priorities, so regulation of the practice of acupuncture is important, as well as excellent communication between practitioners. In addition, continuing research is mandatory, using validated methodology and reporting principles as outlined in the CONSORT and STRICTA recommendations.

Black Cohosh and Breast Cancer A Systematic Review

Background. Many women use black cohosh as a natural treatment for menopausal symptoms. However, controversy exists around safety in breast cancer, because of its purported estrogenic activity. We conducted a systematic review of black cohosh use in women with or at risk of breast cancer.Methods. We searched MEDLINE, Embase, the Cochrane Library, and AMED from inception to July 2012 and October 2012 for human interventional or observational data pertaining to the safety and efficacy of black cohosh in patients with or at risk of breast cancer, including an assessment of the effect of black cohosh on estrogen responsive tissues. Results. Of 450 records, we included 26 articles: 14 randomized controlled trials, 7 uncontrolled trials, and 5 observational studies.The evidence on efficacy for ho t flashes is divided, with some benefits seen when compared with baseline, but not when compared with placebo. Two observational studies found no association between black cohosh and risk of breast cancer, whereas 2 studies reported significant reductions in risk of primary breast cancer among postmenopausal women (adjusted odds ratio = 0.47, 95% confidence interval = 0.27-0.82), and risk of recurrence (adjusted hazard ratio = 0.75, 95% confidence interval = 0.63-0.89). Seventeen trials showed no significant impact on circulating hormone levels or proliferation in estrogen responsive tissues. Conclusions. Current evidence does not support an association between black cohosh and increased risk of breast cancer. There is a lack of evidence supporting the efficacy of black cohosh for reduction of hot flashes in breast cancer patients. Given conflicting but promising results, and apparent safety, further research is warranted.