Multiple Choice and Discussion Questions

The term “integrative medicine” (IM) or integrative oncology is used to more accurately describe how complementary therapies are being used today in oncology practice. The old terminology, “complementary and alternative medicine” (CAM) is controversial since the words “complementary” and “alternative” have completely different meanings and should not be connected by an “and” but by an “or.” Complementary therapies as defined by the National Center for Complementary and Alternative Medicine are those therapies used to com­plement or to be used alongside conventional methods of therapy, whereas alternative methods refer to those therapies that are used instead of known conventional therapies and have not been shown to be effective. CAM is tremendously popular helping people deal with wellness and health concerns. In the United States, an estimated $36 to $47 billion is spent annually by the public on CAM methods of therapy, and in a National Health Interview Survey in 2007, 37% of adults used at least one form of CAM. CAM practices have become very popular in individuals with a chronic disease such as hematologic malignancies and cancer.

The major categories of integrative medicine include mind–body approaches, body-based manipulative therapies, acupuncture, and natural products. Mind–body approaches include prayer, meditation, mindfulness meditation, guided imagery, music therapy, creative arts therapy, self hypnosis, yoga, tai chi, and qigong. Body-based manipulative therapies include chiropractic and massage therapy. Natural products include dietary supplements, for example antioxidants as well as herbs and botanicals.

The major reason why patients use integrative therapies or remedies not prescribed by their hematologist or oncologist is in an effort to improve their treatment outcome to manage their symptoms and to be a participant in their own care. Patients therefore should be referred for an integrative oncology consultation to assist the primary oncologist in:

1. Advising the physician and patient about the use of various supplements and antioxidants, healthy nutrition, and practicing physical activity
   
2. Making appropriate recommendations about nonpharmacologic approaches in managing the patient’s symptoms from the cancer and its treatment
   
3. Addressing the fact that the majority of cancer patients experience anxiety, stress, and/or depression during the course of their disease.

Mind–body therapies are generally not in the portfolio of an oncologist’s recommendations while managing their cancer patients, yet mind–body therapies are frequently studied interventions in patients with chronic diseases such as cancer. The most common reasons why patients use these therapies are to manage their pain, fatigue, anxiety, and stress. Chronic stress has been shown to decrease immune function, perhaps through the mechanism of decreasing natural killer cells and impairing the effectiveness of DNA repair. In the 1970s, Dr Herbert Benson studied Tibetan monks as they meditated and experienced the “relaxation response.” The mind–body techniques available to cancer patients include meditation, mindfulness meditation, guided imagery, and hypnosis. In addition, music therapy and physical activities such as yoga, tai chi, and qigong also are related mind–body programs.

Randomized clinical trials (RCTs) have demonstrated that relaxation training and guided imagery significantly reduce nausea and anxiety. When compared to medication, relaxation therapy showed similar decreases in anxiety and depression, although medication might have been slightly faster in its effect. Other randomized trials have shown decreases in tension, depression, anger, and fatigue during relaxation training and/or imagery. In children, hypnosis has been found to be especially effective. In an RCT comparing hypnosis or nonhypnotic distraction such as the relaxation techniques versus joining a placebo attention control group, the children in the hypnosis group reported significant reduction in anticipatory and chemotherapy-induced nausea and vomiting.

Mind–body therapies have also been used to alleviate pain. In an RCT examining the effects of the relaxation response therapy (RRT) versus reiki therapy in men being treated with external-beam radiotherapy for prostate cancer, RRT improved emotional well-being and eased anxiety, while reiki therapy had a positive effect on anxiety. Expressive arts therapy and music therapy as well as repetitive exercise, yoga, tai chi, qigong, and Pilates also may reduce stress and anxiety.

Music therapy is considered a mind–body intervention, and it uses a variety of active and passive music experiences. Randomized trials have shown statistically significant improvements in mood and physical discomfort. Music therapy has also been shown to be an effective adjunct to antiemetic therapy. Yoga has been studied to determine whether there is a related reduction in symptoms of depression and anxiety. In a 12-week yoga intervention in healthy subjects, it was demonstrated that there was greater improvement in mood and anxiety than a metabolically matched walking exercise.

In summary, mind–body therapies can reduce anxiety, temper adverse effects of chemotherapy and radiation treatments, relieve pain, and possibly stimulate immune responses. By reducing stress and anxiety, these therapies can help patients deal with a wide range of relationship issues and decision making as they move through the diagnostic and therapeutic phases of their malignancy. Mind–body approaches have very minimal risk and potentially significant benefits. Most importantly, they are often self-taught and therefore low cost. Mind–body practices should be considered as an adjunct to usual care regardless of whether patients are beginning or recovering from chemotherapy.

1. True
   
2. False
   
3. Debated

The answers are still debated, and below are the pros and cons of the use of antioxidants.

Antioxidants (such as beta-carotene; lycopene; vitamins C, E, and A; and other substances, such as coenzyme Q10 and quercetin) are among the most common classes of supplements used by patients with cancer; with use directed for cytotoxic effects, for synergy with conventional therapy, or to lessen the toxicity of conventional therapy. An estimate of use by cancer patients varies considerably, with rates ranging from 13% to 87% depending on the survey and the type of cancer studied.

Antioxidants are substances that counteract free radicals and prevent them from causing tissue and organ damage. Evidence supporting the potential role of antioxidants in preventing and treating disease include preclinical studies, which have correlated oxidative stress and an antioxidant-depleted diet with the development of diseases, including cancer. Much of the controversy surrounding antioxidants and cancer therapy has arisen because radiation therapy and certain classes of chemotherapy agents exert some of their anticancer effects through the generation of reactive oxygen species, or free radicals. The anthracyclines (e.g., doxorubicin), platinum-containing complexes (e.g., cisplatin and carboplatin), and alkylating agents (e.g., cyclophosphamide and ifosfamide) are good examples. The theoretical concern is that antioxidants might interfere with or counteract the activities of these anticancer agents. However, to date, preclinical experiments and clinical studies have not definitively shown an impact on treatment outcome. An observational cohort study from the Fred Hutchinson Cancer Research Center in Seattle evaluating the prevalence of supplement use in persons before receiving hematopoietic stem cell transplant and the association of select supplements with outcomes found that pretransplant intake of vitamin C (≥500 mg/day) or vitamin E (≥400 International Units/day) was associated with increased risk of relapse or mortality.

Specific examples include the interactions of antioxidant supplements with the proteosome inhibitor, bortezomib. Vitamin C inhibited the in vitro multiple myeloma cell cytotoxicity of bortezomib. Green tree polyphenols and dietary supplements such as quercetin bind and inhibit the activity of bortezomib on malignant B-cell and multiple myeloma cells in vitro. In summary, these studies suggest that antioxidant supplements should be avoided in patients receiving certain chemotherapeutic classes of drugs and radiation therapy.

Specific recommendations for clinical practice at the current time include the following:

• Patients should be advised to avoid dietary antioxidant supplements above the basic nutritional requirements during radiation therapy and alongside certain chemotherapeutic classes that are associated with high oxidative stresses.
  
• Use of antioxidant supplements while receiving chemotherapy associated with low oxidative stress (e.g., purine and pyrimidine analogs, antimetabolites, monoclonal antibodies, vinca alkaloids, taxanes, and corticosteroids) is less likely to be associated with interactions. Caution should be taken with other agents (e.g., antiangiogenic agents and tyrosine kinase inhibitors) for which there is insufficient information.