Why do some cancer patients receiving chemotherapy choose to take complementary and alternative medicines and what are the risks?
- Conflict of interest: none
Complementary and alternative medicine (CAM) cover a broad and diverse group of treatments and products that do not tend to be widely used by conventional healthcare professions. CAM that is systemically absorbed is the most likely to interfere with concurrent chemotherapy and potentially cause harm to cancer patients. Patients receiving chemotherapy may be consuming CAM to treat cancer, to lessen chemotherapy side effects, for symptom management, or to treat conditions unrelated to their cancer. A small proportion of cancer patients decide to use CAM alone to treat cancer and delay conventional treatment. Cancer patients may be influenced in their CAM decision-making by others: practitioners, family, friends, spouse and even casual acquaintances met in waiting rooms and support groups. This influence may range from encouraging and supporting the patient's decision through to making the decisions for the patient. When tested in rigorous clinical trials, no CAM cancer treatments alone have shown benefit beyond placebo. With the exception of ginger to treat chemotherapy-induced nausea, there is no compelling evidence overriding risk to take complementary medicines for supportive care during chemotherapy treatment. There is, however, established evidence to use mind–body complementary therapies for supportive care during chemotherapy treatment.
The majority of patients receiving chemotherapy will consider taking complementary and alternative medicines (CAM). The motivation to take CAM in the palliative setting is to improve quality of life and increase chances of survival, whereas the most popular motivation for taking CAM in the curative setting is to lessen perceived chemotherapy side effects. Whatever the motivation, use of CAM is rarely evidence based, and although there are putative benefits for many CAM, very rarely is the potential for harm discussed. This review will consider systemically absorbed CAM and their possible interactions with chemotherapy, looking at misconceptions as well as positive alternatives.
CAM cover a broad and diverse group of treatments and products that do not tend to be widely used by conventional healthcare professions. The decision to use these forms of treatment may or may not be practitioner driven. CAM can be administered through physical and mind therapies such as acupuncture and meditation or through systemic absorption by administration of biologically active substances such as herbs, vitamins, minerals and dietary supplements. CAM such as traditional Chinese medicine (TCM) may combine mind–body therapies with biologically active substances. For example, a TCM practitioner may recommend acupuncture and/or biologically active herbs, and naturopaths may combine mind therapies with herbs and dietary supplements.
CAM that are systemically absorbed are the most likely to interfere with concurrent chemotherapy and potentially cause harm to cancer patients.[5-10] As biologically active CAM, such as herbal products, are being sought by cancer patients with increasing frequency, cancer specialists require an understanding of the CAM selection process to promote open disclosure and provide appropriate guidance and professional support,[12, 13] particularly at the time of the patient receiving chemotherapy.
CAM consumers are not necessarily hostile to conventional medicine, and it is logical for a person suffering from cancer to look for potential health benefits from other sources such as CAM. Cancer patients would prefer to accept CAM treatment through their conventional providers if it were offered, and cancer patients integrating CAM with their conventional care feel they benefit from both.
Cancer patients, as in the general population, are most likely to take CAM if they have higher education, are female and have higher than average income. Disease progression, fear of recurrence, race, physician dissatisfaction, comorbidity, higher social status, being married, living in a metropolitan area, normal weight, nonsmokers and prior CAM use have been shown to be correlated with greater CAM use by cancer patients.[6, 16] In Australia, a significant proportion of cancer patients use at least one form of complementary medicine or therapy, more often biologically based, with overall prevalence measured at 65%.
Reasons for CAM Use by Cancer Patients
Cancer diagnosis is a crucial time for CAM decision-making by patients. CAM selection decisions have been shown to coincide with standard medical decisions. Initial diagnosis and conventional medicine discussions with the treating oncologist are very important in terms of the decision to use (or not to use) CAM. Evidence links increased CAM use to lack of satisfaction with initial oncology specialist consultation and proffered options of standard treatment. A CAM discussion with an informed healthcare provider, particularly in regard to safety with standard treatment, should be provided to cancer patients as near to cancer diagnosis as possible.
Treating non-cancer conditions
Patients receiving chemotherapy may be receiving complementary therapy or consuming CAM, regularly or occasionally, for conditions unrelated to their cancer. For example, an acupuncturist may be sought regularly to treat or prevent migraine, glucosamine is regularly taken to treat osteoarthritis, and echinacea is taken occasionally to treat cold symptoms. Glucosamine and echinacea each have the potential for interaction with chemotherapy.[5, 18, 19]
Lessening side effects of treatment
Patients receiving chemotherapy may take CAM to lessen chemotherapy side effects or for disease symptom management. Patients being treated with chemotherapy for curative intent tend to use herbs in the hope of preventing adverse reactions to their chemotherapy. Many cancer patients take biologically active CAM, especially antioxidants, as vitamin and mineral supplements, with the intention of lessening side effects from chemotherapy or to “boost” immunity. Up to 80% of women with breast cancer take antioxidants during cancer treatment.
Some patients receiving chemotherapy take CAM to treat their cancer. Although there are published and ongoing studies on CAM use to treat cancer, definitive evidence is lacking.[9, 13]
The use of CAM by palliative patients with advanced cancer is linked to a wish to improve quality of life, to improve their immune system and to increase hope for chances of survival.[2, 3] A small proportion of cancer patients, 8% in one study, decide to select CAM alone to treat cancer. Delaying conventional care for the treatment of cancer, through choosing CAM use alone, has been documented to worsen patient outcome.[22-24]
Factors Influencing CAM Selection
Family and friends
Cancer patients are likely to be influenced in their decision-making to take CAM by significant others: family, friends, spouse, and even casual acquaintances met in waiting rooms and support groups. This influence may range from encouraging and supporting the patient's decision through to making the decisions for the patient.[1, 8, 25] Men who select CAM to treat or support cancer mainly receive their CAM information and motivation from female relatives or friends. Family and friends who influence cancer patients' CAM decisions feel that the patient does not have the ability to make their own CAM decisions, and can be particularly insistent and persuasive to the patient when they regard themselves as having CAM knowledge or expertise.
It has been estimated that adult Australians make the same number of visits to CAM practitioners as they do medical practitioners. Many medical practitioners are unaware of their patients' CAM practitioner consultations. This has implications for both their conventional medicine and CAM use, as cancer patients who visit both a CAM and medical practitioner may be receiving differing points of view.
With the exception of chiropractors, osteopaths and TCM practitioners, CAM practitioners in Australia are not government-regulated professions, although there are a number of voluntary CAM associations. As most CAM practitioners in Australia are unregulated, there is great variety of education, background and views which may be expressed within each CAM discipline. Naturopaths are the largest group of unregulated CAM practitioners in Australia, of which 10% practice without any training or qualifications.
CAM practitioners in Australia may use flawed techniques such as live blood analysis to diagnose conditions such as vitamin and mineral deficiencies through to cancer.[31, 32] Live blood analysis originates from German researcher Gunther Enderlein, who in 1925 used dark-field microscopy to observe blood phenomena not able to be seen in stained samples, and postulated, among other things, that microbes he observed caused particular illnesses. Enderlein's theory has since been disproven through further microbial and molecular research; live blood analysis is difficult to standardize, diagnostic reliability is low, and it cannot detect cancer.
There have been occasions when CAM practitioners have strayed out of their area of expertise and advised patients about their prescribed medicines. Shop assistants have also been found to give advice on prescribed medicines as exemplified by a health food store assistant in Canada advising a breast cancer patient to stop her prescribed drug tamoxifen.
Psychopathic traits of superficial charm and pathological lying, when exhibited by a quack practitioner giving cancer patients the very words they want to hear such as “cancer cure,” can lead the vulnerable patient into their grasp. Quack practitioners may range from having no training at all to being among recognized professions.
Quack health practitioners may be evangelical in their attempts to convert and there is often conflict of interest, most often personal financial gain, between the information base and the person promoting it.[38, 39] Quack practitioners may recommend that cancer patients use only CAM, and can be very effective at demonizing conventional medicine.[40, 41] The consequence of this for a cancer patient is the possibility of delaying or even forgoing standard conventional treatment altogether.[41-43]
Cancer patients may not value scientific evidence and many believe that CAM will benefit their cancer even if studies have proved lack of efficacy of the CAM selection. Flawed CAM, marketed using pseudoscience, may be very appealing to the cancer patient looking for alternatives. Pseudoscience has been defined as “claims presented so they seem scientific even though they lack supporting evidence and credibility.”
Although the Internet has many reputable, informative sites for cancer patients, unscrupulous promoters of pseudoscience have a platform that allows them to reach a wide audience largely without regulation.[9, 40, 41, 43] Newspaper reports of CAM cancer treatments have been also found to mislead. Biologically active CAM cancer treatments are those most published in Australian newspapers, with two-thirds of articles describing CAM use in the context of a cure.
Safety of CAM
Cancer patients who take biologically active CAM may be compromising their health in a number of ways: through direct adverse effects, potential drug interactions, or by taking poisonous CAM or CAM that contains toxic contaminants.
Direct adverse effects
Direct adverse effects such as allergic reactions, gastrointestinal complaints, photosensitivity, skin reactions and hepatotoxicity have been reported as side effects to CAM commonly used by cancer patients. For example, echinacea, used to bolster immunity, has caused allergic reactions including anaphylaxis; St John's wort, used to treat depression, may cause photosensitivity; black cohosh, used to improve menopausal symptoms, may cause gastrointestinal upset and hepatotoxicity; and milk thistle, used as a “detoxifier,” has caused gastrointestinal problems and skin reactions. Probiotics taken by cancer patients to diminish chemotherapy-induced diarrhea is normally well tolerated; however, there have been case reports of probiotic sepsis in immunocompromised patients.[47, 48]
The bioavailability and pharmacological activity of plant-based CAM may vary considerably through differing standards of practice during preparation,[49, 50] and some CAM preparations may be contaminated with toxic impurities. The herbal combination PC-SPES (PC = prostate cancer-SPES = Latin for hope), formulated to treat prostate cancer, was marketed in the United States from 1966 until it was withdrawn from sale in 2002, at which time it was estimated that as many as 10 000 prostate cancer patients were taking it. PC-SPES was found to contain varying amounts of synthetic drugs (warfarin, diethylstilboestrol and indomethacin) in addition to the blend of herbal constituents stated on the label.
Unknown active constituents
Herbal medicine practitioners generally believe that the original plant tissue should be used in preference to isolated active constituents. Secondary constituents within the plant are viewed as having a positive role in the absorption, metabolism and excretion of major active constituents. However, it is possible that unknown secondary constituents may be problematic when considering integration of complementary medicines with standard chemotherapy treatment.
Australian Government regulations for quality and safety of ingested CAM
The Australian Therapeutic Goods Administration (TGA) has developed a two-tier labeling system to identify medicines that it has deemed suitable for supply in Australia. Registered medicines, labeled “AUST R,” have been assessed by the TGA for quality, safety and efficacy, while listed medicines, labeled “AUST L,” have been assessed for quality and safety only. The overwhelming majority of biologically active CAM such as vitamin, mineral and herbal products are listed medicines. Manufacturers of listed medicines are required to hold some kind of evidence for efficacy that they can provide if asked by the TGA.
The effectiveness of the TGA's administration of complementary medicines has been questioned in a 2011 audit report commissioned by the Department of Health and Ageing. The audit noted that up to 90% of complementary products were noncompliant with regulatory requirements and that advertisements making misleading therapeutic claims were going unchallenged. The audit acknowledged that the TGA had limited resources and suggested targeting serial offenders and companies that intentionally try to avoid regulation. Furthermore, not all CAM products (e.g. teas) are marketed as medicines and consequently avoid regulation by the TGA. Similarly, CAM practitioners may sell patient-specific “remedies” without pharmaceutical check, also avoiding TGA scrutiny.
Interaction Potential of CAM
Interactions with CAM may render conventional chemotherapy either more toxic or subtherapeutic, thus compromising treatment. Clinical trial data may potentially be skewed if CAM with the potential for interaction are taken concurrently with a trial drug but not adjusted for in subsequent analysis.
As cancer treatment often produces adverse effects in patients, interactions and resultant adverse effects of CAM may be hidden, but it has been estimated that in the population of patients receiving chemotherapy and taking CAM, at least 27% are at risk of a clinically relevant interaction. The interaction mechanism of action for CAM with chemotherapy has been postulated to occur at an enzyme level through metabolic pathways or through altering ATP-binding cassette transporters. Biologically active CAM interactions and potential interactions with chemotherapy are less documented than with commonly prescribed drugs.
Antioxidants and chemotherapy
The use of antioxidants by cancer patients receiving chemotherapy remains controversial. Critics point to the fact that the primary mechanism of action of chemotherapy agents, such as the alkylating agents, anthracyclines, podophyllin derivatives, platinum compounds and camptothecins, is the generation of reactive oxygen species (ROS), which induces apoptosis in cancer cells. Antioxidants may inhibit ROS, thereby protecting the cancer cell from death.[58-60] Countering this argument is that some types of chemotherapeutic drugs such as the taxanes, the vinca-alkaloids and the antimetabolites do not depend on ROS as their primary mechanism of action for anticancer effects, and antioxidants may therefore help through preventing free radical-induced side effects. Robust human studies examining which antioxidants should be used, in what specific dose and for which chemotherapy and cancer type, are lacking at this time. Further work needs to be done before recommendations for antioxidant use can be given to patients receiving chemotherapy.
Reviews of studies on antioxidant supplementation to reduce chemotherapy toxicity have found that there is some potential for beneficial effects, and no evidence of reduction in chemotherapy efficacy with concurrent antioxidant supplementation. Caution should be shown with this result as for example, more recently, ascorbic acid, which is sometimes taken for its antioxidant effects, inhibits antitumor activity through blocking proteasome inhibition caused by the chemotherapy drug bortezomib. There is also some concern that consumption of purified antioxidants, often taken in large quantities, is quite different from safe dietary intake and may upset normal physiological balance, proving hazardous.
CAM Use Declaration to Conventional Health Providers
CAM consumption by cancer patients is often not revealed to their cancer specialists, particularly if the patient is not asked, and many cancer patients who consider CAM to be harmless may not admit to CAM use even when they are specifically asked to give this information. Cancer patients appear to prefer their healthcare providers to initiate discussions regarding use of CAM. This may be due to the anticipation of a negative response from their healthcare provider and patients not wishing to risk their relationship with their oncologists. It is possible that a neutral or indifferent response may be wrongly interpreted by the patient as a negative response. Indifference may be that the conventional providers see the CAM as harmless or at least to have mild interaction potential that is not worthy of consideration. Actively asking, being nonjudgmental and explaining potential negative consequences may help achieve honesty in CAM use information from patients.
The Placebo/Nocebo Effect
The word placebo comes from the Latin “I shall please,” and the placebo effect is often assumed to be only psychological. The placebo effect is, in fact, far more complex and is not constant; differing placebos invoke a greater effect than others for the same condition and patient belief in an intervention produces a greater placebo response. Physiological mechanisms of action such as dopamine release (Parkinson's disease) and endogenous opioid release (pain) caused by placebo interventions have been measured.[70, 71] The placebo effect becomes greater in proportion to the number of visits and other interactions with health professionals that patients may have, and is also linked to previous positive responses from clinical interventions. Cancer patients, through belief in a certain CAM and/or CAM practitioner, will experience a placebo benefit whether the intervention works or not, and are not easily swayed by evidence to the contrary. This may be problematic for the cancer specialist, particularly when trying to guide a patient away from potentially harmful CAM, as patient CAM choices may also dictate engagement with conventional care.
The “nocebo effect” has been described as a phenomenon directly opposite to the placebo effect. A nocebo effect occurs when verbal suggestions of negative outcomes result in a patient to expecting and actually experiencing clinical worsening of the condition. It would seem logical that if a cancer patient is told by a significant person to them that chemotherapy will diminish their cancer outcome, there is a possibility of the nocebo effect actually worsening that patient's response to chemotherapy.
CAM with Evidence
There have been very few phase III trials performed on unpatented botanicals due to the complexity and high cost of this level of research. As CAM treatment may involve multiple herbs and treatment modalities, it has been suggested that CAM should be studied as a whole, and not limited to conventional scientific research methods. Study designs that allow traditional CAM practitioners to use complex modalities to treat patients have limitations, as outcomes may be too broad for meaningful conclusions and may not constitute evidence of scientific value. Anecdotal evidence and encouraging case studies for CAM have not been able to be repeated in more rigorous study settings. When properly tested in double-blinded, placebo-controlled clinical trials, the use of CAM alone for cancer treatment has not shown benefit.[69, 77] There is, however, some encouraging evidence for certain CAM when used as adjuvants with standard cancer interventions to treat cancer.[13, 78, 79] Ginger has been shown in a randomized, double-blinded trial to significantly reduce chemotherapy-induced nausea compared with placebo (Table 1).
Table 1. Oral CAM with evidence for chemotherapy supportive care
|Chemotherapy-induced nausea|| |
- Significantly reduced chemotherapy-induced nausea compared with placebo in a randomized, double-blinded trial
|Chemotherapy-induced diarrhea|| |
- Decreased fluorouracil chemotherapy-induced diarrhea without toxicity
|Case report of death in a non-cancer, immune-deficient patient receiving chemotherapy and steroids to treat an autoimmune disease. The patient ate self-selected supermarket yoghurt and succumbed to the Lactobacillus rhamnosus probiotic infection.|||
|Case report of sepsis infection by probiotic lactobacillus acidophilus in a patient with mantle cell lymphoma undergoing hematopoietic SCT|||
Fish oil supplement
- Provided benefit over standard care to patients with nonsmall cell lung cancer through maintenance of weight and muscle mass during chemotherapy administration
Mind–body complementary therapies can significantly reduce stress, enhance immunity and quality of life, and may increase length of survival for cancer patients. Mind–body therapy includes relaxation, meditation, imagery, hypnosis, biofeedback, self-expression, mild exercise, massage and acupuncture. Although study evidence for the efficacy of mind–body therapies has been questioned due to the difficulty of producing, and often the lack of, study placebo controls, benefit over standard care is proven and mind–body therapies are safe to use as adjuvants with chemotherapy (Table 2).
Table 2. Mind–body CAM with evidence for chemotherapy supportive care
- Benefit for chemotherapy-induced acute vomiting
|Acupressure (acupuncture points stimulated by pressure)|| |
- Benefit for chemotherapy-induced nausea and vomiting
|Moxibustion (acupuncture points stimulated by heat)|| |
- Benefit for chemotherapy-induced acute vomiting
|Mild exercise|| |
- Reduces fatigue and enhances life satisfaction
- Yoga has been shown to be a useful practice for women recovering from breast cancer treatments to reduce stress, improve quality of life and well-being, and to reduce persistent posttreatment fatigue
- Decreased chemotherapy-induced nausea and vomiting
|Imagery and relaxation (e.g. imagining immune cells as powerful medieval knights or big brooms dispatching cancer cells)|| |
- Modulates immune functioning during treatment
- Decreased chemotherapy-induced nausea and vomiting
- Reflexology decreased anxiety during chemotherapy
- Shown to alter immune patterns by decreasing stress
- Decreases anxiety and depression
- Reduces chemotherapy-induced anxiety
|Self-expression (includes written or verbal expression, artwork, humor and movement)|| |
- Written emotional expression has shown a positive effect on outlook and decreased dark feelings in patients with breast cancer
As CAM use may potentially lessen the effectiveness of chemotherapy, and many cancer patients are likely to consider CAM harmless and won't necessarily volunteer information regarding their use even when specifically asked, cancer specialists need to promote open disclosure and provide appropriate guidance and resources to effectively dissuade patients from CAM that may cause harm. The paucity of evidence for efficacy and safety for the use of complementary medicines during chemotherapy treatment may be countered by the fact that mind–body therapies have established evidence and may be recommended to patients looking for a complementary approach while receiving chemotherapy.