SIZE XSSIZE SMSIZE MDSIZE LG

Complementary and Alternative Medicine Use Among Cancer Patients and the Role of the Oncology Pharmacist

Telyssa Anderson, PharmD MBA BCOP
Clinical Pharmacy Specialist
Stem Cell Transplantation and Cellular Therapy
The University of Texas MD Anderson Cancer Center
Houston, TX

As the treatment of various malignancies advances, cancer patients are now living longer than ever before and potentially facing long-term side effects from the therapies used in their treatment. Patients are increasingly seeking new ways to either treat their malignancy with less risk of adverse effects or manage the side effects they are experiencing. One outlet many patients are turning to is complementary and alternative medicine (CAM).1-5

To gain a better understanding of the public’s opinion on cancer and the care that cancer patients receive, the American Society of Clinical Oncology (ASCO) created an annual Cancer Opinion Survey. The most recent survey took place in July and August 2018, and the results were released in October 2018. Almost 5,000 U.S. adults 18 years of age and older responded to the survey, and of that cohort an astounding 39% reported the belief that cancer could be cured using alternative methods alone in place of standard treatments.1 That percentage increases to 47% for the youngest cohort who responded to the survey, those 18–37 years of age.

In addition, 75% of survey respondents felt that complementary therapies were a good supplement to standard cancer treatment.1 These findings highlight the importance of CAM in cancer treatment and the need for providers working in oncology to be knowledgeable about these therapies and willing to discuss them with their patients.

What Is CAM?
It is important to understand the difference between complementary medicine and alternative medicine because the terms are often mistakenly used interchangeably. According to the National Center for Complementary and Integrative Health (NCCIH), complementary medicine refers to “a non-mainstream practice used together with conventional medicine,” and alternative medicine refers to “a non-mainstream practice used in place of conventional medicine.”6

Why Are Cancer Patients Seeking CAM?
Many studies have been conducted to determine why cancer patients are increasingly interested in CAM therapies. When reviewing these studies, one notes a large lack of consistency in the definition of CAM, which somewhat limits the ability to draw generalizable conclusions. One systematic review including 52 such studies reported that the most common reasons cancer patients seek out CAM are a perceived beneficial response or strong belief in CAM, a desire for control over their treatment, and hope in it as a last-resort option.7 In addition, studies have found that cancer patients and survivors with unmet needs are more likely to turn to CAM to help fulfill what they deem missing from conventional medicine.8,9 Most often, patients felt that their malignancy was treated well; their unmet need related to their symptoms or to the side effects of treatment.9 Across several studies, the most common characteristics of users of CAM were younger age, female, higher education level, and higher income.9-11

In recent years CAM has received increased media attention, and advertising for CAM products has become more prevalent with advances in instantly accessible technology and increases in social media outlets. Various studies have been conducted to elucidate the accuracy and level of evidence found on CAM websites, and the results are troubling. Misinformation, misleading claims, and a lack of references to peer-reviewed literature abound, which significantly biases cancer patients in favor of these products when no proven benefit exists.12-14 Moreover, patients approach information about CAM in different ways. Some seek the opinion of their physician or pharmacist, while others find advertisements, testimonials, or personal experience to be more valid.15 Studies also suggest that the stage of cancer could influence a patient’s willingness to try CAM. Those with late-stage disease are often more likely to turn to CAM as a last resort and a way to maintain hope.15 To complicate things further, these products are easily obtainable without the need for a prescription from a licensed medical provider, which increases the likelihood that patients will self-medicate with these therapies without consulting their medical care team.9

Pros and Cons of Using CAM in Cancer Therapy
Again, it’s important to separate complementary medicine from alternative medicine. Several studies have documented the negative impact on survival when alternative therapies are used in place of conventional, proven cancer treatments.16-21 A recent observational study compared outcomes of 281 cancer patients who chose alternative medicine, defined as “other-unproven: cancer treatments administered by non-medical personnel,” to that of 560 matched patients who chose to receive conventional treatment. Overall, alternative medicine was associated with poorer 5-year overall survival compared to conventional treatment (54.7% vs. 78.3%; p < .001) across all included cancer types. Breast cancer patients had a fivefold increase in the incidence of death with alternative medicine; colorectal and lung cancer patients had a fourfold and twofold increase, respectively.10

Even if complementary rather than alternative medicine is used, these agents can still have associated adverse effects, including hepatotoxicity, nephrotoxicity, allergic reactions, and gastrointestinal disturbances.22-25 Patients may view these therapies as safe because they are believed to be natural, but that is not always the case. As a result of the Dietary Supplement Health and Education Act of 1994 (DSHEA), complementary agents are not considered to be drugs or foods but rather supplements, meaning that the U.S. Food and Drug Administration (FDA) has no oversight concerning their true safety and efficacy.26-29 Although manufacturers are required to list the ingredients in their products, the FDA has no authority to test their products before they are brought to market for sale to patients.29 Product quality therefore may be variable, and instances of contamination with microorganisms, heavy metals, and pesticides have been documented.22 These contaminants could pose a threat to any consumer but may be especially dangerous to a cancer patient who is also receiving immunosuppressive therapies. DSHEA also prohibits manufacturers of alternative products from making disease-specific claims in reference to their products; however, some manufacturers do so anyway.29,30

A concern about drug interactions is legitimate when herbal supplements are used concomitantly with conventional cancer therapies. Robust studies identifying these interactions are largely lacking, although some agents have been better researched than others. Garlic, St. John’s wort, echinacea, ginseng, valerian, and kava, for example, have relatively well-documented interactions with commonly prescribed anticancer agents.31-33 More information exists on interactions between herbals and commonly prescribed medications like antihypertensives, which may also be relevant to cancer patients.34-36 Drug interactions can occur at any step of the pharmacokinetic process, including absorption, distribution, metabolism, or excretion of an anticancer agent, but most interactions are known to occur as a result of altered metabolism related to cytochrome P450 enzymes.33 Patients could potentially experience reduced effects of their therapy, negating the therapeutic benefit, or enhanced concentrations of anticancer drugs, resulting in severe toxicities.9,33,37,38 In either case, the patient would be placed at an increased and unnecessary risk.

CAM is often viewed as consisting exclusively of herbal or natural supplements, but the term refers to much more. Mind-body approaches such as expressive arts, exercise, massage, acupuncture, lifestyle counseling, meditation, and many other activities fall into the realm of CAM as well, and many patients are interested in incorporating these approaches into their overall care. This is likely where the main benefit of CAM lies—as an adjunctive treatment to assist with the palliative or supportive care of cancer patients.39 Several mind-body approaches have been shown to have beneficial effects on symptoms such as anxiety, insomnia, mood, pain, and gastrointestinal disturbances caused by cancer and its treatments.40-53 These therapies should be explored with patients interested in incorporating CAM into their overall cancer care as a safe alternative to using potentially harmful herbal products.

How Can Clinical Pharmacists Educate Cancer Patients About CAM?
A key element of assisting in the safe use of CAM is being open to a conversation about these therapies with your patients. You should approach the subject in a nonjudgmental way and make patients feel as comfortable as possible opening up to you and being honest about what they are taking or are considering taking.54,55 This is especially important because CAM therapies can potentially have harmful adverse effects or cause significant drug interactions, as discussed. An attempt should be made to determine the reason behind the patient’s interest in CAM, what the patient’s goals are for CAM therapy, whether the patient has had any prior experience or exposure to CAM either personally or via family and friends, and also how the information on CAM is being obtained.

Although many nonreputable websites provide information on CAM, patients can be directed to a handful of reliable online resources for more information (Table 1 - see PDF). The NCCIH provides many resources, including a page titled “Herbs at a Glance” with reliable information on selected herbals that patients may be interested in using.56 In addition, Memorial Sloan Kettering Cancer Center has created a smartphone application called “About Herbs”that can be a helpful resource for both providers and patients. It lists several herbal products, as well as complementary therapies such as acupuncture or tai chi, and when a therapy is chosen, the user may select from “Professional” and “Consumer” versions of the material. Information provided includes a clinical summary, mechanism of action, purported uses, warnings for patients, adverse reactions, and drug interactions.57

Because nearly 40% of ASCO survey responders believe that alternative therapies alone can cure cancer, it is critical to share results of the clinical studies that clearly demonstrate that this belief is simply false. The lack of regulation, lack of known clinical data, and, in many cases, lack of clinical data on herbal supplements should be shared with patients in an objective way, and patients should generally be advised to avoid such products during their cancer treatment. Providers should strongly urge patients to undergo conventional treatments, using CAM in a strictly complementary way under the guidance of their oncology medical team.

Conclusion
CAM has existed as a treatment modality for centuries and remains of interest to both the medical community and patients. Belief in these therapies among cancer patients and their caregivers is on the rise, but evidence supporting their use is not necessarily keeping pace. On the basis of existing data, the use of herbal supplements during cancer treatment is likely ill advised, because the risk of harm is far more proven and documented than the potential benefits. Pharmacists can play a crucial role in broaching the subject of CAM and educating patients about the potential dangers of using these therapies in place of, or along with, conventional treatments.

The mind-body approaches that also fall under the umbrella of CAM likely provide a safer complementary therapy for patients who would like to explore other options for symptom management. In recent years, the more inclusive term integrative oncology has been replacing CAM. Unlike alternative therapy, integrative oncology strives to incorporate complementary therapies with a reasonable amount of high-quality scientific evidence on their safety and efficacy into conventional medical therapies.31,55 The goal is to focus on all aspects of well-being, including physical, mental, emotional, functional, spiritual, social, and communal well-being, and to facilitate the coordination of care between providers to achieve this goal.6 Most National Cancer Institute–designated comprehensive cancer centers have developed or are developing integrative oncology programs to assist with this initiative, and guidelines are being established to support providers who participate in these programs.58-63 These centers should serve as resources for cancer patients seeking complementary therapies and represent the future of CAM in this patient population.

References

  1. The Harris Poll. Harris Insights & Analytics LLC, A Stagwell Company. ASCO 2018 Cancer Opinions Survey, October 2018.
  2. Bernstein BJ, Grasso T. Prevalence of complementary and alternative medicine use in cancer patients. Oncology (Williston Park, NY). 2001;15(10):1267-1272; discussion 1272-1268, 1283.
  3. Ernst E, Cassileth BR. The prevalence of complementary/alternative medicine in cancer: a systematic review. Cancer. 1998;83(4):777-782.
  4. Ashikaga T, Bosompra K, O’Brien P, Nelson L. Use of complimentary and alternative medicine by breast cancer patients: prevalence, patterns and communication with physicians. Support Care Cancer. 2002;10(7):542-548.
  5. Richardson MA, Sanders T, Palmer JL, Greisinger A, Singletary SE. Complementary/alternative medicine use in a comprehensive cancer center and the implications for oncology. J Clin Oncol. 2000;18(13):2505-2514.
  6. Complementary, Alternative, or Integrative Health: What’s in a Name? 2018; available at https://nccih.nih.gov/health/integrative-health. Accessed November 16, 2018.
  7. Verhoef MJ, Balneaves LG, Boon HS, Vroegindewey A. Reasons for and characteristics associated with complementary and alternative medicine use among adult cancer patients: a systematic review. Integr Cancer Ther. 2005;4(4):274-286.
  8. Mao JJ, Palmer SC, Straton JB, et al. Cancer survivors with unmet needs were more likely to use complementary and alternative medicine. J Cancer Surviv. 2008;2(2):116-124.
  9. Tascilar M, de Jong FA, Verweij J, Mathijssen RH. Complementary and alternative medicine during cancer treatment: beyond innocence. Oncologist. 2006;11(7):732-741.
  10. Johnson SB, Park HS, Gross CP, Yu JB. Use of alternative medicine for cancer and its impact on survival. J Natl Cancer Inst. 2018;110(1).
  11. The Use of Complementary and Alternative Medicine in the United States. 2018; Available at https://nccih.nih.gov/research/statistics/2007/camsurvey_fs1.htm#about. Accessed November 25, 2018.
  12. Martin-Facklam M, Kostrzewa M, Schubert F, Gasse C, Haefeli WE. Quality markers of drug information on the Internet: an evaluation of sites about St. John’s wort. Am J Med. 2002;113(9):740-745.
  13. Matthews SC, Camacho A, Mills PJ, Dimsdale JE. The internet for medical information about cancer: help or hindrance? Psychosomatics. 2003;44(2):100-103.
  14. Schmidt K, Ernst E. Assessing websites on complementary and alternative medicine for cancer. Annals of Oncology: Official Journal of the European Society for Medical Oncology. 2004;15(5):733-742.
  15. Verhoef MJ, Mulkins A, Carlson LE, Hilsden RJ, Kania A. Assessing the role of evidence in patients’ evaluation of complementary therapies: a quality study. Integr Cancer Ther. 2007;6(4):345-353.
  16. Angell M, Kassirer JP. Alternative medicine--the risks of untested and unregulated remedies. N Engl J Med. 1998;339(12):839-841.
  17. Chang EY, Glissmeyer M, Tonnes S, Hudson T, Johnson N. Outcomes of breast cancer in patients who use alternative therapies as primary treatment. Am J Surg. 2006;192(4):471-473.
  18. Coppes MJ, Anderson RA, Egeler RM, Wolff JE. Alternative therapies for the treatment of childhood cancer. N Engl J Med. 1998;339(12):846-847.
  19. Ernst E. Intangible risks of complementary and alternative medicine. J Clin Oncol. 2001;19(8):2365-2366.
  20. Han E, Johnson N, DelaMelena T, Glissmeyer M, Steinbock K. Alternative therapy used as primary treatment for breast cancer negatively impacts outcomes. Ann Surg Oncol. 2011;18(4):912-916.
  21. Joseph K, Vrouwe S, Kamruzzaman A, et al. Outcome analysis of breast cancer patients who declined evidence-based treatment. World J Surg Oncol. 2012;10:118.
  22. De Smet PA. Health risks of herbal remedies: an update. Clinical Pharmacol Ther. 2004;76(1):1-17.
  23. Werneke U, Earl J, Seydel C, Horn O, Crichton P, Fannon D. Potential health risks of complementary alternative medicines in cancer patients. Br J Cancer. 2004;90(2):408-413.
  24. Navarro VJ, Khan I, Bjornsson E, Seeff LB, Serrano J, Hoofnagle JH. Liver injury from herbal and dietary supplements. Hepatology. 2017;65(1):363-373.
  25. Palmer ME, Haller C, McKinney PE, et al. Adverse events associated with dietary supplements: an observational study. Lancet. 2003;361(9352):101-106.
  26. Bent S, Ko R. Commonly used herbal medicines in the United States: a review. Am J Med. 2004;116(7):478-485.
  27. Parkman CA. Regulatory issues in CAM. Case Manager. 2004;15(6):26-29.
  28. Cohen MH. Complementary and integrative medical therapies, the FDA, and the NIH: definitions and regulation. Dermatol Ther. 2003;16(2):77-84
  29. Dietary Supplement Health and Education Act of 1994, 21 United States Code sections 301, 321, 343, 343-2, 350b (1994).
  30. Morris CA, Avorn J. Internet marketing of herbal products. JAMA. 2003;290(11):1505-1509.
  31. Rosenthal DS, Dean-Clower E. Integrative medicine in hematology/oncology: benefits, ethical considerations, and controversies. Hematology Am Soc Hematol Educ Program. 2005:491-497.
  32. Ulbricht C, Chao W, Costa D, Rusie-Seamon E, Weissner W, Woods J. Clinical evidence of herb-drug interactions: a systematic review by the natural standard research collaboration. Curr Drug Metab. 2008;9(10):1063-1120.
  33. Sparreboom A, Cox MC, Acharya MR, Figg WD. Herbal remedies in the United States: potential adverse interactions with anticancer agents. J Clin Oncol. 2004;22(12):2489-2503.
  34. De Smet PA. Herbal remedies. N Engl J Med. 2002;347(25):2046-2056.
  35. Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med. 1998;158(20):2200-2211.
  36. Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: a systematic review. Drugs. 2001;61(15):2163-2175.
  37. Lawenda BD, Kelly KM, Ladas EJ, Sagar SM, Vickers A, Blumberg JB. Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy? J Natl Cancer Inst. 2008;100(11):773-783.
  38. Block KI, Koch AC, Mead MN, Tothy PK, Newman RA, Gyllenhaal C. Impact of antioxidant supplementation on chemotherapeutic efficacy: a systematic review of the evidence from randomized controlled trials. Cancer Treat Rev. 2007;33(5):407-418.
  39. Ernst E. The role of complementary and alternative medicine in cancer. Lancet Oncol. 2000;1:176-180.
  40. Ernst E, Pittler MH, Wider B, Boddy K. Mind-body therapies: are the trial data getting stronger? Altern Ther Health Med. 2007;13(5):62-64.
  41. Cohen L, Warneke C, Fouladi RT, Rodriguez MA, Chaoul-Reich A. Psychological adjustment and sleep quality in a randomized trial of the effects of a Tibetan yoga intervention in patients with lymphoma. Cancer. 2004;100(10):2253-2260.
  42. Bower JE, Woolery A, Sternlieb B, Garet D. Yoga for cancer patients and survivors. Cancer Control. 2005;12(3):165-171.
  43. Chandwani KD, Thornton B, Perkins GH, et al. Yoga improves quality of life and benefit finding in women undergoing radiotherapy for breast cancer. J Soc Integr Oncol. 2010;8(2):43-55.
  44. Oh B, Butow PN, Mullan BA, et al. Effect of medical Qigong on cognitive function, quality of life, and a biomarker of inflammation in cancer patients: a randomized controlled trial. Support Care Cancer. 2012;20(6):1235-1242.
  45. Chaoul A, Milbury K, Sood AK, Prinsloo S, Cohen L. Mind-body practices in cancer care. Curr Oncol Rep. 2014;16(12):417.
  46. Archie P, Bruera E, Cohen L. Music-based interventions in palliative cancer care: a review of quantitative studies and neurobiological literature. Support Care Cancer. 2013;21(9):2609-2624.
  47. Garcia MK, McQuade J, Haddad R, et al. Systematic review of acupuncture in cancer care: a synthesis of the evidence. J Clin Oncol. 2013;31(7):952-960.
  48. Cassileth BR, Vickers AJ. Massage therapy for symptom control: outcome study at a major cancer center. J Pain Symptom Manage. 2004;28(3):244-249.
  49. Russell NC, Sumler SS, Beinhorn CM, Frenkel MA. Role of massage therapy in cancer care. J Altern Complement Med. 2008;14(2):209-214.
  50. Mao JJ, Wagner KE, Seluzicki CM, et al. Integrating oncology massage into chemoinfusion suites: a program evaluation. J Oncol Pract. 2017;13(3):e207-e216.
  51. Lamas K, Lindholm L, Stenlund H, Engstrom B, Jacobsson C. Effects of abdominal massage in management of constipation—a randomized controlled trial. Int J Nurs Stud. 2009;46(6):759-767.
  52. Lai TK, Cheung MC, Lo CK, et al. Effectiveness of aroma massage on advanced cancer patients with constipation: a pilot study. Complement Ther in Clin Pract. 2011;17(1):37-43.
  53. Cunningham JE, Kelechi T, Sterba K, Barthelemy N, Falkowski P, Chin SH. Case report of a patient with chemotherapy-induced peripheral neuropathy treated with manual therapy (massage). Support Care Cancer. 2011;19(9):1473-1476.
  54. Cauffield JS. The psychosocial aspects of complementary and alternative medicine. Pharmacotherapy. 2000;20(11):1289-1294.
  55. Lopez G, Mao JJ, Cohen L. Integrative oncology. Med Clin North Am. 2017;101(5):977-985.
  56. Herbs at a Glance. Available at https://nccih.nih.gov/health/herbsataglance.htm Accessed November 18, 2018.
  57. About Herbs. (2018). Memorial Sloan Kettering Cancer Center. (Version 1.3) [Mobile application software]. Retrieved from http://itunes.apple.com.
  58. Cassileth BR, Deng GE, Gomez JE, Johnstone PA, Kumar N, Vickers AJ. Complementary therapies and integrative oncology in lung cancer: ACCP evidence-based clinical practice guidelines (2nd ed.). Chest. 2007;132(3 Suppl):340s-354s.
  59. Lyman GH, Greenlee H, Bohlke K, et al. Integrative therapies during and after breast cancer treatment: ASCO endorsement of the SIO Clinical Practice Guideline. J Clin Oncol. 2018;36(25):2647-2655.
  60. Deng GE, Frenkel M, Cohen L, et al. Evidence-based clinical practice guidelines for integrative oncology: complementary therapies and botanicals. J Soc Integr Oncol. 2009;7(3):85-120.
  61. Greenlee H, Balneaves LG, Carlson LE, et al. Clinical practice guidelines on the use of integrative therapies as supportive care in patients treated for breast cancer. J Natl Cancer Inst Monogr. 2014;2014(50):346-358.
  62. Lopez G, McQuade J, Cohen L, et al. Integrative oncology physician consultations at a comprehensive cancer center: analysis of demographic, clinical and patient reported outcomes. J Cancer. 2017;8(3):395-402.
  63. Brauer JA, El Sehamy A, Metz JM, Mao JJ. Complementary and alternative medicine and supportive care at leading cancer centers: a systematic analysis of websites. J Altern Complement Med. 2010;16(2):183-186.
xs
sm
md
lg