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Integrative medicine for oncology requires ‘educated, evidence-based approach’

The prevalence of integrative medicine approaches has transformed care in many specialties, perhaps none more so than oncology.

Patients often turn to these options — which range from mind-body practices such as yoga, acupuncture or meditation, to herbal or vitamin supplements or even specialized diets — in hopes they will relieve nausea, insomnia or other treatment side effects. In some cases, they seek nothing more than moments of peace or hope amid the fear and stress of chemotherapy and radiation.

In a study presented at this year’s Oncology Nursing Society Congress, Hill and colleagues showed essential oil aromatherapy and 30 minutes of foot reflexology prior to brachytherapy reduced pain by 60% and anxiety by 20% among women with cervical cancer.

Although sometimes referred to as complementary and alternative medicine, or CAM, the terminology encompassing these approaches has evolved to reflect the benefits patients derive when combined with traditional anticancer treatments.

“We call it ‘integrative medicine’ because that’s what it is — the deliberate, informed, and personalized delivery of these approaches alongside conventional care — as opposed to using these approaches as pure alternatives,” Lorenzo Cohen, PhD, director of the integrative medicine program at The University of Texas MD Anderson Cancer Center, told HemOnc Today. “There are situations when taking an educated, evidence-informed approach exploring some of these alternative agents may lead to relief of symptoms or even antitumor effects.”

Most patients use integrative therapy in conjunction with conventional chemotherapy and radiation regimens to alleviate symptoms, according to Lorenzo Cohen, PhD.
Most patients use integrative therapy in conjunction with conventional chemotherapy and radiation regimens to alleviate symptoms, according to Lorenzo Cohen, PhD. “It’s a very small percentage who are using these approaches alone as true alternative medicine seeking a cure. But these patients cannot — and should not — be ignored,” he said.

Source: Nick de la Torre.

Although uncommon, in extreme instances, patients may discontinue conventional therapy — or, in some cases, reject it altogether — in favor of alternative approaches.

A more common problem arises when patients take herbs or supplements without knowing they might interfere with their standard treatments. Certain practices — such as yoga and meditation — generally are thought to be safe, but there are safety issues with the massive number of ingestible products on the market that do not undergo the same testing and regulation as FDA-approved pharmaceuticals.

“Under the guidance of a good integrative oncologist or medical oncologist, they may have utility, but further investigation is necessary,” Cohen said.

HemOnc Today spoke with oncologists and integrative medicine specialists about techniques that may alleviate symptoms such as fatigue, pain or sexual dysfunction among patients with cancer; the potential for these approaches to cause harm; and what clinicians must know so they can have informed conversations with their patients.

Recommended approaches

Studies showed 48% to 88% of patients with cancer report using CAM as part of their therapy, according to a paper by Johnson and colleagues published this year in JAMA Oncology.

“Many of us are taking some kind of vitamin or supplement whether we have cancer or not,” Gary H. Lyman, MD, MPH, senior lead in health care quality and policy at Fred Hutch’s Hutchinson Institute for Cancer Outcomes Research, told HemOnc Today. “While it may seem like a reasonable thing to do, we want to make sure patients have evidence-based information on these products.”

That isn’t always the case.

A study presented at this year’s European Society for Medical Oncology Congress showed a majority of patients who used complementary medicines were poorly informed about safety and the risk for interactions with anticancer therapies.

Researchers surveyed 152 outpatients with sarcoma, gastrointestinal stromal tumors or desmoid tumors. About half (51%) reported using any complementary medicine in their lifetime, and 44% reported that their cancer diagnosis sparked their interest in such treatments.

Sixty percent of patients acknowledged they had insufficient knowledge about the safety of integrative medicine, and only 7% reported receiving any information about the safety of these approaches from oncologists.

“Patients mostly accessed information on complementary and alternative medicines on the internet or through other media, friends and healing professionals,” study researcher Peter Hohenberger, MD, head of the division of surgical oncology at thoracic surgery at Medical Faculty Mannheim at University of Heidelberg in Germany, said in a press release. “In sharp contrast with this, when it came to finding information on side effects of cancer therapies or how to handle them, almost half of patients asked their oncologist.”

Patients’ low-risk perception of integrative therapy should be addressed by their oncologists, according to Markus Joerger, MD, PhD, of Cantonal Hospital in St. Gallen, Switzerland.

“Patients tend to believe that supplements or herbs are generally safe, but they are not without risk,” Joerger, who was not involved with the study, said in the release. “In daily practice, if you don’t know what your patient is taking as alternative medicine, the risk of drug-drug interactions can significantly increase and have an impact on clinical outcomes.

“Patients have to realize that they can discuss any health-related choices with their oncologist and be advised on different options when they wish to reduce stress related to cancer treatment, or more in general to feel better,” he added.

Lyman — along with Heather Greenlee, ND, PhD, associate member of the public health sciences and clinical research divisions at Fred Hutchinson Cancer Research Center, and medical director of the integrative medicine program at Seattle Cancer Care Alliance — and colleagues updated clinical practice guidelines from the Society for Integrative Oncology (SIO) to educate physicians about how to have such conversations.

“One of the goals of developing clinical practice guidelines is to provide clinicians and patients with the tools that they need to have a productive conversation on which complementary approaches are safe and effective,” Greenlee told HemOnc Today. “It is difficult to standardize these kinds of conversations.”

The SIO guidelines — endorsed by ASCO — recommend certain integrative therapies during breast cancer treatment to address a variety of symptoms, such as anxiety, stress, depression, fatigue, quality of life, nausea and vomiting, peripheral neuropathy and pain.

Greenlee and colleagues recommend music therapy, meditation, stress management and yoga for anxiety and stress; and meditation, relaxation, yoga, massage and music therapy for depression or mood disorders.

The guidelines state meditation and yoga may improve quality-of-life parameters, whereas acupressure and acupuncture are recommended for chemotherapy-induced nausea and vomiting.

Conversely, the guidelines state acetylLcarnitine should not be used to protect against chemotherapyinduced peripheral neuropathy, and that there is a lack of evidence to support the use of the vast majority of ingested dietary herbs and supplements.

“We know that a large percentage of oncology patients are using or are interested in using complementary therapies,” Greenlee said. “With these guidelines as a tool in hand, our hope is that more clinicians will be comfortable initiating these conversations with patients.”

Potential benefits

There is limited research examining the benefit of integrative medicine approaches to manage side effects of cancer and its treatments.

Jun J. Mao, MD, MSCE, chief of the integrative medicine service at Memorial Sloan Kettering Cancer Center, and colleagues compared 8 weeks of acupuncture with cognitive behavioral therapy among 160 cancer survivors who had been clinically diagnosed with insomnia disorder.

“We set out to do a study to answer a question between the two treatments: Which is more effective for insomnia [among] individuals with cancer?” he said during a press cast. “Our hope is that by doing this research, we can help patients and clinicians pick the right treatment for patients to manage their sleep.”

Results, presented at this year’s ASCO Annual Meeting, showed an 8.3-point (95% CI, 7.3-9.4) reduction in insomnia severity in the acupuncture group, compared with a 10.9-point (95% CI, 9.8-12) reduction among those who received cognitive behavioral therapy (difference, 2.6 points; 95% CI, 1.1-4.1; P = .0007).

Physical and mental health quality-of-life parameters improved among both groups, and neither group experienced noteworthy adverse events.

“Cognitive behavioral therapy for insomnia is a highly effective therapy and considered [the] gold standard of treatment; however, not everyone accepts this treatment,” Mao said. “It is a highly specialized therapy that isn’t quite available in many cancer centers or communities.”

Acupuncture also has been shown to alleviate joint paint among patients with breast cancer.

Dawn Hershman, MD, leader of the breast cancer program at Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian/Columbia University Medical Center, and colleagues compared the effect of three approaches: real acupuncture administered in twice-weekly sessions for 6 weeks, followed by one session per week for 6 additional weeks; sham acupuncture administered in the same schedule; or no acupuncture.

Results, presented at last year’s San Antonio Breast Cancer Symposium showed a true statistical difference between mean Brief Pain Inventory scores for real acupuncture vs. sham acupuncture (0.92 points lower; 95% CI, 0.2-1.65; P = .01), as well as for real acupuncture vs. no treatment (0.96 points lower; 95% CI, 0.24-1.67; P = .01).

Fifty-eight percent of women who received real acupuncture had a clinically meaningful 2-point change, compared with 31% in the sham acupuncture group and 30% in the control group.

“We were motivated to think of ways of reducing joint pain caused by aromatase inhibitors because so many patients suffer with this side effect, and often patients do not want to take more medications,” Hershman told HemOnc Today at the time of the presentation. “Our study gives both patients and providers confidence that this approach to treating symptoms can be effective and safe. However, not all acupuncture is the same, and we would encourage the acupuncture community who treat patients with breast cancer to read our prior publications describing the methods we used.”

Acupuncture has been found to be effective for a number of symptoms, Cohen said.

“Most data show that it can be used to control nausea or pain, but there is also some evidence for hot flashes or aromatase inhibitor-induced arthralgias,” he said. “There is also evidence that acupuncture can be used for neuropathy and sleep disorders.”

Chinese medicine informs the practice of acupuncture based on “patterns of disharmony,” according to Doug McDaniel, DACM, integrative medicine program manager at Roswell Park Comprehensive Cancer Center.

Doug McDaniel, DACM
Doug McDaniel

“Patients are diagnosed prior to each treatment, and specific points are chosen based upon that diagnosis that reflect the patient’s pattern of disharmony at that moment in time,” McDaniel said. “This means that each patient treated for chemotherapy-induced nausea may have a different pattern of disharmony and will accordingly be treated with different points based upon this pattern. This also means that each patient may present differently at each visit, and point prescriptions may be modified at each treatment session to optimize treatment effectiveness based on the pattern presenting that day.”

The effects of yoga on cancer-related symptoms also have been studied extensively.

Ben-Josef and colleagues investigated whether a yoga practice could improve fatigue, erectile dysfunction, urinary incontinence and overall quality of life among men with prostate cancer undergoing radiotherapy.

Men assigned yoga reported less fatigue (P < .0001) and greater improvements in sexual health scores (P = .0333) than those in the control group. Researchers reported improved quality of life in terms of emotional, physical and social scores, but not functional scores.

A range of mindfulness techniques — from the traditional, such as yoga and meditation, to the more experimental, such as hypnosis, guided imagery or dichromatic breathing — can be useful for patients with cancer, Cohen said.

“There is a fair amount of evidence that some of these techniques, particularly yoga, can improve fatigue and sleep parameters,” he said. “Patients report improvements in cancer-related symptoms.”

Stress and anxiety also may be improved through meditation, music therapy and yoga, Lyman said.

“However, most of the data are in breast cancer at the moment,” he said.

Researchers at Roswell Park are studying integrative therapies like mindfulness, McDaniel said.

“Although there is evidence that acupuncture, mindfulness, yoga and others help patients, we also know that more research needs to be done,” he said.

McDaniel urged people to be cautious about esoteric modalities.

“Some of them have little to no data supporting their use,” he added.

Potential harm

Not all studies of integrative medicine have proven positive.

A study by Amraoui and colleagues, published in August in JAMA Network Open, showed that a 15-minute hypnosis session before general anesthesia offered benefits regarding fatigue, anxiety and patient satisfaction among women undergoing breast cancer surgery. However, the intervention did not reduce postoperative pain, the study’s primary endpoint.

Beyond a lack of benefit, some integrative medicines — particularly supplements or herbs — may be detrimental to patient safety.

In a study by McCune and colleagues, 76 patients undergoing cancer treatment completed a questionnaire to assess herb and vitamin use. The researchers investigated the frequency of interactions between herbs or vitamins and chemotherapy; communication between doctors and patients regarding these treatments; and potential interactions with chemotherapy.

Results showed herbs or vitamins were used by 78% of patients, 27% of whom were potentially at risk for a drug-drug interaction.

More than 85% of the cohort reported willingness to discontinue herb or vitamin use in light of suspicion of a detrimental interaction.

“There is not enough good research supporting the use of herbs and supplements during cancer treatment,” McDaniel said. “The problem with many studies that have been performed is the methodology and small sample sizes, making it difficult to draw strong conclusions. My philosophy is that any modality must first be proven to be safe. If there is no evidence of safety, then that modality should not be considered.”

Further, the FDA does not regulate these products, Cohen said.

“Contaminants could be present or the level of bioactive substances may be not what is listed on the label,” he said. “In fact, it is these bioactive substances that are the reason they purportedly have a beneficial effect on symptoms and tumor growth in the first place and, if they are not regulated, this could cause a problem.”

Drug-herb interactions should raise as many red flags as drug-drug interactions, such as the use of serotonin reuptake inhibitors for depression during chemotherapy, Cohen added.

“This type of metabolic overlap is always of concern,” he said. “That said, there is some evidence — at least in breast cancer — that ginseng can alleviate fatigue, and ginger may be useful for controlling nausea. Outside of those areas, it becomes a bit more challenging.”

In a study published in 2016 in Cancer, Ben-Arye and colleagues found that herbal medicine use had several potential negative effects.

Researchers distributed a questionnaire to 339 health care professionals in the Middle East, where herbal medicine use is prevalent, to assess herbal supplement used by their patients.

They identified 44 herbal and three nonherbal supplements, 29 of which had safety concerns. Fifteen herbs altered pharmacodynamics with traditional cancer drugs, 18 herbs had direct toxic effects and seven herbs increased in vitro response of cancer cells to chemotherapy.

“It is important to consider that any supportive care or CAM treatment that a patient seeks out needs to be evidence-based,” McDaniel said. “It is important to know that it is safe and that it will not negatively impact the effectiveness of their conventional treatment regimen. It also is important to know that it will most likely have a positive effect on treating the symptom or supporting their health.”

Refusing standard treatment

A study published this year in JAMA Oncology revealed that the use of alternative medicine in place of conventional treatments was associated with decreased survival among patients with curable cancer.

This increased mortality risk appeared driven largely by the fact that patients who chose alternative medicine were more likely to refuse conventional cancer therapy.

“The fact that complementary medicine use is associated with higher refusal of proven cancer treatments, as well as increased risk for death, should give providers and patients pause,” study author Skyler Johnson, MD, chief resident in radiation oncology at Yale School of Medicine, said in a press release. “Unfortunately, there is a great deal of confusion about the role of complementary therapies. Although they may be used to support patients experiencing symptoms from cancer treatment, it looks as though they are either being marketed or understood to be effective cancer treatments.”

Johnson and colleagues compared OS among patients with nonmetastatic breast, prostate, lung or colorectal cancers treated with complementary medicine (n = 258) or without (n = 1,032).

Results showed a greater proportion of patients who received complementary medicine refused surgery (7% vs. 0.1%), chemotherapy (43.1% vs. 3.2%), radiotherapy (53% vs. 2.3%) and hormone therapy (33.7% vs. 2.8%; P < .001 for all).

Fewer patients who received complementary therapy achieved 5-year OS (82.2% vs. 86.6%; P = .001).

Multivariate analysis revealed an independent association between complementary therapy and mortality risk (HR = 2.08; 95% CI, 1.5-2.9). However, when treatment delay or refusal rates were factored into the multivariate model, the association lost significance (HR = 1.39; 95% CI, 0.83-2.33).

“Supplements are occasionally associated with early termination of chemotherapy,” Lyman said. “In short, many patients are or become distrustful of conventional therapies.”

Johnson and colleagues defined complementary medicine as “other” or “unproven” treatments administered by nonmedical personnel. However, it is unclear whether the findings from this study are often observed among patients who practice yoga, meditation or mindfulness approaches, according to Lyman.

“The studies that have been done on the subject of patients rejecting or discontinuing traditional therapies are fraught with confounding factors, including that patients who make this choice are often self-selecting,” he said. “These are not prospective, randomized controlled trials. They may not be the same types of patients who use integrative approaches in a complementary fashion to alleviate symptoms.”

For Cohen, it’s a matter of numbers.

“The vast majority of patients are either using only conventional chemotherapy and/or radiation regimens, etc, or they’re using integrative medicine to alleviate symptoms and improve outcomes,” he said. “It’s a very small percentage who are using these approaches alone as true alternative medicine seeking a cure. But these patients cannot — and should not — be ignored.”

Talking with patients

Emerging data suggest clinicians are not discussing integrative approaches with their patients, and that they do not feel they have enough knowledge of the subject.

“As we know patients are using these therapies, it’s unethical not to have these conversations,” Cohen said.

Chang and colleagues assessed knowledge and attitudes about complementary medicine in a cohort of 219 patients, 301 volunteers without cancer and 156 health care professionals.

More than half (58.8%) of health care professionals reported their knowledge of complementary medicine was inadequate, and 79.2% reported not being up to date with available evidence.

“Many people in the field believe we shouldn’t be talking about these things or discussing any treatments in the absence of large randomized controlled trials,” Lyman said. “But, even if patients are using therapies that are not recommended or don’t have supporting evidence, they should not be dismissed or shut out. It is more important that the provider know what the patient is taking, regardless of what it is.”

Lee and colleagues sent a survey to 1,000 random ASCO members to determine communication patterns about integrative approaches, including physician education about herbs and supplements, discussion with patients regarding their use and knowledge of adverse events.

Results, published this year in Journal of Clinical Oncology, showed that 41% of 392 oncologists discussed use of herbs and supplements with patients, but only 26% of those discussions were initiated by the oncologist. Approximately two-thirds of oncologists reported insufficient knowledge on the topic, while 59% reported receiving no education about these approaches.

“We have seen that integrative medicine is not addressed often enough,” Lyman said. “In some cases, the doctor fails to initiate the discussion and, in others, the patient is either embarrassed about their use or doesn’t think it’s relevant to what they’re doing.”

Conversations surrounding integrative medicine should be holistic, McDaniel said.

“I like to ask how they are feeling at this moment, what things in their life have changed, what things can they no longer do that they would still like to do, and what their health and wellness goals are during and after treatment,” he said. “I try to look at the whole person and to help the patient realize they are not their disease, and that what is happening right now is not necessarily going to be forever.

“I start by asking what is troubling them most and then offer small, achievable suggestions to integrate appropriate supportive care modalities into their treatment regimen,” McDaniel added. “The closer to diagnosis that I can get a patient on board with this, the better.”

Safety should be a critical component of these discussions, Cohen said.

“We encourage our patients to turn to a well-known, safe behavioral strategy to control a symptom rather than a pharmacological product,” he said. “[Patients with cancer] are on so many different treatments that if there is a nonpharmacological approach, we recommend trying that first.”

Many integrative therapies can be quite costly to pursue, and patients may be wasting money that could be better spent on proven approaches such as diet and exercise, McDaniel said. Rather, clinicians should steer patients toward fundamentals of good health.

“Lifestyle choices that support enhancing [the health and well-being of a person with cancer] are key to helping alleviate symptoms that may arise from either their treatment or their disease,” he said, citing proper nutrition, regular exercise, hydration, rest and stress management as cornerstones. “I also recommend patients do something that they like every day that is just for them. This could be listening to music, reading a book, watching a movie, talking a walk in nature or journaling — whatever it is that helps to support them living in the moment and enjoying life.”

Looking ahead

Despite the prevalence of analyses evaluating various integrative approaches, experts with whom HemOnc Today spoke still emphasized a need for sound data on their use.

“Studies need to be designed to look at real-world situations of how the modality is practiced on a daily basis,” McDaniel said. “For example, true acupuncture was compared to sham acupuncture in an effort to develop standardized point protocols to treat specific symptoms. Results showed there was no difference between the true and sham acupuncture groups, but there was usually a positive difference between both true and sham acupuncture and conventional care if that was included in the study.”

Although herbal medicines are those most likely to cause an interaction with anticancer therapies, studies have suggested they could carry antitumor effects.

For example, plant-derived polyphenols, flavonoids and brassinosteroids have been studied as potential anticancer agents, according to Greenwell and Rahman. Such medicinal plants may induce antioxidant activity, inhibition of cancer cell growth, induction of apoptosis, target specificity and cancer cell cytotoxicity.

Thus, it also would be beneficial to have more basic science on herbal medicine, McDaniel said.

“Some of the research that has been done has shown that a particular herb and a particular chemotherapeutic agent are both effective in eradicating the same cancer cell; however, the mechanism of action is different for each agent,” he said. “This could lead to using these two different approaches in the same treatment to enhance the effectiveness of the treatment.”

As it stands, the fact integrative medicine is such a broad category may inhibit understanding of its use.

“We need to distinguish more clearly among the many types of integrative therapies, and we need to understand more clearly who is more likely to use which approaches,” Lyman said. “We also need to look more closely at who is using them to alleviate symptoms and who is using them in place of conventional therapy.”

Increased knowledge surrounding all of these areas may lead to improved access for important symptom relief, as well as greater physician acceptance of their benefits, Cohen said.

“The more we know about these approaches and products, that will bring us one step closer to insurance coverage for them,” he said. — by Rob Volansky

Click here to read the POINTCOUNTER, “Should hem/oncs recommend integrative therapies to their patients?”

References:

Amraoui J, et al. JAMA Network Open. 2018;doi:10.1001/jamanetworkopen.2018.1164.

Ben-Arye E, et al. Cancer. 2016;doi:10.1002/cncr.29796.

Ben-Josef AM, et al. Int J Radiat Oncol Biol Phys. 2017;doi:10.1016/j.ijrobp.2017.03.043.

Chang KH, et al. BMC Cancer. 2011;doi:10.1186/1471-2407-11-196.

Greenlee H, et al. CA Cancer J Clin. 2017;doi:10.3322/caac.21397.

Greenwell M and Rahman PK. Int J Pharm Sci Res. 2015;doi:10.13040/IJPSR.0975-8232.6(10).4103-12.

Hershman DL, et al. Abstract GS4-04. Presented at: San Antonio Breast Cancer Symposium; Dec. 5-9, 2017; San Antonio.

Hill C, et al. The effect of aromatherapy and foot reflexology on pain and anxiety during brachytherapy for cervical cancer. Presented at: Oncology Nursing Society Congress; May 17-20, 2018; Washington, D.C.

Johnson SB, et al. JAMA Oncol. 2018;doi:10.1001/jamaoncol.2018.2487.

Lee RT et al. J Clin Oncol. 2018.doi:10.1200/JCO.2014.55.8676.

Lyman GH, et al. J Clin Oncol. 2018;doi:10.1200/JCO.2018.79.2721.

Mao JJ, et al. Abstract 10001. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.

McCune JS, et al. Support Care Cancer. 2004;12:454-62.

Sungu-Winkler K-T, et al. Abstract 1655P-PR. Presented at: ESMO Congress; Oct. 19-23, 2018.

For more information:

Lorenzo Cohen, MD, can be reached at The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030; email: lcohen@mdanderson.org.

Heather Greenlee, ND, PhD, can be reached at Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA, 98109-1024; email: hgreenlee@fredhutch.org.

Gary H. Lyman, MD, MPH, can be reached at Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA, 98109-1024; email: glyman@fredhutch.org.

Jun J. Mao, MD, MSCE, can be reached at Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065; email: maoj@mskcc.org.

Doug McDaniel, DACM, can be reached at Roswell Park Comprehensive Cancer Center, Elm and Carlton Sts., Buffalo, NY 14263; email: douglas.mcdaniel@roswellpark.org.

Disclosures: Cohen, Greenlee, Lyman, Mao and McDaniel report no relevant financial disclosures.

The prevalence of integrative medicine approaches has transformed care in many specialties, perhaps none more so than oncology.

Patients often turn to these options — which range from mind-body practices such as yoga, acupuncture or meditation, to herbal or vitamin supplements or even specialized diets — in hopes they will relieve nausea, insomnia or other treatment side effects. In some cases, they seek nothing more than moments of peace or hope amid the fear and stress of chemotherapy and radiation.

In a study presented at this year’s Oncology Nursing Society Congress, Hill and colleagues showed essential oil aromatherapy and 30 minutes of foot reflexology prior to brachytherapy reduced pain by 60% and anxiety by 20% among women with cervical cancer.

Although sometimes referred to as complementary and alternative medicine, or CAM, the terminology encompassing these approaches has evolved to reflect the benefits patients derive when combined with traditional anticancer treatments.

“We call it ‘integrative medicine’ because that’s what it is — the deliberate, informed, and personalized delivery of these approaches alongside conventional care — as opposed to using these approaches as pure alternatives,” Lorenzo Cohen, PhD, director of the integrative medicine program at The University of Texas MD Anderson Cancer Center, told HemOnc Today. “There are situations when taking an educated, evidence-informed approach exploring some of these alternative agents may lead to relief of symptoms or even antitumor effects.”

Most patients use integrative therapy in conjunction with conventional chemotherapy and radiation regimens to alleviate symptoms, according to Lorenzo Cohen, PhD.
Most patients use integrative therapy in conjunction with conventional chemotherapy and radiation regimens to alleviate symptoms, according to Lorenzo Cohen, PhD. “It’s a very small percentage who are using these approaches alone as true alternative medicine seeking a cure. But these patients cannot — and should not — be ignored,” he said.

Source: Nick de la Torre.

Although uncommon, in extreme instances, patients may discontinue conventional therapy — or, in some cases, reject it altogether — in favor of alternative approaches.

A more common problem arises when patients take herbs or supplements without knowing they might interfere with their standard treatments. Certain practices — such as yoga and meditation — generally are thought to be safe, but there are safety issues with the massive number of ingestible products on the market that do not undergo the same testing and regulation as FDA-approved pharmaceuticals.

“Under the guidance of a good integrative oncologist or medical oncologist, they may have utility, but further investigation is necessary,” Cohen said.

HemOnc Today spoke with oncologists and integrative medicine specialists about techniques that may alleviate symptoms such as fatigue, pain or sexual dysfunction among patients with cancer; the potential for these approaches to cause harm; and what clinicians must know so they can have informed conversations with their patients.

PAGE BREAK

Recommended approaches

Studies showed 48% to 88% of patients with cancer report using CAM as part of their therapy, according to a paper by Johnson and colleagues published this year in JAMA Oncology.

“Many of us are taking some kind of vitamin or supplement whether we have cancer or not,” Gary H. Lyman, MD, MPH, senior lead in health care quality and policy at Fred Hutch’s Hutchinson Institute for Cancer Outcomes Research, told HemOnc Today. “While it may seem like a reasonable thing to do, we want to make sure patients have evidence-based information on these products.”

That isn’t always the case.

A study presented at this year’s European Society for Medical Oncology Congress showed a majority of patients who used complementary medicines were poorly informed about safety and the risk for interactions with anticancer therapies.

Researchers surveyed 152 outpatients with sarcoma, gastrointestinal stromal tumors or desmoid tumors. About half (51%) reported using any complementary medicine in their lifetime, and 44% reported that their cancer diagnosis sparked their interest in such treatments.

Sixty percent of patients acknowledged they had insufficient knowledge about the safety of integrative medicine, and only 7% reported receiving any information about the safety of these approaches from oncologists.

“Patients mostly accessed information on complementary and alternative medicines on the internet or through other media, friends and healing professionals,” study researcher Peter Hohenberger, MD, head of the division of surgical oncology at thoracic surgery at Medical Faculty Mannheim at University of Heidelberg in Germany, said in a press release. “In sharp contrast with this, when it came to finding information on side effects of cancer therapies or how to handle them, almost half of patients asked their oncologist.”

Patients’ low-risk perception of integrative therapy should be addressed by their oncologists, according to Markus Joerger, MD, PhD, of Cantonal Hospital in St. Gallen, Switzerland.

“Patients tend to believe that supplements or herbs are generally safe, but they are not without risk,” Joerger, who was not involved with the study, said in the release. “In daily practice, if you don’t know what your patient is taking as alternative medicine, the risk of drug-drug interactions can significantly increase and have an impact on clinical outcomes.

“Patients have to realize that they can discuss any health-related choices with their oncologist and be advised on different options when they wish to reduce stress related to cancer treatment, or more in general to feel better,” he added.

Lyman — along with Heather Greenlee, ND, PhD, associate member of the public health sciences and clinical research divisions at Fred Hutchinson Cancer Research Center, and medical director of the integrative medicine program at Seattle Cancer Care Alliance — and colleagues updated clinical practice guidelines from the Society for Integrative Oncology (SIO) to educate physicians about how to have such conversations.

PAGE BREAK

“One of the goals of developing clinical practice guidelines is to provide clinicians and patients with the tools that they need to have a productive conversation on which complementary approaches are safe and effective,” Greenlee told HemOnc Today. “It is difficult to standardize these kinds of conversations.”

The SIO guidelines — endorsed by ASCO — recommend certain integrative therapies during breast cancer treatment to address a variety of symptoms, such as anxiety, stress, depression, fatigue, quality of life, nausea and vomiting, peripheral neuropathy and pain.

Greenlee and colleagues recommend music therapy, meditation, stress management and yoga for anxiety and stress; and meditation, relaxation, yoga, massage and music therapy for depression or mood disorders.

The guidelines state meditation and yoga may improve quality-of-life parameters, whereas acupressure and acupuncture are recommended for chemotherapy-induced nausea and vomiting.

Conversely, the guidelines state acetylLcarnitine should not be used to protect against chemotherapyinduced peripheral neuropathy, and that there is a lack of evidence to support the use of the vast majority of ingested dietary herbs and supplements.

“We know that a large percentage of oncology patients are using or are interested in using complementary therapies,” Greenlee said. “With these guidelines as a tool in hand, our hope is that more clinicians will be comfortable initiating these conversations with patients.”

Potential benefits

There is limited research examining the benefit of integrative medicine approaches to manage side effects of cancer and its treatments.

Jun J. Mao, MD, MSCE, chief of the integrative medicine service at Memorial Sloan Kettering Cancer Center, and colleagues compared 8 weeks of acupuncture with cognitive behavioral therapy among 160 cancer survivors who had been clinically diagnosed with insomnia disorder.

“We set out to do a study to answer a question between the two treatments: Which is more effective for insomnia [among] individuals with cancer?” he said during a press cast. “Our hope is that by doing this research, we can help patients and clinicians pick the right treatment for patients to manage their sleep.”

Results, presented at this year’s ASCO Annual Meeting, showed an 8.3-point (95% CI, 7.3-9.4) reduction in insomnia severity in the acupuncture group, compared with a 10.9-point (95% CI, 9.8-12) reduction among those who received cognitive behavioral therapy (difference, 2.6 points; 95% CI, 1.1-4.1; P = .0007).

Physical and mental health quality-of-life parameters improved among both groups, and neither group experienced noteworthy adverse events.

“Cognitive behavioral therapy for insomnia is a highly effective therapy and considered [the] gold standard of treatment; however, not everyone accepts this treatment,” Mao said. “It is a highly specialized therapy that isn’t quite available in many cancer centers or communities.”

PAGE BREAK

Acupuncture also has been shown to alleviate joint paint among patients with breast cancer.

Dawn Hershman, MD, leader of the breast cancer program at Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian/Columbia University Medical Center, and colleagues compared the effect of three approaches: real acupuncture administered in twice-weekly sessions for 6 weeks, followed by one session per week for 6 additional weeks; sham acupuncture administered in the same schedule; or no acupuncture.

Results, presented at last year’s San Antonio Breast Cancer Symposium showed a true statistical difference between mean Brief Pain Inventory scores for real acupuncture vs. sham acupuncture (0.92 points lower; 95% CI, 0.2-1.65; P = .01), as well as for real acupuncture vs. no treatment (0.96 points lower; 95% CI, 0.24-1.67; P = .01).

Fifty-eight percent of women who received real acupuncture had a clinically meaningful 2-point change, compared with 31% in the sham acupuncture group and 30% in the control group.

“We were motivated to think of ways of reducing joint pain caused by aromatase inhibitors because so many patients suffer with this side effect, and often patients do not want to take more medications,” Hershman told HemOnc Today at the time of the presentation. “Our study gives both patients and providers confidence that this approach to treating symptoms can be effective and safe. However, not all acupuncture is the same, and we would encourage the acupuncture community who treat patients with breast cancer to read our prior publications describing the methods we used.”

Acupuncture has been found to be effective for a number of symptoms, Cohen said.

“Most data show that it can be used to control nausea or pain, but there is also some evidence for hot flashes or aromatase inhibitor-induced arthralgias,” he said. “There is also evidence that acupuncture can be used for neuropathy and sleep disorders.”

Chinese medicine informs the practice of acupuncture based on “patterns of disharmony,” according to Doug McDaniel, DACM, integrative medicine program manager at Roswell Park Comprehensive Cancer Center.

Doug McDaniel, DACM
Doug McDaniel

“Patients are diagnosed prior to each treatment, and specific points are chosen based upon that diagnosis that reflect the patient’s pattern of disharmony at that moment in time,” McDaniel said. “This means that each patient treated for chemotherapy-induced nausea may have a different pattern of disharmony and will accordingly be treated with different points based upon this pattern. This also means that each patient may present differently at each visit, and point prescriptions may be modified at each treatment session to optimize treatment effectiveness based on the pattern presenting that day.”

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The effects of yoga on cancer-related symptoms also have been studied extensively.

Ben-Josef and colleagues investigated whether a yoga practice could improve fatigue, erectile dysfunction, urinary incontinence and overall quality of life among men with prostate cancer undergoing radiotherapy.

Men assigned yoga reported less fatigue (P < .0001) and greater improvements in sexual health scores (P = .0333) than those in the control group. Researchers reported improved quality of life in terms of emotional, physical and social scores, but not functional scores.

A range of mindfulness techniques — from the traditional, such as yoga and meditation, to the more experimental, such as hypnosis, guided imagery or dichromatic breathing — can be useful for patients with cancer, Cohen said.

“There is a fair amount of evidence that some of these techniques, particularly yoga, can improve fatigue and sleep parameters,” he said. “Patients report improvements in cancer-related symptoms.”

Stress and anxiety also may be improved through meditation, music therapy and yoga, Lyman said.

“However, most of the data are in breast cancer at the moment,” he said.

Researchers at Roswell Park are studying integrative therapies like mindfulness, McDaniel said.

“Although there is evidence that acupuncture, mindfulness, yoga and others help patients, we also know that more research needs to be done,” he said.

McDaniel urged people to be cautious about esoteric modalities.

“Some of them have little to no data supporting their use,” he added.

Potential harm

Not all studies of integrative medicine have proven positive.

A study by Amraoui and colleagues, published in August in JAMA Network Open, showed that a 15-minute hypnosis session before general anesthesia offered benefits regarding fatigue, anxiety and patient satisfaction among women undergoing breast cancer surgery. However, the intervention did not reduce postoperative pain, the study’s primary endpoint.

Beyond a lack of benefit, some integrative medicines — particularly supplements or herbs — may be detrimental to patient safety.

In a study by McCune and colleagues, 76 patients undergoing cancer treatment completed a questionnaire to assess herb and vitamin use. The researchers investigated the frequency of interactions between herbs or vitamins and chemotherapy; communication between doctors and patients regarding these treatments; and potential interactions with chemotherapy.

Results showed herbs or vitamins were used by 78% of patients, 27% of whom were potentially at risk for a drug-drug interaction.

More than 85% of the cohort reported willingness to discontinue herb or vitamin use in light of suspicion of a detrimental interaction.

“There is not enough good research supporting the use of herbs and supplements during cancer treatment,” McDaniel said. “The problem with many studies that have been performed is the methodology and small sample sizes, making it difficult to draw strong conclusions. My philosophy is that any modality must first be proven to be safe. If there is no evidence of safety, then that modality should not be considered.”

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Further, the FDA does not regulate these products, Cohen said.

“Contaminants could be present or the level of bioactive substances may be not what is listed on the label,” he said. “In fact, it is these bioactive substances that are the reason they purportedly have a beneficial effect on symptoms and tumor growth in the first place and, if they are not regulated, this could cause a problem.”

Drug-herb interactions should raise as many red flags as drug-drug interactions, such as the use of serotonin reuptake inhibitors for depression during chemotherapy, Cohen added.

“This type of metabolic overlap is always of concern,” he said. “That said, there is some evidence — at least in breast cancer — that ginseng can alleviate fatigue, and ginger may be useful for controlling nausea. Outside of those areas, it becomes a bit more challenging.”

In a study published in 2016 in Cancer, Ben-Arye and colleagues found that herbal medicine use had several potential negative effects.

Researchers distributed a questionnaire to 339 health care professionals in the Middle East, where herbal medicine use is prevalent, to assess herbal supplement used by their patients.

They identified 44 herbal and three nonherbal supplements, 29 of which had safety concerns. Fifteen herbs altered pharmacodynamics with traditional cancer drugs, 18 herbs had direct toxic effects and seven herbs increased in vitro response of cancer cells to chemotherapy.

“It is important to consider that any supportive care or CAM treatment that a patient seeks out needs to be evidence-based,” McDaniel said. “It is important to know that it is safe and that it will not negatively impact the effectiveness of their conventional treatment regimen. It also is important to know that it will most likely have a positive effect on treating the symptom or supporting their health.”

Refusing standard treatment

A study published this year in JAMA Oncology revealed that the use of alternative medicine in place of conventional treatments was associated with decreased survival among patients with curable cancer.

This increased mortality risk appeared driven largely by the fact that patients who chose alternative medicine were more likely to refuse conventional cancer therapy.

“The fact that complementary medicine use is associated with higher refusal of proven cancer treatments, as well as increased risk for death, should give providers and patients pause,” study author Skyler Johnson, MD, chief resident in radiation oncology at Yale School of Medicine, said in a press release. “Unfortunately, there is a great deal of confusion about the role of complementary therapies. Although they may be used to support patients experiencing symptoms from cancer treatment, it looks as though they are either being marketed or understood to be effective cancer treatments.”

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Johnson and colleagues compared OS among patients with nonmetastatic breast, prostate, lung or colorectal cancers treated with complementary medicine (n = 258) or without (n = 1,032).

Results showed a greater proportion of patients who received complementary medicine refused surgery (7% vs. 0.1%), chemotherapy (43.1% vs. 3.2%), radiotherapy (53% vs. 2.3%) and hormone therapy (33.7% vs. 2.8%; P < .001 for all).

Fewer patients who received complementary therapy achieved 5-year OS (82.2% vs. 86.6%; P = .001).

Multivariate analysis revealed an independent association between complementary therapy and mortality risk (HR = 2.08; 95% CI, 1.5-2.9). However, when treatment delay or refusal rates were factored into the multivariate model, the association lost significance (HR = 1.39; 95% CI, 0.83-2.33).

“Supplements are occasionally associated with early termination of chemotherapy,” Lyman said. “In short, many patients are or become distrustful of conventional therapies.”

Johnson and colleagues defined complementary medicine as “other” or “unproven” treatments administered by nonmedical personnel. However, it is unclear whether the findings from this study are often observed among patients who practice yoga, meditation or mindfulness approaches, according to Lyman.

“The studies that have been done on the subject of patients rejecting or discontinuing traditional therapies are fraught with confounding factors, including that patients who make this choice are often self-selecting,” he said. “These are not prospective, randomized controlled trials. They may not be the same types of patients who use integrative approaches in a complementary fashion to alleviate symptoms.”

For Cohen, it’s a matter of numbers.

“The vast majority of patients are either using only conventional chemotherapy and/or radiation regimens, etc, or they’re using integrative medicine to alleviate symptoms and improve outcomes,” he said. “It’s a very small percentage who are using these approaches alone as true alternative medicine seeking a cure. But these patients cannot — and should not — be ignored.”

Talking with patients

Emerging data suggest clinicians are not discussing integrative approaches with their patients, and that they do not feel they have enough knowledge of the subject.

“As we know patients are using these therapies, it’s unethical not to have these conversations,” Cohen said.

Chang and colleagues assessed knowledge and attitudes about complementary medicine in a cohort of 219 patients, 301 volunteers without cancer and 156 health care professionals.

More than half (58.8%) of health care professionals reported their knowledge of complementary medicine was inadequate, and 79.2% reported not being up to date with available evidence.

“Many people in the field believe we shouldn’t be talking about these things or discussing any treatments in the absence of large randomized controlled trials,” Lyman said. “But, even if patients are using therapies that are not recommended or don’t have supporting evidence, they should not be dismissed or shut out. It is more important that the provider know what the patient is taking, regardless of what it is.”

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Lee and colleagues sent a survey to 1,000 random ASCO members to determine communication patterns about integrative approaches, including physician education about herbs and supplements, discussion with patients regarding their use and knowledge of adverse events.

Results, published this year in Journal of Clinical Oncology, showed that 41% of 392 oncologists discussed use of herbs and supplements with patients, but only 26% of those discussions were initiated by the oncologist. Approximately two-thirds of oncologists reported insufficient knowledge on the topic, while 59% reported receiving no education about these approaches.

“We have seen that integrative medicine is not addressed often enough,” Lyman said. “In some cases, the doctor fails to initiate the discussion and, in others, the patient is either embarrassed about their use or doesn’t think it’s relevant to what they’re doing.”

Conversations surrounding integrative medicine should be holistic, McDaniel said.

“I like to ask how they are feeling at this moment, what things in their life have changed, what things can they no longer do that they would still like to do, and what their health and wellness goals are during and after treatment,” he said. “I try to look at the whole person and to help the patient realize they are not their disease, and that what is happening right now is not necessarily going to be forever.

“I start by asking what is troubling them most and then offer small, achievable suggestions to integrate appropriate supportive care modalities into their treatment regimen,” McDaniel added. “The closer to diagnosis that I can get a patient on board with this, the better.”

Safety should be a critical component of these discussions, Cohen said.

“We encourage our patients to turn to a well-known, safe behavioral strategy to control a symptom rather than a pharmacological product,” he said. “[Patients with cancer] are on so many different treatments that if there is a nonpharmacological approach, we recommend trying that first.”

Many integrative therapies can be quite costly to pursue, and patients may be wasting money that could be better spent on proven approaches such as diet and exercise, McDaniel said. Rather, clinicians should steer patients toward fundamentals of good health.

“Lifestyle choices that support enhancing [the health and well-being of a person with cancer] are key to helping alleviate symptoms that may arise from either their treatment or their disease,” he said, citing proper nutrition, regular exercise, hydration, rest and stress management as cornerstones. “I also recommend patients do something that they like every day that is just for them. This could be listening to music, reading a book, watching a movie, talking a walk in nature or journaling — whatever it is that helps to support them living in the moment and enjoying life.”

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Looking ahead

Despite the prevalence of analyses evaluating various integrative approaches, experts with whom HemOnc Today spoke still emphasized a need for sound data on their use.

“Studies need to be designed to look at real-world situations of how the modality is practiced on a daily basis,” McDaniel said. “For example, true acupuncture was compared to sham acupuncture in an effort to develop standardized point protocols to treat specific symptoms. Results showed there was no difference between the true and sham acupuncture groups, but there was usually a positive difference between both true and sham acupuncture and conventional care if that was included in the study.”

Although herbal medicines are those most likely to cause an interaction with anticancer therapies, studies have suggested they could carry antitumor effects.

For example, plant-derived polyphenols, flavonoids and brassinosteroids have been studied as potential anticancer agents, according to Greenwell and Rahman. Such medicinal plants may induce antioxidant activity, inhibition of cancer cell growth, induction of apoptosis, target specificity and cancer cell cytotoxicity.

Thus, it also would be beneficial to have more basic science on herbal medicine, McDaniel said.

“Some of the research that has been done has shown that a particular herb and a particular chemotherapeutic agent are both effective in eradicating the same cancer cell; however, the mechanism of action is different for each agent,” he said. “This could lead to using these two different approaches in the same treatment to enhance the effectiveness of the treatment.”

As it stands, the fact integrative medicine is such a broad category may inhibit understanding of its use.

“We need to distinguish more clearly among the many types of integrative therapies, and we need to understand more clearly who is more likely to use which approaches,” Lyman said. “We also need to look more closely at who is using them to alleviate symptoms and who is using them in place of conventional therapy.”

Increased knowledge surrounding all of these areas may lead to improved access for important symptom relief, as well as greater physician acceptance of their benefits, Cohen said.

“The more we know about these approaches and products, that will bring us one step closer to insurance coverage for them,” he said. — by Rob Volansky

Click here to read the POINTCOUNTER, “Should hem/oncs recommend integrative therapies to their patients?”

References:

Amraoui J, et al. JAMA Network Open. 2018;doi:10.1001/jamanetworkopen.2018.1164.

Ben-Arye E, et al. Cancer. 2016;doi:10.1002/cncr.29796.

Ben-Josef AM, et al. Int J Radiat Oncol Biol Phys. 2017;doi:10.1016/j.ijrobp.2017.03.043.

Chang KH, et al. BMC Cancer. 2011;doi:10.1186/1471-2407-11-196.

Greenlee H, et al. CA Cancer J Clin. 2017;doi:10.3322/caac.21397.

Greenwell M and Rahman PK. Int J Pharm Sci Res. 2015;doi:10.13040/IJPSR.0975-8232.6(10).4103-12.

Hershman DL, et al. Abstract GS4-04. Presented at: San Antonio Breast Cancer Symposium; Dec. 5-9, 2017; San Antonio.

Hill C, et al. The effect of aromatherapy and foot reflexology on pain and anxiety during brachytherapy for cervical cancer. Presented at: Oncology Nursing Society Congress; May 17-20, 2018; Washington, D.C.

Johnson SB, et al. JAMA Oncol. 2018;doi:10.1001/jamaoncol.2018.2487.

Lee RT et al. J Clin Oncol. 2018.doi:10.1200/JCO.2014.55.8676.

Lyman GH, et al. J Clin Oncol. 2018;doi:10.1200/JCO.2018.79.2721.

Mao JJ, et al. Abstract 10001. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.

McCune JS, et al. Support Care Cancer. 2004;12:454-62.

Sungu-Winkler K-T, et al. Abstract 1655P-PR. Presented at: ESMO Congress; Oct. 19-23, 2018.

For more information:

Lorenzo Cohen, MD, can be reached at The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030; email: lcohen@mdanderson.org.

Heather Greenlee, ND, PhD, can be reached at Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA, 98109-1024; email: hgreenlee@fredhutch.org.

Gary H. Lyman, MD, MPH, can be reached at Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA, 98109-1024; email: glyman@fredhutch.org.

Jun J. Mao, MD, MSCE, can be reached at Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065; email: maoj@mskcc.org.

Doug McDaniel, DACM, can be reached at Roswell Park Comprehensive Cancer Center, Elm and Carlton Sts., Buffalo, NY 14263; email: douglas.mcdaniel@roswellpark.org.

Disclosures: Cohen, Greenlee, Lyman, Mao and McDaniel report no relevant financial disclosures.