Complementary and alternative medicine (CAM) generally refers to a variety of approaches that are not considered part of Western medicine. Complementary medicine refers to therapies used together with conventional medicine, while alternative medicine refers to therapies used as a substitute for conventional medicine, which is generally not recommended (National Center for Complementary and Integrative Health, 2016). For example, CAM includes the practices of hypnotherapy, food supplements, homeopathy, massage, acupuncture and nutrition, to name a few. It is not clear if patients know the important distinction between complementary and alternative practices, however.
There are some grey areas within the practice of nutrition. Naturopaths and nutritional therapists are often termed ‘alternative’, as supplements may be prescribed as part of their advice. Although dietetic therapy is not usually termed ‘complementary’, dietitians may recommend supplements or therapies with a good evidence base to complement medical treatments, or to use as an alternative when all conventional treatments have failed. Therefore, for the purpose of this article, dietetic interventions were also included when looking at the use of CAM.
CAM has been used for thousands of years, with records of almost every ancient society using CAM-type disciplines before conventional medicine evolved. For example, the Chinese used acupuncture, traumatology, manipulative therapies, moxibustion and herbs (Tui na), exercise (qigong), and dietary therapy to treat medical problems. Chinese herbal medicines are one of the most commonly used types of traditional Chinese medicine treatment (Huang et al, 2014). In the Indian subcontinent Ayurvedic medicine developed. The basic principle was to prevent illness; this is accomplished through the use of herbal remedies, yoga and, meditation, with diet and lifestyle changes (Niemi and Ståhle, 2016).
The literature on CAM
In Western Australia, a drop-in centre within a cancer department offering complementary therapies appeared to enable coping with the diagnosis and treatment of cancer by facilitating comfort and increasing perceptions of personal control. The centre also helped some participants to make sense of their experience with cancer (Williams et al, 2014).
In a recent review of systematic review data, yoga (specifically), physical exercise (more generally), cognitive behavioural therapy (CBT), and mindfulness-based stress reduction (MBSR) programmes showed benefit in terms of quality of life in cancer survivors (Duncan et al, 2017). A recent Cochrane review evaluated 14 small studies of cancer patients using massage therapy. Although benefits were noted, none of them showed clinically significant benefits for symptom relief (Shin et al, 2016).
Many cancer patients use CAMs, but may not be aware of the potential side effects. There are no studies quantifying such side effects, but there is some evidence of patient risk mainly from case reports. Some herbal medicines have been extensively studied and there is clinical evidence for both potential benefits and risks, as shown by Hermann and Von Richter (2012). There are certainly supplement-drug combinations that may result in serious consequences in cancer patients. For example, the concurrent use of enzyme inducers such as St John's wort (Hypericum perforatum) can affect many drugs. St John's wort has been shown to cause a 44% reduction in the time that imatinib remains at therapeutic blood levels (McCune et al, 2004).
For UK health professionals working in cancer care, the topic of CAM is generally an unsupported area, both in terms of education and funding. Perhaps this is because the NHS offers only a small number of complementary therapies, recommended as complementary to treatment.
Attitudes of health professionals may vary and may depend on job role. In one study within a German palliative care cancer centre, 365 professionals were questioned on the topic. Eighty-five per cent of the doctors and 99% of the nurses claimed to be interested in CAM. In the same centre, 25 patients were asked about CAM. In the palliative setting, 40% of patients were interested in CAM, mainly in biological-based rather than relaxation-type therapies. Surprisingly, patients were more likely than health professionals to say that scientific evidence is most important in relation to using CAM (Muecke et al, 2016).
In a US study that recorded inpatients' interest in CAM, more than 40% of those questioned said they would be interested in using vitamins/nutritional supplements, special diets and manual therapies, such as massage and osteopathy, if these were to be offered during their hospital stay. Ninety-five per cent of patients were interested in at least one form of CAM. More than 75% expressed interest in nutritional counselling and massage combined (Liu et al, 2016).
Reasons to use CAM are multifactorial. In a Turkish systematic review of 12 gynaecological and breast cancer studies, patients used CAM to improve immunity, reduce the side effects of treatment, and for physical and psychological relaxation. The frequency of CAM use varied between 40% and 95%. From CAM options, herbal medicines, vitamins/minerals were used most frequently in eight of the studies (Akpunar et al, 2015).
A Serbian survey found that approximately 65% of patients believed that CAM would strengthen their immunity, and up to one-third of CAM users believed that CAM would cure their malignant disease. Most patients expected better effects of the standard treatment if aided by CAM (Berat and Radulovic, 2014).
An Australian survey conducted over two sites found that 19% of patients claimed that the main reason for CAM use was based on the recommendation of a doctor. ‘Improving immune system’ was the most common expectation of CAM at both sites (39% and 50%). More than half of CAM users felt that it was effective (51% and 54 %), as reported by Hunter et al (2016).
Breast cancer patients are particularly well studied in terms of CAM use. In a French survey, 184 breast cancer patients responded, with 37% reporting using at least one CAM. Therapies using substances, such as homeopathy and phytotherapy, were the most commonly used (80%) before physical activity (42%) and dietary methods (31%). A total of 66% of users felt that these treatments demonstrated evidence of efficacy and 75% thought that they were not associated with side effects. The main goal for use was improvement of treatment-related symptoms (28%); the secondary goal was increasing general health status (20%), as reported by Saghatchian et al (2014).
In a Palestinian survey of herbal CAM use in 115 breast cancer patients, 103 patients responded to the survey; 68% of these patients used herbal remedies. Women with breast cancer used 46 plant species belonging to 32 families (the Brassicaceae and Lamiaceae families were the most prevalent). Ephedra alata was the most commonly used plant species in the treatment of breast cancer. Herbal remedy users were more likely to use herbal remedies instead of chemotherapy. The most commonly stated reason for using these remedies was the belief in boosting the patient's immune system to fight cancer (Jaradat et al, 2016).
In a Malaysian study of 546 breast cancer patients undergoing chemotherapy, 386 (71%) reported using some form of CAM, which included ‘prayer for health’, and 160 (29%) were non-CAM users. The most common CAM was natural products (83%) and the most popular of these were vitamin and mineral supplements (n=168), cleansing/detoxifying diets (n=68), antioxidant capsules/tablets (n=61), cactus juice (n=47) and spirulina (n=43). Mind and body therapies (51%) were the second most popular, including relaxation exercises (n=67), followed by massages (n=60), meditation (n=52), tai chi (n=33), yoga (n=29) and therapeutic/healing touch (n=24). Traditional medicines were the third most popular, including traditional Malay medicines (n=96), traditional Chinese medicines (n=24) and homeopathy (n=11). CAM users (36% of the 546 patients) were more likely to have advanced cancer compared with non-CAM users. The CAM users were less likely to have their chemotherapy on schedule than non-CAM users. Most mind and body therapies were perceived to be more helpful by their users than the use of natural products and traditional medicine (Chui et al, 2014).
In a US survey of 764 women who had previously had breast cancer, four distinct classes of CAM users emerged. These were:
In a US survey of 2508 women with gynaecological cancer, 534 (21%) responded. Overall, 464 women (87% of CAM question respondents) had used at least one CAM therapy during the previous 12 months. The most commonly used CAM categories were biologically based approaches (83%), mind and body interventions (31%), and manipulative and body-based therapies (19%). The most commonly used individual CAM therapies were vitamins and minerals (78%), herbal supplements (28%), spiritual healing and prayer (15%), and deep breathing relaxation exercises (13%) (Abdallah et al, 2015).
A few studies have assessed the effects of CAM on quality of life. A Turkish study in a mixed cancer population of 147 patients undergoing either chemotherapy or radiotherapy showed that regular use of CAM had a statistically significant positive relationship to average quality-of-life scores. Regular users of CAM reported finding it effective and suggested it to others (Korkmaz et al, 2016). In a Lebanese breast cancer population, CAM use was not significantly related to quality of life (Naja et al, 2015). In another study looking at breast cancer patients in Malaysia, there was no significant difference in global health status scores and quality of life. CAM users did, however, report significantly higher sexual enjoyment scores than non-users. CAM users reported more systemic therapy side effects and breast symptoms, but it is unclear if CAM was taken to resolve already existing symptoms or if it had caused these problems (Chui et al, 2015).
Neuroendocrine tumours
Neuroendocrine cells are distributed throughout the body, eg within glands (hypothalamus, pituitary), tissues (adrenal medulla), and cells scattered within organs with other specialised functions (for example within the gastrointestinal tract or the lung). Neuroendocrine tumours (NETs) may arise from any of these sites and may be secretory or non-secretory, leading to heterogeneous presentations. They include functioning and non-functioning gastroenteropancreatic tumours, catecholamine-secreting tumours, medullary thyroid cancer and pituitary tumours (Barakat et al, 2004).
Aim
There is no literature to date on CAM use among patients with NETs. The aim of the present study was to determine what types of CAM patients with a NET diagnosis undergoing chemotherapy choose, and what CAMs they find most useful.
Method
A pilot study was conducted in January 2017. Patients with NETs undergoing certain treatments were identified for clinical audit from a NET nurse chemotherapy database at the Royal Free Hospital, London. All living patients who had completed intravenous chemotherapy during the previous 3 years were selected from this database. A CAM questionnaire was used to capture retrospective data, and it was sent out to 75 patients along with a covering letter to explain the reason for investigating patient CAM behaviour, as seen in Figure 1. As previously mentioned, dietetics would not normally be included in CAM, but the clinic does have access to a NET dietitian who may give advice that complements chemotherapy. Within the Royal Free Hospital, the Complementary Therapies Department includes access to massage therapists, and the Oncology Psychological Support Service provides counsellors. Therefore these services were listed as options within the questionnaire because it was interesting to find out which therapies patients found useful.
A stamped, addressed envelope was also provided to allow patients to return forms without incurring any expense. An additional four patients were given the questionnaire directly in clinic and this was returned to the researcher afterwards, making 79 in total.
Results
Fifty one patients (51/79) returned the questionnaire, a response rate of 64%. Of those who responded, 33 (65%) patients used at least one form of CAM during chemotherapy. Some patients used up to six CAM types during chemotherapy.
Type of CAM selected by patients
Table 1 shows the different types of CAM used by patients in the study. Of 18 patients using massage, 17 used aromatherapy massage. Fourteen patients took vitamin and mineral supplements. Three people took products that were in doses exceeding 100% of the nutrient reference value (NRV); 3 others did not disclose names or doses of supplements and so may have also exceeded NRVs. Probiotics were taken by 4 patients. Four patients took various teas (Table 1).
| Type of CAM | Number of patients |
|---|---|
| Aromatherapy massage | 17 |
| Vitamin and mineral supplements | 14 |
| Dietary suggestions from a dietitian | 4 |
| Various teas | 4 |
| Yoga/pilates | 4 |
| Probiotics | 4 |
| Turmeric/curcumin supplements | 4 |
| Other herbal supplements | 3 |
| Meditation | 2 |
| Supplementary juice/shake | 2 |
| Shiatsu massage | 1 |
| Acupuncture | 1 |
| Osteopathy | 1 |
| Counselling | 1 |
| Homeopathic therapy | 1 |
| Reflexology | 1 |
Frequency
Thirteen patients took supplemental vitamins and minerals daily. Other supplements, including herbal, homeopathic, teas, turmeric and probiotics, were mostly taken daily. All patients who had massages in most cases had them monthly.
CAMs found to be most useful by patients
Table 2 lists the CAMs that patients found most useful. The CAM that patients felt was most useful during chemotherapy was massage (aromatherapy and shiatsu were both included in the questionnaire). Getting enough good quality sleep and exercises such as swimming, which are not CAM, were listed as helpful additional activities by four patients. These respondents mentioned that these additional practices helped them the most because they helped them to relax. In addition to answering the questions, five patients wrote on the questionnaire that they would have liked to have more information on CAM during chemotherapy.
| Most useful CAM | Number of patients |
|---|---|
| Massage | 9 |
| Non-specified exercise | 3 |
| Turmeric supplements | 2 |
| Osteopathy | 1 |
| Dietary suggestions from a dietitian | 1 |
| Reflexology | 1 |
| Sleep | 1 |
| Counselling | 1 |
| Supplementary juice/shake | 1 |
Discussion
The response rate of 64% was reasonable, considering many patients may have been unwell and therefore unable to reply. To increase the number of responses, it may have been better for the researchers to have given the questionnaires face to face.
Sixty-seven per cent of patients responding used at least one form of CAM during chemotherapy. Although this use reflects interest, many patients would have liked more information on which CAM might be helpful during this form of treatment.
In a Serbian study of cancer patients undergoing chemotherapy, more than 50% used CAM in each of the three sampling periods (1993, 2000, and 2007). Ten per cent of the patients stated that their treating doctors were the ones who had suggested using CAM, which rose to 30% in the 2008 survey. However, it was not clear which forms of CAM the doctors were recommending (Berat and Radulovic, 2014).
A Turkish study involving 147 cancer patients undergoing either chemotherapy or radiotherapy assessed the use of CAM and dietary supplements including green tea, garlic, pomegranate juice, pollen, and herbal tea, which were significantly related to improved quality-of-life scores (Korkmaz et al, 2016). A more recent Turkish study conducted with 397 mixed cancer patients undergoing chemotherapy demonstrated that most (92%) resorted to religious and cultural approaches, and 34% used nutritional and herbal products besides medical treatment. These included stinging nettle (22%), fennel flower (20%), and herbal products that were advertised by herbalists in the media (10%). It was determined that most of the patients resorting to complementary or alternative medicine were women (53%), housewives (51%), and patients with a history of cancer in the family (38%) (Üstündag et al, 2015).
In Malaysia, 546 breast cancer patients surveyed while on chemotherapy were more likely to use CAM (71%) than non-CAM users. CAM users were more likely to have a tertiary education, have high household incomes and have advanced cancer compared with non-CAM users. However, CAM users were less likely to have their chemotherapy on schedule than non-CAM users (Chui et al, 2014).
A recent CAM study in Italy showed that 49% of cancer patients undergoing conventional cancer therapy used at least one form of CAM (Berretta et al, 2017).
The authors' present study reported a higher CAM use (65%) than the other UK surveys of cancer patients, although the previous surveys included only supplemental medicines (Werneke et al, 2004; Alsanad et al, 2016). Overall, potentially hazardous probiotic and high-dose antioxidant use was found in 21% of patients in the present study, higher than a comparable UK study in which 18 (11%) reported using supplements in higher than recommended doses. In that study, 12% of patients had to be issued health warnings owing to contraindications (Werneke et al, 2004), but this was not possible in a retrospective study.
The most popular CAM the NET patients chose was massage. It was also the CAM that was felt to be most useful during chemotherapy. A previous US study by Liu et al (2016) found that cancer inpatients were interested in massage, but to date this has not been reported in NET patients undergoing chemotherapy. A study by Ho et al (2017) provided insight into the benefits of massage, where 15 female cancer patients found that aromatherapy massage brought:
The safety of CAM during chemotherapy is of importance, and three patients reported use of potentially contraindicated supplements. These patients took vitamin and mineral supplements that contained ≥100% NRVs of antioxidant. Some studies indicate that taking antioxidant supplements may interfere with chemotherapy and radiation therapy, by reducing their effectiveness. It is possible that taking antioxidant supplements during treatment can protect normal tissues from the damaging side effects of treatments, and may improve tumour response and patient survival (Norman et al, 2003; Bairati et al, 2006; Ladas and Kelly, 2010). Conversely, there are some studies suggesting that antioxidants may protect tumour cells, in addition to healthy cells, from the oxidative damage intentionally caused by conventional treatments. This, in turn, may reduce the effectiveness of the treatments (Conklin, 2000; Block et al, 2007; 2008; Lawenda et al, 2008). More research is needed to definitively settle the question of whether taking antioxidants during cancer treatment could be harmful or helpful (Greenlee et al, 2009; 2012).
There are other risks of interactions when biologically based CAM are used to complement conventional cancer treatment. In a UK study of 318 patients, 164 (51%) used CAMs and 133 different combinations were recorded. Of these, 10% took herbal remedies only, 42% supplements only, and 47% took a combination of both. In all, 18 (11%) reported taking supplements in higher than recommended doses. Health warnings were issued to 20 (12%) patients. Most warnings concerned echinacea in patients with lymphoma. Further warnings were issued for cod liver oil/fish oils, evening primrose oil, gingko, garlic, ginseng, kava kava and beta-carotene (Werneke et al, 2004). A later UK study of 375 cancer patients receiving treatment found that 127 out of 375 (34%) consumed herbal or dietary supplements, amounting to 101 different products. Most combinations with cancer treatment were assessed as having ‘no interaction’, 22 combinations were categorised as ‘doubt about outcomes of use’, six combinations as ‘potentially hazardous outcome’, one combination as an interaction with ‘significant hazard’, and one combination as an interaction of ‘life-threatening outcome’. Despite this, most patients did not report any noticeable adverse events (Alsanad et al, 2016).
The herbal teas taken by patients in the present survey included peppermint, ginger, red bush, green, turmeric, pepper, camomile and fennel. Chinese herb mixtures, including those taken as tea, may contain compounds that interact with cytochrome P450 metabolism (Zeller et al, 2013). Respondents in the authors' present study did not always specify exact contents and doses of mixtures used.
Probiotics use was not high, with four patients (8%) taking them. The responses did not detail strains and doses however. Probiotics are generally not recommended during chemotherapy in the UK because of the risk of developing neutropenia. Very rare incidents of illness with Saccharomyces boulardii yeast probiotics have been reported (Cesaro et al, 2000). It is not known whether other species carry the same risk in oncology patients as in haematology patients who have been reported to develop Lactobacillus bacteremia after hematopoietic cell transplant (Cohen et al, 2016). Research suggests probiotic use during chemotherapy is of benefit, however (Whyand and Caplin, 2014).
Turmeric extract was taken by four patients, although there are no studies of usage in patients with other types of cancer. It has been shown to have antioxidant, anti-inflammatory and antitumour effects (Zubair et al, 2017). Curcumin, which is the main curcuminoid found in turmeric root, is the active polyphenol-containing compound that has been used during chemotherapy in other cancers with success. It has a good safety record, although there are some known drug-herb interactions relevant to other cancers or prescription medicines reported by the Memorial Sloan Kettering Cancer Center (2019). In colorectal cancer, curcumin may enhance sensitivity to 5-FU chemotherapy (Shakibaei et al, 2014) and slow down cell invasion (Chen et al, 2006). An ongoing clinical trial of curcumin and FOLFOX chemotherapy called CUFOX will determine the success of adding curcumin to advanced colorectal cancer treatment (Irving et al, 2015). Although these extracts have antioxidant action, there are no papers on adverse events in NET patients on chemotherapy, and the antitumour action in NETs and other cells requires more research.
In the present study, it is not clear whether or not patients reported their CAM use to their oncologist, but two studies showed that most patients do not disclose using CAM to their doctor. This was partly because of a lack of or perceived lack of knowledge about CAM by the doctor, but also the expectation of a negative reaction from the doctor concerning the application of CAM in their case (Robinson and McGrail, 2004; Saxe et al, 2008). Industries built around CAM tend not to be regulated. Unfortunately, knowledge of safety in using CAM in cancer is sometimes lacking in both medical and CAM practitioners because reliable reading materials, training and courses are scarce. Despite this, in-depth interviews of 31 cancer and multiple sclerosis patients in Norway found that patients generally view CAM as safer options than conventional medicine (Salamonsen, 2016).
A Canadian survey of 29 oncologists found that 10 (34%) recommended yoga to patients to improve physical activity, fatigue, stress, insomnia, and muscle or joint stiffness. Fifteen others were hesitant or unlikely to suggest yoga for their patients because they had no knowledge of yoga as a therapy, and 11 (38%) believed that scientific evidence to support its use is lacking. All 29 respondents would recommend that their patients participate in a clinical trial to test the efficacy of yoga in cancer (McCall et al, 2015).
A Turkish study of mixed cancer patients, with some on chemotherapy, found 68% usage of herbal medicines. Sixty six per cent stated that their usage of herbal medicines was based on material from the media and the web, and 64% stated that they received information about herbal medicines from relatives and friends. Under one-quarter (24%) of patients reported their CAM use to their doctor (Tuna et al, 2013).
Exploring patients' experience of CAM enables health professionals to gain insights into the needs, preferences and values of NET patients.
Limitations
This was only a small pilot study looking at CAM use in 51 NET patients in a UK oncology clinic. It does not reflect behaviour of UK NET patients not on treatment, or on somatostatin analogues and peptide receptor radionuclide therapy.
Recommendations
This study led to the following recommendations:
Conclusion
CAM use by NET patients is popular and includes practices that aim to support both physical and emotional health. Massage and taking vitamin and mineral supplements were most widely used. Massage, despite it irregular use, was reported to be the most useful.