14. Integrative medicine – Cervical Carcinoma
Major changes in the chapter on integrative medicine
The definition of integrative medicine has been adapted. The chapter has been expanded to include the use of probiotics and coffee in integrative medicine.
C.C. Hack, M.W. Beckmann
14.1 Introduction
The aim in complementary and alternative medicine, which is often summed up in the term “integrative medicine,” is to improve the patient’s general well-being and/or quality of life and in this way make a distinct contribution to overcoming the disease. More and more healthy and ill individuals are making use of these options, known as “complementary and alternative.” Examples include homeopathy, acupuncture, yoga, hypnosis, mediation, phytotherapy, dietary approaches, nutritional supplements, and exercise. These forms of medicine are becoming increasingly popular both among patients and among physicians, and many people already regard them as components of current medical practice [476]. Women in particular appear to be very receptive to these methods. It is often difficult to obtain information about the safety of the treatments offered, due to a scarcity or absence of data. In view of the prevalence of these methods, conventional medicine needs to engage with the treatment approaches involved in order to identify their potential benefits and also to prevent harm to patients.
14.2 Definition of terms
Integrative medicine is an umbrella term that refers to the interplay of scientific evidence-based medicine (“conventional medicine”) and complementary experience-based medicine (“complementary medicine”). Complementary methods that are intended to contribute to holistic care are included in this approach as a supplement to current medical concepts [477], [478]. The term “complementary and alternative medicine” (CAM)) is not clearly defined.
14.3 Spread of alternative and complementary medicine
With regard to usage, a Canadian study has shown that patients with cervical carcinoma generally use methods from the field of complementary and alternative medicine (CAM) less often in comparison with patients with other gynecological tumor entities [479]. According to a study conducted in Connecticut, 87% of patients with cervical carcinoma used methods supplementary to conventional cancer therapy — mainly vitamins (80.3%) and prayer (69.7%), followed by massage (38.5%), herbal infusions/teas (36.1%), and visualization/meditation (31.3%) [482]. Whether and to what extent these data are applicable to Germany or Europe is questionable. In general, some 40% of all tumor patients use methods from complementary and alternative medicine, although the prevalence varies in relation to tumor entity and country [514]. The relevant prioritization in relation to usage and choice of methods is based on intercultural differences in the area of lay etiology.
14.4 Counseling on the field of complementary and alternative medicine (CAM)
Advice on complementary and alternative medicine (CAM) should be given to patients. If patients make use of such methods, it should be documented.
- Consensus
- Strong consensus
In view of the widespread use of the above methods and their potential interactions with radiotherapy and/or chemotherapy, it is important from a medical point of view to inform patients about the potential for interactions. In addition, patients wish to have objective information about the methods [484]. Medical necessity, on the one hand, and the patient’s wishes on the other, need to be taken into account (see the Level 3 “Guideline Complementary Medicine in the Treatment of Oncology Patients” [77]).
14.5 Value of alternative medicine methods
Alternative medicine treatment options — i.e., measures that attempt to treat women who have cervical carcinoma while avoiding the methods of conventional medicine — shall be rejected.
- Consensus
- Strong consensus
There are no reliable data on the efficacy of alternative treatment methods in cervical carcinoma, only two case reports in which the course of the disease was progressive. With the use of nonspecific homeopathic therapy, vitamin C and mistletoe lectins (subcutaneous) [485], one patient who initially had Pap IVa findings developed a cervical carcinoma. All conventional measures were declined, and subsequent treatment with locoregional hyperthermia, Horvi-Reintoxin enzyme therapy, and a combination therapy with Carnivora, mistletoe and the drug ukrain led in the end to a dramatic course and death at the age of 42 [482]. The second case also had a fatal course [486]. The Federal Institute for Drugs and Medical Products (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM) has classified ukrain as a suspect substance. This classification means that ukrain may neither be circulated as a medication in Germany nor administered in patients. The BfArM has in particular informed members of the healing professions that the importation of ukrain is illegal [515], [516].
Studies on alternative medicine in other tumor entities have without exception shown less favorable survival figures when alternative methods are used [488], [489], [490], [508], [509], [510]. These methods should therefore be rejected.
14.6 Value of complementary medicine methods
Among the complementary medicine methods, a distinction is made between measures that improve the efficacy of the treatment or improve the prognosis and those that are intended to reduce the side effects of treatments. The majority of the methods are excluded under Section 135 of the German Social Security Code V (Sozialgesetzbuch, SGB) and are therefore not panel-physician services that can be charged to statutory health insurance.
14.6.1 Improvement in efficacy of treatment or prognosis
14.6.1.1 Hyperbaric oxygen (HBO) therapy
Various methods have been promoted in the past in which increased oxygen saturation in tissue is intended to enhance the efficacy of conventional treatment measures. However, as long ago as the 1970s, it was shown in a small randomized study including 82 cervical carcinoma patients who were receiving radiotherapy that additional hyperbaric oxygen therapy did not offer any treatment benefits in relation to local control, survival, or side effects, and according to the authors it was of no clinical value [517].
14.6.2 Reduction of side effects
14.6.2.1 Mistletoe therapy
The only study on mistletoe therapy in cervical carcinoma concludes that it is advantageous in relation to overall survival. However, the study has substantial methodological deficiencies; for example, the way in which patients were selected for the matched-pair analysis is not reported [498]. A survival advantage has not so far been demonstrated in relation to other tumor entities [511]. Mistletoe therapy is said to have benefits in relation to quality of life, but high-quality research studies are still awaited [511].
14.6.2.2 Enzyme therapy
In a prospective, randomized study including 120 Indian patients, additional enzyme therapy with papain, trypsin, and chymotrypsin alongside radiotherapy was tested in cervical carcinoma. The analysis of the findings showed significant differences in favor of the group receiving enzyme treatment with regard to radiotherapy-related skin reactions and gastrointestinal and urogenital symptoms [512]. On the basis of these data, further research would be useful, but a general recommendation for enzyme therapy cannot at present be made.
14.6.2.3 Vitamins, antioxidants, selenium
Few data are available on the use of antioxidants and vitamins during active conventional treatment for cervical carcinoma. There are at present two contradictory hypotheses:
- The high-dose vitamin therapy variant is said to increase the effectiveness of radiotherapy on malignant cells and to reduce the toxicity for healthy cells. A similar finding has been demonstrated for vitamin E in cervical cell lines [518], [502].
- Antioxidants intercept the free radicals that are generated during radiotherapy and in vitro thus protect the cancer cells from the radiotherapy.
Both of these theories are based on experimental in vitro studies [502]. Little research has so far been conducted on this topic and on the transferability of the findings to the in vivo situation, and there is insufficient research in connection with cervical carcinoma. A study in which a group of women undergoing radiotherapy for cervical carcinoma received a combination of vitamin C (60 mg), vitamin E (10 mg), vitamin A (1000 IU), and selenium (50 mg) showed evidence of reduced apoptosis in the study group in comparison with the control group who did not receive this type of supplementation [499]. Patient-relevant end points such as overall survival and disease-free survival were not investigated. Relevant data are also not available for any other tumor entities [519]. According to the data reported by Halperin et al., topically administered vitamin C did not relieve radiation dermatitis [520].
A multicenter, randomized phase 3 study has been published on uterine carcinoma (endometrial and cervical carcinoma) that investigated the effects of supplementation with sodium selenite on the adverse effects of radiotherapy. The study only included 81 patients with uterine carcinomas (11 of whom had cervical carcinomas) and confirmed selenium deficiency. It was found that diarrhea occurred significantly less often (20.5% versus 44.5%) with selenium supplementation. There was no evidence of a less favorable recurrence-free survival or overall survival. A recent Cochrane analysis in 2011 did not find any evidence of a cancer-preventive effect of selenium supplementation [521].
Several studies have investigated vitamin A in connection with cervical carcinoma. In a small randomized study (n = 42), an improved immune reaction and a trend towards a lower rate of recurrence was noted with vitamin A administration [522], [513]. An uncontrolled study observed a stronger response to radiotherapy with a combination of retinoids and interferons [523]. There is some evidence that vitamin A may be of value in cervical carcinomas [524].
The above research evidence is not sufficient for a recommendation in favor of prophylactic administration of vitamin preparations, antioxidants, and/or selenium to prevent adverse side effects in the treatment of patients with cervical carcinoma.
14.6.2.4 Healing touch
“Healing touch” is an energy treatment that is intended to support the balance of physical, mental, emotional, and spiritual well-being and to stimulate self-healing forces. The method is popular both in the USA and also increasingly in Germany. A randomized, three-armed study on it, including 51 patients with cervical carcinoma, has been published that tested changes in the adverse effects of radio(chemo)therapy relative to healing touch and to a form of relaxation therapy, in comparison with the standard treatment [525]. The analysis of the data showed that with healing touch there was a significantly lower decline in natural killer cells in comparison with patients who underwent relaxation exercises during the treatment and those who received only conventional therapy. There were also benefits with healing touch with regard to depression [525]. No negative effects were observed, and potential long-term effects were not reported.
Reliable larger studies investigating the efficacy of healing touch in the treatment of cervical carcinoma patients in relation to patient-relevant clinical parameters are not yet available, so that the use of the method must be classed as experimental.
14.6.2.5 Phytotherapy
A large number of prescription and nonprescription drugs, as well as nutritional supplements and foodstuffs, are summed up under the umbrella term “phytotherapy.” It is often not possible for any conclusions to be drawn regarding the safety of nonprescription drugs and nutritional supplements and they therefore have to be checked on a case-by-case basis.
A systematic review with a meta-analysis on cervical carcinoma is available in relation to phytotherapy. The review concludes that complementary phytotherapy can both improve the efficacy of conventional therapy and also alleviate its side effects, but that methodologically high-quality studies with better validity are required before it can be recommended [526]. The herbs most often used were astragalus root, ginseng root, Chinese angelica root, poria fungus (Wolfiporia extensa (Peck) Ginns), licorice root, turmeric root, and the rhizome of Pinellia. The review refers exclusively to Chinese studies whose transferability to Germany is limited. In vitro studies show that these agents have a similar profile of effects in cervical carcinoma cells [527], [524], [528], [529], [530]. It has been shown in in-vitro studies that genistein in combination with radiotherapy also inhibits cell growth and triggers apoptosis [531].
A clinical study on the effect of an extract of Agaricus blazei in 100 patients with cervical, ovarian, or endometrial carcinoma (39 with active treatment, 61 in the placebo group) during carboplatin-containing chemotherapy showed significantly increased activity of NK cells (P [276832 et al. 2011].
In preclinical studies, a drug from Indian Siddha medicine (Rasagenthi Mezhugu) showed evidence of efficacy in relation to DNA damage and increased apoptosis [533].
The validity of these studies and in vitro investigations is insufficient for a qualitative evaluation of the clinical application of phytotherapies alongside recognized oncological treatments for cervical carcinoma.
14.6.2.6 Probiotics
Radiotherapy-induced diarrhoea is one of the most common side effects of radiotherapy for cervical cancer. A randomized controlled trial of 57 cervical carcinoma patients demonstrated a significant effect on the incidence and severity of radiotherapy-induced diarrhea [534]. The incidence of diarrhea was lower in the group treated with probiotics (Lactobacillus acidophilus LA-5 plus Bifidobacterium animalis subsp. lactis BB-12) than in the placebo group (53.8% vs. 82.1%, P [Han, E. et al. 2011]. The use of loperamide was lower in the probiotic group than in the placebo group (P [Han, E. et al. 2011]. Supplementation of a probiotic consisting of Lactobacillus and Bifidobacterium strains may therefore reduce chemotherapy-induced and radiation-induced diarrhea in patients with cervical carcinoma. However, a general recommendation for probiotic therapy cannot be made due to the paucity of data.
14.6.2.7 Coffee
A randomized controlled trial was conducted, including 114 patients with endometrial, ovarian, cervical, or tubal carcinoma after complete stage-appropriate surgery to determine whether consumption of coffee postoperatively accelerated the recovery of bowel function [535]. The time to onset of bloating, defecation, and ability to tolerate food was significantly reduced in comparison with the control group (P [Bagenal, F. S. et al. 1990].
Larger, better-powered studies examining the efficacy of postoperative coffee consumption on bowel function are not yet available, and its use should therefore be regarded as experimental.
14.6.3 Conclusions for practice
Scientifically based complementary medical treatment of cervical carcinoma is hardly possible at the present time. For most of the methods, the studies that are available are too few and too poor in quality. The methods mentioned (and also others) can therefore not be recommended. Further well-planned research studies with a clear focus on individual agents or methods and on the specific characteristics of patients with cervical carcinoma appear to be useful and necessary.
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