Complementary therapies for cancer

INTRODUCTION  Complementary and alternative medicine (CAM) is defined by the National Center for Complementary and Alternative Medicine as a group of diverse medical and health care systems, practices, and products that are not normally considered to be conventional medicine . Included in this type of therapy are herbs, acupuncture, chiropractic, and massage, among others. Use of these therapies is common in the general population .

Studies published between 2000 and 2004 found that 48 to 88 percent of patients with cancer used a CAM approach at least in part . However, patients may not reveal the use of CAM unless specifically asked. In one study, disclosure of the use of these therapies increased from 7 to 43 percent when directed questions were added to standard history taking .

Users of CAM are generally not dissatisfied with conventional medicine, but find alternatives to be more congruent with their own values, beliefs, and philosophical orientations toward health and life . In addition, communication between oncologists and patients about CAM is poor, infrequent, and mostly initiated by patients or their kin .

Factors reported to be associated with use of CAM therapies in cancer patients include:

  • Increased psychosocial stress (eg, anxiety, depression)
  • Being given a less hopeful prognosis
  • Having the feeling of "nothing to lose"
  • Attending support groups

Despite the current popularity of CAM, most mainstream oncologists have little understanding of these therapies . However, patients with cancer report feeling that their doctors "should be more interested in, more informed about, and more willing to discuss unconventional therapies" . Although many patients assume that CAM is associated with beneficial effects, at least one Norwegian longitudinal study of 515 cancer patients suggests that CAM use may be associated with shorter survival.

A review of the available evidence regarding CAM in cancer therapy is presented here. The primary focus is on results from clinical trials; uncontrolled trials are considered in areas where controlled studies are not available.

ALTERNATIVE CANCER TREATMENTS  For the purpose of this discussion, alternative cancer treatments (ACTs) are defined as CAM therapies that are promoted for reducing tumor burden or prolonging the life of cancer patients. These are typically biologically active, and promoted as replacements for, rather than adjuncts to, mainstream therapy. The use of ACTs dates back to the 1940s with the use of Koch antitoxins, and new therapies have been introduced each decade, including Hoxsey treatment in the 1950s, krebiozen in the 60s, laetrile in the 70s (which continues to be marketed to the public ), immunotherapy in the 80s, and Di Bella therapy in the 90s .

All of these therapies have evolved through a strikingly similar life-cycle; initially they were aggressively promoted by interested parties based on anecdotal evidence. Mainstream oncologists eventually succumbed to mounting pressure, conducting rigorous clinical trials. When these turned out to be negative, proponents claimed that the studies were flawed and that a conspiracy was underway to discredit a valuable therapy. In the end, each of these therapies submerged into a medical subculture, and cancer patients continued to be attracted to them despite the lack of scientific evidence to support their use.

The following ACTs are currently popular and will be discussed in more detail :

  • Dietary treatments
  • Herbal medicinal products
  • Non-herbal supplements

Dietary treatments  Proponents of "alternative" diets claim that prolongation of life through adherence to a specific diet is an achievable goal for cancer patients. However, a systematic review of the evidence found that none of the many dietary regimens has been convincingly shown to cure cancer or significantly prolong the life of cancer patients .

  Gerson regimen  One retrospective comparative analysis reported a six-fold increase in five-year survival rates of melanoma patients treated with the Gerson diet (a low sodium, high potassium, lactovegetarian diet that emphasizes fresh vegetables, fruit juices, and vitamin supplements), but the flawed methodology limits the reliability of this study .

  Macrobiotic diets  Scientific evidence of benefit from a macrobiotic diet (a high-complex carbohydrate, low fat vegetarian diet) in cancer patients is limited to two methodologically flawed retrospective studies; no controlled trials are available. In addition, one-third of cancer patients on a macrobiotic diet experience problems due to weight loss, the restrictive and unpalatable nature of the regimen, time spent preparing the food, and the expense and inaccessibility of some ingredients.

  Kelley-Gonzalez regimen The Kelley-Gonzalez regimen refers to a program of dietary restriction, intake of digestive aids (eg, pepsin and pancreatic enzymes), and a "detoxification" regimen that includes frequent coffee enemas . In one study that included 36 patients with unresectable or incompletely resected pancreatic cancer, only 11 were considered assessable for outcome for various reasons. The median survival of treated patients was 17 months, compared to a literature control of four to six months. A trial comparing this therapy with gemcitabine for pancreatic cancer was underway at Columbia University, but accrual issues forced a redesign of the study, which now compares outcome in patients who elect to receive the Gonzalez regimen with an externally matched group who receive standard gemcitabine-based combination chemotherapy.

  Selected vegetables and herb mix  Selected vegetables and herb mix (SV) is a blended, boiled, and freeze-dried product containing ingredients with purported immune-stimulatory and anticancer properties: soybeans, mushrooms, mung beans, red dates, scallion, garlic, lentils, leek, hawthorn fruit, onion, ginseng, angelica, dandelion, senegal root, licorice, ginger, olives, sesame seeds, and parsley. Two small studies have been conducted in patients with cancer. In a matched-control study involving patients with stage III/IV non-small cell lung cancer (NSCLC), median survival duration among the 11 patients who ingested SV daily was three-fold longer than that of 13 patients who did not receive the supplement (15 versus 4 months). A similar suggestion of prolonged survival was noted in a second study of 18 patients with stage III/IV NSCLC who had either rejected or failed to respond to conventional therapies. The median survival was 33.5 months for the 12 patients who used SV for two months or longer, and at five years, 50 percent of the patients remained alive.

When these data were presented to the Cancer Advisory Panel for Complementary and Alternative Medicine, SV was judged worthy of further definitive research. Further information can be found at the NCI website (

Herbal medicinal products  Numerous herbal medicinal products (HMPs) are promoted as an alternative cancer treatment. The examples listed below represent only a brief selection.

  Green tea  Green tea is derived from the plant Camellia sinensis, and contains a number of biologically active polyphenols. Herbal products are widely used as CAMs in cancer patients. Green tea is the most widely used herbal product, used by 24 to 30 percent of all cancer patients.

The polyphenols in green tea have a variety of biologic activities that might influence tumor behavior . There are only limited data on possible clinical efficacy:

  • A case control study in China suggested that consumption of large amounts of green tea may have a protective effect against the development of prostate cancer.
  • A phase I study in lung cancer patients and a phase II study in prostate cancer patients showed no antitumor activity .
  • Consumption of large amounts of green tea may correlate with improved survival in patients with ovarian cancer .

Green tea can interact in a variety of ways with conventional cancer treatments . The polyphenols in green tea inhibit multiple cytochrome p450 enzymes that are important in drug metabolism; as a result, green tea could increase the plasma concentrations of a variety of chemotherapeutic agents (eg, anthracyclines and taxanes), possibly increasing drug toxicity. On the other hand, some drug-metabolizing enzymes are induced, which might lead to resistance to other chemotherapeutic agents.

  Essiac  Essiac is an herbal mixture originally formulated by a Canadian Ojibwa healer that has become popular in North America. The formula consists of burdock root (Arctium lappa), turkey rhubarb (Rheum palmatum), sheep or sheepshead sorrel (Rumex acetosella), and the inner bark of slippery elm (Ulmus fulva). Later, watercress, blessed thistle, red clover, and kelp were added.

In vitro studies of the individual components of this mixture have demonstrated some evidence of biological activity, including antioxidant, antiestrogenic, immunostimulant, and antitumor actions. However, an attempted systematic review did not find a single published clinical trial evaluating this mixture in patients with cancer . The author concluded that there is no definitive evidence of its utility, but that Essiac is unlikely to cause serious adverse effects.

  Mistletoe  Mistletoe extracts contain mistletoe lectins and viscotoxins (including viscum fraxini-2). In vitro they modify intracellular protein synthesis, stimulate cytokine production, inhibit tumor colonizations, and induce cell necrosis. In vitro, simultaneous treatment of human cervix carcinoma HeLa or breast carcinoma MCF-7 cells with mistletoe lectins rendered them more sensitive to the induction of apoptosis by tumor necrosis factor. In another report, recombinant mistletoe lectin demonstrated antitumor activity after local intraperitoneal injection into human ovarian cancer-bearing SCID mice.

Three independent systematic reviews of the clinical evidence in patients with cancer arrived at negative conclusions. A few randomized controlled clinical trials have been reported in Europe. In one report, adjuvant mistletoe therapy did not affect survival in patients with resected squamous cell cancer of the head and neck. In the largest study, 677 women undergoing mastectomy for breast cancer were randomly assigned to parenteral mistletoe (Helixor) with or without radiation therapy, to chemotherapy with cyclophosphamide, methotrexate, and fluorouracil with or without radiation therapy, or to no treatment. A statistically significant survival advantage was noted for the Helixor arm compared to no treatment, but there was no difference between the Helixor arm and the chemotherapy arm.

In contrast, at least two series have suggested improvements in survival in patients receiving mistletoe:

  • A study in patients receiving standard therapy for malignant glioma found that complementary immunotherapy with a galactoside-specific lectin from mistletoe (ML-1) resulted in a statistically significant improvement in survival in patients with stage III and IV disease compared to controls (20 versus 10 months).
  • A second report involved 10,226 patients with cancers of the large bowel, breast, stomach, or lung who were enrolled in prospective nonrandomized, and randomized matched-pair studies, nested within a prospective long-term epidemiological cohort study. A total of 1668 patients were treated with Iscador and 8475 received neither Iscador nor any other mistletoe product (control patients). In the pool of 396 matched pairs, the mean survival duration was significantly longer in the Iscador group (4.23 versus 3.05 years). Similar results were noted in the nonrandomized matched-pair study, and in the two randomized matched-pair studies.

Antitumor efficacy of a mistletoe extract against hepatocellular carcinoma (HCC) was suggested in an uncontrolled trial involving 23 patients with unresectable disease who received weekly subcutaneous injections of the viscotoxin viscum fraxini-2 . There were three complete and two partial responses (overall response rate 22 percent), and the median progression-free survival duration for the three complete responders ranged from 8 to 38 months. Treatment was reasonably well-tolerated.

These results require confirmation. One group concluded: "we cannot recommend the use of mistletoe extracts in the treatment of cancer patients with an exception for patients involved in clinical trials". There have been case reports of hepatitis associated with mistletoe use. However, it is not clear if the liver disease was due to mistletoe itself, or to other compounds often mixed with it.

  PC-SPES  PC-SPES is an herbal dietary supplement consisting of seven Chinese and one American herbal extract. The name of the product emphasizes its intention: PC stands for 'prostate cancer' and spes is Latin for 'hope'. The eight herbs were selected for their immune stimulating, cytotoxic, and cytostatic properties.

PC-SPES has potent estrogenic activity. In men with advanced prostate cancer, decreases in serum prostate specific antigen, Improvement in bone scans, and objective shrinkage of soft tissue measurable disease have been reported with PC-SPES. However, adulteration and toxicity (an acquired bleeding diathesis) forced a recall of this compound by the United States Food and Drug Administration in February 2002. As a result, it is no longer commercially available.

  Sho-saiko-to  Sho-saiko-to is a traditional Chinese herbal mixture that contains extracts of seven medicinal herbs. It is widely administered in Japan to patients with chronic hepatitis and cirrhosis. Sho-saiko-to inhibits stellate cell activation and reduces hepatic fibrosis in vitro and in vivo. It also inhibits chemical hepatocarcinogenesis in animals, acts as a biological response modifier, and suppresses the proliferation of hepatoma cells by inducing apoptosis.

A prospective study of 260 cirrhotic patients found that a daily oral dose of sho-saiko-to (7.5 g) in addition to conventional therapy reduced the cumulative incidence of hepatocellular carcinoma over five years of follow-up compared with controls (p = 0.071). The difference was significant in patients who were hepatitis B surface antigen (HBsAg) negative (p = 0.024). Survival was also improved with sho-saiko-to therapy (p = 0.053), and again, the difference was significant in those who were HBsAg negative. Based on these results, the use of sho-saiko-to seems promising, but more clinical trials are required to be sure.

  St. John's wort  St. John's wort has primarily been used to treat depression. An extract of St. John's wort, hypericin, has been noted to have a cytotoxic effect on tumor cells after photoactivation. In vitro studies and in vivo investigations in mice have demonstrated that intralesional hypericin has the potential for use in a number of tumors, including bladder, squamous cell, pancreatic, and prostate cancer.

The only human study has involved intralesional injection of hypericin into basal cell and squamous cell carcinomas of the skin. Injection with the extract three to five times per week was followed by irradiation with visible light. The authors claim that hypericin displayed selective tumor-targeting; penetration in the surrounding tissues did not induce necrosis or cell loss, and generation of a new epithelium at the surface of the malignancy was noticed. Clinical remissions were observed after six to eight weeks. These preliminary results require replication in a randomized trial.

Concerns have been raised about potential interactions of St John's wort with other medications and treatments in patients with cancer

  Astragalus  The Chinese herb astragalus membranaceous is postulated to potentiate host immune function. A meta-analysis of randomized 34 trials found that the addition of astragalus to chemotherapy was associated with a reduced risk of death, an improved response rate, and a better performance status. However, significant methodologic limitations in these trials prevented definitive conclusions about the efficacy of this herb.

Nonherbal supplements  Among the nonherbal supplements that have been evaluated are melatonin, shark and bovine cartilage, hydrazine, and thymus extracts.

  Melatonin  Melatonin, a normal secretion of the pineal gland, has captured public attention because of its effects on mood, sleep, and jet-lag. It has also been suggested that melatonin stimulates the immune system, and has antioxidant, anticancer, and antiaging properties.

Several studies have tested the efficacy of melatonin supplementation for slowing tumor progression. One randomized, controlled trial suggested that patients with unresectable brain metastases from solid tumors who were treated with melatonin (20 mg daily by mouth, at 8 PM) experienced a significantly longer survival compared with those receiving supportive care only.

In a second report, patients with metastatic solid tumors who were treated with melatonin experienced less weight loss that those treated with supportive care alone, despite similar caloric intake. The authors hypothesized that the improvement in neoplastic cachexia was related to the effect of melatonin on decreasing the blood concentration of tumor necrosis factor.

Melatonin has also been evaluated in combination with aloe vera, which may have immunomodulating properties. In one report, 50 patients with advanced solid malignancies for whom no effective standard anticancer therapy existed, were treated either with melatonin (920 mg per day) or with melatonin and aloe vera tincture (1 mL twice daily). No response was seen in the former group while two partial responses were observed in the group treated with aloe vera. This result awaits confirmation through a more rigorous trial.

  Shark and bovine cartilage  Shark and bovine cartilage are claimed to have anti-angiogenesis effects that might contribute to an inhibition of malignant growth. Shark cartilage, in particular, is marketed aggressively with claims that it can cure cancer; such claims are usually based upon anecdotal data. Initial reports of positive results from a Cuban trial of shark cartilage were aired on the television news magazine "60 Minutes" in 1994, but were not followed by a published scientific article.

However, two published clinical studies have failed to show any evidence of antitumor activity. In a randomized trial, 84 patients with metastatic breast or colorectal cancer received standard care plus either shark cartilage or placebo. No difference was seen in either survival or duration on study.

A compound with antitumor activity in a human stem cell assay and antimetastatic properties has been isolated from bovine cartilage. Although one study that included 31 patients with various cancers reported a 90 percent response rate with a combination of oral and subcutaneous bovine cartilage extract, others have not confirmed this finding.

  Hydrazine  Hydrazine is a chemical with a variety of actions. It is an inhibitor of the enzyme phosphoenolpyruvate carboxykinase, a key enzyme in mammalian gluconeogenesis, a metabolic pathway that is thought to play a role in cancer cachexia. Four controlled trials have been reported. The first study, which randomly assigned 64 patients with lung cancer to receive chemotherapy with or without hydrazine (60 mg three times daily) failed to show a significant difference in survival between the two groups. Three subsequent trials, two in lung cancer, and one in colorectal cancer, also failed to demonstrate a positive impact of hydrazine on survival.

  Coenzyme Q10  Coenzyme Q10 (also known as Vitamin Q10, ubiquinone, or ubidecarenone) has been widely promoted for patients undergoing treatment for cancer, based upon the suggestion that it might improve tolerance for chemotherapy. Previous randomized clinical studies have not supported any benefit from this molecule in patients with heart failure.

Several studies evaluated coenzyme Q10 for possible cardioprotective effects in association with anthracycline therapy. Two of these suggested a possible cardioprotective effect, but all had serious design flaws, and no definitive conclusions could be drawn. Although there were no adverse effects with coenzyme Q10, the molecule has procoagulant activity and may interfere with warfarin therapy.

  Thymus extracts Several in-vitro studies have demonstrated that thymus extracts restore lymphocyte function, improve immunological variables, activate natural killer cells, and increase cytotoxic activity as well as mitogen-induced interferon levels in human lymphocytes. In addition, animal experiments have suggested that thymus extracts inhibit tumor growth.

A systematic review located 13 randomized, controlled trials of thymus extracts for various human cancers. Five of these studies suggested that thymus extract therapy may have some benefit. However, the low average methodological quality of the trials and overt contradictions in terms of outcomes prevented firm conclusions. Thymus preparations can cause severe allergic reactions and possibly serious infections when injected.

  Shiitake mushroom extract  Shiitake mushrooms are among the most consumed mushrooms in the world, and they have been used in traditional Asian medicine for over 2000 years. In vitro, several polysaccharide components exhibit antitumor activity. The antitumor efficacy of a shiitake mushroom extract was tested in an open-label study in which 62 men with advanced prostate cancer received oral extracts of shiitake mushroom daily for six months. The clinical endpoint was the tumor marker, serum prostate specific antigen (PSA). By six months, 23 patients had a rising PSA, while 38 remained stable. No patient had a conventional PSA response, defined as a reduction of 50 percent of serum PSA over baseline. The authors concluded that shiitake mushroom extract alone was an ineffective treatment for men with clinical advanced prostate cancer.

COMPLEMENTARY SUPPORTIVE CARE  Complementary therapies are adjuncts to mainstream care that may be used to manage cancer symptoms, adverse effects of therapy or improve quality of life. In contrast to alternative therapies, many complementary therapies have been shown to be of benefit in patients with cancer.

Acupuncture  Acupuncture has been studied in patients with cancer to reduce chemotherapy-induced nausea and vomiting, for pain control, and to reduce vasomotor symptoms in men treated with gonadotrophin analogues for prostate cancer. Some reports suggest acupuncture also may have a role in patients with radiation-induced xerostomia , or persistent chemotherapy-related fatigue.

  Nausea and vomiting  Several different techniques have been used to stimulate the pericardium 6 (P6 or neiguan) site commonly thought to be useful in the management of chemotherapy-induced nausea and vomiting. These include manual stimulation with the insertion of fine needles , eletrostimulation through needles  or percutaneously, and by noninvasive pressure on the skin over the P6 pressure point.

The potential benefits and limitations of these approaches are illustrated by two of the larger randomized trials:

  • Low frequency electroacupuncture at classic antiemetic acupuncture points was evaluated in a trial in which 104 women with breast cancer were randomly assigned to the active intervention, mock electrostimulation on the same schedule, or no intervention. All patients received concurrent three drug antiemetic pharmacotherapy and highly emetogenic chemotherapy. The number of emesis episodes occurring during the five days was significantly lower for patients receiving electroacupuncture compared with those receiving the mock procedure or antiemetic pharmacotherapy alone (median number of episodes, 5, 10, and 15, respectively). During the nine day follow-up period, no significant differences were observed between groups, suggesting that the observed effect had a limited duration.
  • A lack of benefit from acupuncture was suggested in a trial in which 80 patients undergoing high-dose chemotherapy with autologous hematopoietic stem cell transplantation were randomly assigned to ondansetron plus either invasive acupuncture at P6 or non-skin penetrating placebo acupuncture. There were no significant differences between the groups in the rate of emesis or retching, nausea, or use of rescue antiemetics.

A systematic review in 2005 examined the results from 11 randomized trials with 1247 patients receiving chemotherapy regimens of moderate or high emetogenicity. Overall, acupuncture-point stimulation significantly reduced the proportion of patients with acute vomiting (31 versus 22 percent). However, the mean number of emetic episodes was not significantly decreased and no benefit was apparent in the control of delayed emesis. Electrostimulation through acupuncture needles appeared to be the most effective modality. However, not all studies utilized state-of-the-art antiemetics and the role of acupuncture remains uncertain.

  Pain control  Although some trials have suggested that acupuncture can be useful in ameliorating cancer pain, a systematic review concluded that the value of acupuncture has not been established

  Vasomotor symptoms  Preliminary evidence suggests a potential benefit of acupuncture for the treatment of vasomotor symptoms in men receiving gonadotropin analogues for prostate cancer. In one pilot study, electroacupuncture to a fixed set of acupuncture points for 30 minutes twice weekly for two weeks followed by once weekly for 10 weeks resulted in a significant decrease in the number of hot flashes per day for the six men who continued therapy for more than two weeks (7.9 at baseline compared to 2.5 after 10 weeks of treatment)

Hypnotherapy  Several (mostly small) randomized, controlled trials have demonstrated the usefulness of hypnotherapy in palliative cancer care, with efficacy in controlling pain and nausea/vomiting in various settings. Hypnosis may be particularly useful for reducing the anticipatory emesis associated with chemotherapy . In addition, hypnosis can be useful in children for preventing anxiety and pain due to procedures such as lumbar puncture or bone marrow aspiration

The use of hypnotherapy has also been evaluated as an adjunct to radiation therapy in a randomized study. In a study of 69 patients undergoing curative radiotherapy for a variety of cancers, benefit could not be documented with formal instruments assessing anxiety and quality of life, although patients reported an improved sense of both overall and mental well-being.

It is unclear to what extent these effects are due to specific or nonspecific (placebo) effects. A review that summarized all published clinical trials of hypnotherapy concluded that there is encouraging, albeit not compelling, evidence to suggest that hypnotherapy is helpful for controlling anxiety and pain as well as nausea and vomiting in cancer patients.

Behavioral intervention  Behavioral intervention encompasses a number of techniques, which have been applied separately and in combination. In a randomized trial with 115 patients, a structured multidisciplinary program including cognitive, emotional, physical, social, and spiritual interventions was useful in patients receiving radiation therapy for advanced cancer. Those receiving the active intervention were able to maintain their quality of life during the four week treatment period, while the control group who did not receive this adjunctive treatment had a significant decrease in quality of life. Six months after the intervention, the quality of life was similar in the two groups.

Relaxation therapy  Relaxation techniques such as imagery, breathing exercises , manual massage, music therapy, music therapy, and reflexology have been used to reduce symptoms and increase the quality of life in cancer patients. In one randomized study, 96 women receiving chemotherapy for newly diagnosed breast cancer were assigned to receive either regular relaxation training and imagery or standard care only. The experimental group experienced better quality of life than the control group.

Manual massage therapy can convey intensive relaxation to both the body and the mind. In a retrospective series of 1290 cancer patients in which pain, fatigue, anxiety, and nausea were assessed before and after massage therapy, moderate to severe symptoms decreased by approximately 50 percent. Therapeutic benefits persisted for at least 48 hours in outpatients, although the total duration of benefit was not reported.

Not all behavioral interventions have been shown to be effective. Although many studies are encouraging, we need to determine which approaches are best for what type of patient and to establish how these interventions compare to conventional methods used in palliative care .

Therapeutic touch Several clinical trials have tested the effectiveness of therapeutic touch (Reiki) to reduce anxiety or improve well being in cancer patients. Some of these studies have yielded positive results. Due to weaknesses in study design, however, it is unclear whether the observed effects were due to specific therapeutic or nonspecific (placebo) effects.

Self-help and support groups  There is a trend for increasing participation in support groups among cancer patients. Although patients attending these groups do so mainly for psychosocial support, the data are conflicting as to whether these interventions prolong survival. Initial reports suggested a survival benefit. However, these benefits were not confirmed in later studies and a meta-analysis showed no significant effect on survival.

Ginseng and fatigue  A beneficial effect of ginseng on chemotherapy-induced fatigue was noted in a small pilot double blind trial of 20 patients who were randomly assigned to ginseng supplements or placebo (from the same manufacturer) during chemotherapy. In a preliminary report, the patients receiving ginseng had significantly less fatigue, and a better sense of overall health and quality of life. Despite these favorable results, this is an extremely small study, and independent confirmation is needed.

Fish oil for symptom control  Fish oil, which contains alpha-3 omega fatty acids, has been studied as a pharmacologic treatment for cancer-related anorexia/cachexia.

At least one trial has examined the benefit of fish oil for control of cancer-related symptoms in addition to anorexia. Sixty patients with a variety of cancers were randomly assigned to fish oil capsules or placebo in addition to their conventional treatments . Among the 60 patients who both began and completed two weeks of their allotted therapy (27 dropped out during treatment because they could not tolerate the regimen), supplemental fish oil did not influence appetite, fatigue, nausea, weight loss, caloric intake, nutritional status or sense of well-being.

SAFETY ISSUES WITH COMPLEMENTARY AND ALTERNATIVE TREATMENTS  While many forms of complementary and alternative medicine (CAM) for cancer are associated with minimal or no risk, this is not true for all such therapies. Potential toxicities include direct toxicity of CAM medications and procedures, indirect effects of CAM due to interactions with other medications, and also the risk to the patient who uses CAM to avoid or delay established, effective treatment in the management of malignant disease

Direct toxicity of CAM medications and procedures  A variety of herbal medications may produce serious side effects.  Quality control of these preparations can be a major concern. Pertinent issues include variability in biologic potency in different crops, the realistic possibility of fungal or bacterial contamination, the use of incorrect plant species, and consumer fraud. One of the most severe examples of the potential for harm with herbal preparations is the development of renal failure and urothelial cancer in individuals who thought they were using the herbal preparation Stephania tetrandra for weight loss, but who actually received the Chinese herb Aristolochia fangchi because of a manufacturing error. Numerous examples of potential side effects associated with the more commonly used herbal and other types of CAM . Adverse events due to herbal remedies should be reported to the United States Food and Drug Administration (800-FDA-1088).

Reported adverse effects of acupuncture include transmission of an infectious agent through needle insertion, broken, forgotten, or misapplied needles, pneumothorax, transient hypotension, minor bleeding, contact dermatitis, and pain. Therapeutic deep massage can result in hematoma, particularly in anticoagulated or thrombocytopenic patients, and other serious complications have been reported. Finally, severe complications of enema therapy include infection with enteric pathogens, severe dehydration and electrolyte imbalance, and death .

Interactions of CAM with conventional treatment  Many botanical agents are pharmacologically active, raising concerns about potential interactions with conventional therapy, both cytotoxic agents, and other medical therapies.

A list of potential interactions for individual natural products can be found in the drug information section of each agent. Common chemotherapy agents metabolized through the cytochrome p450 system and the specific isoenzymes responsible for their metabolism are summarized What follows are selected examples of potential interactions:

  • St John's wort induces CYP3A4  , which can lead to subtherapeutic levels of chemotherapeutic agents that are metabolized by CYP3A4 (eg, taxanes, irinotecan, imatinib).
  • Essiac consists of multiple biologically active ingredients, which may act synergistically with chemotherapeutic agents by its inhibition of CYP3A, or through the cytotoxic or immunosuppressive activities of anthraquinones present in this mixture [6] .
  • As noted previously, the polyphenols in green tea inhibit multiple cytochrome p450 enzymes, which are important in drug metabolism, and induce other drug-metabolizing enzymes
  • Because it can inhibit the cytochrome p450 system, milk thistle has the potential to decrease the metabolism of some cytotoxic agents such as paclitaxel and doxorubicin.
  • Panax ginseng and ginkgo biloba increase the functional activity of several drug-metabolizing enzymes of the CYP family, and should be avoided in patients receiving cytotoxic agents metabolized by CYP3A4 or CYP2C19.
  • Others have shown that pretreatment of cancer cells with some botanical agents (eg, berberine, a constituent of huanglian) reduces the sensitivity of these cells to chemotherapy-induced apoptosis
  • PC-SPES, which is no longer commercially available in the United States, has been associated with elevations in the prothrombin time, which may promote bleeding in patients with drug or disease-induced thrombocytopenia.

An extensive, although not all-inclusive, listing of herbs and their actions that may interact with certain drugs is found in the following tables. As examples, herbs with laxative properties may interact with antidiarrheal drugs, while those having anticoagulant effects may interact with warfarin.

  • Allergenic herbs
  • Amine, alkaloid, and sympathomimetic herbs
  • Anticoagulant and coagulant herbs
  • Cardioactive herbs
  • Diuretic herbs
  • Herbs affecting blood sugar
  • Herbs affecting lipids
  • Hormonally active herbs
  • Hypertensive herbs
  • Hypotensive herbs
  • Immunostimulating herbs
  • Irritant herbs
  • Laxative herbs
  • Sedative herbs

Delay or avoidance of conventional therapy of known benefit  While not directly a "toxic" effect of CAM, it is important to acknowledge that their use may result in a significant delay in instituting conventional treatment that is of documented benefit for a specific condition . Furthermore, it is often required or "recommended" that only natural substances be ingested for the duration of the CAM treatment, as non-natural products are alleged to negate the benefit of the therapy. This philosophy of care could lead to the rejection of effective medical therapies such as opioid analgesics, regardless of the severity of pain.

CONCLUSION  There is no compelling evidence that any alternative therapy is effective in patients with cancer. Meanwhile, the search for effective alternative therapies continues to be intense. It is important to note that claims of efficacy should be supported with acceptable evidence by those who make these claims, rather than rejected through research carried out by those who doubt them.

Outlandish and irresponsible claims continue to be published in the medical literature: "With classic homeopathy it is possible to treat people suffering from cancer. The patients can be helped palliatively as well as curatively" . Thus, it is understandable that oncologists are concerned about the high level of acceptance of alternative therapies by cancer patients. On the other hand, outright rejection of these treatments might be counter-productive for the following reasons:

  • Every now and then impressive case reports emerge from credible sources. An open mind might therefore be a good general policy.
  • Outright rejection alienates patients and negatively affects the therapeutic relationship.

In the interest of our patients, we should discuss the (lack of) evidence for alternative therapies openly and objectively. This includes the fact that some treatments carry considerable risks, and some are neither associated with prolongation of life nor an enhanced quality of life. A poorly documented potential problem is the potential interaction of dietary supplements with other medicinal agents .

The role of complementary therapies in palliative and supportive cancer is a different matter and seems more promising. Several of these therapies have at least some potential for improving quality of life. The common denominator in achieving this goal may turn out to be the promotion of relaxation. Proponents of these therapies have repeatedly argued that it would be inhumane not to provide such treatments if patients want them. Oncologists should certainly not hinder patients from seeking such help. On the other hand, one should still insist that the usefulness of these therapies be demonstrated beyond reasonable doubt. The use of ineffective supportive treatments is ethically problematic; for instance, it might lead to a situation where such therapies replace others with proven effectiveness.

The often emotional conflicts between opponents and proponents of complementary medicine are, to a large degree, a regrettable artifact caused by the lack of reliable evidence in this area. If more convincing data existed there would be far less room for disagreement. It follows that more research efforts (and research funds) should be directed towards creating reliable evidence. In the United States, the new National Institutes of Health (NIH) Center for Complementary and Alternative Medicine and the National Cancer Institute are supporting well designed studies of alternative medicine. Information on CAM is available through the NCI website (, and in registry of systematic reviews of CAM (not limited to cancer) produced by a CAM field group within the Cochrane Collaborative (