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Safety Issues in Using Complementary and Alternative Medicine

From the Department of Hematology/Medical Oncology and Taussig Cancer Center, The Cleveland Clinic Foundation, Cleveland, OH.

Address reprint requests to Maurie Markman, MD, The Cleveland Clinic Cancer Center (R35), The Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195; email: markmam{at}ccf.org

ABSTRACT

PURPOSE: A number of reports have documented the apparent increasing popularity of complementary and alternative medicine (CAM) among cancer patients. Unfortunately, there are limited available published data regarding the potential toxicity of a variety of CAM strategies.

METHODS: A review of the medical literature was undertaken to highlight the potential side effects of CAM.

RESULTS: Although many CAM approaches are quite safe, both minor and major toxicities have been documented, including emesis, hypersensitivity reactions, cardiovascular events, neurologic dysfunction, hepatic and renal failure, and the development of malignant disease.

CONCLUSION: It is important that oncologists are aware of what nonprescription CAM medications are being taking by their patients and have a basic understanding of the potential toxicities of these agents.

THE INCREASING popularity of complementary and alternative medicine (CAM) among individuals diagnosed with cancer is well documented.^1-9 Explanations for use of a variety of different CAM strategies include a desire of patients to experience greater control over the course of their illness, to seek strategies that reduce the side effects, and to improve on the effectiveness of "conventional" therapy.^10,11

While many forms of CAM are associated with no or minimal risk to a patient, this is not true for all such therapies. This brief report provides a broad overview into the potential toxicities associated with CAM, including 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
It is well established that a variety of herbal medications may produce serious side effects. Quality control of these preparations can be a major concern. Issues include variability in biologic potency in different crops, the very realistic possibility of contamination (eg, fungus, bacteria), and use of the incorrect plant species.¹² In addition, in this unregulated industry, it is extremely difficult to guard against consumer fraud.

To date, one of the most severe examples of the potential for harm associated with herbal medications is that of the development of renal failure and urothelial carcinoma in individuals who used the Chinese herb Aristolochia fangchi.^13,14 Because of a manufacturing error, this herb replaced another preparation (Stephania tetrandra) used in a weight-reducing pill. More than 40 individuals who took this pill developed progressive renal failure, and almost 50% were also found to have a urothelial cancer.¹³

There are numerous examples of potential side effects associated with the more commonly used herbal and other types of CAM medications (Table 1).^15-26 In addition, new toxic effects of a variety of herbal preparations continue to be reported. For example, kava, a widely touted natural sleep medication, has been associated with severe liver dysfunction, leading in at least one case to hepatic failure and the requirement for a liver transplant.¹⁸ Other herbal medications have been shown to be associated with hepatotoxicity.¹⁹

Both acupuncture and chiropractic medicine, although generally quite safe, can be associated with annoying and more serious side effects.^28,29 Reported toxicities of acupuncture include transmission of an infectious organism through needle insertion, broken, forgotten, or misapplied needles, pneumothorax, transient hypotension, minor bleeding, contact dermatitis, and pain.²⁸ With cervical spinal manipulations there is a small but finite risk of a cerebrovascular accident.²⁹

INDIRECT EFFECTS OF CAM DUE TO INTERACTIONS WITH OTHER MEDICATIONS
With the recognition that cancer patients are taking a variety of CAM medications, there has been a heightened awareness of the potential for negative interactions between such agents and physician-prescribed drugs. It is now well established that St John’s wort, through induction of the cytochrome P450 system, can increase the rate of metabolism of certain pharmaceutical agents, leading to reduced (and potentially ineffective) blood levels.^30-33 Reduced concentrations of cyclosporine,^31,32 indinavir,³⁰ and (most recently) irinotecan (CPT-11)³³ have been documented in individuals taking St John’s wort. This observation is not merely an interesting laboratory artifact, as evidenced by the fact low cyclosporine concentrations were shown in several patients taking St John’s wort who rejected their heart transplants.³¹

A number of CAM medications have also been revealed to have a potentially adverse impact on surgery, due to interactions with anesthetic agents, inhibition of platelet function, excessive sedation, or hypertensive effects.³⁴ As a result, patients scheduled to undergo surgery for cancer (or any other condition) should be asked about any nonprescription medications they have taken during the previous several-week period.

TOXICITY OF THE METHOD OF CAM ADMINISTRATION
Certain CAM medications are administered without adequate, or any, quality control. One classic example was the "immunoaugmentative therapy" of Burton, in which samples of the infected material revealed evidence of hepatitis virus.³⁵ Severe complications of "enema therapy," including infection with enteric pathogens, severe dehydration and electrolyte imbalance, and death, have been reported.^36-38

DELAY OR AVOIDANCE OF CONVENTIONAL THERAPY OF KNOWN BENEFIT
While not directly a "toxic" effect of CAM, it is important to acknowledge that CAM use may result in a significant delay in patients seeking care for cancer and instituting treatment of documented benefit in the condition.^39-41 A particularly distressing feature of certain CAM approaches is the absolute requirement that only natural substances are ingested.³⁸ This "philosophy of care" could lead to the rejection of the use of narcotic analgesia, regardless of the severity of pain. It is apparently suggested that if narcotics (nonnatural, synthetic products) are used, they will "negate" the beneficial effects of the "natural remedies" on the cancer. It is difficult to imagine a more inhumane therapeutic philosophy for the management of advanced malignancy.

In conclusion, a variety of CAM strategies are increasingly popular with the public in general and cancer patients in particular. Unfortunately, there is currently essentially no regulation by any governmental body of the safety of CAM medications.⁴² Despite the rhetoric to the contrary, a number of these agents have the potential to produce minor or major side effects. The issue of legal liability for adverse outcomes must also be considered.⁴³ These considerations lead to the conclusion that it is critically important that oncologists know what nonprescription CAM medications are being taken by their patients and the potential toxic effects of these agents.

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