Potentially Dangerous Complementary and Alternative Medicine (CAM) Use by Ovarian Cancer Patients

Introduction

The use of complementary or alternative medicine (CAM) has increased substantially over the last decade.^1,2 When common activities such as praying for a cure and use of standard multi-vitamins are excluded from the definition of CAM treatments, CAM use has been reported by slightly less than half of all Americans in the United States and nearly half of all cancer patients. ³ Although most CAM treatments, particularly mind–body and energetic-therapy forms of CAM, are presumably safe (although of unknown efficacy), there are several ingestible CAM substances including herbal remedies, teas, and supplements, which, because of their potential to increase adverse surgical outcomes, are considered contraindicated for use by patients undergoing surgery.^4–6 Ingestible CAM substance use is fairly common. Supplements are among the most commonly used forms of CAM treatment in the United States; however, studies of CAM use by cancer patients have often examined the wide variety of CAM activities being used by cancer patients and rarely focused on CAM supplements or, more importantly, specific CAM supplements that, although probably safe for use by healthy individuals, pose a potential safety concern when used during specific treatments for cancer.

When used at the time of surgery, some herbal substances are thought to have the potential to prolong bleeding times. Others can affect the actions of pharmacologic agents including anesthesia, narcotic analgesics, and antibiotics. Substances of concern include herbs and vitamins with anti-platelet activity that have the potential to prolong bleeding time, including garlic (Allium sativum), ginkgo (Ginkgo biloba), fish oils, vitamin E, ginger (Zingiber officinale), and ginseng (Panax ginseng).^7–11 Although most of the evidence suggesting a need for caution in the use of these substances comes from in vitro studies, the case for these herbs' having significant anti-platelet activity is fairly strong. There have been case reports of bleeding adverse events associated with use of ginkgo,^12,13 and with garlic.^7,8 However, there has been no systematic study of the effects of these substances on bleeding in vivo. Case reports have suggested that ginger and cranberry (Vaccinium macrocarpon) can dramatically increase bleeding problems in association with the use of warfarin. In the case of cranberry the mechanism for this interaction is incompletely understood. ¹⁴ Herbs with the potential for additive sedative effects include kava kava (Piper methysticum) and valerian (Valeriana officinalis). Other herbs of concern include passionflower (Passiflora incarnata), and Saint John's wort (Hypericum perforatum), which can affect the metabolism of medications. These concerns have been described in depth in several review articles.^4–6 Review articles discussing the concerns associated with these substances generally advise that for safety reasons these CAM substances be avoided for a period of 1–2 weeks prior to the surgery, after which time they can be resumed. These recommendations have, however, been put forward without any systematic study of the actual effect on rates of bleeding-related adverse effects associated with the specific CAM substances of potential concern.

Particularly in the absence of evidence that use of these CAM supplements of concern is either common or associated with significantly elevated risks for adverse outcomes associated with excessive bleeding, there are significant barriers for physicians associated with compliance with these conservative guidelines regarding CAM use by patients. These include the need to take time from other important issues to be discussed at a critical point in treatment, and the potential for the conversation itself to have unfortunate effects on the patient–physician relationship. This study sought to answer the question about the extent of this potential problem, namely, how frequently do women with ovarian cancer actually use any of the CAM substances, herbs, and supplements, about which there is concern regarding their potential to increase bleeding during surgery, during the week immediately prior to their initial surgery for ovarian cancer?

Methods

Results

Of the 447 ovarian cancer patients who were believed to still be alive, 388 had up-to-date contact information and were approached and offered the opportunity to participate. Six of those approached were determined to be deceased and 219 (56% of those potentially eligible) returned questionnaires. As illustrated in Table 1, of the 219 participating patient survivors, 60 (27%) were <2 years post-diagnosis, 81 (37%) were 2–5 years post-diagnosis, and 78 (36%) were >5 years post-diagnosis. Responding patients were also predominantly survivors of advanced stage disease, with 62% reporting that their ovarian cancer had been originally diagnosed at stage III or IV. Only 19% of women reported a diagnosis of stage I disease and 14 (6%) reported diagnosis at stage II disease. Approximately 12% of the sample did not know the stage of their cancer at the time of its diagnosis and 7 (3%) did not respond to the question about stage of disease. A total of 209 women reported that their initial treatment included surgery. The specific procedures that were performed during the surgery to remove the cancer are provided in Table 1. Almost 80% (n=175) of ovarian cancer patients reported using some form of CAM, including participating in a CAM activity (i.e., yoga or meditation), consuming an ingestible CAM substance, and/or receiving care from a CAM practitioner (i.e., chiropractor, naturopathic physician, or acupuncturist) at some point during or after their diagnosis with ovarian cancer.

Table 2 summarizes the number of women who reported an initial surgery for their cancer (n=209) and who also reported using garlic, ginseng, cranberry, ginkgo, fish oil, flaxseed oil, vitamin E, passionflower, or St. John's wort at the time of their initial surgery. In total, 31% (n=65) of women reported taking one or more of these substances at the time of their surgery and 63 (30%) reported taking two or more. Fish oil, used by 35 women, was the most commonly used of these, followed by vitamin E (n=26), flaxseed (n=16) and cranberry (n=14). A total of 11 women reported using garlic, 2 used ginkgo, 1 used St. John's wort, and 2 reported using ginseng. None of the women reported using passionflower. Of the 65 women using one or more substances of potential concern, all but 1 were at risk for increased bleeding associated with their CAM use.

Of the 65, 12 (18%) reported having consulted with the conventional physician who was involved in preparing them for surgery about their use of any of the CAM substances and 9 women (14%) received the substance from a CAM provider. The questionnaire did not explicitly ask women if they had discussed use of these substances during the week prior to their ovarian cancer surgery with the prescribing CAM provider. Therefore, it is unknown if the CAM provider was actually aware of the surgery, as women may use substances recommended to them or given to them for a previous condition or prevention (e.g., using cranberry concentrates for suspected urinary tract infections without confirmation of diagnosis). Rates of consultations with conventional providers ranged from 0% for garlic (used by 11 women) to 50% of the 2 using ginkgo.

We also asked women if, at the time of their diagnosis, they had planned to use CAM as part of their ovarian cancer treatment plan. Women were asked specifically: “When you were first diagnosed with ovarian cancer, did you intend to include CAM practices in your treatment plan?” Of the 209 women who had surgery, 207 (99%) answered this question. Most (∼59%) said “No – I planned to rely on the care of my oncologist and regular doctor,” 25% said “Maybe – I wasn't sure but planned to check out all of my options,” and 14% said “Yes, definitely – I knew I'd be seeking complementary care to supplement the care by my oncologist and other regular doctors.” Only 2% said they didn't know if they would include CAM practices in their treatment plan. When compared with their self-reported use of CAM at the time of the survey, 100% of those who reported knowing they would be seeking complementary care used one of the various forms of CAM included in our “any CAM” variable, and 46% reported using one or more of the potentially contraindicated herbs or supplements at the time of their initial surgery. Of those who reported that maybe they would use CAM, 33% used a contraindicated substance at the time of their initial surgery. Of those with no plans to use CAM at the time of their diagnosis, 26% used one of the contraindicated herbs or supplements at the time of their initial surgery. That is to say, slightly more than one quarter of the participating women who reported no plans to use CAM and an intention to rely on the advice of their oncologist alone at the time of their diagnosis were taking one or more contraindicated substance at the time of their initial surgery. This appears to suggest these women did not consider the substance they were using at the time of their surgery to be “complementary or alternative medicine”.

Analyses were conducted to examine variables predictive of the use of herbs and supplements at the time of initial surgery for ovarian cancer and no association was found between use of these substances and the age, ethnic background, or education of women (data not shown). Similarly, in this sample, no statistically significant associations were found between use of herbs and supplements and women's stage, the date of their diagnosis (years since diagnosis at time of the survey), or surgery type.

Discussion

Herbs and supplements are readily available without prescription in health food, drug, and grocery stores, and may be used by women in the general population including those with ovarian cancer or soon to be diagnosed with ovarian cancer without discussion with any form of medical provider. Some foods with biological activity beyond their nutritive value (garlic, ginger, and cranberry) are also widely available over the counter in concentrated or dried forms, often encapsulated or available as tablets. In this sample of ovarian cancer patient survivors from two practices in western Washington State, 31% of women reported use of one or more of a short list of CAM substances that could be considered potentially contraindicated at the time of their initial surgical treatment for ovarian cancer, because of a potential risk for adverse outcomes associated with excessive bleeding. Use of multiple contraindicated substances simultaneously was also common, potentially increasing the risks.

This is not to say, however, that at all these women are likely experience ill effects because of their use of CAM substances at the time of their initial surgery, only that those women may be at risk for such ill effects. Recommendations that women avoid the use of these herbs and supplements are based on a limited body of evidence, mostly in vitro evidence. There is a clear need for more research regarding the extent to which most of these CAM substances actually increase the rates of risk of adverse bleeding-related outcomes in doses commonly taken by patients. Specifically, more detailed information on dosages of CAM, and combinations of CAM substances used by women immediately prior to surgery are needed. As this was a retrospective survey, it was not possible to document doses reliably and no attempt was made to collect those data, nor was it determined whether adverse outcomes associated with excessive bleeding did occur among those women using CAM substances at the time of their surgery. With a limited sample of women, and only modest rates of transfusion, there would be little power for such an analysis; this is a limitation of the study. A larger study in which limitations associated with retrospective reporting of CAM use over long periods of time, and actual rates of bleeding-related adverse events are recorded, would be helpful.

Most women who ingested contraindicated substances indicated that they did not consult with either a conventional or a CAM provider about their use of herbs and supplements at the time of their surgery. Indeed, had their physicians asked about “complementary or alternative medicine” use most would have reported use of a variety of CAM activities posing little or no risk, and many of these patients might not have reported their use of the substance or substances of concern, as it appears that many women may not consider their use of herbs or concentrated food nutraceuticals to be “complementary or alternative medicine” at all. As these substances are commonly used by the general public, and are routinely available in non-alternative settings (grocery stores), they may not be associated with CAM use in many women's minds. Indicative of this were several surprising findings in this work, one being the fact that more than one quarter (26%) of women using these substances at the time of their surgery reported having no initial plans to use CAM during their ovarian cancer treatment.

Although CAM use is generally associated with younger ages and higher levels of education, use of contraindicated supplements did not demonstrate that pattern in this sample, and use of these substances was not predicted by age or education.

Conclusions

For physicians seeking to reduce contraindicated use based on current theoretical concerns, simply asking women about their plans regarding CAM use may not be sufficient. Those who report plans to use CAM are likely to co-use herbs and supplements. However, most women report planning on relying only on the advice of their conventional oncologist, and these women may also be using herbs and supplements associated with potential risks. Physicians seeking to advise their patients may have to consider asking about not only CAM but about “supplements” and “herbs” specifically, perhaps even asking about substances of concern individually by name, as was done in this study.

When patients did report consulting with providers about the CAM substances used used, the reported rates of consultation with conventional providers were generally as high or higher than the rates of consultation with CAM providers. Physicians cannot assume that CAM use issues are being overseen by a professional licensed CAM provider who is educating patients with up-to-date advice about CAM safety. Given that almost one third of ovarian cancer patients in this study reported the use of potentially contraindicated substances prior to surgery, there is a clear need to better understand the risks associated with the use of herbs and supplements among women undergoing surgery, and to educate providers and patients about the possible dangers.