Life Over Cancer Blog

Getting the Most Out of Tamoxifen

By Keith Block, MD

Many women with breast cancer are aware of a recent long-term British study showing that taking the generic drug tamoxifen for five years resulted in a significantly lower risk of their cancer returning when compared to only taking the drug for two years.  In this clinical trial, nearly 3,500 breast cancer patients were studied for over 10 years.  The findings, published in the 1 May 2011 Journal of Clinical Oncology, showed that breast cancer returned in around 40% of those who took tamoxifen for five years, compared to 46% among those who took it for two years.

The Challenge of Balancing Hormone Therapy and Bone Health

By Keith I. Block, MD

As you probably know, hormonal therapy is considered standard treatment for women - and men - with estrogen receptor-positive breast cancer, and tens of thousands of patients, predominantly women, receive this treatment each year.  The most widely used option for premenopausal women—first introduced in the 1970s—is Tamoxifen, which blocks the activity of estrogen by binding to the hormone’s receptor site.  In more recent years, for postmenopausal women, Tamoxifen has been upstaged by aromatase inhibitors (AIs), drugs that block production of estrogen.  (AIs generally follow two years of Tamoxifen for premenopausal women.)  Both AIs and Tamoxifen, used either separately or together in sequence comprise an essential conventional strategy for curbing the risk of breast cancer recurrence.  And some recent data suggests that AIs may be more effective in preventing early relapses.

Despite the therapeutic usefulness of AIs, these drugs are not without a downside.  AIs have toxic effects on the bones and heart.  Indeed, the common finding in all studies to date that have compared AIs with Tamoxifen is an increased risk of bone loss, and an increased risk of fractures in women taking AIs.  AIs are basically amplifying a problem that is already quite rampant in postmenopausal women: Immediately after menopause, women typically lose bone at an annual rate of 3 to 5%, mostly due to a decrease in circulating estrogens [Source: May-June 2011 issue of CA: A Cancer Journal for Clinicians].  The use of AIs further accelerates this process, and yet at least three out of every four survivors with osteoporosis may go undiagnosed by their healthcare providers, as reported in a 1 October 2005 issue of Cancer.

There are several strategies to consider when receiving AIs.  The first is to incorporate a bone-building program that includes a high-quality calcium supplement (either calcium citrate or calcium hydroxyapatite) along with vitamin D3.  This combo has been shown to reduce the rate of bone loss and decrease the rate of fractures.  However, the likelihood of bolstering bone health is far greater when women include other bone building nutrients such as magnesium, potassium, vitamin C, vitamin K, carotenoids, and several B vitamins.  Though boron (a component of many bone building formulas) may be helpful in trace amounts, it can enhance the activity of estrogen and thus is best minimized.

Epidemological studies indicate that people on predominantly vegetarian diets have the strongest bones over the long term.  Though dairy is a good calcium source, the research suggests that eating more dairy does little to curb osteoporosis or promote bone health.  One suggested reason for this is that increased intake of animal protein leads to a urinary excretion of calcium. Thus, the more dairy and other proteins consumed, the higher the risk for calcium loss.  I recommend a plant-based diet centered around an abundance of vegetables – emphasize broccoli, collards, kale and other cruciferous and leafy green vegetables, as these tend to have higher calcium levels than other vegetables – as well as berries, cherries and grapes.  These fruits provide several health benefits and can help reduce inflammation, which we know plays a role in osteoporosis (One of the major contributing factors to osteoporosis in women is withdrawal of estrogen during menopause.  Human and animal experiments have implicated pro-inflammatory cytokines as key biochemical contributors to the accelerated bone loss at menopause).  Other health promoting foods like soy, nuts and seeds contain highly bio-available calcium as well.  Daily weight-bearing exercise and avoidance of caffeine, alcohol, refined sugar, and high-phosphorous junk foods can be extremely helpful as well.

To counteract bone loss, many oncologists recommend the use of bisphosphonates like Fosamax, Boniva® (generic name: ibandronate) and Zometa® (zoledronic acid).  These drugs have been shown to significantly increase bone mass and reduce the risk of fractures.  Their effectiveness would likely be further improved by the addition of a vegetable-rich diet, along with the supplement advice I outlined above.  In fact, I believe it is essential that women who elect to take bisphosphonates also include these diet and lifestyle recommendations.

Given the widespread problem of osteoporosis, it comes as no surprise that bisphosphonates are currently among the most-prescribed drugs in America.  The downside is that these drugs have been linked with joint pain, allergic reactions, GI distress and other symptoms.  On rare occasions, they can even promote a terrible condition called osteonecrosis of the jaw—that is, the death of tissue in the jaw bone.  

Against this grim-sounding backdrop, many breast cancer survivors with ongoing bone loss want to know whether it’s really necessary for them to continue with bisphosphonates.  Unfortunately, there is not a simple answer to this question.  Nonetheless, to continue taking AIs without bisphosphonates on board requires very cautious monitoring by your physician.  Even with such monitoring, there remains a substantial risk of bone loss.  The other option is to switch from AIs back to Tamoxifen, which could actually improve bone health over the long term.  If this strategy is chosen, I would recommend routine gynecologic exams and including both nutrients and herbs that are synergistic with Tamoxifen, as well as some that counter formation of blood clots.  This option and topic deserves further attention, and will be considered in a future blog. 

For more information on The Block Center for Integrative Cancer Treatment, visit BlockMD.com.

 

What “Growing Evidence?”

One More Baseless Attack on Herbs and Chemotherapy!

By Keith I. Block, MD

Recently a colleague of mine emailed me a media report issued by Northwestern Memorial Hospital titled “Popular Herbal Supplements May Adversely Affect Chemotherapy Treatment.”  The first line of the article states: “Acai berry, cumin, herbal tea, turmeric and long-term use of garlic – all herbal supplements commonly believed to be beneficial to your health – may negatively impact chemotherapy treatment, according to a new report presented at the recent American Society of Clinical Oncology (ASCO) meeting in Chicago.”

The Northwestern Memorial report goes on to note that researchers have uncovered “growing evidence that these popular supplements may intensify or weaken the effect of chemotherapy drugs and in some cases, may cause a toxic, even lethal reaction.”  June M. McKoy, MD, a geriatrician at Northwestern Memorial and lead investigator on the ASCO presentation, urged cancer patients to discuss supplements with their doctors before beginning treatment—and to stop taking all herbal supplements while receiving chemotherapy.

The phrase “lethal reaction” caught my eye.  I had to wonder, exactly what was this claim based on?  In early May of this year, in a LOC blog article titled "How Supplements Can Help Protect Against the Toxic Side Effects of Chemotherapy,” [http://www.lifeovercancerblog.com/life-over-cancer-blog/2011/05/how-supplements-can-help-protect-against-the-toxic-side-effects-of-chemotherapy.html#more] I highlighted a number of herbals and other supplements that may be useful when taken during cancer treatment.  Among these was curcumin, the main substance in turmeric, and one of the herbs cited in the ASCO report as problematic.  So while I have reviewed many studies in the past, I decided to revisit curcumin, while also researching the other herbs mentioned as potential no-no’s for people receiving chemotherapy.

Here is what I found.  First of all, it is abundantly clear that most of the concern about herb-drug interaction in chemotherapy is not based on actual studies involving humans, or even animals for that matter.  As confirmed by a 2010 paper in Explore titled “Evidence-based management of herb-drug interaction in cancer chemotherapy,” the concern is almost entirely theoretical, with very little direct evidence of adverse reactions.  On the flip side, there is considerable preclinical evidence for therapeutic benefit when these herbs are combined with chemotherapy.

Let’s start with curcumin.  Dozens of laboratory studies have found that this botanical enhances the effectiveness of chemotherapy drugs in treating various types of tumors.  What’s really remarkable is that most of the interactions are synergistic, meaning that curcumin actually multiplies the effectiveness of various chemotherapy drugs (cisplatin, 5-FU, Taxol, and Gemzar). In many reports, in fact, curcumin has been shown to sensitize the cancer cells to the effects of the chemotherapy drug, while also eliminating cancer cells that were resistant to chemotherapy.

One of the most recent reports, published in the 24 May 2011 European Journal of Cancer, notes that in mice, curcumin not only reduces toxic side effects of the chemotherapy drug mitomycin-C (MMC), but also increases the drug’s tumor-killing potential.  The researchers propose that “the combination treatment of MMC and curcumin may be of significant therapeutic benefit in treating breast cancer.”  Green tea is thought to further enhance the anti-cancer punch of curcumin.  A February 2011 report in Cancer Science boldly proposed that green tea, together with curcumin, may improve all chemo regimens going forward.  While this has yet to be demonstrated in a clinical trial, current evidence suggests this potential exists.  Quite a contrast with Dr. McKoy’s dire warning of a possible “toxic, lethal reaction!”

My research team and I examined the list mentioned in the Northwestern Memorial report: Acai berry, Cumin, and long-term use of garlic (“herbal tea” is too imprecise a term to research).  We checked on both studies that gave theses herbs with chemo drugs, as well as studies of how these supplements might cause levels of chemo drugs to increase or decrease in the body because of enzyme effects.  No studies of Acai berry have shown any adverse effect; instead, they indicate that Acai can help prevent carcinogenesis and inhibit tumor growth.  As for Cumin, there appears to be no research at all on the common spice cumin that links it with chemo drugs.  For a relative of cumin called black cumin, the research is overwhelmingly favorable, with at least five studies reporting that the herb renders cancer cells more vulnerable to the killing effects of chemotherapy.  None of these studies showed any evidence of interference with chemotherapy.

There have been some contradictory studies about the interactions of garlic with chemo drugs and its capacity to alter drug levels in the body.  One possible concern is that large amounts of garlic may have a blood-thinning effect; this means it should not be taken in large amounts by patients with low platelet levels due to chemotherapy, or patients taking certain anticoagulant drugs.  Whether garlic affects drug levels was reviewed by Stacy Shord of the University of Illinois at Chicago in a recent article in Integrative Cancer Therapies.  Dr Shord found little evidence to indicate that garlic had negative interactions with chemotherapy, although it has a well-known interaction with some AIDS drugs, which has not been reported yet to carry over to chemo drugs.  In one of the relatively few actual clinical trials of herb-drug interactions, researchers found that in women with advanced breast cancer, taking a garlic supplement during chemo caused blood levels of Taxotere (docetaxol) to be somewhat elevated, though the result was not found to be statistically significant.  This would suggest increased efficacy, with the possibility of increased toxicity, although the lack of significant results casts doubt on the reality of the effect.  Lab studies also show that garlic may protect normal cells in the heart and intestines from adverse chemo drug effects. 

One botanical that can be problematic in the context of chemotherapy is St. John’s wort (SJW), which has a strong effect on enzymes that both activate drugs and excrete them from the body.  Clinical studies indicate that taking SJW at a daily dose of 900 mg may significantly reduce the effectiveness of the anti-cancer drugs Camptosar (CPT-11, irinotecan) and Gleevec (imatinib).  Since SJW is a popular herb for reducing depression—a common problem among people with cancer—such interactions ARE A CONCERN and should be watched for.  Given these facts, until we have more definitive data, I would certainly recommend avoiding SJW during chemotherapy.  Also, to be on the safe side, patients should not take large amounts of garlic supplements when they are suffering from or at considerable risk for low platelet levels during chemotherapy, or when they are taking anticoagulant drugs for blood clots. (Note: I consider a small routine amount of garlic use in cooking is safe and would only be a concern with a marked thrombocytopenia - platelets below 40,000).

In Conclusion:

There is no doubt that some particular interactions between herbal medicines and chemotherapy drugs exist and can have serious clinical consequences.  The problem is that the media’s sensational coverage of these interactions usually leads to a blanket rejection of all herbs and supplements during chemotherapy—as was the case with the Northwestern Memorial report.  This is truly unfortunate, because most of these plant substances have a very wide margin of safety and moreover, may improve treatment outcomes, as suggested by the vast majority of evidence to date.  Here are just a few examples of the herbs that show beneficial potential based on clinical studies:  ginger, for countering nausea caused by chemotherapy, milk thistle for repairing liver damage from specific chemo drugs, astragalus (demonstrated in multiple randomized controlled trials) for improving chemotherapy response, outcome and for offsetting immunosuppresion, and ginseng for overcoming fatigue during chemotherapy. 

As always, I encourage patients to discuss any herbal supplement use – in fact, all supplement and vitamin use – with their healthcare practitioner, not only to help avoid any potential interactions with medications, but to also make sure they are taking what is right for them.  It’s important to keep in mind that most supplements are designed for general health, not specifically for cancer patients.  Supplement quality will vary not only from brand to brand, but if a company manufactures multiple supplements, not all of them will necessarily pass independent testing.  And when it comes to treating cancer or preventing a recurrence, the need for a personalized program is a must.