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5:13 AM   April 21, 2014
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Herbs Might Muddy Chemo Outcomes

By Narda Robinson, DVM, DO, Dipl. ABMA, FAAMA

Can herbs improve chemotherapy outcomes? Likely, some can. Can they also interfere with chemo and interact unpredictably? Yes. Is there enough evidence to determine in advance which herbs will help and which ones harm?1-2 Not often, but the list of known effects is growing, raising the index of suspicion when clinicians encounter unexpected blood dyscrasias and organ injury.

Chinese herbs in particular have drawn scientists’ attention regarding their impact, for better or worse, on cancer patients’ overall health.
Even oncologists in China are encouraging colleagues to maintain a watchful eye for surprise sequelae from traditional Chinese medicine (TCM). One paper admonished: “[P]rofessional complacency about TCM use is becoming less acceptable as the knowledge base of TCM-induced toxicities and interactions expands. Being rich sources of bioactive xenobiotics, TCMs are frequent causes of puzzling complications, including hepatotoxicity, nephrotoxicity, and hematologic disorders.”3

While some traditional Chinese herbal medicines (TCHMs) are chemo- and radio-sensitizing and cause conventional treatment to work more strongly, others directly antagonize medication through one or more mechanisms.

Toxicity from Chinese herbs co-administered with chemotherapy may lead to diagnostic dilemmas when clinicians misattribute problems to the drug rather than the TCHM product, thereby delaying discontinuation of the appropriate culprit.4

In fact, Chinese herbalists in Taiwan who work directly with herbs in the raw form are finding themselves at increased risk of liver and bladder cancer, possibly due to the heavy metal contamination of TCHMs and/or the intrinsic toxic of some ingredients.5 This heightened risk for urologic cancers, chronic and unspecified nephritis, renal failure, and renal sclerosis “highlights the urgent need for safety assessments of Chinese herbs.”6

Public perception holds that TCHMs protect cancer patients’ health and well-being during chemotherapy.7 A double-blind, randomized, placebo-controlled study questioned this assumption and showed that TCHMs did not significantly reduce any of the hematologic toxicities (leukopenia, neutropenia and thrombocytopenia) associated with adjuvant chemotherapy for breast and colon cancer.8

Three licensed, experienced TCHM practitioners from China prescribed herbal formulae to patients on an individualized basis, since many believe this approach yields superior benefits. Even the idea that individualizing TCHMs produces better outcomes could be more folklore than fact.9

As Ernst et al reported, “[A]lmost all individualized herbal medicine is practiced without the support of any rigorous evidence about effectiveness whatsoever.”110

They continue, “The lack of standardization and use of multiple herbs in a single prescription also greatly multiply the safety risks. There are additional risks associated with variability in the diagnostics skills of the practitioner, their awareness or lack of awareness of potential interactions, and their ability or inability to identify red flag symptoms indicating serious diseases requiring immediate mainstream medical treatment.

“Given the risks and lack of supporting evidence, the use of individualized herbal medicine cannot be recommended in any indication.”
The likelihood of TCHM toxicity and interactions multiply, in part, due to the sheer number of herbal (and animal) ingredients in each mixture. Most have never been tested in typical veterinary species, worsening confusion.11-13

The complexity of assessing herb-drug interactions even in one species, the human primate, reveals the daunting number of considerations required. Take, for example, the herb astragalus, a plant commonly employed for cancer treatment that potentiates host immune function.
A 2006 meta-analysis of randomized trials concluded that, when combined with platinum-based chemotherapy, Chinese herbal formulations containing astragalus improved survival, increased tumor response, and reduced toxicity from the chemotherapy in human patients with non-small-cell lung cancer.14

Critics of this meta-analysis questioned the findings, citing unevenness in treatment methods.15

Only two of the 30 studies utilized astragalus as a single agent; the rest involved combinations. The species of astragalus studied in each case was unclear; was it Astragalus membranaceus (huang qi), whose major constituents include triterpene saponins and polysaccharaides in the roots, or was another plant in the astragalus genus substituted in some cases?

How did the amount of astragalus in each mixture compare, given that single-herb preparations putatively contained 100 percent astragalus while in others it was only one of up to 17 herbs.

Finally, which part of the plant was used and how was it prepared? Decoctions, fluid extracts and dry matter vary considerably in their active components.

Although these and other questions linger, the potential for Chinese herbs to one day participate legitimately within a methodical, evidence-informed herb and chemotherapy regimen seems imminent. To this end, one group, the nonprofit Consortium for Globalization of Chinese Medicine (www.tcmedicine.org) has assembled a broad collective of scientists from academia and industry.

Researchers are conducting national and international collaborative clinical trials along with experimental animal and in-vitro studies. They aim to fulfill four basic regulatory requirements: batch-to-batch consistency in Chinese herbal preparations; evidence-based clinical effectiveness; safety; and rational understanding of mechanisms of actions, sites of biochemical impact, active ingredients and drug-herb interactions.16

Recommending TCHMs based on rigorously derived discoveries in botanical research allows practitioners to discard untestable, abstract mechanisms of action that claim TCHM herbs “resolve stagnation, invigorate Qi and remove phlegm/damp accumulation.”17

Instead, medical professionals need to insist on instruction that describes TCHM actions in simple, biological language, especially when scientific investigations have already shown how they work.

For example, as mentioned previously, astragalus upregulates host immune response and reduces chemotherapy toxicity while Oldenlandia diffusa directly attacks tumor cells through apoptosis. One can then defend incorporating these two herbs into a TCHM combination with others that work through additive or synergistic means.

An oncologist might choose a third herb, perhaps, that inhibits abnormal gene transcription activity (Coix lachrymal) and a fourth that promotes tumor necrosis (Glycyrrhiza glabra).18

Until more becomes known of how TCHMs affect veterinary cancer patients on chemotherapy, “Caution should be taken when anticancer drugs are used in combination with herbal medicines, particularly for cytotoxic anticancer drugs with narrow therapeutic indices. Monitoring plasma concentrations of concurrently administered anticancer drugs and observing for possible signs of clinical toxicity are necessary when herbal remedies are used concurrently.”19

Computerized databases are further assisting oncologists by enabling determination of relevant, potential interactions between anticancer drugs and Chinese herbs.20  <Home>

Narda Robinson, DVM, DO, Dipl. ABMA, FAAMA, oversees complementary veterinary education at Colorado State.

FOOTNOTES

1. Shord SS, Shah K, and Lukose A.Drug-botanical interactions: a review of the laboratory, animal, and human data for 8 common botanicals. Integrative Cancer Therapies. 2009;8(3):208-227.

2. Davis VL, Jayo MJ, Ho A, et al.Black cohosh increases metastatic mammary cancer in transgenic mice expressing c-erbB2. Cancer Res. 2008;68(20):8377-8383.

3. Chiu J, Yau T, and Epstein RJ.  Complications of traditional Chinese/herbal medicines (TCM) – a guide for perplexed oncologists and other cancer caregivers.  Support Care Cancer.  2009;17:231-240.

4. Chiu J, Yau T, and Epstein RJ.  Complications of traditional Chinese/herbal medicines (TCM) – a guide for perplexed oncologists and other cancer caregivers.  Support Care Cancer.  2009;17:231-240.

5.Liu S-H, Liu Y-F, Liou S-H, et al.  Mortality and cancer incidence among physicians of traditional Chinese medicine:  a 20 year national follow-up study.  Occup Environ Med.  2010;67:166-169.

6. Yang H-Y, Wang J-D, Lo T-C, et al.  Increased mortality risk for cancers of the kidney and other urinary organs among Chinese herbalists.  J Epidemiol.  2009;19(1):17-23.

7. Chiu J, Yau T, and Epstein RJ.  Complications of traditional Chinese/herbal medicines (TCM) – a guide for perplexed oncologists and other cancer caregivers.  Support Care Cancer.  2009;17:231-240.

8. Mok TSK, Yeo W, Johnson PJ, et al.  A double-blind placebo-controlled randomized study of Chinese herbal medicine as complementary therapy for reduction of chemotherapy-induced toxicity. Annals of Oncology.  2007;18:768-774. 

9. DiNatale C. Chapter 36:  Clinical application of Chinese Herbal Medicine for Companion Animals. In Xie H, Preast V (eds.): Xie’s Chinese Veterinary Herbology.  Ames, Iowa:  Blackwell Publishing, 2010.  P. 570.

10. Guo R, Canter PH, and Ernst E. A systematic review of randomized clinical trials of individualized herbal medicine in any indication. Postgrad Med J. 2007;83:633-637. 

11. McCulloch M, See C, Shu XJ, et al.  Astragalus-based Chinese herbs and platinum-based chemotherapy for advanced non-small-cell lung cancer:  meta-analysis of randomized trials.  J Clin Oncol.  2006;24:419-430.

12. Konstantinovic LM, Cutovic MR, Milovanovic AN, et al. Low-level laser therapy for acute neck pain with radiculopathy: a double-blind placebo-controlled randomized study. Pain Medicine. 2010;11:1169-1178

13. McCulloch M, See C, Shu X-J, et al. Astragalus-based Chinese herbs and platinum-based chemotherapy for advanced non-small-cell lung cancer: meta-analysis of randomized trials.  J Clin Oncol. 2006;24:419-430.

14. Firenzuoli F, Gori L, Di Simone L, et al. Important bias in the Astragalus meta-analysis.  J Clin Oncol. 2006;24(19):3215-3216.

15. Sze DM-Y and Chan GC-F. Supplements for immune enhancement in hematologic malignancies.  Hematology. 2009: 313-319.

16. DiNatale C. Chapter 36: Clinical application of Chinese Herbal Medicine for Companion Animals. In Xie H, Preast V (eds.): Xie’s Chinese Veterinary Herbology. Ames, Iowa: Blackwell Publishing, 2010. P. 570.

17. McCulloch MF, See C, Shu X-J, et al. Important bias in the Astragalus meta-analysis [Reply].  J Clin Oncol. 2006;24(19):3216-3217.

18. Yang A-K, He S-M, Liu L, et al.  Herbal interactions with anticancer drugs: mechanistic and clinical considerations.  Current Medicinal Chemistry. 2010;17:1635-1678.

19. Yap KY-L, Kuo EY, Lee JJJ, et al. An onco-informatics database for anticancer drug interactions with complementary and alternative medicines used in cancer treatment and supportive care:  an overview of the OncoRx project. Support Care Cancer. 2010;18:883-891.

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