Page 2536 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 156 Integrative Therapies in Patients With Hematologic Diseases 2259

advised not to eat green leafy and cruciferous vegetables or to consume inhibitor of CYP3A4 metabolism as well as a potent source of vitamin
green tea because they are rich in vitamin K and might interfere with K, green tea may interact with prescribed anticancer drugs or antico-
the anticoagulant effect. An alternative is to allow the patient to agulant therapies. However, green tea polyphenols have been shown
consume a healthful diet and adjust the warfarin dose accordingly to to have antiproliferative activity against a wide variety of cell lines,
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maintain the desired INR. including CLL, multiple myeloma, and human promyelocytic
leukemia HL-60. Epigallocathechin-3-gallate (EGCG) is the specific
Omega-3 Fatty Acids green tea polyphenol that is an antioxidant with chemopreventive
Fish oil is the most commonly used natural product among adults and chemotherapeutic actions. Present in situ in the beverage, EGCG
and its use has increased from the 2007 to 2012 NHIS survey. has also been prepared as green tea extract (GTE) supplements and
Omega-3 fatty acids have been reported in isolated cases to potentiate even more concentrated EGCG capsules that patients can purchase
the anticoagulant effects of warfarin. Omega-3 fatty acids may lower in health food and supplement emporiums. The publication of the
thromboxane A 2 levels within the platelet as well as decrease factor CLL data has led to increased use of EGCG in patients with low-
VII levels. These factors, which make the omega-3s attractive as grade lymphomas. A phase I study in patients with asymptomatic
antiinflammatory and cardiovascular agents, need to be borne in stage 0 to II CLL demonstrated that the Polyphenon E preparation
mind in patients on warfarin therapy. Taken in the absence of war- use was well tolerated in 33 participants and that the majority of
farin, omega-3s are not believed to be a significant cause of bleeding participants had decreased total lymphocyte counts, lymphadenopa-
at doses of less than 4000 mg/day. Epidemiologic data suggest an thy, or both (NCT00262743). Of note, when taken on an empty
inverse relationship between the intake of marine omega-3 fatty acids stomach, GTE preparations have been associated with a risk of hepa-
and the development of a number of hematologic malignancies and totoxicity. The question of whether health benefits against hemato-
the good risk-to-benefit profile. logic malignancies can be achieved by simply drinking an as yet
The role of omega-3 fatty acids may be instrumental in symptom undetermined quantity of the beverage or higher dose preparations
management among individuals with hematologic malignancies. such as GTE or EGCG is not known.
Evidence suggests that doses of up to 4000 mg/day may help alleviate Patients with multiple myeloma are now frequently advised by
nausea/vomiting associated with cancer therapy. Studies have been their oncologists not to consume green tea at all because of its
performed in both adults and children with cancer. Other studies potential to negate the treatment effects of bortezomib, found in
suggest that omega-3 fatty acids may help prevent cognitive decline mouse studies.
in children who have received whole body radiation. While the latter Other commonly used OTC products include turmeric, melato-
is still in its infancy, evidence evaluated from the pediatric literature nin, medicinal mushrooms, and Chinese herbs. Studies are being
suggest that this may be beneficial for pediatric malignancies as well. conducted regarding their efficacy and safety.

Vitamin D3 Antioxidants
Vitamin D is one of the few remaining vitamins that has not been Antioxidants (e.g., beta-carotene; lycopene; vitamins C, E, and A) are
shown to be ineffective in protecting against malignant disease. An substances that counteract free radicals and prevent them from
ongoing randomized clinical trial is currently looking at a two-by-two causing tissue and organ damage. They are among the most common
factorial design of omega-3 fatty acids and vitamin D3 supplementa- classes of supplements used by patients with hematologic malignan-
tion in older adults to assess cancer risk reduction, among other cies. Their use is directed for cytotoxic effects, for synergy with
endpoints. At the same time, increasing evidence suggests that conventional therapy, or to lessen the toxicity of conventional therapy.
vitamin D deficiency may be related to the risk of a number of solid Estimates of antioxidant use by patients with cancer have varied
tumors, particularly breast, colon, prostate, and pancreas. An inverse considerably, with rates ranging from 13% to 87% depending on the
relationship has been described between the development of NHL survey, the type of disease studied, and a variety of other individual
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and sun exposure, particularly recreational, nonoccupational sun and demographic factors. Specific prevalence data on the use of
exposure. One proposed explanation for this unexpected finding is antioxidants among patients with only hematologic malignancies has
that sun exposure is actually a surrogate marker of vitamin D status, generally not been reported in the surveys. With survival of childhood
and it is actually vitamin D sufficiency that is protective against ALL exceeding 90% for standard-risk groups, extreme caution should
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lymphoma. In a metaanalysis of eight studies to date, the investiga- be exercised in combining antioxidant supplementation with the
tors found no conclusive evidence that vitamin D was providing the effective treatment.
observed benefit, although serum levels were not available in any of Evidence supporting the potential role of antioxidants in prevent-
the studies. Hence it may be appropriate in view of the widespread ing and treating disease include preclinical studies. These studies have
incidence of vitamin D insufficiency, especially in older adults, for correlated oxidative stress and an antioxidant-depleted diet with the
integrative oncologists to measure 25-hydroxy-vitamin D levels in development of diseases, including cancer. Increased consumption of
patients with hematologic malignancies and supplement with a fat- green tea (which contains the anticarcinogenic agent, EGCG) has
soluble vitamin D3 preparation to bring the levels into sufficient or been associated with a reduced incidence of leukemia. In addition,
optimal range. Moreover, with the inclusion of high-dose steroids for decreases in antioxidant enzymes or the micronutrients thiol, vitamin
many hematologic malignancies, adequate D3 becomes essential in E, vitamin C, beta-carotene, or zinc and increases in the production
the maintenance of bone health during and after treatment. of reactive oxygen species have been reported in leukemia patients.
Preclinical evidence suggests that vitamin D may have a role in In one study in children with ALL, higher levels of oxidative stress
the treatment of hematologic malignancies. 42,43 A recent review on at diagnosis were associated with a poor prognosis.
the role of vitamin D for the treatment of AML and ALL concluded In another prospective observational study conducted among
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that differentiation-based therapy may be further enhanced by the children with ALL, low plasma and dietary antioxidant levels
addition of vitamin D. To date, there are no published clinical trials directly correlated with treatment-related toxicity. These types of data
describing the use of vitamin D for the treatment of hematologic have led many patients with hematologic malignancies to take anti-
cancers. Most clinical studies have explored its effect on treatment- oxidant supplements primarily in conjunction with conventional
related toxicities especially among children and adolescents with ALL. cancer treatment.
While data appears encouraging, additional trials are necessary before Much of the controversy surrounding antioxidants and cancer
the inclusion of vitamin D3 into the standard of care for hematologic therapy has arisen because radiation therapy and certain classes of
malignancies. chemotherapy agents exert some of their anticancer effects through
the generation of reactive oxygen species or free radicals. Some of
Green Tea these agents include the anthracyclines (e.g., doxorubicin), platinum-
Green tea (Camellia sinensis) is an increasingly consumed beverage containing complexes (e.g., cisplatin and carboplatin), and alkylating
being sought after for multiple potential beneficial health effects. An agents (e.g., cyclophosphamide and ifosfamide). The theoretical