Interactions Between CAM and Conventional Oncologic Therapy

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Concurrent use of botanicals with conventional treatments raises the risk of interactions,76 including herb-drug interactions that reduce the effectiveness of chemotherapy.

The relevant principle of CAM for cancer is that patients should avoid botanical products and other dietary supplements during and for a 2-week washout period before chemotherapy, radiotherapy, or surgery. Botanicals with hormonal effects should not be used concurrently with hormonal therapy.

Metabolic interactions: Many botanicals are known to modify the activity of cytochrome CYP450 3A4, affecting the blood levels of drugs metabolized on this pathway.77 St. John's wort, for example, induces CYP450 3A4 in vitro,77 and in a randomized cross-over study, the plasma concentration of SN-38, irinotecan's active metabolite, was dramatically reduced when patients concurrently used St. John's wort.78 Several other popular botanicals, such as Echinacea and goldenseal, also were shown to modify CYP450 3A4 activity by an in vitro screen.77 Antioxidants: Many cytotoxic therapies, notably radiotherapy, depend on producing oxidative damage within the cancer cell. The activity of radiotherapy depends at least in part on the production of free radicals. Many botanicals, such as grape seed extract and ginseng, contain antioxidant constituents. Patients may unwittingly exacerbate the problem by taking additional antioxidants in the form of other dietary supplements. It is widely thought that concurrent administration of antioxidant supplements may, at least in theory, compromise the effectiveness of radiation therapy and some chemothera-peutic agents.79 Although some researchers believe that concurrent use of antioxidants and cytotoxic therapy80 can produce benefits, suppression of chemotherapy-induced apoptosis by antioxidants has been demonstrated in vitro.81 Moreover, a nonrandomized comparative study recently found poorer survival in patients taking high doses of vitamins, including antioxidants, concurrent with systemic therapy.82 At the very least, caution is advised.

Hormonal interactions: Many botanicals, including soy, chasteberry, dong quai, ginseng, and red clover, contain phytoestrogens, or plant-based estrogen-like substances. These compounds may interfere with antiestrogen therapies such as tamoxifen or raloxifene, or promote the growth of estrogen-sensitive tumors.83,84 Indeed, genistein, the predominant isoflavone in soy products, reduced the inhibitory effect of tamoxifen in a mouse model of breast cancer.85 Similarly, black cohosh increased the proliferation of MCF-7 breast cancer cells in vitro.86,87 Although some authors claim the opposite effect, that is, that botan icals containing phytoestrogens can inhibit breast tumor cell growth or potentiate antiestrogen therapy,88 the possibility of harmful interactions will remain a concern until studies are conducted.

Other chemotherapy interactions: CAM products may interact with chemotherapeutic agents through a number of other mechanisms. In vitro study has shown that berberine, a component of a number of herbs, upregulates the expression of pgp-170, a multidrug-resistant transporter protein, in a number of cancer cell lines, resulting in decreased paclitaxel cytotoxicity.89 Botanicals can also interfere with the conversion of chemotherapy prodrugs to the active form90 or with apoptotic pathways.81

Surgical interactions: Over-the-counter remedies interfere with blood coagulation, posing a risk of bleeding complications in the perioperative period.91 Garlic and vitamin E are common examples. Psychoactive herbs, such as valerian or kava kava, are reported to potentiate the sedative effects of anesthetics.91

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