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Chemotherapy

Also indexed as: Aldesleukin, Altretamine, Asparaginase, Bicalutamide, Bleomycin, Busulfan, Cancer Chemotherapy, Capecitabine, Carboplatin, Carmustine, Chemotherapy Drugs, Chlorambucil, Cladribine, Cytarabine, Dactinomycin, Daunorubicin, Diethylstilbestrol, Diethylstilbestrol, Diethylstilbestrol, Doxorubicin, Estramustine, Etoposide, Floxuridine, Fludarabine, Flutamide, Goserelin, Hydroxyurea, Idarubicin, Ifosfamide, Irinotecan, Leuprolide, Levamisole, Lomustine, Mechlorethamine, Megestrol, Melphalan, Mercaptopurine, Mitomycin, Mitotane, Mitoxantrone, Nilutamide, Pentostatin, Pipobroman, Plicamycin, Procarbazine, Stilphostrol, Streptozocin, Tabloid, Teniposde, Teslac, Testolactone, Thioguanine, Thiotepa, Toremifene, Uracil Mustard, Vercyte, Vinblastine, Vincristine

Illustration

Chemotherapy typically involves the use of several antineoplastic (anticancer) drugs to treat cancer, though some people are treated with single medications. While the drugs in this family are toxic to cancer cells, many are also toxic to healthy cells, which gives rise to numerous side effects. A few drugs used in chemotherapy enhance immune function, while some alter hormonal activity. One anticancer drug, methotrexate, is also used to treat severe cases of rheumatoid arthritis. For interactions involving specific anticancer drugs, refer to the highlighted medications listed below.

Summary of Interactions with Vitamins, Herbs, and Foods
In some cases, an herb or supplement may appear in more than one category, which may seem contradictory. For clarification, read the full article for details about the summarized interactions.

Beneficial May Be Beneficial: Depletion or interference—The medication may deplete or interfere with the absorption or function of the nutrient. Taking these nutrients may help replenish them.

Multiple nutrients (malabsorption)

Taurine
Beneficial May Be Beneficial: Side effect reduction/prevention—Taking these supplements may help reduce the likelihood and/or severity of a potential side effect caused by the medication.

Beta-carotene (mouth sores)*

Chamomile (mouth sores)

Eleuthero (see text)

Ginger (nausea)

Glutamine (mouth sores)

L-Carnitine*

Melatonin (see text)

N-acetyl cysteine (NAC)

Spleen peptide extract (see text)

Thymus peptides (see text)

Vitamin E, topical (mouth sores)

Zinc (taste alterations)
Beneficial May Be Beneficial: Supportive interaction—Taking these supplements may support or otherwise help your medication work better.

Antioxidants*

Melatonin

Milk thistle

PSK
Avoid Avoid: Reduced drug absorption/bioavailability—Avoid these supplements when taking this medication since the supplement may decrease the absorption and/or activity of the medication in the body.

St. John's wort
Avoid Avoid: Adverse interaction—Avoid these supplements when taking this medication because taking them together may cause undesirable or dangerous results.

See Methotrexate (Folic acid)
Check Check: Other—Before taking any of these supplements or eating any of these foods with your medication, read this article in full for details.

Echinacea

Multivitamin-mineral

Vitamin A

Vitamin C
>Interactions common to many, if not all, Chemotherapy drugs are described in this article. Interactions reported for only one or several drugs in this class may not be listed in this article. Some drugs listed in this article are linked to articles specific to that respective drug; please refer to those individual drug articles. The information in this article may not necessarily apply to drugs in this class for which no separate article exists. If you are taking a Chemotherapy drug for which no separate article exists, talk with your doctor or pharmacist.

An asterisk (*) next to an item in the summary indicates that the interaction is supported only by weak, fragmentary, and/or contradictory scientific evidence.

Alkylating agents

  • Busulfan (Myleran®)
  • Carboplatin (Paraplatin® for Injection)
  • Carmustine (BiCNU® for Injection)
  • Chlorambucil (Leukeran®)
  • Cisplatin (Platinol®, Platinol-AQ® Injection)
  • Cyclophosphamide (Cytoxan®, Neosar®)
  • Ifosfamide (Ifex® for Injection)
  • Lomustine (CeeNu®)
  • Mechlorethamine (Mustargen® for Injection)
  • Melphalan (Alkeran®)
  • Pipobroman (Vercyte®)
  • Polifeprosan 20 with Carmustine (Gliadel® Wafer)
  • Streptozocin (Zanosar® for Injection)
  • Thiotepa (Thioplex® for Injection)
  • Uracil Mustard

Antineoplastic antibiotics

  • Bleomycin (Blenoxane®)
  • Dactinomycin (Cosmegen® for Injection)
  • Daunorubicin (Cerubidine® for Injection, DaunoXome® Injection)
  • Doxorubicin (Adriamycin® Injection, Rubex® for Injection, Doxil® Injection)
  • Idarubicin (Idamycin®)
  • Mitomycin (Mutamycin® for Injection)
  • Mitoxantrone (Novantrone® Injection)
  • Pentostatin (Nipent®)
  • Plicamycin (Mithracin®)

Antimetabolites

  • Capecitabine (Xeloda®)
  • Cladribine (Leustatin® Injection)
  • Cytarabine (Cytosar-U® for Injection, Tarabine PFS® Injection, DepoCyt® Injection)
  • Floxuridine (FUDR® for Injection)
  • Fludarabine (Fludara® for Injection)
  • Fluorouracil (Adrucil® for Injection, Efudex®, Fluoroplex®)
  • Mercaptopurine (Purinethol®)
  • Methotrexate (Folex® for Injection, Rheumatrex®)
  • Thioguanine (Tabloid®)

Hormonal agonists/antagonists

  • Anastrozole (Arimidex®)
  • Bicalutamide (Casodex®)
  • Diethylstilbestrol (Stilphostrol®)
  • Estramustine (Emcyt®)
  • Flutamide (Eulexin®)
  • Goserelin (Zoladex®)
  • Leuprolide (Lupron® Injection)
  • Megestrol (Megace®)
  • Nilutamide (Nilandron®)
  • Tamoxifen (Nolvadex®)
  • Testolactone (Teslac®)
  • Toremifene (Fareston®)

Mitotic inhibitors

  • Etoposide (VePesid®)
  • Teniposde (Vumon® Injection)
  • Vinblastine (Alkaban-AQ® Injection,Velban® for Injection, Velsar® for Injection)
  • Vincristine (Oncovin® Injection, Vincasar PFS® Injection)

Immunomodulators

  • Aldesleukin (Proleukin® for Injection)
  • Levamisole (Ergamisol®)

Miscellaneous Antineoplastics

  • Altretamine (Hexalen®)
  • Asparaginase (Elspar®)
  • Docetaxel (Taxotere® for Injection)
  • Hydroxyurea (Hydrea®)
  • Interferon alpha (Roferon-A® Injection, Intron A® for Injection, Alferon N® Injection)
  • Irinotecan
  • Mitotane (Lysodren®)
  • Paclitaxel (Paxene®, Taxol®)
  • Procarbazine (Matulane®)

Interactions with Dietary Supplements

Antioxidants
Chemotherapy can injure cancer cells by creating oxidative damage. As a result, some oncologists recommend that patients avoid supplementing antioxidants if they are undergoing chemotherapy. Limited test tube research occasionally does support the idea that an antioxidant can interfere with oxidative damage to cancer cells.1 However, most scientific research does not support this supposition.

A modified form of vitamin A has been reported to work synergistically with chemotherapy in test tube research.2 Vitamin C appears to increase the effectiveness of chemotherapy in animals3 and with human breast cancer cells in test tube research.4 In a double-blind study, Japanese researchers found that the combination of vitamin E, vitamin C, and N-acetyl cysteine (NAC)—all antioxidants—protected against chemotherapy-induced heart damage without interfering with the action of the chemotherapy.5

A comprehensive review of antioxidants and chemotherapy leaves open the question of whether supplemental antioxidants definitely help people with chemotherapy side effects, but it clearly shows that antioxidants need not be avoided for fear that the actions of chemotherapy are interfered with.6 Although research remains incomplete, the idea that people taking chemotherapy should avoid antioxidants is not supported by scientific research.

A new formulation of selenium (Seleno-Kappacarrageenan) was found to reduce kidney damage and white blood cell–lowering effects of cisplatin in one human study. However, the level used in this study (4,000 mcg per day) is potentially toxic and should only be used under the supervision of a doctor.7

Glutathione, the main antioxidant found within cells, is frequently depleted in individuals on chemotherapy and/or radiation. Preliminary studies have found that intravenously injected glutathione may decrease some of the adverse effects of chemotherapy and radiation, such as diarrhea.8

Glutamine
Though cancer cells use glutamine as a fuel source, studies in humans have not found that glutamine stimulates growth of cancers in people taking chemotherapy.9 10 In fact, animal studies show that glutamine may actually decrease tumor growth while increasing susceptibility of cancer cells to radiation and chemotherapy,11 12 though such effects have not yet been studied in humans.

Glutamine has successfully reduced chemotherapy-induced mouth sores. In one trial, people were given 4 grams of glutamine in an oral rinse, which was swished around the mouth and then swallowed twice per day.13 Thirteen of fourteen people in the study had fewer days with mouth sores as a result. These excellent results have been duplicated in some,14 but not all,15 double-blind research. In another study, patients receiving high-dose paclitaxel and melphalan had significantly fewer episodes of oral ulcers and bleeding when they took 6 grams of glutamine four times daily along with the chemotherapy.16

One double-blind trial suggested that 6 grams of glutamine taken three times per day can decrease diarrhea caused by chemotherapy.17 However, other studies using higher amounts or intravenous glutamine have not reported this effect.18 19

Intravenous use of glutamine in people undergoing bone marrow transplants, a procedure sometimes used to allow very high amounts of chemotherapy to be used, has led to reduced hospital stays, leading to a savings of over $21,000 for each patient given glutamine.20

Magnesium and Potassium
Some chemotherapy drugs (e.g., cisplatin) may cause excessive loss of magnesium and potassium in the urine.21 Three case reports and one review article suggest that both potassium and magnesium supplementation may be necessary to increase low potassium levels.22 23 In one case report, a 32-year-old man with testicular cancer developed severe magnesium deficiency after receiving cisplatin therapy for nine weeks.24 The magnesium deficiency resulted in seizures that were corrected by a combination of injected and oral magnesium therapy. Magnesium deficiency, as seen in this case, is a potentially dangerous medical condition that should only be treated by a doctor.

Melatonin
High amounts of melatonin have been combined with a variety of chemotherapy drugs to reduce their side effects or improve drug efficacy. One study gave melatonin at night in combination with the drug triptorelin to men with metastatic prostate cancer.25 All of these men had previously become unresponsive to triptorelin. The combination decreased PSA levels—a marker of prostate cancer progression—in eight of fourteen patients, decreased some side effects of triptorelin, and helped nine of fourteen to live longer than one year. The outcome of this preliminary study suggests that melatonin may improve the efficacy of triptorelin even after the drug has apparently lost effectiveness.

N-acetyl cysteine (NAC)
NAC, an amino acid–like supplement that possesses antioxidant activity, has been used in four human studies to decrease the kidney and bladder toxicity of the chemotherapy drug ifosfamide.26 27 28 29 These studies used 1–2 grams NAC four times per day. There was no sign that NAC interfered with the efficacy of ifosfamide in any of these studies. Intakes of NAC over 4 grams per day may cause nausea and vomiting.

The newer anti-nausea drugs prescribed for people taking chemotherapy lead to greatly reduced nausea and vomiting for most people. Nonetheless, these drugs often do not totally eliminate all nausea. Natural substances used to reduce nausea should not be used instead of prescription anti-nausea drugs. Rather, under the guidance of a doctor, they should be added to those drugs if needed. At least one trial suggests that NAC, at 1,800 mg per day, may reduce nausea and vomiting caused by chemotherapy.30

Spleen extract
Patients with inoperable head and neck cancer were treated with a spleen peptide preparation (Polyerga®) in a double-blind trial during chemotherapy with cisplatin and 5-FU.31 The spleen preparation had a significant stabilizing effect on certain white blood cells. People taking it also experienced stabilized body weight and a reduction in the fatigue and inertia that usually accompany this combination of chemotherapy agents.

Beta-carotene and Vitamin E
Chemotherapy frequently causes mouth sores. In one trial, people were given approximately 400,000 IU of beta-carotene per day for three weeks and then 125,000 IU per day for an additional four weeks.32 Those taking beta-carotene still suffered mouth sores, but the mouth sores developed later and tended to be less severe than mouth sores that formed in people receiving the same chemotherapy without beta-carotene.

In a study of chemotherapy-induced mouth sores, six of nine patients who applied vitamin E directly to their mouth sores had complete resolution of the sores compared with one of nine patients who applied placebo.33 Others have confirmed the potential for vitamin E to help people with chemotherapy-induced mouth sores.34 Applying vitamin E only once per day was helpful to only some groups of patients in another trial,35 and not all studies have found vitamin E to be effective.36 Until more is known, if vitamin E is used in an attempt to reduce chemotherapy-induced mouth sores, it should be applied topically twice per day and should probably be in the tocopherol (versus tocopheryl) form.

Vitamin A
A controlled French trial reported that when postmenopausal late-stage breast cancer patients were given very large amounts of vitamin A (350,000–500,000 IU per day) along with chemotherapy, remission rates were significantly better than when the chemotherapy was not accompanied by vitamin A.37 Similar results were not found in premenopausal women. The large amounts of vitamin A used in the study are toxic and require clinical supervision.

Zinc
Irradiation treatment, especially of head and neck cancers, frequently results in changes to normal taste sensation.38 39 Zinc supplementation may be protective against taste alterations caused or exacerbated by irradiation. A double-blind trial found that 45 mg of zinc sulfate three times daily reduced the alteration of taste sensation during radiation treatment and led to significantly greater recovery of taste sensation after treatment was concluded.40

Multivitamin-mineral
Many chemotherapy drugs can cause diarrhea, lack of appetite, vomiting, and damage to the gastrointestinal tract. Recent anti-nausea prescription medications are often effective. Nonetheless, nutritional deficiencies still occur.41 It makes sense for people undergoing chemotherapy to take a high-potency multivitamin-mineral to protect against deficiencies.

Taurine
Taurine has been shown to be depleted in people taking chemotherapy.42 It remains unclear how important this effect is or if people taking chemotherapy should take taurine supplements.

L-Carnitine
In a preliminary study, supplementation with 2 grams of L-carnitine twice a day for seven days relieved chemotherapy-induced fatigue in 90% of people who had been treated with the chemotherapy drugs cisplatin or ifosfamide.43 However, because there was no placebo group in the study, one cannot rule out the possibility that the fatigue resolved spontaneously.

Thymus peptides
Peptides or short proteins derived from the thymus gland, an important immune organ, have been used in conjunction with chemotherapy drugs for people with cancer. One study using thymosin fraction V in combination with chemotherapy, compared with chemotherapy alone, found significantly longer survival times in the thymosin fraction V group.44 A related substance, thymostimulin, decreased some side effects of chemotherapy and increased survival time compared with chemotherapy alone.45 A third product, thymic extract TP1, was shown to improve immune function in people treated with chemotherapy compared with effects of chemotherapy alone.46 Thymic peptides need to be administered by injection. People interested in their combined use with chemotherapy should consult a doctor.

Interactions with Herbs

Echinacea (Echinacea purpurea, Echinacea angustifolia)
Echinacea is a popular immune-boosting herb that has been investigated for use with chemotherapy. One study investigated the actions of cyclophosphamide, echinacea, and thymus gland extracts to treat advanced cancer patients. Although small and uncontrolled, this trial suggested that the combination modestly extended the life span of some patients with inoperable cancers.47 Signs of restoration of immune function were seen in these patients.

Eleuthero (Eleutherococcus senticosus)
Russian research has looked at using eleuthero with chemotherapy. One study of patients with melanoma found that chemotherapy was less toxic when eleuthero was given simultaneously. Similarly, women with inoperable breast cancer given eleuthero were reported to tolerate more chemotherapy.48 Eleuthero treatment was also associated with improved immune function in women with breast cancer treated with chemotherapy and radiation.49

Milk thistle (Silybum marianum)
Milk thistle’s major flavonoids, known collectively as silymarin, have shown synergistic actions with the chemotherapy drugs cisplatin and doxorubicin (Adriamycin®) in test tubes.50 Silymarin also offsets the kidney toxicity of cisplatin in animals.51 Silymarin has not yet been studied in humans treated with cisplatin. There is some evidence that silymarin may not interfere with some chemotherapy in humans with cancer.52

Ginger  (Zingiber officinale)
Ginger can be helpful in alleviating nausea and vomiting caused by chemotherapy.53 54 Ginger, as tablets, capsules, or liquid herbal extracts, can be taken in 500 mg amounts every two or three hours, for a total of 1 gram per day.

German chamomile (Matricaria recutita)
A liquid preparation of German chamomile has been shown to reduce the incidence of mouth sores in people receiving radiation and systemic chemotherapy treatment in an uncontrolled study. When 15 drops of chamomile liquid was taken in 100 mL of warm water at least three times daily, the radiation amount required to produce mouth sores doubled, and their overall incidence and severity decreased.55

PSK (Coriolus versicolor)
The mushroom Coriolus versicolor contains an immune-stimulating substance called polysaccharide krestin, or PSK. PSK has been shown in several studies to help cancer patients undergoing chemotherapy. One study involved women with estrogen receptor-negative breast cancer. PSK combined with chemotherapy significantly prolonged survival time compared with chemotherapy alone.56 Another study followed women with breast cancer who were given chemotherapy with or without PSK. The PSK-plus-chemotherapy group had a 25% better chance of survival after ten years compared with those taking chemotherapy without PSK.57 Another study investigated people who had surgically removed colon cancer. They were given chemotherapy with or without PSK. Those given PSK had a longer disease-free period and longer survival time.58 Three grams of PSK were taken orally each day in these studies.

Although PSK is rarely available in the United States, hot-water extract products made from Coriolus versicolor mushrooms are available. These products may have activity related to that of PSK, but their use with chemotherapy has not been studied.

Administration of St. John’s wort has been shown to reduce blood levels of the active form of the anticancer drug irinotecan.59 Consequently, individuals taking irinotecan should not take St. John’s wort.

Interactions with Foods and Other Compounds

Fruit drinks
Often, people who undergo chemotherapy develop aversions to certain foods, sometimes making it permanently difficult to eat those foods. Exposing people to what researchers have called a “scapegoat stimulus” just before the administration of chemotherapy can direct the food aversion to the “scapegoat” food instead of more important parts of the diet. In one trial, fruit drinks administered just before chemotherapy were most effective in protecting against aversions to other foods.60

Ingestion of grapefruit juice along with etoposide has been found to reduce blood levels of the drug.61 Studies with certain other medications suggest that grapefruit juice may affect drug availability, even if it is consumed at a different time of the day. Therefore, individuals taking etoposide should probably avoid grapefruit and grapefruit juice.

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59. Mathijssen RH, Verweij J, de Bruijn P, et al. Effects of St. John's wort on irinotecan metabolism. J Natl Cancer Inst 2002;94:1247–9.

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