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    Fluorouracil

    Topic Contents

    Fluorouracil

    Drug Information

    Fluorouracil is a chemotherapy drug given intravenously (iv) to treat colon , rectum, breast , stomach, and pancreas cancers. Fluorouracil is also available in creams and solutions for topical treatment of some skin cancers and genital warts .

    Note: Many of the interactions described below, in the text and in the Summary of Interactions, have been reported only for specific chemotherapeutic drugs, and may not apply to other chemotherapeutic drugs. There are many unknowns concerning interactions of nutrients, herbs, and chemotherapy drugs. People receiving chemotherapy who wish to supplement with vitamins, minerals, herbs, or other natural substances should always consult a physician.

    Common brand names:

    Carac, Efudex

    Summary of Interactions with Vitamins, Herbs, & Foods

    Types of interactions: Beneficial Adverse Check

    Replenish Depleted Nutrients

    • Taurine

      Taurine has been shown to be depleted in people taking chemotherapy.1 It remains unclear how important this effect is or if people taking chemotherapy should take taurine supplements.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.

    Reduce Side Effects

    • Fruit-Flavored 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.2

    • 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.3 , 4 In fact, animal studies show that glutamine may actually decrease tumor growth while increasing susceptibility of cancer cells to radiation and chemotherapy,5 , 6 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.7 Thirteen of fourteen people in the study had fewer days with mouth sores as a result. These excellent results have been duplicated in some,8 but not all9 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.10

      One double-blind trial suggested that 6 grams of glutamine taken three times per day can decrease diarrhea caused by chemotherapy.11 However, other studies using higher amounts or intravenous glutamine have not reported this effect.12 , 13

      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.14

      In a double-blind study, supplementation with 18 grams of glutamine per day for 15 days, starting five days before the beginning of 5-FU therapy, significantly reduced the severity of drug-induced intestinal toxicity.15

      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.16

    • Melatonin

      Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with 5-FU plus folinic acid and 5-FU plus cisplatin.17

    • Probiotics

      In a preliminary trial, supplementation with a probiotic (Lactobacillus GG) reduced the frequency of severe diarrhea and the incidence of abdominal discomfort related to the use of 5-FU. The amount of Lactobacillus GG used was 10-20 billion organisms per day during the 24 weeks of chemotherapy.18

    • Selenium

      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.19 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.20 Vitamin C appears to increase the effectiveness of chemotherapy in animals21 and with human breast cancer cells in test tube research.22 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.23

      A comprehensive review of antioxidants and chemotherapy leaves open the question of whether supplemental antioxidants definitely help people with chemotherapy side effects, but the article strongly suggests that antioxidants need not be avoided for fear that the actions of chemotherapy would be interfered with.24

      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.25

    • Vitamin B6

      Fluorouracil occasionally causes problems on the skin of the palms and soles. Preliminary reports have appeared showing that 100 mg per day of vitamin B6 can sometimes eliminate the pain associated with this drug-induced condition.26 , 27

    • Wheat Grass
      In a preliminary trial, supplementation with 60 ml (about 2 ounces) per day of whet grass juice for 10 weeks during chemotherapy treatment reduced the severity of side effects in patients receiving a chemotherapy regimen that included 5-fluorouracil28.
    • Beta-Carotene

      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.29 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.30 Others have confirmed the potential for vitamin E to help people with chemotherapy-induced mouth sores.31 Applying vitamin E only once per day was helpful to only some groups of patients in another trial,32 and not all studies have found vitamin E to be effective.33 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.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Chamomile

      A liquid preparation of German chamomile (Matricaria recutita) has been shown to reduce the incidence of mouth sores in people receiving radiation and systemic chemotherapy treatment in an uncontrolled study. 34

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Eleuthero

      Russian research has looked at using eleuthero (Eleutherococcus senticosus) 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.35 Eleuthero treatment was also associated with improved immune function in women with breast cancer treated with chemotherapy and radiation.36

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Ginger

      Ginger (Zingiber officinale) can be helpful in alleviating nausea and vomiting caused by chemotherapy.37 , 38 Ginger powder in tablets or capsules can be taken for nausea, in 500 mg amounts every two or three hours, for a total of 1 gram per day.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • N-Acetyl Cysteine

      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.39 , 40 , 41 , 42 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.43

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Spleen Extracts

      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.44 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.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Spleen Peptide 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.45 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.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Thymus Extracts

      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.46 A related substance, thymostimulin, decreased some side effects of chemotherapy and increased survival time compared with chemotherapy alone.47 A third product, thymic extract TP1, was shown to improve immune function in people treated with chemotherapy compared with effects of chemotherapy alone.48 Thymic peptides need to be administered by injection. People interested in their combined use with chemotherapy should consult a doctor.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.

    Support Medicine

    • Melatonin

      Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with 5-FU plus folinic acid and 5-FU plus cisplatin.49

    • Milk Thistle

      Milk thistle's (Silybum marianum) 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

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • PSK

      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.53 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.54 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.55 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.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.

    Reduces Effectiveness

    • none

    Potential Negative Interaction

    • none

    Explanation Required 

    • Glutathione

      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.56 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.57 Vitamin C appears to increase the effectiveness of chemotherapy in animals58 and with human breast cancer cells in test tube research.59 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.60

      A comprehensive review of antioxidants and chemotherapy leaves open the question of whether supplemental antioxidants definitely help people with chemotherapy side effects, but the article strongly suggests that antioxidants need not be avoided for fear that the actions of chemotherapy would be interfered with.61

      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.62

      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 .63

    • Echinacea

      Echinacea (Echinacea purpurea, Echinacea angustifolia) 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.64 Signs of restoration of immune function were seen in these patients.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Multivitamin

      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.65 It makes sense for people undergoing chemotherapy to take a high-potency multivitamin-mineral to protect against deficiencies.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • 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.66 Similar results were not found in premenopausal women. The large amounts of vitamin A used in the study are toxic and require clinical supervision.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Vitamin A, Vitamin C, and N-Acetyl Cysteine

      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.67 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.68 Vitamin C appears to increase the effectiveness of chemotherapy in animals69 and with human breast cancer cells in test tube research.70 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.71

      A comprehensive review of antioxidants and chemotherapy leaves open the question of whether supplemental antioxidants definitely help people with chemotherapy side effects, but the article strongly suggests that antioxidants need not be avoided for fear that the actions of chemotherapy would be interfered with.72

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Vitamin C

      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.73 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.74 Vitamin C appears to increase the effectiveness of chemotherapy in animals75 and with human breast cancer cells in test tube research.76 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.77

      A comprehensive review of antioxidants and chemotherapy leaves open the question of whether supplemental antioxidants definitely help people with chemotherapy side effects, but the article strongly suggests that antioxidants need not be avoided for fear that the actions of chemotherapy would be interfered with.78

      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.79

      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 .80

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    The Drug-Nutrient Interactions table may not include every possible interaction. Taking medicines with meals, on an empty stomach, or with alcohol may influence their effects. For details, refer to the manufacturers' package information as these are not covered in this table. If you take medications, always discuss the potential risks and benefits of adding a new supplement with your doctor or pharmacist.

    References

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    3. Bozzetti F, Biganzoli L, Gavazzi C, et al. Glutamine supplementation in cancer patients receiving chemotherapy: A double-blind randomized study Nutr 1997;13:748-51.

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    19. Witenberg B, Kalir HH, Raviv Z, et al. Inhibition by ascorbic acid of apoptosis induced by oxidative stress in HL-60 myeloid leukemia cells. Biochem Pharmacol 1999;57:823-32.

    20. Sacks PG, Harris D, Chou TC. Modulation of growth and proliferation in squamous cell carcinoma by retinoic acid: A rationale for combination therapy with chemotherapeutic agents. Int J Cancer 1995;61:409-15.

    21. Taper HS, et al. Non-toxic potentiation of cancer chemotherapy by combined C and K3 vitamin pre-treatment. Int J Cancer 1987;40:575-9.

    22. Kurbacher CM, Wagner U, Kolster B, et al. Ascorbic acid (vitamin C) improves the antineoplastic activity of doxorubicin, cisplatin, and paclitaxel in human breast carcinoma cells in vitro. Cancer Letters 1996:103-19.

    23. Wagdi P, Fluri M, Aeschbacher B, et al. Cardioprotection in patients undergoing chemo- and/or radiotherapy for neoplastic disease. Jpn Heart J 1996;37:353-9.

    24. Weijl NI, Cleton FJ, Osanto S. Free radicals and antioxidants in chemotherapy-induced toxicity. Cancer Treatment Rev 1997;23:209-40 [review].

    25. Hu Y-J, Chen Y, Zhang YQ, et al. The protective role of selenium on the toxicity of cisplatin-contained chemotherapy regimen in cancer patients. Biol Trace Elem Res 1997;56:331-41.

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    31. Lopez I, Goudou C, Ribrag V, et al. Treatment of mucositis with vitamin E during administration of neutropenic antineoplastic agents. Ann Med Intern[Paris] 1994;145:405-8.

    32. Lopez I, Goudou C, Ribrag V, et al. Traitement des mucites par la vitamine E lors de l'administration d'anti-neoplasiques neutropeniants. Ann Med Interne 1994;145:405-8.

    33. Legha SS, Wang YM, Mackay B, et al. Clinical and pharmacologic investigation of the effects of alpha-tocopherol on Adriamycin cardiotoxicity. Ann NY Acad Sci 1982;393:411-8.

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    37. Meyer K, Schwartz J, Crater D, Keyes B. Zingiber officinale (ginger) used to prevent 8-Mop associated nausea. Dermatol Nurs 1995;7:242-4.

    38. Pace JC. Oral ingestion of encapsulated ginger and reported self care actions for the relief of chemotherapy-associated nausea and vomiting. Dissertation Abstr Int 1987;8:3297.

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    40. Slavik M, Saiers JH. Phase I clinical study of acetylcysteine's preventing ifosfamide-induced hematuria. Sem Oncol 1983;10(suppl 1):62-5.

    41. Loehrer PJ, Williams SD, Einhorn LH. N-Acetylcysteine and ifosfamide in the treatment of unresectable pancreatic adenocarcinoma and refractory testicular cancer. Sem Oncol 1983;10(suppl 1):72-5.

    42. Morgan LR, Donley PJ, Harrison EF. The control of ifosfamide induced hematuria with N-acetylcysteine. Proc Am Assoc Cancer Res 1981;22:190.

    43. De Blasio F, et al. N-acetyl cysteine (NAC) in preventing nausea and vomiting induced by chemotherapy in patients suffering from inoperable non small cell lung cancer (NSCLC). Chest 1996;110(4, Suppl):103S.

    44. Borghardt J, Rosien B, Gortelmeyer R, et al. Effects of a spleen peptide preparation as supportive therapy in inoperable head and neck cancer patients. Arzneimittelforschung 2000;50:178-84.

    45. Borghardt J, Rosien B, Gortelmeyer R, et al. Effects of a spleen peptide preparation as supportive therapy in inoperable head and neck cancer patients. Arzneimittelforschung 2000;50:178-84.

    46. Cohen MH, Chretien PB, Ihde DC, et al. Thymosin fraction V and intensive combination chemotherapy. Prolonging the survival of patients with small-cell lung cancer. JAMA 1979;241:1813-5.

    47. Macchiarini P, Danesi R, Del Tacca M, Angeletti CA. Effects of thymostimulin on chemotherapy-induced toxicity and long-term survival in small cell lung cancer patients. Anticancer Res 1989;9:193-6.

    48. Shoham J, Theodor E, Brenner HJ, et al. Enhancement of the immune system of chemotherapy-treated cancer patients by simultaneous treatment with thymic extract, TP-1. Cancer Immunol Immunother 1980;9:173-80.

    49. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688-92.

    50. Scambia G, De Vincenzo R, Ranelletti FO, et al. Antiproliferative effect of silybin on gynaecological malignancies: Synergism with cisplatin and doxorubicin. Eur J Cancer 1996;32A:877-82.

    51. Gaedeke J, Fels LM, Bokemeyer C, et al. Cisplatin nephrotoxicity and protection by silibinin. Nephrol Dial Transplant 1996;11:55-62.

    52. Invernizzi R, Bernuzzi S, Ciani D, Ascari E. Silymarine during maintenance therapy of acute promyelocytic leukemia. Haemotologia 1993;78:340-1.

    53. Toi M, Hattori T, Akagi M, et al. Randomized adjuvant trial to evaluate the addition of tamoxifen and PSK to chemotherapy in patients with primary breast cancer. Cancer 1992;70:2475-83.

    54. Iino Y, Yokoe T, Maemura M, et al. Immunochemotherapies versus chemotherapy as adjuvant treatment after curative resection of operable breast cancer. Anticancer Res 1995;15:2907-12.

    55. Mitomi T, Tsuchiya S, Iijima N, et al. Randomized, controlled study on adjuvant immunochemotherapy with PSK in curatively resected colorectal cancer. The Cooperative Study Group of Surgical Adjuvant Immunochemotherapy for Cancer of Colon and Rectum (Kanagawa). Dis Colon Rectum 1992;35:123-30.

    56. Witenberg B, Kalir HH, Raviv Z, et al. Inhibition by ascorbic acid of apoptosis induced by oxidative stress in HL-60 myeloid leukemia cells. Biochem Pharmacol 1999;57:823-32.

    57. Sacks PG, Harris D, Chou TC. Modulation of growth and proliferation in squamous cell carcinoma by retinoic acid: A rationale for combination therapy with chemotherapeutic agents. Int J Cancer 1995;61:409-15.

    58. Taper HS, et al. Non-toxic potentiation of cancer chemotherapy by combined C and K3 vitamin pre-treatment. Int J Cancer 1987;40:575-9.

    59. Kurbacher CM, Wagner U, Kolster B, et al. Ascorbic acid (vitamin C) improves the antineoplastic activity of doxorubicin, cisplatin, and paclitaxel in human breast carcinoma cells in vitro. Cancer Letters 1996:103-19.

    60. Wagdi P, Fluri M, Aeschbacher B, et al. Cardioprotection in patients undergoing chemo- and/or radiotherapy for neoplastic disease. Jpn Heart J 1996;37:353-9.

    61. Weijl NI, Cleton FJ, Osanto S. Free radicals and antioxidants in chemotherapy-induced toxicity. Cancer Treatment Rev 1997;23:209-40 [review].

    62. Hu Y-J, Chen Y, Zhang YQ, et al. The protective role of selenium on the toxicity of cisplatin-contained chemotherapy regimen in cancer patients. Biol Trace Elem Res 1997;56:331-41.

    63. De Maria D, Falchi AM, Venturino P. Adjuvant radiotherapy of the pelvis with or without reduced glutathione: a randomized trial in patients operated on for endometrial cancer. Tumori 1992;78:374-6.

    64. Lersch C, Zeuner M, Bauer A, et al. Nonspecific immunostimulation with low doses of cyclophosphamide (LDCY), thymostimulin, and Echinacea purpurea extracts (Echinacin) in patients with far advanced colorectal cancers: Preliminary results. Cancer Invest 1992;10:343-8.

    65. Dreizen S, McCredie KB, Keating MJ, Andersson BS. Nutritional deficiencies in patients receiving cancer chemotherapy. Postgrad Med 1990;87(1):163-70.

    66. Israel L, Hajji O, Grefft-Alami A, et al. Augmentation par la vitamine A des effets de la chimiotherapie dans les cancers du sein metastases apres la menopause. Ann Med Interne 1985;136:551-4.

    67. Witenberg B, Kalir HH, Raviv Z, et al. Inhibition by ascorbic acid of apoptosis induced by oxidative stress in HL-60 myeloid leukemia cells. Biochem Pharmacol 1999;57:823-32.

    68. Sacks PG, Harris D, Chou TC. Modulation of growth and proliferation in squamous cell carcinoma by retinoic acid: A rationale for combination therapy with chemotherapeutic agents. Int J Cancer 1995;61:409-15.

    69. Taper HS, et al. Non-toxic potentiation of cancer chemotherapy by combined C and K3 vitamin pre-treatment. Int J Cancer 1987;40:575-9.

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