IfosfamideSkip to the navigation
Common brand names:Ifex
Summary of Interactions with Vitamins, Herbs, & Foods
Replenish Depleted Nutrients
Magnesium and Potassium
The chemotherapy drug cisplatin may cause excessive loss of magnesium and potassium in the urine.1 , 2 Preliminary reports suggest that both potassium and magnesium supplementation may be necessary to increase low potassium levels.3 , 4 Severe magnesium deficiency caused by cisplatin therapy has been reported to result in seizures.5 Severe magnesium deficiency is a potentially dangerous medical condition that should only be treated by a doctor. People receiving cisplatin chemotherapy should ask their prescribing doctor to closely monitor magnesium and potassium status.
The chemotherapy drug cisplatin may cause kidney damage, resulting in depletion of calcium and phosphate.6The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
The chemotherapy drug cisplatin may cause depletion of sodium due to kidney damage which sometimes occurs in people treated with cisplatin.7The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Taurine has been shown to be depleted in people taking chemotherapy.8 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
Acetyl-L-carnitine in the amount of 1,000 mg three times per day for eight weeks has been shown to improve nerve damage (neuropathy) caused by the chemotherapy drug cisplatin.9
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.10
High-dose cisplatin chemotherapy is associated with kidney toxicity and damage, which may be reduced by glutathione administration.11 , 12 , 13 , 14 Nerve damage is another frequent complication of high amounts of cisplatin. Preliminary evidence has shown that glutathione injections may protect nerve tissue during cisplatin therapy without reducing cisplatin's anti-tumor activity.15 , 16 , 17 There is no evidence that glutathione taken by mouth has the same benefits.
Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with cisplatin plus etoposide and cisplatin plus 5-FU.18
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.19
In one human study, administration of 4,000 mcg per day of a selenium product, Seleno-Kappacarrageenan, reduced the kidney damage and white blood cell-lowering effects of the chemotherapy drug cisplatin.20 The amount of selenium used in this study is potentially toxic and should only be used under the supervision of a doctor. In another study, patients being treated with cisplatin and cyclophosphamide for ovarian cancer were given a multivitamin preparation, with or without 200 mcg of selenium per day. Compared with the group not receiving selenium, those receiving selenium had a smaller reduction in white blood cell count and fewer chemotherapy side effects such as nausea, hair loss, weakness, and loss of appetite.21
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.22 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.
In a preliminary trial, taking wheat grass in the amount of 60 ml (about 2 ounces) per day during chemotherapy reduced the incidence of certain chemotherapy-related side effects (including anemia and a decline in white blood cell counts) in women with breast cancer. Taking wheat grass did not appear to interfere with the anticancer effect of the chemotherapy. The chemotherapy used in this study was a combination of 5-fluorouracil, doxorubicin, and cyclophosphamide.23
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.24 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.25 Others have confirmed the potential for vitamin E to help people with chemotherapy-induced mouth sores.26 Applying vitamin E only once per day was helpful to only some groups of patients in another trial,27 and not all studies have found vitamin E to be effective.28 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.
In a preliminary study, the addition of oral vitamin E (300 IU per day) to cisplatin chemotherapy significantly reduced the incidence of drug-induced damage to the nervous system (neurotoxicity).29 A similar protective effect was seen in another trial in which 600 IU of vitamin E per day was used.30
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. 31
Ginger (Zingiber officinale) can be helpful in alleviating nausea and vomiting caused by chemotherapy.32 , 33 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.
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.34 , 35 In fact, animal studies show that glutamine may actually decrease tumor growth while increasing susceptibility of cancer cells to radiation and chemotherapy,36 , 37 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.38 Thirteen of fourteen people in the study had fewer days with mouth sores as a result. These excellent results have been duplicated in some,39 but not all,40 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.41
One double-blind trial suggested that 6 grams of glutamine taken three times per day can decrease diarrhea caused by chemotherapy.42 However, other studies using higher amounts or intravenous glutamine have not reported this effect.43 , 44
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.45
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.46 , 47 , 48 , 49 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.50
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.51 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.52 Vitamin C appears to increase the effectiveness of chemotherapy in animals53 and with human breast cancer cells in test tube research.54 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.55
A comprehensive review of antioxidants and chemotherapy leaves open the question of whether supplemental antioxidants definitely help people with chemotherapy side effects, but neither does it show that antioxidants should be avoided for fear that the actions of chemotherapy are interfered with.56 Although research remains incomplete, the idea that people taking chemotherapy should avoid antioxidants is not supported by scientific research.
Irradiation treatment, especially of head and neck cancers, frequently results in changes to normal taste sensation.57 , 58 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.59
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.60 Silymarin also offsets the kidney toxicity of cisplatin in animals.61 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.62
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.63 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.64 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.65 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.
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.66 A related substance, thymostimulin, decreased some side effects of chemotherapy and increased survival time compared with chemotherapy alone.67 A third product, thymic extract TP1, was shown to improve immune function in people treated with chemotherapy compared with effects of chemotherapy alone.68 Thymic peptides need to be administered by injection. People interested in their combined use with chemotherapy should consult a doctor.
Potential Negative Interaction
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.69 Similar results were not found in premenopausal women. The large amounts of vitamin A used in the study are toxic and require clinical supervision.
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.70 Eleuthero treatment was also associated with improved immune function in women with breast cancer treated with chemotherapy and radiation.71
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.72 People undergoing chemotherapy should talk to their doctor about whether supplementing with a multivitamin-mineral will protect them against deficiencies.
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5. van de Loosdrecht AA, Gietema JA, van der Graaf WT. Seizures in a patient with disseminated testicular cancer due to cisplatin-induced hypomagnesaemia. Acta Oncol 2000;39:239-40.
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9. Bianchi G, Vitali G, Caraceni A, et al. Symptomatic and neurophysiological responses of paclitaxel- or cisplatin-induced neuropathy to oral acetyl-L-carnitine. Eur J Cancer 2005;41:1746-50.
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11. Fontanelli R, Spatti G, Raspagliesi F, et al. A preoperative single course of high-dose cisplatin and bleomycin with glutathione protection in bulky stage IB/II carcinoma of the cervix. Ann Oncol 1992;3:117-21.
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18. Lissoni P, Barni S, Mandalà, 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.
19. Osterlund P, Ruotsalainen T, Korpela R, et al. Lactobacillus supplementation for diarrhoea related to chemotherapy of colorectal cancer: a randomised study. Br J Cancer 2007;97:1028-34.
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21. Sieja K, Talerczyk M. Selenium as an element in the treatment of ovarian cancer in women receiving chemotherapy. Gynecol Oncol 2004;93:320-7.
22. 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.
23. Bar-Sela G, Tsalic M, Fried G, Goldberg H. Wheat grass juice may improve hematological toxicity related to chemotherapy in breast cancer patients: a pilot study. Nutr Cancer 2007;58:43-8.
24. Mills EE. The modifying effect of beta-carotene on radiation and chemotherapy induced oral mucositis. Br J Cancer 1988;57:416-7.
25. Wadleigh RG, Redman RS, Graham ML, et al. Vitamin E in the treatment of chemotherapy-induced mucositis. Am J Med 1992;92:481-4.
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28. 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.
29. Pace A, Savarese A, Picardo M, et al. Neuroprotective effect of vitamin E supplementation in patients treated with cisplatin chemotherapy. J Clin Oncol2003;21:927-31.
30. Argyriou AA, Chroni E, Koutras A, et al. Vitamin E for prophylaxis against chemotherapy-induced neuropathy: a randomized controlled trial. Neurology2005;64:26-31.
31. Carl W, Emrich LS. Management of oral mucositis during local radiation and systemic chemotherapy: A study of 98 patients. J Prosthet Dent 1991;66:361-9.
32. Meyer K, Schwartz J, Crater D, Keyes B. Zingiber officinale (ginger) used to prevent 8-Mop associated nausea. Dermatol Nurs 1995;7:242-4.
33. 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.
34. 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.
35. van Zaanen HCT, van der Lelie H, Timmer JG, et al. Parenteral glutamine dipeptide supplementation does not ameliorate chemotherapy-induced toxicity. Cancer 1994;74:2879-84.
36. Klimberg VS, McClellan JL. Glutamine, cancer, and its therapy. Am J Surg 1996;172:418-24.
37. Souba WW. Glutamine and cancer. Ann Surg 1993;218:715-28 [review].
38. Skubitz KM, Anderson PM. Oral glutamine to prevent chemotherapy induced stomatitis: a pilot study. J Lab Clin Med 1996;127:223-8.
39. Anderson PM, Schroeder G, Skubitz KM. Oral glutamine reduces the duration and severity of stomatitis after cytotoxic cancer chemotherapy. Cancer 1998;83:1433-9.
40. Okuno SH, Woodhouse CO, Loprinzi CL, et al. Phase III controlled evaluation of glutamine for decreasing stomatitis in patients receiving fluorouracil (5-FU)-based chemotherapy. Am J Clin Oncol 1999;22:258-61.
41. Cockerham MB, Weinberger BB, Lerchie SB. Oral glutamine for the prevention of oral mucositis associated with high-dose paclitaxel and melphalan for autologous bone marrow transplantation. Ann Pharmacother 2000;34:300-3.
42. Muscaritoli M, Micozzi A, Conversano L, et al. Oral glutamine in the prevention of chemotherapy-induced gastrointestinal toxicity Eur J Cancer 1997;33:319-20.
43. 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.
44. van Zaanen HCT, van der Lelie H, Timmer JG, et al. Parenteral glutamine dipeptide supplementation does not ameliorate chemotherapy-induced toxicity. Cancer 1994;74:2879-84.
45. MacBurney M, Young LS, Ziegler TR, Wilmore DW. A cost-evaluation of Glutamine-supplemented parenteral nutrition in adult bone marrow transplant patients. J Am Diet Assoc 1994;94:1263-6.
46. Holoya PY, Duelge J, Hansen RM, et al. Prophylaxis of ifosfamide toxicity with oral acetylcysteine. Sem Oncol 1983;10(suppl 1):66-71.
47. Slavik M, Saiers JH. Phase I clinical study of acetylcysteine's preventing ifosfamide-induced hematuria. Sem Oncol 1983;10(suppl 1):62-5.
48. 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.
49. Morgan LR, Donley PJ, Harrison EF. The control of ifosfamide induced hematuria with N-acetylcysteine. Proc Am Assoc Cancer Res 1981;22:190.
50. 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.
51. 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.
52. Sacks PG, Harris D, Chou T-C. 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.
53. 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.
54. 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.
55. 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.
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59. Ripamonti C, Zecca E, Brunelli C, et al. A randomized, controlled clinical trial to evaluate the effects of zinc sulfate on cancer patients with taste alterations caused by head and neck irradiation. Cancer 1998;82:1938-45.
60. 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.
61. Gaedeke J, Fels LM, Bokemeyer C, et al. Cisplatin nephrotoxicity and protection by silibinin. Nephrol Dial Transplant 1996;11:55-62.
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63. 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.
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