CyclophosphamideSkip to the navigation
Cyclophosphamide is a chemotherapy drug used primarily to treat various forms of cancer. It is also used less commonly to treat some noncancer diseases.
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:Cytoxan, Cytoxan Lyophilized, Neosar
Summary of Interactions with Vitamins, Herbs, & Foods
Replenish Depleted Nutrients
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
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
Patients being treated with cyclophosphamide and cisplatin 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.3
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.4 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.
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.5 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.The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
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. 6The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
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.7 Eleuthero treatment was also associated with improved immune function in women with breast cancer treated with chemotherapy and radiation.8
Ginger (Zingiber officinale) can be helpful in alleviating nausea and vomiting caused by chemotherapy.9 , 10 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.11 , 12 In fact, animal studies show that glutamine may actually decrease tumor growth while increasing susceptibility of cancer cells to radiation and chemotherapy,13 , 14 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.15 Thirteen of fourteen people in the study had fewer days with mouth sores as a result. These excellent results have been duplicated in some,16 but not all17 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.18
One double-blind trial suggested that 6 grams of glutamine taken three times per day can decrease diarrhea caused by chemotherapy.19 However, other studies using higher amounts or intravenous glutamine have not reported this effect.20 , 21
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.22
Intravenous injections of the antioxidant, glutathione, may protect the bladder from damage caused by cyclophosphamide. Preliminary evidence suggests, but cannot confirm, a protective action of glutathione in the bladders of people on cyclophosphamide therapy.23 There is no evidence that glutathione taken by mouth has the same benefits.
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.24 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.
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.25 , 26 , 27 , 28 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.29
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.30
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.31 Others have confirmed the potential for vitamin E to help people with chemotherapy-induced mouth sores.32 Applying vitamin E only once per day was helpful to only some groups of patients in another trial,33 and not all studies have found vitamin E to be effective.34 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.
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.35 A related substance, thymostimulin, decreased some side effects of chemotherapy and increased survival time compared with chemotherapy alone.36 A third product, thymic extract TP1, was shown to improve immune function in people treated with chemotherapy compared with effects of chemotherapy alone.37 Thymic peptides need to be administered by injection. People interested in their combined use with chemotherapy should consult a doctor.
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.38 However, most scientific research does not support this supposition.
Cyclophosphamide requires activation by the liver through a process called oxidation. In theory, antioxidant nutrients (vitamin A, vitamin E, beta-carotene and others) might interfere with the activation of cyclophosphamide. There is no published research linking antioxidant vitamins to reduced cyclophosphamide effectiveness in cancer treatment. In a study of mice with vitamin A deficiency, vitamin A supplementation enhanced the anticancer action of cyclophosphamide.39 Another animal research report indicated that vitamin C may increase the effectiveness of cyclophosphamide without producing new side effects.40 Preliminary human research found that adding antioxidants (beta-carotene, vitamin A, and vitamin E) to cyclophosphamide therapy increased the survival of people with small-cell lung cancer treated with cyclophosphamide.41 It is too early to know if adding antioxidants to cyclophosphamide for cancer treatment is better than cyclophosphamide alone. Vitamin A can be toxic in high amounts.
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.42 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.43 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.44 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.
Potential Negative Interaction
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.45 Signs of restoration of immune function were seen in these patients.
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.46 People undergoing chemotherapy should talk to their doctor about whether supplementing with a multivitamin-mineral will protect them against deficiencies.
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.47 Similar results were not found in premenopausal women. The large amounts of vitamin A used in the study are toxic and require clinical supervision.In a study of mice with vitamin A deficiency, vitamin A supplementation enhanced the anticancer action of cyclophosphamide.48
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.49 However, most scientific research does not support this supposition.
Cyclophosphamide requires activation by the liver through a process called oxidation. In theory, antioxidant nutrients (vitamin A, vitamin E, beta-carotene and others) might interfere with the activation of cyclophosphamide. There is no published research linking antioxidant vitamins to reduced cyclophosphamide effectiveness in cancer treatment. Another animal research report indicated that vitamin C may increase the effectiveness of cyclophosphamide without producing new side effects.50 Preliminary human research found that adding antioxidants (beta-carotene, vitamin A, and vitamin E) to cyclophosphamide therapy increased the survival of people with small-cell lung cancer treated with cyclophosphamide.51 It is too early to know if adding antioxidants to cyclophosphamide for cancer treatment is better than cyclophosphamide alone. Vitamin A can be toxic in high amounts.
1. Desai TK, Maliakkal J, Kinzie JL, et al. Taurine deficiency after intensive chemotherapy and/or radiation. Am J Clin Nutr 1992;55:708-11.
2. Mattes RD. Prevention of food aversions in cancer patients during treatment. Nutr Cancer 1994;21:13-24.
3. Sieja K, Talerczyk M. Selenium as an element in the treatment of ovarian cancer in women receiving chemotherapy. Gynecol Oncol 2004;93:320-7.
4. 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.
5. Mills EE. The modifying effect of beta-carotene on radiation and chemotherapy induced oral mucositis. Br J Cancer 1988;57:416-7.
6. 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.
7. Kupin VJ. Eleutherococcus and Other Biologically Active Modifiers in Oncology. Moscow: Medexport, 1984, 21.
8. Kupin VI, Polevaya YB, Sorokin AM. Eleutherococcus extract treatment for immunostimulation in cancer patients. Vopr Onkol 1986;32:21-6 [in Russian].
9. Meyer K, Schwartz J, Crater D, Keyes B. Zingiber officinale (ginger) used to prevent 8-Mop associated nausea. Dermatol Nurs 1995;7:242-4.
10. 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.
11. 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.
12. 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.
13. Klimberg VS, McClellan JL. Glutamine, cancer, and its therapy. Am J Surg 1996;172:418-24.
14. Souba WW. Glutamine and cancer. Ann Surg 1993;218:715-28 [review].
15. Skubitz KM, Anderson PM. Oral glutamine to prevent chemotherapy induced stomatitis: a pilot study. J Lab Clin Med 1996;127:223-8.
16. Anderson PM, Schroeder G, Skubitz KM. Oral glutamine reduces the duration and severity of stomatitis after cytotoxic cancer chemotherapy. Cancer 1998;83:1433-9.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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.
22. 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.
23. Nobile MT, Vidili MG, Benasso M, et al. A preliminary clinical study of cyclophosphamide with reduced glutathione as uroprotector. Tumori 1989;75:257-8.
24. Lissoni P, Cazzanga M, Tancini G, et al. Reversal of clinical resistance to LHRH analogue in metastatic prostate cancer by the pineal hormone melatonin: efficacy of LHRH analogue plus melatonin in patients progressing on LHRH analogue alone. Eur Urol 1997;31:178-81.
25. Holoya PY, Duelge J, Hansen RM, et al. Prophylaxis of ifosfamide toxicity with oral acetylcysteine. Sem Oncol 1983;10(suppl 1):66-71.
26. Slavik M, Saiers JH. Phase I clinical study of acetylcysteine's preventing ifosfamide-induced hematuria. Sem Oncol 1983;10(suppl 1):62-5.
27. 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.
28. Morgan LR, Donley PJ, Harrison EF. The control of ifosfamide induced hematuria with N-acetylcysteine. Proc Am Assoc Cancer Res 1981;22:190.
29. 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.
30. 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.
31. Wadleigh RG, Redman RS, Graham ML, et al. Vitamin E in the treatment of chemotherapy-induced mucositis. Am J Med 1992;92:481-4.
32. 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.
33. 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.
34. 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.
35. 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.
36. 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.
37. 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.
38. 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.
39. Ghosh J, Das S. Role of vitamin A in prevention and treatment of sarcoma 180 in mice. Chemotherapy 1987;33:211-8.
40. 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.
41. Jaakkola K, Lahteenmaki P, Laakso J, et al. Treatment with antioxidant and other nutrients in combination with chemotherapy and irradiation in patients with small-cell lung cancer. Anticancer Res 1992;12:599-606.
42. 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.
43. 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.
44. 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.
45. 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.
46. Dreizen S, McCredie KB, Keating MJ, Andersson BS. Nutritional deficiencies in patients receiving cancer chemotherapy. Postgrad Med 1990;87(1):163-70.
47. 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.
48. Ghosh J, Das S. Role of vitamin A in prevention and treatment of sarcoma 180 in mice. Chemotherapy 1987;33:211-8.
49. 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.
50. 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.
51. Jaakkola K, Lahteenmaki P, Laakso J, et al. Treatment with antioxidant and other nutrients in combination with chemotherapy and irradiation in patients with small-cell lung cancer. Anticancer Res 1992;12:599-606.
Last Review: 04-29-2014
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