Fluorouracil

Brand Names:

Clinical Names: Fluorouracil, 5-FU, 5-Fluorouracil

Summary

generic name: Fluorouracil, 5-FU, 5-Fluorouracil

type of drug: Cytotoxic chemotherapy.

used to treat: Cancer.

overview of interactions:
• nutrient affecting drug performance: Vitamin A

• nutrient affected by drug: Vitamin B1 (Thiamine)

• nutrient affecting drug performance: Lentinus edodes (Shiitake Mushroom)





Interactions

nutrient affecting drug performance: Vitamin A

• mechanism: Animal studies indicate that vitamin A may enhance antitumor effect of 5-Fluorouracil.
(Nakagawa, M, et al. Jpn J Cancer Res 1985 Sep;76(9):887-894.)

• nutritional support: Supplementation with vitamin A might enhance the therapeutic efficacy of 5-FU. However, individuals being treated with 5-Fluorouracil should consult their prescribing physician and/or a nutritionally trained healthcare professional before starting such a program of supplementation. High doses of vitamin A can be toxic. Women who could become pregnant should avoid dosages over 10,000 IU (3,000 mcg) per day of vitamin A because it can cause birth defects; though the 5-FU itself presents significant risks for causing birth defects. Generally, dosages up to 25,000 IU (7,500 mcg) of vitamin A per day are considered safe for postmenopausal women and males.

nutrient affected by drug: Vitamin B1 (Thiamine)

• mechanism: 5-Fluorouracil inhibits the conversion of thiamine to thiamine pyrophosphate. (Basu TK, et al. Int J Vitam Nutr Res. 1974;44(1):53-58; Aksoy M, et al. Eur J Cancer. 1980 Aug;16(8):1041-1045; Basu TK. Int J Vitam Nutr Res Suppl. 1983;24:225-233.)

nutritional support: Thiamine supplementation might counteract some of the adverse effects of taking 5-FU and prevent thiamine depletion. Thiamine is essentially non-toxic and the dosages in the range of 20-25 mg per day, as found in most multivitamin formulas, are probably significant enough to prevent depletion. However, individuals being treated with 5-Fluorouracil should consult their prescribing physician and/or a nutritionally trained healthcare professional before starting such a program of supplementation.

nutrient affecting drug performance: Lentinus edodes (Shiitake Mushroom)

• research: Taguchi and other researchers have found that patients suffering from advanced or recurrent, stomach and colo-rectal cancer who were administered lentinan intravenously in combination with mitomycine C + 5-FU (MF) or tegafur (FT) demonstrated statistically significance improvement in life span prolongation as compare to those who were treated with MF or FT alone. These researchers also noted that improvement of host immune responses was observed in the group treated with lentinan, and hematological survey showed that incidence rate of abnormal value was significantly low in LNT treated group. Similar research suggests that lentinan may also be effective for the patients with advanced or recurrent breast cancer as an agent for supportive therapy.
(Taguchi T. Gan To Kagaku Ryoho. 1983 Feb;10(2 Pt 2):387-393.)

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Do not rely solely on the information in this article.

The information presented in Interactions is for informational and educational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, case reports, and/or traditional usage with sources as cited in each topic. The results reported may not necessarily occur in all individuals and different individuals with the same medical conditions with the same symptoms will often require differing treatments. For many of the conditions discussed, treatment with conventional medical therapies, including prescription drugs or over-the-counter medications, is also available. Consult your physician, an appropriately trained healthcare practitioner, and/or pharmacist for any health concern or medical problem before using any herbal products or nutritional supplements or before making any changes in prescribed medications and/or before attempting to independently treat a medical condition using supplements, herbs, remedies, or other forms of self-care.


References

Aksoy M, et al. Thiamin status of patients treated with drug combinations containing 5-fluorouracil. Eur J Cancer. 1980 Aug;16(8):1041-1045.

Basu TK, Dickerson JW, Raven RW, Williams DC. The thiamine status of patients with cancer as determined by the red cell transketolase activity. Int J Vitam Nutr Res. 1974;44(1):53-58.

Basu TK. Vitamins - cytotoxic drug interaction. Int J Vitam Nutr Res Suppl. 1983;24:225-233.

Labriola D, Livingston R. Possible interactions between dietary antioxidants and chemotherapy. Oncology (Huntingt). 1999 Jul;13(7):1003-1008; discussion 1008, 1011-1012.
Abstract: Many patients treat themselves with oral antioxidants and other alternative therapies during chemotherapy, frequently without advising their conventional health care provider. No definitive studies have demonstrated the long-term effects of combining chemotherapeutic agents and oral antioxidants in humans. However, there is sufficient understanding of the mechanisms of action of both chemotherapeutic agents and antioxidants to predict the obvious interactions and to suggest where caution should be exercised with respect to both clinical decisions and study interpretation. This article will describe these potential interactions and areas of concern, based on the available data. It will also suggest several potential courses of action that clinicians may take when patients indicate that they are taking or plan to use alternative therapies.

Nakagawa M, Yamaguchi T, Ueda H, Shiraishi N, Komiyama S, Akiyama S, Ogata J, Kuwano M. Potentiation by vitamin A of the action of anticancer agents against murine tumors. Jpn J Cancer Res 1985 Sep;76(9):887-894.
Abstract: Combinations of retinol palmitate (RP) and six different anticancer agents were examined to determine their effects on the life-span of mice bearing ascites sarcoma 180 or P388 leukemia. With ascites sarcoma 180, administration of a fixed dose of RP (3.3 mg/kg) considerably enhanced the antitumor effects of 5-fluorouracil (5-FU) (5 mg/kg, or 20 mg/kg), methotrexate (MTX) (0.5 mg/kg, or 1 mg/kg) and 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU) (12.5 mg/kg), when given by intraperitoneal injection. However RP failed to potentiate the antitumor effects of adriamycin (ADM) and 6-mercaptopurine (6-MP) against sarcoma 180. With P388 leukemia, RP (167 mg/kg, or 333 mg/kg) enhanced the antitumor effects of 6-MP (25 mg/kg, or 50 mg/kg), MTX (1 mg/kg, or 2 mg/kg), ADM (0.2 mg/kg), ACNU (5 mg/kg) and cis-dichlorodiammine-platinum (CDDP) (1 mg/kg) to a considerable extent, but it did not potentiate the antitumor effect of 5-FU. The combination of RP with ACNU or CDDP was particularly effective against P388 leukemia.

Taguchi T. [Lentinan]. Gan To Kagaku Ryoho. 1986 Oct;13(11):3294-3304. [Article in Japanese]

Taguchi T, Furue H, Kimura T, Kondo T, Hattori T, Itoh I, Ogawa N.  [Results of phase III study of lentinan]. Gan To Kagaku Ryoho. 1985 Feb;12(2):366-78. [Article in Japanese]
Abstract: A follow-up survey of survivals (Oct. 1 '80 to May 1, '84) in a randomized controlled study (Aug. '79 to Sept. 30' 80) of lentinan in combination administration with chemotherapeutic agents such as 5FU + mitomycin C or tegafur on patients with advanced or recurrent gastrointestinal cancer has shown that lentinan has been effective in such cases with regard to the following facts: 1) A life span prolongation effect at the end-point has been observed with statistical significance in lentinan treated patients as was found in the phase III study. 2) Using the life table analysis method, a higher rate of survival has been observed in the lentinan treated group, especially in combination with tegafur for gastric cancer, clearly showing such high survival rates as 12.97% (P less than 0.05) at two years after, and 9.51% (P less than 0.05) and 3.81%, at three and four years after respectively, and for colorectal cancer, 9.10% and 4.55% at two years and three years after, respectively.

Taguchi T. [Effects of lentinan in advanced or recurrent cases of gastric, colorectal, and breast cancer]. Gan To Kagaku Ryoho. 1983 Feb;10(2 Pt 2):387-393. [Article in Japanese]
Abstract: In order to evaluate clinical efficacy of Lentinan (LNT), a purified polysaccharide extracted from Lentinus edodes, randomized controlled studies with envelope method have been conducted on the patients with advanced or recurrent, stomach, colo-rectal and breast cancer. Administration condition of LNT for gastrointestinal cancer was designed as the following: LNT was administered intravenously at doses of 1 mg/person/day twice a week or 2 mg/person/day once a week in combination with mitomycine C + 5-FU (MF) or tegafur (FT). Control therapy was the administration of MF or FT alone. Survival curve drawn by Kaplan-Meier's method showed that life span prolongation effect of LNT was observed with statistical significance (P less than 0.05 or P less than 0.01) by use of generalized Wilcoxon's test. Moreover, improvement of host immune responses was observed in LNT treated group, and hematological survey showed that incidence rate of abnormal value was significantly low in LNT treated group. Thus, LNT should be effective for the patients with advanced or recurrent stomach or colo-rectal cancer in combination with chemotherapeutic agents such as MF or FT. Regarding advanced or recurrent breast cancer, study is underway. LNT has been administered as an agent for supportive therapy to the patients with complete response, partial response or stable diseases which were induced by prior surgery of oophorectomy. Again, life span prolongation effect of LNT has been observed with statistical significance (P less than 0.05). This result suggests that LNT would also be effective for the patients with advanced or recurrent breast cancer as an agent for supportive therapy.