Skip to content
Bending the Curve Trial by Trial
?

Pyrimidine analogues and fluoropyrimidinesUsed in a few countriesDerivative of an earlier drugNeeds review

Doxifluridine

Also known as 5'-deoxy-5-fluorouridine, 5'-DFUR, 5'-dFUrd

An oral prodrug of fluorouracil, 5'-deoxy-5-fluorouridine, which is also the intermediate metabolite of capecitabine. It has been studied in gastric, colorectal and breast cancer; a 2023 report says it has been used for various solid cancers.

From discovery to approval

  1. c. 1980 · Earliest report found

    The earliest record found is a 1980 European Journal of Cancer paper by Bollag and Hartmann, titled as reporting tumour inhibitory effects of a new fluorouracil derivative, 5'-deoxy-5-fluorouridine (title only). Capecitabine papers from 1998 identify this compound, 5'-dFUrd, as doxifluridine.[2][1][3]

  2. No approval is recorded on this site.

How it works

It is converted to fluorouracil by thymidine phosphorylase, which is present at high levels in many solid tumours; the fluorouracil formed is broken down by dihydropyrimidine dehydrogenase. Efficacy in xenografts correlated with the ratio of these two enzymes.[1]

Where it came from and why

No source read states why it was made. The 1998 capecitabine work shows its property of conversion to fluorouracil by thymidine phosphorylase in tumours, which was then used to design capecitabine as a prodrug of it.

Cancers

  • Gastric cancer

    A 2013 phase 3 trial (855 patients) tested adjuvant mitomycin-C with short-term doxifluridine against a longer doxifluridine plus cisplatin regimen after D2 gastrectomy; a 2023 retrospective propensity-matched study compared adjuvant doxifluridine with S-1.[4]

  • Colorectal cancer

    A phase II study of 60 patients with metastatic colorectal cancer combined irinotecan with oral doxifluridine.[5]

  • Gastric, colorectal and breast cancer (phase II)

    A Japanese-language report analysed survival in a phase II study of 5'-DFUR in gastric, colorectal and breast cancer.[6]

Family and partners

Derived from: Fluorouracil (5-FU)

Worth knowing

  • A 2008 phase II report calls doxifluridine an intermediate form of capecitabine; the 1998 xenograft study states that capecitabine is converted to fluorouracil through this intermediate.[5]
  • In 24 human cancer xenograft lines, 5'-dFUrd (doxifluridine) inhibited tumour growth by more than 50% in 15 lines and capecitabine in 18, whereas fluorouracil did so in 1 and tegafur plus uracil in 5.[1]
  • In the 2013 phase 3 trial, 5-year recurrence-free survival was 61.1% with the short-term doxifluridine regimen and 57.9% with the intensified regimen (hazard ratio 1.10, 95% CI 0.89 to 1.35; P = 0.39).[4]
  • In a 2023 propensity-matched retrospective analysis (48 patients per group), 5-year overall survival was 77.1% with doxifluridine and 75.0% with S-1 (P = 0.729).[7]

References

  1. Ishikawa T, Sekiguchi F, Fukase Y, Sawada N, Ishitsuka H. Positive correlation between the efficacy of capecitabine and doxifluridine and the ratio of thymidine phosphorylase to dihydropyrimidine dehydrogenase activities in tumors in human cancer xenografts. Cancer Res. 1998;58(4):685-90. PubMed
  2. Bollag W, Hartmann HR. Tumor inhibitory effects of a new fluorouracil derivative: 5'-deoxy-5-fluorouridine. Eur J Cancer (1965). 1980;16(4):427-32. PubMedDOI
  3. Ishitsuka H. Capecitabine: preclinical pharmacology studies. Invest New Drugs. 2000;18(4):343-54. PubMedDOI
  4. Kang YK, Chang HM, Yook JH, Ryu MH, Park I, Min YJ, et al. Adjuvant chemotherapy for gastric cancer: a randomised phase 3 trial of mitomycin-C plus either short-term doxifluridine or long-term doxifluridine plus cisplatin after curative D2 gastrectomy (AMC0201). Br J Cancer. 2013;108(6):1245-51. PubMedDOI
  5. Kato T, Mishima H, Ikenaga M, Murata K, Ishida H, Fukunaga M, et al. A phase II study of irinotecan in combination with doxifluridine, an intermediate form of capecitabine, in patients with metastatic colorectal cancer. Cancer Chemother Pharmacol. 2008;61(2):275-81. PubMedDOI
  6. Taguchi T. [Survival and changes of clinical laboratory data in phase II study with 5'-DFUR]. Gan To Kagaku Ryoho. 1996;23(8):1019-29. PubMed
  7. Jeong JY, Seo SH, Kim KH, An MS, Baik H, Kang SH, et al. Doxifluridine versus Tegafur/Gimeracil/Oteracil (S-1) as adjuvant chemotherapy for patients with gastric cancer after gastrectomy: A propensity score-matched analysis. Asian J Surg. 2023;46(9):3656-3662. PubMedDOI
  8. Calabresi F, Repetto M. Doxifluridine in advanced colorectal cancer. J Surg Oncol Suppl. 1991;2:124-8. PubMedDOI