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Bending the Curve Trial by Trial
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Pyrimidine analogues and fluoropyrimidinesUsed in a few countriesDerivative of an earlier drugNeeds review

Carmofur

Also known as HCFU, 1-hexylcarbamoyl-5-fluorouracil

An oral prodrug of fluorouracil carrying a hexylcarbamoyl group, developed in Japan. A 2022 review says it has been in clinical use there since 1981 for colorectal cancer, and was later introduced in China, Korea and Finland.

From discovery to approval

  1. 1976 · First described

    A 1976 paper in Gan (Hoshi and colleagues) tested the antitumour activity of 1-hexylcarbamoyl-5-fluorouracil in a variety of experimental tumours. A 1980 review says the compound was developed at the National Cancer Center, with a phase I study under way in Japan.[2][3][1][4]

  2. No approval is recorded on this site.

How it works

It is a prodrug of fluorouracil, which then acts as described for that drug. A 2022 review reports better gastrointestinal stability and superior antiproliferative activity than fluorouracil, and recent interest in it as an acid ceramidase inhibitor.[1]

Where it came from and why

The 1976 abstract found a wider tumour spectrum and better oral therapeutic ratios in the L-1210 and C-1498 leukaemia systems than fluorouracil and 1-(2-tetrahydrofuryl)-5-fluorouracil, the compound now called tegafur. The reason carmofur was synthesised is not stated in the abstracts read.

Cancers

  • Colorectal cancer

    A 2001 individual patient data meta-analysis pooled 614 patients from three trials of long-term oral carmofur after curative resection of colorectal cancer, and reported a survival and disease-free survival benefit.[5]

  • Breast, head and neck, pancreatic and other cancers

    A 2022 review says carmofur has shown antitumour activity in breast, head and neck, pancreatic, gastrointestinal and solid brain tumours.[1]

Family and partners

Derived from: Fluorouracil (5-FU)

Worth knowing

  • A 2022 review says carmofur has been in clinical use in Japan since 1981 for colorectal cancer and was later introduced in China, Korea and Finland.[1]
  • In the 1976 study, the oral therapeutic ratio in the L-1210 system was 4.5 for carmofur, compared with 1.9 for fluorouracil and 1.0 for 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur, FT-207).[2]
  • In the 2001 pooled analysis of three trials, carmofur gave a significant survival benefit (2p = 0.032) and disease-free survival benefit (2p = 0.021).[5]
  • The 1980 review reports that in the phase I study the characteristic subjective symptoms were a hot sensation and pollakisuria, and that no haematologic or serum biochemical changes were noted.[3]
  • A 2022 review notes that carmofur has attracted interest as an acid ceramidase inhibitor and as a lead compound for several non-cancer conditions.[1]

References

  1. Islam MM, Mirza SP. Versatile use of Carmofur: A comprehensive review of its chemistry and pharmacology. Drug Dev Res. 2022;83(7):1505-1518. PubMedDOI
  2. Hoshi A, Iigo M, Nakamura A, Yoshida M, Kuretani K. Antitumor activity of 1-hexylcarbamoyl-5-fluorouracil in a variety of experimental tumors. Gan. 1976;67(5):725-31. PubMed
  3. Taguchi T. Review of a new antimetabolic agent 1-hexylcarbamoyl-5-fluorouracil (HCFU). Recent Results Cancer Res. 1980;70:125-32. PubMedDOI
  4. Yamashita K, Sutou H, Maruden A, Takenouchi T, Morita K, Ariyoshi T. A nine-month chronic toxicity study of tegafur-uracil mixture (UFT) in dogs. J Toxicol Sci. 1988;13(2):97-132. PubMedDOI
  5. Sakamoto J, Kodaira S, Hamada C, Ito K, Maehara Y, Takagi H, et al. An individual patient data meta-analysis of long supported adjuvant chemotherapy with oral carmofur in patients with curatively resected colorectal cancer. Oncol Rep. 2001;8(3):697-703. PubMed