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Bending the Curve Trial by Trial
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Other cytotoxics, enzymes and natural productsObsoleteOrigin unclearNeeds review

Razoxane

Also known as ICRF-159, ICRF 159

An oral bisdioxopiperazine that inhibits topoisomerase II without trapping it on DNA. The earliest reports found (1969) concern acute leukaemia, lymphosarcoma and experimental metastasis; later studies covered soft tissue sarcoma and colorectal cancer. No current regulatory label was found.

From discovery to approval

  1. 1969 · Earliest report found

    The earliest reports found are from 1969: a preliminary clinical assessment of ICRF 159 in nine patients with acute leukaemia or lymphosarcoma, and a Nature paper titled 'Control of malignant metastases by ICRF 159' (title only). A 2026 review says razoxane was discovered in the 1960s. No source read describes its synthesis.[2][3][4][5]

  2. No approval is recorded on this site.

How it works

A 1995 yeast genetic study supports DNA topoisomerase II as the main cellular target of ICRF-159. Unlike amsacrine and etoposide, it inhibits the enzyme's activity without stabilising an enzyme-DNA covalent complex.[1]

Where it came from and why

No source read says why razoxane was made. Le Serve and Hellmann (2008) report that treatment with ICRF 159 profoundly modified the structure and arrangement of tumour blood vessels, which they say may affect the escape of malignant cells and the flow of anticancer drugs through the tumour.

Cancers

  • Soft tissue sarcoma

    In a randomised study (144 patients entered between 1978 and 1988), among 82 patients with gross disease radiotherapy plus razoxane gave a higher response rate than radiotherapy alone (74% versus 49%).[6]

  • Colorectal cancer (adjuvant)

    A randomised trial of oral adjuvant razoxane after resection enrolled 272 patients (133 control, 139 treated) and found a significant prolongation of time to recurrence for Dukes' C patients only.[7]

Worth knowing

  • A 2026 review says razoxane was approved for cancer treatment but lacks the cell-killing activity of other agents and was a commercial failure; it blocks the cell cycle at the G2/M boundary.[4]
  • In the adjuvant colorectal trial, acute leukaemia occurred in three patients (2.45%) after prolonged exposure to razoxane.[7]

References

  1. Ishida R, Hamatake M, Wasserman RA, Nitiss JL, Wang JC, Andoh T. DNA topoisomerase II is the molecular target of bisdioxopiperazine derivatives ICRF-159 and ICRF-193 in Saccharomyces cerevisiae. Cancer Res. 1995;55(11):2299-303. PubMed
  2. Hellmann K, Newton KA, Whitmore DN, Hanham IW, Bond JV. Preliminary clinical assessment of I.C.R.F. 159 in acute leukaemia and lymphosarcoma. Br Med J. 1969;1(5647):822-4. PubMedDOI
  3. Hellmann K, Burrage K. Control of malignant metastases by ICRF 159. Nature. 1969;224(5216):273-5. DOI
  4. Rothman J. Use of Razoxane as a radiosensitizer for the treatment of soft tissue sarcomas. Expert Rev Anticancer Ther. 2026;26(7):891-903. PubMedDOI
  5. Le Serve AW, Hellmann K. Metastases and the normalization of tumour blood vessels by ICRF 159: a new type of drug action. Clin Exp Metastasis. 2008;25(4):283-8. PubMedDOI
  6. Rhomberg W, Hassenstein EO, Gefeller D. Radiotherapy vs. radiotherapy and razoxane in the treatment of soft tissue sarcomas: final results of a randomized study. Int J Radiat Oncol Biol Phys. 1996;36(5):1077-84. PubMedDOI
  7. Gilbert JM, Hellmann K, Evans M, Cassell PG, Taylor RH, Stoodley B, et al. Randomized trial of oral adjuvant razoxane (ICRF 159) in resectable colorectal cancer: five-year follow-up. Br J Surg. 1986;73(6):446-50. PubMedDOI