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Anthracyclines and anthracenedionesIn useDerivative of an earlier drug

Valrubicin

Also known as Valstar, AD 32, N-trifluoroacetyladriamycin-14-valerate

A semisynthetic analogue of doxorubicin instilled into the bladder instead of being injected. The US label lists BCG-refractory carcinoma in situ of the bladder in patients for whom immediate cystectomy would carry unacceptable morbidity or mortality.

From discovery to approval

  1. 1975 · Earliest report found

    A 1975 Cancer Research paper by Israel, Modest and Frei described N-trifluoroacetyladriamycin-14-valerate (AD 32), an adriamycin analogue with greater antitumour activity than adriamycin in two mouse leukaemia systems. The 1998 US label names valrubicin as N-trifluoroacetyladriamycin-14-valerate and carries the AD 32 header; a 1999 review calls valrubicin AD-32.[2][3][4][5]

  2. 1998-09-25 · FDA regular

    Valstar sterile solution 40 mg/mL for intravesical therapy of BCG-refractory carcinoma in situ of the urinary bladder in patients for whom immediate cystectomy would be associated with unacceptable morbidity or mortality. The type regular is an inference: the letter has no accelerated-approval wording.[6]

How it works

The label says it inhibits the incorporation of nucleosides into nucleic acids, causes chromosomal damage and arrests the cell cycle in G2. It does not bind strongly to DNA; its metabolites interfere with the normal DNA breaking-resealing action of topoisomerase II.[1]

Where it came from and why

The 1975 abstract reports greater activity and less toxicity than adriamycin in mice and concludes that substituting the glycosidic amino group can retain or enhance the effectiveness of anthracyclines. A 1978 paper called AD 32 a superior analogue under development in the authors' laboratories.

Cancers

  • Bladder carcinoma in situ, BCG-refractory

    The 1998 approval letter and the 2024 US label list intravesical therapy of BCG-refractory carcinoma in situ of the urinary bladder in patients for whom immediate cystectomy would be associated with unacceptable morbidity or mortality.[6]

  • Bladder carcinoma in situ, open-label study

    In 90 patients with recurrent carcinoma in situ after multiple intravesical therapies, six weekly instillations of 800 mg valrubicin produced a complete response in 19 patients (21%).[7]

Family and partners

Derived from: Doxorubicin

Worth knowing

  • The 1998 label warns that valrubicin induced a complete response in only about 1 in 5 patients with BCG-refractory carcinoma in situ and that delaying cystectomy could allow metastatic bladder cancer to develop.[5]
  • In the 90-patient study, 7 of the 19 complete responders remained disease-free at the last evaluation, with a median follow-up of 30 months.[7]
  • A 1999 review reports that valrubicin entered cells more rapidly than doxorubicin in vitro and that systemic absorption after intravesical use was minimal.[4]
  • The 2024 DailyMed label gives 'Initial U.S. Approval: 1981', which conflicts with the FDA approval letter of 25 September 1998 and the Drugs@FDA history; this profile uses the 1998 date.[1]

References

  1. Endo USA, Inc. Valstar (valrubicin) solution, for intravesical use: prescribing information (revised 07/2024). DailyMed, set ID e96f30a0-6662-11de-8f80-0002a5d5c51b, published 4 November 2024. Source
  2. Israel M, Modest EJ, Frei E 3rd. N-trifluoroacetyladriamycin-14-valerate, an analog with greater experimental antitumor activity and less toxicity than adriamycin. Cancer Res. 1975;35(5):1365-8. PubMed
  3. Israel M, Wilkinson PM, Pegg WJ, Frei E 3rd. Hepatobiliary metabolism and excretion of adriamycin and N-trifluoroacetyladriamycin-14-valerate in the rat. Cancer Res. 1978;38(2):365-70. PubMed
  4. Onrust SV, Lamb HM. Valrubicin. Drugs Aging. 1999;15(1):69-75; discussion 76. PubMedDOI
  5. U.S. Food and Drug Administration. Valstar (valrubicin) sterile solution for intravesical instillation: label, 1998 (NDA 020892, original approval). Source
  6. U.S. Food and Drug Administration. Approval letter, NDA 20-892, Valstar (valrubicin) sterile solution for intravesical instillation, 25 September 1998. Source
  7. Steinberg G, Bahnson R, Brosman S, Middleton R, Wajsman Z, Wehle M. Efficacy and safety of valrubicin for the treatment of Bacillus Calmette-Guerin refractory carcinoma in situ of the bladder. The Valrubicin Study Group. J Urol. 2000;163(3):761-7. PubMed
  8. U.S. Food and Drug Administration. Drugs@FDA: Approval date(s) and history, letters, labels, reviews for NDA 020892 (Valstar, valrubicin). Page read 2026-10-29. Source