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Other antitumour antibioticsIn useNatural product

Dactinomycin

Also known as Actinomycin D, Cosmegen

An actinomycin antibiotic made by Streptomyces parvullus, given by injection. The 2018 US label lists Wilms tumour, rhabdomyosarcoma, Ewing sarcoma, metastatic nonseminomatous testicular cancer and gestational trophoblastic neoplasia.

From discovery to approval

  1. 1940 · Earliest report found

    Reviews credit Waksman and Woodruff with first describing the actinomycins: a 2015 chapter dates this to 1940, and a 2009 review names actinomycin A as the first antibiotic isolated from actinomycetes. Neither review dates actinomycin D itself. The original papers are cited by title only.[2][3][4][5][6]

  2. 1964-12-10 · FDA regular

    Dactinomycin for injection (Cosmegen), NDA 050682, original approval, classed as a new molecular entity (Type 1) with priority review in the Drugs@FDA history. The original label and letter are not available there, so the indication at approval is not stated here; the 2018 label lists Wilms tumour, rhabdomyosarcoma, Ewing sarcoma, metastatic nonseminomatous testicular cancer, gestational trophoblastic neoplasia and regional perfusion. The type regular is an inference: no accelerated-approval wording was found.[7]

  3. 2018-08-15 · FDA regular

    Supplements 033 and 034 of NDA 050682: a modified dosing regimen for Ewing sarcoma (1250 micrograms per square metre intravenously once every 3 weeks for 51 weeks, in a multi-agent regimen, replacing 15 micrograms per kilogram daily for 5 days) and conversion of the package insert to the Physician's Labeling Rule format. The letter read is the replacement letter for S-034, which corrected a dosing error in the first letter; it keeps the effective date of 15 August 2018. The type regular is an inference: no accelerated-approval wording was found.[8]

How it works

The 2018 US label calls it a cytotoxic actinomycin that binds DNA and inhibits RNA synthesis, and says its cytotoxic activity was shown in animal models of several human cancers.[1]

Where it came from and why

The titles of Waksman and Woodruff's 1940 and 1941 papers place the work in the study of antibacterial substances made by soil microorganisms. The reviews cited do not say why actinomycin D was later tested in cancer; Farber's group reported clinical studies of it, with special reference to Wilms tumour, in 1960.

Cancers

  • Wilms tumour

    The US label lists Wilms tumour in adults and children as part of a multi-phase combination regimen. In the fourth National Wilms' Tumor Study, 1,687 children given vincristine with single-dose or divided-dose dactinomycin had similar two-year relapse-free survival (91.3% and 91.4% in the low-risk group).[9]

  • Rhabdomyosarcoma and Ewing sarcoma

    The 2018 US label lists both, each as part of a multi-phase combination chemotherapy regimen, in adults and children.[1]

  • Testicular cancer and gestational trophoblastic neoplasia

    The 2018 US label lists metastatic nonseminomatous testicular cancer in a multi-phase combination regimen, and gestational trophoblastic neoplasia in post-menarchal patients as a single agent or in combination.[1]

Worth knowing

  • A 2009 review calls actinomycin D the oldest microbial metabolite used in cancer therapy.[4]
  • A 2024 tribute to Sidney Farber says he introduced actinomycin D to treat Wilms tumour.[10]
  • In 2018 the US label for Cosmegen was converted to the Physician's Labeling Rule format and a new dosing regimen for Ewing sarcoma was added: 1250 micrograms per square metre once every 3 weeks for 51 weeks, within a multi-agent regimen.[8]
  • The 2024 generic dactinomycin injection label (Hisun) carries the same indications as the 2018 Cosmegen label, whereas Drugs@FDA lists the Cosmegen application itself as discontinued.[11]

On this site

References

  1. U.S. Food and Drug Administration. Cosmegen (dactinomycin for injection), prescribing information, NDA 050682 supplement 034 (action date 15 August 2018; Initial U.S. Approval 1964). Source
  2. Waksman SA, Woodruff HB. Bacteriostatic and Bactericidal Substances Produced by a Soil Actinomyces. Experimental Biology and Medicine. 1940;45(2):609-614. DOI
  3. Waksman SA, Woodruff HB. Actinomyces antibioticus, a New Soil Organism Antagonistic to Pathogenic and Non-pathogenic Bacteria. J Bacteriol. 1941;42(2):231-49. PubMedDOI
  4. Demain AL, Sanchez S. Microbial drug discovery: 80 years of progress. J Antibiot (Tokyo). 2009;62(1):5-16. PubMedDOI
  5. Weber GF. Drugs that Suppress Proliferation (section: DNA Damaging Drugs). In: Molecular Therapies of Cancer. Cham: Springer International Publishing; 2015. p. 113-162. doi:10.1007/978-3-319-13278-5_3. DOISource
  6. FARBER S, D'ANGIO G, EVANS A, MITUS A. Clinical studies on actinomycin D with special reference to Wilms' tumor in children. Ann N Y Acad Sci. 1960;89:421-5. PubMedDOI
  7. U.S. Food and Drug Administration. Drugs@FDA: Approval date(s) and history, letters, labels, reviews for NDA 050682 (Cosmegen, dactinomycin). Page read 2026-10-29. Source
  8. U.S. Food and Drug Administration. Supplement approval letter (replacement), NDA 050682/S-034, Cosmegen (dactinomycin for injection), Recordati Rare Diseases; effective approval date 15 August 2018. Source
  9. Green DM, Breslow NE, Beckwith JB, Finklestein JZ, Grundy PE, Thomas PR, et al. Comparison between single-dose and divided-dose administration of dactinomycin and doxorubicin for patients with Wilms' tumor: a report from the National Wilms' Tumor Study Group. J Clin Oncol. 1998;16(1):237-45. PubMedDOI
  10. Kumar Upadhyay A, Prakash A, Kumar A, Jena S, Sinha N, Sharma S. Dr. Sidney Farber (1903-1973): Founder of Pediatric Pathology and the Father of Modern Chemotherapy. Cureus. 2024;16(8):e68286. PubMedDOI
  11. DailyMed. Dactinomycin for injection, Hisun Pharmaceuticals USA, Inc. (ANDA207232), SPL set id 95d5c152-aa00-41e6-83e8-8df374a56447, version 8, effective 8 May 2024 (text read through the openFDA drug label API). Source