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Topoisomerase inhibitorsIn useDerivative of an earlier drug

Etoposide

Also known as VP-16, VP 16-213, VePesid

A semisynthetic derivative of podophyllotoxin given by injection or by mouth. The US label lists refractory testicular tumours and first-line small cell lung cancer, both in combination with other chemotherapy.

From discovery to approval

  1. 1973 · Earliest report found

    The label calls etoposide a semisynthetic derivative of podophyllotoxin. The earliest paper found that names it is Stähelin's 1973 report of the activity of VP 16-213 in experimental tumours (title only).[2][3][4][1]

  2. 1983-11-10 · FDA regular

    Etoposide injection (Vepesid), NDA 018768, 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 current generic label lists refractory testicular tumours and first-line small cell lung cancer. The type regular is an inference: no accelerated-approval wording was found.[5]

How it works

The label says the predominant effect appears to be DNA strand breaks through interaction with DNA topoisomerase II or formation of free radicals, with the main effect at the G2 phase in mammalian cells; it does not interfere with microtubule assembly.[1]

Where it came from and why

A 1998 history says podophyllin-containing materials had been used as folk medicines for centuries, and that in the 1950s scientists began a search for a more effective podophyllotoxin derivative. The papers cited do not state the properties that led to the choice of etoposide.

Cancers

  • Small cell lung cancer

    In a phase II study of 47 patients with small cell carcinoma of the bronchus, 24 had a true objective response; median survival was 225 days. The US label lists first-line treatment with other chemotherapy.[6]

  • Testicular and other germ cell tumours

    In a randomised trial of 261 men with disseminated germ-cell tumours, etoposide replaced vinblastine in a cisplatin and bleomycin regimen. The US label lists refractory testicular tumours.[7]

Worth knowing

  • A 1998 history says podophyllin-containing materials have been used as folk medicines for centuries.[3]
  • In the 1987 randomised trial, among 244 evaluable patients, 74% of those given the vinblastine regimen and 83% of those given the etoposide regimen became disease-free with or without subsequent surgery (not significant); the etoposide regimen caused substantially fewer paresthesias, abdominal cramps and myalgias.[7]
  • A 2006 review says hypersensitivity reactions are more common with etoposide and teniposide than with etoposide phosphate, because the first two are formulated with sensitising solubilisers.[8]
  • In the 1978 phase II study of 47 patients with small cell carcinoma of the bronchus, three patients were alive and well at more than 27 months; side effects were minimal, and alopecia was common.[6]

On this site

References

  1. DailyMed. Etoposide injection, BluePoint Laboratories (ANDA074529), SPL set id 0dddbe44-b4f4-431f-9011-8a54abbd4cbf, version 2, effective 20 May 2026 (text read through the openFDA drug label API). Source
  2. Stähelin H. Activity of a new glycosidic lignan derivative (VP 16-213) related to podophyllotoxin in experimental tumors. Eur J Cancer (1965). 1973;9(3):215-21. PubMedDOI
  3. Hande KR. Etoposide: four decades of development of a topoisomerase II inhibitor. Eur J Cancer. 1998;34(10):1514-21. PubMedDOI
  4. Stähelin HF, von Wartburg A. The chemical and biological route from podophyllotoxin glucoside to etoposide: ninth Cain memorial Award lecture. Cancer Res. 1991;51(1):5-15. PubMed
  5. U.S. Food and Drug Administration. Drugs@FDA: Approval date(s) and history, letters, labels, reviews for NDA 018768 (Vepesid, etoposide). Page read 2026-10-29. Source
  6. Tucker RD, Ferguson A, Van Wyk C, Sealy R, Hewitson R, Levin W. Chemotherapy of small cell carcinoma of the lung with V.P. 16-213. Cancer. 1978;41(5):1710-4. PubMedDOI
  7. Williams SD, Birch R, Einhorn LH, Irwin L, Greco FA, Loehrer PJ. Treatment of disseminated germ-cell tumors with cisplatin, bleomycin, and either vinblastine or etoposide. N Engl J Med. 1987;316(23):1435-40. PubMedDOI
  8. Hartmann JT, Lipp HP. Camptothecin and podophyllotoxin derivatives: inhibitors of topoisomerase I and II - mechanisms of action, pharmacokinetics and toxicity profile. Drug Saf. 2006;29(3):209-30. PubMedDOI