Teniposide

From discovery to approval

1. 1970 · Earliest report found

   The label calls teniposide a semisynthetic derivative of podophyllotoxin that differs from etoposide by a thenylidene group. The earliest paper found is Stähelin's 1970 report on VM 26 as a podophyllum compound with a new mechanism of action (title only).^[2][3][1]

2. 1992-07-14 · FDA regular

   Teniposide injection (Vumon), NDA 020119, original approval, classed as a new molecular entity (Type 1) with priority review and orphan status in the Drugs@FDA history. The original label and letter are not available there, so the indication at approval is not stated here; the 2015 label lists induction therapy for refractory childhood acute lymphoblastic leukaemia. The type regular is an inference: no accelerated-approval wording was found.^[4]

How it works

The label says it is a phase-specific drug acting in late S or early G2, causing single- and double-stranded DNA breaks, and that its mechanism appears related to inhibition of type II topoisomerase, since it does not intercalate into DNA.^[1]

Where it came from and why

A 1998 history says that in the 1950s scientists began a search for a more effective podophyllotoxin derivative, which led to this class. The papers cited do not state why teniposide was chosen for development.

Cancers

• Childhood acute lymphoblastic leukaemia

  The 2015 US label lists induction therapy in refractory childhood acute lymphoblastic leukaemia. A 1994 review describes combining teniposide with cytarabine, first in refractory disease and then in front-line therapy.^[5]

• Lymphomas and solid tumours

  A 1972 clinical screening report said VM26 induced apparently complete remissions and pronounced though incomplete regressions in Hodgkin's disease, reticulosarcoma and bladder cancer, and incomplete regressions in lymphosarcoma.^[6]

Worth knowing

• A 1975 report of 39 children with cancer who had failed conventional treatment, given teniposide or etoposide, saw definite clinical responses in nine of 29 with acute leukaemia and none in ten with solid tumours; the authors described these as the first results reported with both drugs in childhood cancer.^[7]
• A 2006 review says leukopenia and thrombocytopenia occur in 65% and 80% of patients after conventional doses of teniposide.^[8]
• The authors of a 1994 review of epipodophyllotoxins in childhood cancer reported a projected overall "cure rate" of about 75% in their last acute lymphoblastic leukaemia trial and attributed it in part to early use of epipodophyllotoxins.^[5]

References

1. U.S. Food and Drug Administration. Teniposide injection (Vumon), prescribing information, NDA 020119 supplement 013 (action date 2 March 2015). Source
2. Stähelin H. 4'-Demethyl-epipodophyllotoxin thenylidene glucoside (VM 26), a podophyllum compound with a new mechanism of action. Eur J Cancer (1965). 1970;6(4):303-11. PubMedDOI
3. Hande KR. Etoposide: four decades of development of a topoisomerase II inhibitor. Eur J Cancer. 1998;34(10):1514-21. PubMedDOI
4. U.S. Food and Drug Administration. Drugs@FDA: Approval date(s) and history, letters, labels, reviews for NDA 020119 (Vumon, teniposide). Page read 2026-10-29. Source
5. Rivera GK, Pui CH, Santana VM, Pratt CB, Crist WM. Epipodophyllotoxins in the treatment of childhood cancer. Cancer Chemother Pharmacol. 1994;34 Suppl:S89-95. PubMedDOI
6. Clinical screening of epipodophyllotoxin VM26 in malignant lymphomas and solid tumours [no author listed]. Br Med J. 1972;2(5816):744-8. PubMed 4556544. PubMed
7. Rivera G, Avery T, Pratt C. 4'-demethylepipodophyllotoxin 9-(4,6-o-2-thenylidene-beta-D-glucopyranoside) (NSC-122819; VM-26) and 4'-demethylepipodophyllotoxin 9-(4.6-0-ethylidene-beta-D-glucopyranoside) (NSC-141540; VP-16-213) in childhood cancer: preliminary observations. Cancer Chemother Rep. 1975;59(4):743-9. PubMed
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