Semi-synthetic derivative of podophyllotoxin, active against a number of tumors: germ cell neoplasms, small cell lung carcinoma and malignant lymphoma.
93 cases reported up to 1996.
3 deaths.
High incidence in children with Hodgkin’s disease.
Risk factors
Intravenous route.
Clinical manifestations

Hypotension, bronchospasm, facial flushing, exanthema, dyspnea, fever, chills, tachycardia, chest tightness, cyanosis, hypertension (rare).
Urticaria is uncommon.
Diagnostic methods
No in vivo or in vitro method is currently available for diagnosis.
Non specific histamine release.
The role of polysorbate 80 (Tween 80) used as an excipient in the parenteral formulation is doubtful.
Lowering of the infusion rate.
Continuing administration without modification (65% successful)
Premedication with antihistamines and/ or corticosteroids.


  1. Hoetelmans R.M., Schornagel J.H, ten Bokkel Huinink W.W, Beijnen J.H, "Hypersensitivity reactions to etoposide", Ann. Pharmacother, 1996; 30 (4): 367-71
  2. Hudson M.M, Weinstein H.J,Donaldson S.S, Greenwald C, Kun L, Tarbell N.J, Humphrey W.A, Rupp C, Marina N.M, Wilimas J, Link M.P, "Acute hypersensitivity reactions to etoposide in a VEPA regimen for Hodgkin’s disease", J. Clin. Oncol., 1993; 11 (6): 1080-4
  3. Kellie S.J, Crist W.M, Pui C.H, Crone M.E, Fairclough D.L, Rodman J.H, "Hypersensitivity reactions to epidophyllotoxins in children with acute lymphoblastic leukemia", Cancer. 1991; 67: 1070-5
  4. Eschalier A, Lavarenne J, Burtin C, Renoux M, Chapuy E, Rodriguez M, "Study of histamine release induced by acute administration of anti tumor agents in dogs", Cancer Chemother. Pharmacol., 1988; 21: 246-50

As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.