Etoposide, adverse effects

Myelosuppression is a dose-limiting adverse effect of etoposide and teniposide. Leukopenia is the most common adverse effect associated with oral and intravenous etoposide. Nadirs in neutrophil counts generally occur within 7-14 days. Severe forms following conventional etoposide doses can be expected in about 17% of patients. Thrombocytopenia occurs in 23% of etoposide-treated patients and about 9% are severe (counts below 50 X 10 /1). Leukopenia and thrombocytopenia occur... 

This mode of action is not unique since the natural product colchicine, from the autumn crocus Colchicum autumnale (once used as a treatment for gout), also binds to tubulin and disrupts microtubule assembly. It was never seriously considered as an anti-cancer drug owing to its low therapeutic index that is, the dose required to produce clinical benefit was not much greater than the dose causing serious adverse effects or even death. A third plant product with similar biological properties, podophyllotoxin from the American Mayapple, provided the stimulus for research that led to the discovery of another excellent anti-cancer drug - etoposide. 

Adverse effects of etoposide are nausea and vomiting, hair loss and bone marrow suppression. 

Etoposide is mostly excreted unchanged by the kidneys. The adverse effects of etoposide include nausea and vomiting, headache, weakness, paresthesia, hypotension, palpitation, tachycardia, bone marrow depression, leukopenia, thrombocytopenia, and reversible alopecia. 

The leukaemic cells in the bone marrow of a patient with acute T-lym-phocyte leukaemia were totally cleared when ciclosporin 8.3 mg/kg orally twice daily was given with etoposide 100 to 300 mg daily for 2 to 5 days, but the adverse effects were severe (mental confusion, renal and hepatic toxicity). The patient died from respiratory failure precipitated by a chest infection. ... 

Neurotoxicity occurs in under 1% of patients who receive teniposide or etoposide, and is more common after high dosages. Adverse nervous system effects, including headache, transient mental confusion, and vertigo, may be related to the blood alcohol concentration, since teniposide and etoposide formulations contain alcohol (103). 

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