The podophyllotoxin derivatives etoposide and teniposide are active in the treatment of a variety of malignant conditions. Both represent chemical modifications of podophyllin, an extract of Podophyllum peltatum (May apple, mandrake, Indian apple, wild lemon, or duck's foot), a plant long used as a folk remedy and recognized in the 19th century to be effective in the treatment of cancer. While etoposide is active in the treatment of many cancers and is widely used, it has a number of limitations due to its lack of water solubility. Etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ) is a water-soluble prodrug of etoposide that is rapidly and completely converted to the parent compound after intravenous dosing. The pharmacokinetic profile of etoposide after treatment with either etoposide or etoposide phosphate is identical. Toxicity and clinical activity also are the same. Because etoposide phosphate is water soluble and can be made up to a concentration of 20 mg/mL, however, it can be given as a 5-minute bolus, in high doses in small volumes, and as a continuous infusion. Furthermore, it is not formulated with polyethylene glycol, polysorbate 80 (Tween; ICI Americas, Wilmington, DE), and ethanol, and does not cause acidosis when given at high doses. The easier-to-use etoposide phosphate represents an improved formulation of etoposide.