To contribute to effective and safe outpatient treatment, we investiga
ted the metabolism of trofosfamide (Trofo) after oral administration.
We analyzed Trofo metabolism in 15 patients aged from 3 to 73 years wh
o were treated with 150 or 250 mg/m(2) Trofo in combination with etopo
side. Serum samples were collected with 13 patients after oral adminis
tration, and Trofo and its dechloroethylated metabolites were quantifi
ed by gas chromatography. Urine samples were collected from five patie
nts and analyzed by same method. Ifosfamide (Ifo) was the main metabol
ite in serum and urine (AUC(Trofo):AUC(Ifo) 1:13), whereas cyclophosph
amide (Cyclo) was formed in smaller amounts (AUC(Ifo):AUC(Cyclo) 18:1)
. Ifo and Cyclo were further oxidized in the chloroethyl side chains t
o form 2- and 3-dechloroethylifosfamide in varying quantities. The uri
nary excretion of Trofo and its dechloroethylated metabolites amounted
to about 10% of the total dose. Our results confirm former in vitro o
bservations about the metabolism of Trofo. The main side-chain metabol
ites Ifo and Cyclo can be further activated by oxidation and formation
of their respective phosphoramide mustards. Hence, Trofo is an intere
sting agent for oral chemotherapy.