Hypersensitivity pneumonitis associated with the use of trofosfamide

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Trofosfamide (Ixoten; Baxter Oncology, Germany) is an alkylating agent that, as with other oxazaphosphorine derivatives, has to be activated by hepatic cytochrome P450 oxidases. The bioavailability is nearly 100% after oral application, and the main metabolites are 4-hydroxytrofosfamide, and 4-hydroxyifosfamide. The main side-chain metabolites ifosfamide and cyclophosphamide can be further activated by oxidation and formation of their respective phosphoramide mustards. Oral continuous low-dose therapy has been the most widely used schedule. The toxicity profile consists mainly of dose-dependent hematotoxicity and, rarely, hemorrhagic cystitis. Nausea and vomiting are infrequently seen. Higher grades of nephrotoxicity or neurotoxicity—side-effects that typically limit the use of ifosfamide—have not been reported with low-dose continuous trofosfamide treatment. We report herein a case of a 83-year-old female patient with a disseminated malignant peripheral nerve sheath tumor treated with trofosfamide developing pulmonal toxicity. To our knowledge, this is the first reported case of exogenous allergic alveolitis after exposure to this drug.

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