title: Hypersensitivity pneumonitis associated with the use of trofosfamide.
abstract: 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.
authors.affiliation: Medical Center II, Department of Oncology, Hematology, Rheumatology, Immunology, University of Tübingen, Germany.
authors.forename: H-G
authors.initials: HG
authors.lastname: Kopp
authors.forename: L
authors.initials: L
authors.lastname: Kanz
authors.forename: J T
authors.initials: JT
authors.lastname: Hartmann
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000542:Alveolitis, Extrinsic Allergic / Q000139:chemically induced* / Q000150:complications; D000971:Antineoplastic Combined Chemotherapy Protocols; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000378:metabolism; D003556:Cystitis / Q000139:chemically induced / Q000150:complications; D004334:Drug Administration Schedule; D005260:Female; D005269:Femur / Q000473:pathology; D005858:Germany; D006801:Humans; D007069:Ifosfamide / Q000009:adverse effects / Q000378:metabolism; D009325:Nausea / Q000139:chemically induced / Q000150:complications; D009362:Neoplasm Metastasis / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology; D018317:Nerve Sheath Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology; D010752:Phosphoramide Mustards / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism; D011239:Prednisolone / Q000008:administration & dosage / Q000627:therapeutic use; D011658:Pulmonary Fibrosis / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy; D014839:Vomiting / Q000139:chemically induced / Q000150:complications
chemical_list: D010752:Phosphoramide Mustards; D003520:Cyclophosphamide; D011239:Prednisolone; C003726:trofosfamide; D007069:Ifosfamide