title: Response of metastatic recurrent neuroblastoma to nitisinone: a modulator of tyrosine metabolism.
abstract: Nitisinone blocks the tyrosine pathway and may be effective in treating neuroblastoma. A 33-month-old male with heavily treated metastatic, recurrent, N-MYC amplified neuroblastoma received nitsinone (0.8 mg/kg/day escalated to 5.0 mg/kg/day). Dramatic tumor regression and resolution of pain without toxicity were observed. At 10 weeks, the tumor progressed. Nitisinone, low dose cyclophosphamide and doxorubicin subsequently produced a very good partial response. At 18 months the disease progressed. The child succumbed 21 months after starting nitisinone. Nitisinone produced an increase in tyrosine and catecholamine metabolite (HVA, VMA, and metanephrines) levels. Nitisinone may be a promising agent in metastatic neuroblastoma.
authors.affiliation: Pediatric Oncology, Roger Maris Cancer Center, Fargo, North Dakota 58122, USA. nathankobrinsky@meritcare.com
authors.forename: Nathan L
authors.initials: NL
authors.lastname: Kobrinsky
authors.forename: Diane E
authors.initials: DE
authors.lastname: Sjolander
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003512:Cyclohexanones / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D017809:Fatal Outcome; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009447:Neuroblastoma / Q000188:drug therapy* / Q000556:secondary; D009579:Nitrobenzoates / Q000009:adverse effects / Q000627:therapeutic use*; D012074:Remission Induction; D016896:Treatment Outcome; D014443:Tyrosine / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D003512:Cyclohexanones; D004791:Enzyme Inhibitors; D009579:Nitrobenzoates; D014443:Tyrosine; C077073:nitisinone