title: Retinoblastoma CSF metastasis cured by multimodality chemotherapy without radiation.
abstract: OBJECTIVE
  Cerebrospinal fluid (CSF) metastasis is the most difficult type of retinoblastoma metastasis to cure, even with bone marrow transplant. Most metastatic retinoblastoma cells express P-glycoprotein causing multidrug resistance (MDR). P-glycoprotein-rich blood vessels form blood-brain and blood-eye barriers, inhibit drug entry into central nervous system (CNS) and eyes. High-dose craniospinal radiation is too morbid for treatment of young children. To cure CSF metastasis without radiation, we designed an intensive multimodality chemotherapy regimen.
  
  
  METHODS
  After left eye enucleation, a 4-month-old boy with bilateral International Intraocular Retinoblastoma Classification Group E eyes and CSF metastasis was treated with 7-cycle high-dose carboplatin and etoposide, standard-dose vincristine, and high-dose/short-infusion cyclosporine to inhibit P-glycoprotein. Intraventricular drugs, non-substrate of P-glycoprotein (cytarabine), or less susceptible to MDR (topotecan), contributed to treatment of the metastasis. On achieving complete response, he was consolidated with supralethal-dosage carboplatin, etoposide, and cyclophosphamide, and his bone marrow rescued with autologous cord blood stem cells.
  
  
  RESULTS
  Following 1-cycle systemic chemotherapy and 2-dose intraventricular chemotherapy, the CSF metastasis cleared. The right eye tumor regressed completely. The patient remains in remission 8.3 years after diagnosis and 7.8 years post-transplant.
  
  
  CONCLUSIONS
  Intensive multimodality chemotherapy can cure CSF metastasis in retinoblastoma without incurring extreme morbidity from craniospinal radiation.
authors: Division of Hematology/Oncology, The Hospital for Sick Children, and The University of Toronto, Toronto, Ontario, Canada.
authors: Helen
authors: H
authors: Dimaras
authors: Elise
authors: E
authors: Héon
authors: Andrew
authors: A
authors: Budning
authors: John J
authors: JJ
authors: Doyle
authors: William
authors: W
authors: Halliday
authors: Brenda L
authors: BL
authors: Gallie
authors: Helen S L
authors: HS
authors: Chan
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D016543:Central Nervous System Neoplasms / Q000134:cerebrospinal fluid / Q000556:secondary / Q000628:therapy*; D002555:Cerebrospinal Fluid; D003131:Combined Modality Therapy; D036101:Cord Blood Stem Cell Transplantation; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D015353:Eye Enucleation; D006801:Humans; D007223:Infant; D008297:Male; D011379:Prognosis; D019572:Retinal Neoplasms / Q000134:cerebrospinal fluid / Q000473:pathology / Q000628:therapy*; D012175:Retinoblastoma / Q000134:cerebrospinal fluid / Q000556:secondary / Q000628:therapy*; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D003561:Cytarabine; D014750:Vincristine; D005047:Etoposide; D003520:Cyclophosphamide; D016190:Carboplatin