title: Topotecan and vincristine combination is effective against advanced bilateral intraocular retinoblastoma and has manageable toxicity.
abstract: BACKGROUND
  New, effective chemotherapeutic agents are needed for intraocular retinoblastoma.
  
  
  METHODS
  This institutional clinical trial sought to estimate the rate of response to 2 courses of vincristine and topotecan (VT) window therapy in patients with bilateral retinoblastoma and advanced disease (Reese-Ellsworth group IV or V) in at least 1 eye. The topotecan dose started at 3 mg/m(2) /day for 5 days and was adjusted to target a systemic exposure of 140 ± 20 ng/mL · hour. The vincristine dose was 0.05 mg/kg for patients <12 months of age and 1.5 mg/m(2) for those >12 months of age at diagnosis.
  
  
  RESULTS
  From February 2005 to June 2010, 27 patients received VT window therapy. Median age at enrollment was 8.1 months (range, 0.7-22.1 months). Twenty-four patients (88.9%) responded to window therapy (95% confidence interval = 71.3%-96.9%). Hematologic toxicity comprised grade 4 neutropenia (n = 27), grade 3 anemia (n = 19), and grade 3/4 thrombocytopenia (n = 16). Thirteen patients had grade 3 nonhematologic toxicity. Granulocyte colony-stimulating factor support was added after 10 patients had been treated, and it significantly reduced the duration of grade 4 neutropenia (median, 7 vs 24 days; P < .001). Pharmacokinetic studies showed rapid changes in topotecan clearance rates during the first year of life.
  
  
  CONCLUSIONS
  The combination of topotecan and vincristine is effective for the treatment of advanced intraocular retinoblastoma. Granulocyte colony-stimulating factor treatment alleviates the duration of grade 4 neutropenia. Appropriate topotecan starting doses for patients 0-3, 3-6, 6-9, 9-12, and >12 months of age are specified.
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. ibrahim.qaddoumi@stjude.org
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Qaddoumi
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Billups
authors.forename: Michael
authors.initials: M
authors.lastname: Tagen
authors.forename: Clinton F
authors.initials: CF
authors.lastname: Stewart
authors.forename: Jianrong
authors.initials: J
authors.lastname: Wu
authors.forename: Kathleen
authors.initials: K
authors.lastname: Helton
authors.forename: M Beth
authors.initials: MB
authors.lastname: McCarville
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Merchant
authors.forename: Rachel
authors.initials: R
authors.lastname: Brennan
authors.forename: Tammy M
authors.initials: TM
authors.lastname: Free
authors.forename: Vicki
authors.initials: V
authors.lastname: Given
authors.forename: Barrett G
authors.initials: BG
authors.lastname: Haik
authors.forename: Carlos
authors.initials: C
authors.lastname: Rodriguez-Galindo
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Wilson
mesh_terms: D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D008297:Male; D009503:Neutropenia / Q000139:chemically induced; D019572:Retinal Neoplasms / Q000188:drug therapy*; D012175:Retinoblastoma / Q000188:drug therapy*; D015996:Survival Rate; D013921:Thrombocytopenia / Q000139:chemically induced; D059004:Topoisomerase I Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D059004:Topoisomerase I Inhibitors; D016179:Granulocyte Colony-Stimulating Factor; D014750:Vincristine; D019772:Topotecan