Topotecan and vincristine combination is effective against advanced bilateral intraocular retinoblastoma and has manageable toxicity

Ibrahim Qaddoumi, Catherine A. Billups, Michael Tagen, Clinton F. Stewart, Jianrong Wu, Kathleen Helton, M. Beth McCarville, Thomas E. Merchant, Rachel Brennan, Tammy M. Free, Vicki Given, Barrett G. Haik, Carlos Rodriguez-Galindo, Matthew W. Wilson

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

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/m2/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/m2 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.

Original languageEnglish
Pages (from-to)5663-5670
Number of pages8
JournalCancer
Volume118
Issue number22
DOIs
StatePublished - Nov 15 2012

Keywords

  • first year of life
  • pharmacokinetic
  • retinoblastoma
  • topotecan
  • toxicity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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