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

Authors

  • Ibrahim Qaddoumi MD, MS,

    Corresponding author
    1. Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee
    2. Department of Pediatrics, University of Tennessee Health Sciences Center, Memphis, Tennessee
    • St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678
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    • Fax: (901) 595-3122

  • Catherine A. Billups MS,

    1. Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee
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  • Michael Tagen PhD,

    1. Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee
    Current affiliation:
    1. Discovery Medicine and Clinical Pharmacology, Bristol-Myers Squibb, Princeton, New Jersey.
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  • Clinton F. Stewart PharmD,

    1. Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee
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  • Jianrong Wu PhD,

    1. Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee
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  • Kathleen Helton MD,

    1. Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee
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  • M. Beth McCarville MD,

    1. Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee
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  • Thomas E. Merchant DO, PhD,

    1. Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee
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  • Rachel Brennan MD,

    1. Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee
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  • Tammy M. Free CRRP,

    1. Department of Cancer Center Administration, St. Jude Children's Research Hospital, Memphis, Tennessee
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  • Vicki Given CRA-RN,

    1. Department of Cancer Center Administration, St. Jude Children's Research Hospital, Memphis, Tennessee
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  • Barrett G. Haik MD,

    1. Department of Surgery, St. Jude Children's Research Hospital, Memphis, Tennessee
    2. Department of Ophthalmology (Hamilton Eye Institute), University of Tennessee Health Sciences Center, Memphis, Tennessee
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  • Carlos Rodriguez-Galindo MD,

    1. Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee
    2. Department of Pediatrics, University of Tennessee Health Sciences Center, Memphis, Tennessee
    Current affiliation:
    1. Dana-Farber Children's Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts.
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  • Matthew W. Wilson MD

    1. Department of Surgery, St. Jude Children's Research Hospital, Memphis, Tennessee
    2. Department of Ophthalmology (Hamilton Eye Institute), University of Tennessee Health Sciences Center, Memphis, Tennessee
    3. Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee
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  • This work was presented in part at the annual meeting of the American Academy of Ophthalmology, October 2009, San Francisco, CA; the American Society of Clinical Oncology, June 2011, Chicago, IL; and at the International Society of Ocular Oncology, November 2011; Buenos Aires, Argentina.

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. Cancer 2012. © 2012 American Cancer Society.

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