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- Title
Topotecan and vincristine combination is effective against advanced bilateral intraocular retinoblastoma and has manageable toxicity.
- Authors
Qaddoumi, Ibrahim; Billups, Catherine A.; Tagen, Michael; Stewart, Clinton F.; Wu, Jianrong; Helton, Kathleen; McCarville, M. Beth; Merchant, Thomas E.; Brennan, Rachel; Free, Tammy M.; Given, Vicki; Haik, Barrett G.; Rodriguez-Galindo, Carlos; Wilson, Matthew W.
- 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.
- Subjects
RETINOBLASTOMA; TOPOTECAN; VINCRISTINE; COMBINATION drug therapy; DRUG efficacy; DRUG toxicity; PHARMACOKINETICS; THERAPEUTICS
- Publication
Cancer (0008543X), 2012, Vol 118, Issue 22, p5663
- ISSN
0008-543X
- Publication type
Article
- DOI
10.1002/cncr.27563