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The effect of topotecan in advanced intraocular retinoblastoma with manageable toxicity.

9540 Background: There is a need to identify new effective chemotherapeutic agents for the treatment of intraocular retinoblastoma (RB).


METHODS
An institutional protocol (RET5) for the study and treatment of patients with intraocular RB stratified patients into three groups according to laterality and stage of disease. The primary objective of RET5 was to estimate the response of window therapy for patients with bilateral RB in whom at least one eye was Reese-Ellsworth IV or V. Window therapy consisted of 2 courses of vincristine and topotecan (VT with G-CSF support). Patients with ≥ partial response received 3 more courses of VT alternating with 6 courses of vincristine and carboplatin. The topotecan dose started at 3 mg/m2/day, and was adjusted to attain a target systemic exposure of 140 ± 20 ng/ml*hr. Carboplatin was administered to achieve an area under the curve of 6.5 mg/ml/min. The dose of vincristine dose was 0.05 mg/kg if age at diagnosis < 12 months and 1.5mg/m2 if age at diagnosis > 12 months.


RESULTS
From 2/2005 until 6/2010, a total of 27 patients were treated VT window therapy. The median age at enrollment was 8.1 months (range, 0.7 to 22.1 months). Twenty-four of 27 patients (88.9%) responded to the VT window with a response rate 88.9% and a 95% Blyth-Still-Casella CI, 71.3%-96.9%. Hematologic toxicity in the form of grade 4 neutropenia (n=27), grade 3 anemia (n=19) and grade 3-4 thrombocytopenia (n=16) were observed during the VT window. Thirteen patients developed grade 3 non-hematologic toxicity. G-CSF support was added after treating 10 patients. Patients treated with GCSF (n=17) had a significant shorter duration of grade 4 neutropenia (median, 7 days) compared to patients without G-CSF (n=10) (median, 24 days) (Wilcoxon rank sum test p<0.0001).


CONCLUSIONS
Topotecan is an effective agent in the treatment of advanced intraocular RB. The use of GCSF alleviated toxicity, especially the duration of grade 4 neutropenia.