Good long term results of multidrug resistance-reversal chemotherapy for advanced intraocular retinoblastoma without upfront elective consolidation radiation
Authors: Helen S. L. Chan, Elise Heon, Nesan Bandali, Andrew S. Budning, Brenda L. Gallie
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

4732 

PURPOSE: Radiation increases secondary cancer risk, and cosmetic complications in heritable retinoblastoma patients. In 2 multidrug resistance-reversal chemotherapy trials without upfront radiation, we treated consecutively, 66 Groups A-D eyes in 43 newly diagnosed patients (Trial 1), and 30 such eyes in 19 patients (Trial 2). We report mature results for advanced Groups C/D eyes. METHODS: In Trial 1 since 1991, we treated 13 D eyes (11 patients) and 18 C eyes (16 patients), with carboplatin (22 mg/kg), etoposide (9 mg/kg) and vincristine (0.05 mg/kg), with cyclosporine (33 mg/kg/day for 2 days as 3-hour infusions), no Neupogen support, and only focal therapy consolidation. In Trial 2 since 2000, we treated 14 Group D eyes (10 patients) and 7 Group C eyes (7 patients), with higher dose carboplatin (28 mg/kg) and etoposide (12 mg/kg), the same vincristine and cyclosporine dosages, with Neupogen support, and again only focal therapy consolidation. For both trials, radiation or enucleation for recurrent disease was considered treatment failure. RESULTS: For Trial 1, eye event-free rates (median followup 8.5 years) were 23% for Group D (3/13) and 78% for Group C (14/18). Ten Group D eyes (9 patients) failed: 6 had one eye enucleated and retained the other eye, 1 had remaining eye enucleated, and 1 had both while 1 had remaining eye radiated. Four Group C eyes (4 patients) failed: 2 had one eye enucleated and retained the other eye, and 2 had remaining eye radiated but second enucleation when this failed. For Trial 2, eye event-free rates (median followup 3 years) were 57% for Group D (8/14) and 71% for Group C (5/7). Six Group D eyes (5 patients) failed: 3 had one eye enucleated and retained the other eye, 1 had radiation to one eye and enucleation of the other eye, and 1 had radiation to remaining eye. Two Group C eyes (2 patients) failed: both had one eye enucleated and retained the other eye. Hematopoietic toxicity rates (fever/neutropenia admission 16.7%, sepsis 0%, blood transfusion 15.6%, platelet transfusion 18.6%) for the Neupogen-supported higher-dose Trial 2 were not significantly different (P = 0.88; 2-sided t-test of myelotoxicity) from toxicity rates (16.3%, 1.5%, 5%, 8%) for standard-dose Trial 1. CONCLUSIONS: With higher dose cyclosporine-modulated chemotherapy in Trial 2, no child lost both eyes, while 100% with Group C eyes and 86% with Group D eyes avoided radiation. Although followup is shorter with Trial 2, the outcomes indicate that most children can avoid radiation while retaining vision in one or both eyes. Higher dosages of carboplatin and etoposide with cyclosporine have acceptable and reversible hematopoietic toxicity, and appear to improve success rates for the highest risk Group D eyes. By reserving radiation only for relapses in their one remaining eye, children with Groups C/D eyes avoided serious long term tumorigenic and cosmetic morbidity.