Abstract 767: Cyclosporin-modulated intensified-dosage chemotherapy for saving eyes with Group D intraocular retinoblastoma
Authors: Helen S.L. Chan, Elise Héon, A Linn Murphree, Paulita P. Astudillo, Helen Dimaras, Furqan Shaikh, Brenda L. Gallie
Journal: Cancer Research (2014)

Abstract PURPOSE: Cyclosporin (CSA) inhibits the multidrug resistance P-glycoprotein. Since 2000, we tested increased carboplatin and increased etoposide dosages in a cyclosporin-modulated carboplatin-etoposide-vincristine protocol, followed by focal laser/cryotherapy consolidation, to avoid elective radiation of newly diagnosed retinoblastoma (RB) patients, since radiation increases the secondary cancer risk in patients with heritable RB. We report the results for International Classification Groups A, B, C and D intraocular eyes (Ophthalmol Clinic North Am 2005; 18:41-53). METHOD: When Neupogen support became available, we increased the predominantly myelotoxic carboplatin to 28 mg/kg (from 18.7 mg/kg in our previous trial) and etoposide to 12 mg/kg (from 7.7 mg/kg in our previous trial), but kept the predominantly neurotoxic vincristine unchanged at 0.05 mg/kg, modulated by the same cyclosporin schedule (33 mg/kg over 3 hours on each of the 2 days per cycle). We treated 34 eyes in 23 patients: 2 A eyes, 11 B eyes, 6 C eyes and 15 D eyes. This report focuses only on the most difficult to save Group D eyes, and compares results with a non-cyclosporin carboplatin (26 mg/kg) and etoposide (10 mg/kg), vincristine (0.05 mg/kg) regimen. Radiation or enucleation for recurrence was considered failure. RESULTS: We report the long-term results of 15 Group D eyes in 10 patients, at mean followup of 11.1 years and median followup of 10.8 years (range 5.7-13.4 years). Eye event-free rate was 53% for Group D (8/15) eyes. Seven D eyes failed, and 6 were enucleated and 1 radiated. No child lost both eyes. Toxicity rates were acceptable with 15.7% fever-and-neutropenia, 0.7% bacterial sepsis, 9.7% blood transfusion and 27.6% platelet transfusion, and no long-term renotoxicity or ototoxicity. In comparison, at mean followup of 4.5 years (range 0.4-9.8 years), in a previously reported (Pediatr Blood Cancer 2013; 60:688-693) non-cyclosporin regimen, the non-radiation eye event-free rate was 47% for Group D (26/55) eyes, with 5 eyes enucleated, and 24 eyes radiated (19 irradiated eyes retained; 5 irradiated eyes required enucleation). CONCLUSION: This cyclosporin-modulated intensified-dosage protocol was well-tolerated, with a non-radiation eye salvage rate of 53%, and 60% overall if the one irradiated but retained eye was included, in the most difficult to save Group D eyes. No child lost both eyes, and most avoided radiation. This same protocol is being tested in a multicenter trial. Citation Format: Helen S.L. Chan, Elise Héon, A Linn Murphree, Paulita P. Astudillo, Helen Dimaras, Furqan Shaikh, Brenda L. Gallie. Cyclosporin-modulated intensified-dosage chemotherapy for saving eyes with Group D intraocular retinoblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 767. doi:10.1158/1538-7445.AM2014-767