PRIMARY OBJECTIVES: I. Determine the event-free survival at 12 months of pediatric patients' eyes with group D intraocular retinoblastoma treated with systemic chemotherapy comprising vincristine, carboplatin, and etoposide, subtenon carboplatin, and local ophthalmic therapy. (Event defined for each eye individually as needed for nonprotocol therapy including nonprotocol chemotherapy, enucleation or any external-beam radiation) SECONDARY OBJECTIVES: I. Determine the event-free survival at 12 months of pediatric patients' eyes with group C retinoblastoma treated with systemic chemotherapy comprising carboplatin, etoposide, vincristine, subtenon carboplatin, and local ophthalmic therapy. II. Determine the acute and long-term toxic effects of these regimens in these patients, including visual outcome and incidence of secondary malignancies. III. Determine the patterns of failure in patients treated with these regimens, in terms of vitreous vs retinal vs both as sites of recurrence. IV. Determine predictors of failure including findings at the on study examination under anesthesia and response status after six courses of chemotherapy. V. Determine the percentage of group C and D eyes separately that can be preserved without enucleation after failing protocol therapy. OUTLINE: This is a multicenter study. Patients receive vincristine IV over 1 minute on day 1 and carboplatin IV over 1 hour and etoposide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 3 and continuing until blood counts recover. Patients receive subtenon carboplatin to each group C or D eye on day 0 or 1 prior of courses 2-4 only. Treatment repeats every 28 days for 6 courses in the absence of occurrence of extraocular retinoblastoma or a second malignancy. Beginning with course 3 of systemic chemotherapy, patients undergo local ophthalmic therapy comprising local laser and/or cryotherapy on day 1. Patients are followed with ophthalmology exams every 4-12 weeks until 3 years of age, every 6 months until 5 years of age, and then annually for up to 10 years.
Inclusion Criteria: * Diagnosis of bilateral retinoblastoma with at least 1 eye group C or D intraocular retinoblastoma by ophthalmologic examination, defined by the International Classification System for Intraocular Retinoblastoma as the following: * Group C: Discrete localized disease with minimal subretinal and/or vitreous seeding * Subretinal fluid, without prior or concurrent seeding, involving ≤ one quarter of the retina * Local fine vitreous seeding may be present close to discrete tumor * Local subretinal seeding \< 3 mm from tumor * Group D: Diffuse disease with significant vitreous and/or subretinal seeding * Tumor(s) may be massive or diffuse * Subretinal fluid, without prior or concurrent seeding, involving up to total retinal detachment * Diffuse or massive vitreous disease may include "greasy" seeds or avascular tumor masses * Diffuse subretinal seeding may include subretinal plaques or tumor nodules * Prior enucleation of 1 eye allowed provided the remaining eye is group C or D * No tumor present on histologic examination at the cut end of the optic nerve on any eye enucleated prior to study entry * Evidence of choroidal and/or optic nerve invasion past the lumina cribrosa is allowed * No extraocular retinoblastoma clinically or by MRI of brain and orbits with and without gadolinium or CT scan with and without contrast of brain and orbits * No evidence of systemic metastases by bone marrow, lumbar puncture, bone scan, and/or any other additional test * Performance status - Karnofsky 50-100% (over 16 years of age) * Performance status - Lansky 50-100% (16 and under) * Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age * AST and ALT \< 2.5 times ULN for age * Creatinine adjusted according to age as follows: * No greater than 0.4 mg/dL (≤ 5 months) * No greater than 0.5 mg/dL (6 months -11 months) * No greater than 0.6 mg/dL (1 year-23 months) * No greater than 0.8 mg/dL (2 years-5 years) * No greater than 1.0 mg/dL (6 years-9 years) * No greater than 1.2 mg/dL (10 years-12 years) * No greater than 1.4 mg/dL (13 years and over \[female\]) * No greater than 1.5 mg/dL (13 years to 15 years \[male\]) * No greater than 1.7 mg/dL (16 years and over \[male\]) * Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min/1.73m\^2 * Not pregnant or nursing * Fertile patients must use effective contraception * Negative pregnancy test in postmenarchal females * No prior chemotherapy * No other concurrent chemotherapy * No prior radiotherapy * No other concurrent radiotherapy
is designated in this study