Inclusion Criteria:

   - Patient must be < 18 years of age at enrollment

   - Patient must have newly diagnosed intraocular (localized) retinoblastoma and meet one
   of the following criteria:

      - Unilateral Group D retinoblastoma with vitreous seeding; OR

      - Bilateral retinoblastoma with worst eye Group D, with vitreous seeding present
      and the contralateral eye is Group A-C; OR

      - Bilateral retinoblastoma with one Group D eye with vitreous seeding and one Group
      E eye where the Group E eye has been enucleated prior to any therapy. Note
      exclusion for high-risk features

   - Patients must have a performance status corresponding to Eastern Cooperative Oncology
   Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and
   Lansky for patients =<16 years of age

   - Peripheral absolute neutrophil count (ANC) >= 750/uL (must be performed within 7 days
   prior to enrollment unless otherwise indicated)

   - Platelet count >= 75,000/uL (transfusion independent) (must be performed within 7 days
   prior to enrollment)

   - A serum creatinine based on age/gender as follows (must be performed within 7 days
   prior to enrollment; must be repeated prior to the start of protocol therapy if > 7
   days have elapsed from their most recent prior assessment):

      - 1 month to < 6 months = 0.4 (male and female)

      - 6 months to < 1 year = 0.5 (male and female)

      - 1 to < 2 years = 0.6 (male and female)

      - 2 to < 6 years = 0.8 (male and female)

      - 6 to < 10 years = 1.0 (male and female)

      - 10 to < 13 years = 1.2 (male and female)

      - 13 to < 16 years = 1.5 (male) and 1.4 (female)

      - >= 16 years = 1.7 (male) and 1.4 (female) OR - a 24-hour urine Creatinine
      clearance >= 70 mL/min/1.73 m^2 OR - a glomerular filtration rate (GFR) >= 70
      mL/min/1.73 m^2. GFR must be performed using direct measurement with a nuclear
      blood sampling method OR direct small molecule clearance method (iothalamate or
      other molecule per institutional standard)

      - Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates
      are not acceptable for determining eligibility

         - For patients < 1 month of age, serum creatinine levels must be < 1.5 x the
         treating institution's creatinine upper limit of normal (ULN) for patients <
         1 month of age or the creatinine clearance or radioisotope GFR must be >= 70
         mL/min/1.73 m^2

   - Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (must be performed within
   7 days prior to enrollment; must be repeated prior to the start of protocol therapy if
   > 7 days have elapsed from their most recent prior assessment)

   - Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135
   U/L (must be performed within 7 days prior to enrollment; must be repeated prior to
   the start of protocol therapy if > 7 days have elapsed from their most recent prior
   assessment)

      - Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the
      value of 45 U/L

Exclusion Criteria:

   - Patients with evidence of metastatic or extra-orbital spread

   - Patients must not have an invasive infection at time of protocol entry

   - Patients must not have had any prior anti-cancer therapy to the study eye(s),
   including focal, local, or systemic chemotherapy or radiation therapy

      - Note: A study eye is defined as being Group D with vitreous seeding. Patients may
      have had enucleation of one eye as long as the remaining eye is Group D with
      vitreous seeds

   - Patients with no reasonable expectation for any useful vision in the Group D eye as
   determined by the treating physician

   - Patients with bilateral disease who undergo enucleation of a Group E eye prior to
   initiation of therapy and show evidence of high-risk histopathology features in the
   enucleated eye. High-risk histopathology includes choroid involvement >= 3 mm, post
   lamina optic nerve involvement, full thickness scleral invasion or optic nerve
   invasion to the cut end

   - Female patients who are pregnant since fetal toxicities and teratogenic effects have
   been noted for several of the study drugs. A pregnancy test is required for female
   patients of childbearing potential

   - Lactating females who plan to breastfeed their infants

   - Sexually active patients of reproductive potential who have not agreed to use an
   effective contraceptive method for the duration of their study participation

   - All patients and/or their parents or legal guardians must sign a written informed
   consent

   - All institutional, Food and Drug Administration (FDA), and National Cancer Institute
   (NCI) requirements for human studies must be met