• Event-free survival at 2 years [ Designated as safety issue: No ]
  

• Use of nonprotocol chemotherapy at the patient level [ Designated as safety issue: No ]
  
• Enucleation and external beam radiotherapy (EBRT) at the patient and eye levels [ Designated as safety issue: No ]
  
• Response rate at patient and eye levels after the first course [ Designated as safety issue: No ]
  
• Event-free survival rate [ Designated as safety issue: No ]
  
• Toxicity [ Designated as safety issue: Yes ]
  

OBJECTIVES:

Primary

• Determine the 2-year event-free survival of patients with Group B intraocular retinoblastoma treated with neoadjuvant chemoreduction comprising carboplatin and vincristine and standardized local ophthalmic therapy.

Secondary

• Determine the response rate after one course of chemoreduction (before standardized local ophthalmic therapy) in these patients.
• Correlate response rate with event-free survival in patients treated with this regimen.
• Determine the incidence of toxic effects in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive chemoreduction comprising carboplatin IV over 60 minutes followed by vincristine IV over 1-2 minutes on day 1. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. After the first course of chemoreduction, patients undergo standardized local ophthalmic therapy comprising local laser therapy, cryotherapy, and/or radioactive plaque comprising iodine I 125 or ruthenium Ru 106.

Patients are followed every 3-4 weeks until there is no active tumor seen on a minimum of 3 ophthalmic exams under anesthesia, every 6-8 weeks until 3 years of age, every 4-6 months until 10 years of age, and then annually thereafter.

PROJECTED ACCRUAL: A total of 85 patients will be accrued for this study within 3.5 years.

DISEASE CHARACTERISTICS:

• Newly diagnosed Group B intraocular retinoblastoma meeting 1 of the following criteria:

  • Group B tumor(s) in 1 eye
  • Group B tumor(s) in both eyes
  • Group A tumor in 1 eye and Group B tumor(s) in the other eye
  • Group E tumor in 1 eye that has been enucleated and Group B tumor(s) in the remaining eye at the time of enucleation of the Group E tumor

• Defined by the International Classification System for Intraocular Retinoblastoma as follows:

  • Group A: Small tumors (≤ 3 mm) confined to the retina meeting the following criteria:

    • More than 3 mm from fovea
    • More than 1.5 mm from optic disk

  • Group B: Tumors more than 3 mm meeting the following criteria:

    • Confined to the retina in any location
    • Clear subretinal fluid ≤ 6 mm from tumor margin

  • Group E: Must have visual potential OR at least 1 of the following must be present:

    • Tumor in the anterior segment
    • Tumor in or on the ciliary body
    • Neovascular glaucoma
    • Vitreous hemorrhage obscuring the tumor of significant hyphema
    • Phthisical or pre-phthisical eye
    • Orbital cellulitis-like presentation
• Confirmation of diagnosis by CT scan or MRI of the brain and orbits AND an ophthalmologic evaluation under anesthesia within the past 3 weeks
• No choroidal and/or optic nerve invasion past the lamina cribosa
• No evidence of extraocular retinoblastoma clinically or by head and orbital MRI and/or CT scan
• No tumor present on histological exam at the cut end of the optic nerve for any Group E eye enucleated before study entry

PATIENT CHARACTERISTICS:

Age

• 5 and under

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST or ALT < 2.5 times ULN

Renal

• Creatinine clearance (based on Schwartz formula) or radioisotope glomerular filtration rate ≥ 70mL/min

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy
• No other concurrent radiotherapy, including intensity-modulated stereotactic, or proton beam radiotherapy

Surgery

• Prior enucleation of one eye allowed provided the remaining eye is Group B
• No concurrent enucleation

Other

• No prior local ophthalmic therapy for retinoblastoma
• No other prior therapy for retinoblastoma
• No local therapy during chemotherapy course 1