Neoadjuvant Carboplatin and Vincristine and Standard Local Ophthalmic Therapy in Treating Patients With Intraocular Retinoblastoma

PRIMARY OBJECTIVES:

I. 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 OBJECTIVES:

I. Determine the response rate after one course of chemoreduction (before standardized local ophthalmic therapy) in these patients.

II. Correlate response rate with event-free survival in patients treated with this regimen.

III. 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.

Inclusion criteria

• 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 in greatest dimension) confined to the retina, away from foveola and disc 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 not in Group A
• Tumor associated subretinal fluid < 3 mm from the tumor margin with no subretinal seeding
• Group E: Must have ≥ 1 of the following present:

• Tumor touching the lens
• Tumor anterior to anterior vitreous face involving ciliary body or anterior segment
• Diffuse infiltrating retinoblastoma
• Neovascular glaucoma
• Opaque media from hemorrhage
• Tumor necrosis with aseptic orbital cellulites
• Phthisis bulbi
• 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
• Performance status - ECOG 0-2
• Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
• AST or ALT < 2.5 times ULN for age
• Creatinine clearance (based on Schwartz formula) or radioisotope glomerular filtration rate ≥ 70mL/min/1.73 m^2
• No prior chemotherapy
• No other concurrent chemotherapy
• No prior radiotherapy
• No other concurrent radiotherapy, including intensity-modulated stereotactic, or proton beam radiotherapy
• Prior enucleation of one eye allowed provided the remaining eye is Group B
• No concurrent enucleation
• No prior local ophthalmic therapy for retinoblastoma
• No other prior therapy for retinoblastoma
• No local therapy during chemotherapy course 1