Combination Chemotherapy and Melphalan in Treating Younger Patients with Newly Diagnosed Advanced Intra-Ocular Retinoblastoma

Inclusion Criteria

• Intraocular retinoblastoma not previously treated with systemic chemotherapy, radiation therapy, or IA therapy; local retinal therapy such as laser photocoagulation and cryotherapy will be permitted
• Unilateral or bilateral retinoblastoma (RB) patients are eligible
• Patients will be registered on study based on the local exam under anesthesia (EUA) done for diagnostic purposes prior to study entry; the EUA done at study entry should be done within 14 days prior to study entry
• Patients may have had enucleation of one eye, as long as the remaining eye meets the eligibility criteria
• For unilateral retinoblastoma * Group A eye that has failed local therapy * Group B eye that has failed local therapy * Group C eye that has failed local therapy * Group D eye * Group E eye that is not buphthalmic, is not planned for enucleation after first cycle of chemotherapy, and is in a child less than 1 year of age
• For bilateral retinoblastoma * Group A and Group A eyes that have failed local therapy * Group A and Group B eyes that have failed local therapy * Group A and Group C eyes * Group A and Group D eyes * Group A and Group E eyes in which the Group E eye is not planned for enucleation after first cycle of chemotherapy * Group B and Group B eyes that have failed local therapy * Group B and Group C eyes * Group B and Group D eyes * Group B and Group E eyes in which the Group E eye is not planned for enucleation after first cycle of chemotherapy * Group C and Group C eyes * Group C and Group D eyes * Group C and Group E eyes even if early enucleation is planned for the Group E eye * Group D and Group D eyes * Group D and Group E eyes even if early enucleation is planned for the Group E eye * Group E and Group E eyes if at least one eye is not planned for enucleation
• Adequate renal function defined as: creatinine clearance or radioisotope glomerular filtration rate (GFR) 70 mL/min/1.73 m^2 OR a serum creatinine based on age and gender as follows: * Maximum serum creatinine (mg/dL) ** 1 month to < 6 months of age - 0.4 mg/dL (male), 0.4 mg/dL (female) ** 6 months to < 1 year of age - 0.5 mg/dL (male), 0.5 mg/dL (female) ** 1 to < 2 years of age - 0.6 mg/dL (male), 0.6 mg/dL (female) ** 2 to < 6 years of age - 0.8 mg/dL (male), 0.8 mg/dL (female) ** 6 to < 10 years of age - 1.0 mg/dL (male), 1.0 mg/dL (female) ** 10 to < 13 years of age - 1.2 mg/dL (male), 1.2 mg/dL (female) ** 13 to < 16 years of age - 1.5 mg/dL (male), 1.4 mg/dL (female) ** >= 16 years of age - 1.7 mg/dL (male), 1.4 mg/dL (female) *** The threshold creatinine values in this table were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the Centers for Disease Control and Prevention (CDC)
• Absolute neutrophil count > 1000/microliter
• Platelet count > 100,000/microliter
• Total bilirubin less than or equal to 1.5 x upper limit of normal (ULN) for age
• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 5 x upper limit of normal (ULN) for age
• Adequate coagulation system defined as an international normalized ratio (INR) of less than 1.4 and a partial thromboplastin time (PTT) of less than 34
• Women and men of child-bearing potential must agree to use adequate contraception such as hormonal or barrier method of birth control or abstinence prior to study entry and for the duration of study participation; should the subject or the subject’s partner become pregnant or suspect pregnancy while on protocol therapy, the treating physician must be informed immediately

Exclusion Criteria

• Any evidence of extraocular retinoblastoma clinically or by magnetic resonance imaging (MRI) of brain and orbits with and without gadolinium; MRI may be done within 21 days prior to study entry * Evidence of systemic metastases on bilateral bone marrow, lumbar puncture, bone scan (or fludeoxyglucose F-18 [FDG] positron emission tomography [PET] scan), and/or any other additional tests done at study entry; (Note: these tests are required only with specific indications for required observations)
• Patients who have previously been treated with chemotherapy (with the exception of local retinal therapy such as laser photocoagulation and cryotherapy) radiation therapy, or intra-arterial therapy
• Eyes with tumors that are amenable to local therapy with laser or cryotherapy without threat to vision
• Any technical factor that would prohibit use of catheterization of the ophthalmic artery (e.g., small for age infant, untreatable allergy to contrast)
• Abnormal cerebral vasculature noted on magnetic resonance (MR) angiography that would increase the risk of the procedure, including but not limited to an incomplete circle of Willis; other abnormalities that are less severe than an incomplete circle of Willis will be reviewed by the study chair in consultation with a neuro-interventional radiologist
• Any serious ongoing condition, such as an untreated infection or organ dysfunction
• Patients receiving any medications or substances that are inhibitors or inducers of CYP450 enzyme(s) are ineligible
• Pregnant women are excluded from this study; breastfeeding should be discontinued upon start of protocol therapy