Study of Treatment for Patients With Cancer of the Eye -Retinoblastoma
Study of Treatment for Patients With Cancer of the Eye -Retinoblastoma
Retinoblastoma is a childhood cancer which affects the retina of the eye. The retina is the
 light sensitive layer of tissue that lines the back of the eyeball; sends visual messages
 through the optic nerve to the brain. When only one eye is affected, this is known as
 unilateral retinoblastoma and when both eyes are affected, it is called bilateral
 retinoblastoma. Treatment for retinoblastoma is individualized for each patient and is based
 on the form and the stage of the disease (inside the eye or has moved outside). The main goal
 is always to cure the cancer, and save the life of the child. Treatments are also designed
 with the hope of saving the vision, while completely destroying the tumor. Therapies may
 involve surgery, chemotherapy, radiation, and other treatments called focal treatments. Focal
 treatments may be laser therapy, freezing, or heat treatments meant to shrink and kill the
 tumor.

 In this study, researchers want to investigate how different participants respond to
 different therapies that are individualized specifically for them. Participants will be
 divided into three main groups, depending on whether the disease is unilateral or bilateral,
 and the stage of the disease. One of the main objectives of the study is to investigate how
 advanced tumors in children with bilateral disease respond to a new combination of
 chemotherapy with topotecan and vincristine, with G-CSF support. In order to improve results,
 some children with very advanced disease may receive carboplatin chemotherapy given around
 the eye at the same time that they receive topotecan by vein. Also, because children with
 retinoblastoma are diagnosed so early in life and the vision may be significantly impaired,
 this study will investigate how children develop and how the brain adjusts and compensates
 for the visual deficits. Finally, this study also investigates the biology of retinoblastoma,
 in order to understand better how this cancer develops.
This study will determine the following:

 PRIMARY OBJECTIVE:

 -  To estimate the ocular survival and event-free survival of bilateral disease patients
 with advanced intraocular retinoblastoma in either eye (R-E IV-V) responding to the
 vincristine/topotecan window, with alternating cycles of vincristine and carboplatin
 with vincristine, topotecan, and periocular carboplatin, with intensive focal
 treatments.

 SECONDARY OBJECTIVES:

 -  To estimate the ocular survival of eye and event-free survival of eye of bilateral
 disease patients with advanced intraocular retinoblastoma in either eye (R-E IV-V)
 responding to the vincristine/topotecan window, with alternating cycles of vincristine
 and carboplatin with vincristine, topotecan, and periocular carboplatin, with intensive
 focal treatments.

 -  To estimate the ocular survival and event free survival of patients with advanced
 intraocular retinoblastoma (R-E IV-V) not responding to the vincristine/topotecan
 window, with a combination of vincristine, carboplatin, etoposide, and periocular
 carboplatin, with intensive focal treatments.

 -  To estimate the ocular survival and event free survival of eye of patients with advanced
 intraocular retinoblastoma (R-E IV-V) not responding to the vincristine/topotecan
 window, with a combination of vincristine, carboplatin, etoposide, and periocular
 carboplatin, with intensive focal treatments.

 -  To estimate the ocular survival and event-free survival of patients with early stage
 intraocular retinoblastoma (R-E I-III) with vincristine and carboplatin with intensive
 focal treatments.

 -  To estimate the ocular survival of eye and event-free survival of eye of patients with
 early stage intraocular retinoblastoma (R-E I-III) with vincristine and carboplatin with
 intensive focal treatments.

 -  To estimate the response rate of early stage eyes (R-E I-III) in patients with
 contralateral advanced disease treated with vincristine and topotecan.

 -  To estimate the ocular survival and event-free survival of early stage eyes (R-E I-III)
 of patients with contralateral advanced disease treated with vincristine and topotecan.

 -  To describe the outcome of intraocular retinoblastoma with respect to the new
 International Classification for Intraocular Retinoblastoma and the AJCC.

 -  To describe primary visual cortex function in patients with unilateral and bilateral
 retinoblastoma.

 -  To describe the cognitive, adaptive, and social/emotional development of children with
 retinoblastoma.

 -  To describe changes in the pineal gland during treatment in patients with bilateral
 retinoblastoma.

 -  To assess the relation between CYP3A4/5 genotype and the pharmacokinetics and
 pharmacodynamics of topotecan.

 -  To assess the relation between ABCG2 genotype and the pharmacokinetics and
 pharmacodynamics of topotecan.

 -  To determine if carboplatin can produce changes in cochlear function that are detectable
 with measurement of otoacoustic emissions.

 -  To evaluate the need for and feasibility of starting early intervention support during
 the first year after the diagnosis of retinoblastoma.

 EXPLORATORY OBJECTIVES:

 -  To provide insight into molecular pathogenesis of retinoblastoma.

 -  To describe the incidence and type of germline mutations of the RB gene in patients with
 retinoblastoma.
Inclusion Criteria:

 -  Must have newly diagnosed intraocular retinoblastoma, previously untreated. Patients
 previously diagnosed with unilateral retinoblastoma treated surgically (or with focal
 therapies), who develop asynchronous involvement of the contralateral eye, will be
 eligible for study.

 -  Must have a life expectancy of at least 8 weeks.

 -  Must have Performance Status (ECOG) of 0-2.

 -  Patients must have an adequate liver function, as defined by bilirubin less than or
 equal to 3 x normal, and SGOT and SGPT less than or equal to 3x normal.

 -  Patients must have adequate renal function as defined by serum creatinine less than or
 equal to 3x normal for age.

 -  Legal guardians must sign an informed consent indicating that they are aware of this
 study, its possible benefits, and toxic side effects. Legal guardians will be given a
 copy of the consent form.

 Exclusion Criteria:

 -  Previously treated patients

 -  Presence of metastatic disease or orbital involvement

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