Trial Information

A Trial of Intensive Multi-Modality Therapy for Extra-Ocular Retinoblastoma

OBJECTIVES:

I. To estimate the proportion of children with extraocular retinoblastoma who achieve
long-term event-free survival after treatment with aggressive multimodality therapy compared
to historical controls.

II. To estimate the response rate to the induction phase of the regimen. III. To evaluate
the toxicities associated with this regimen.

OUTLINE: This is a multicenter study.

Patients are stratified according to disease stage (stage 2 or 3 [regional extraocular
disease] vs stage 4a [disseminated metastatic disease not involving the CNS, including
extradural/dural disease without parenchymal or leptomeningeal disease] vs stage 4b [CNS
disease, including trilateral retinoblastoma]).

INDUCTION CHEMOTHERAPY: Patients receive vincristine IV on days 0, 7, and 14, cisplatin IV
over 6 hours on day 0, cyclophosphamide IV over 1 hour and etoposide IV over 1 hour on days
1 and 2, and filgrastim (G-CSF) subcutaneously (SC) beginning on day 3 and continuing until
blood counts recover.

Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or
unacceptable toxicity.

After completion of induction chemotherapy, patients with stage 2 or 3 disease who have at
least a partial response proceed to radiotherapy. Patients with stage 4a or 4b disease who
have at least a partial response proceed to high-dose consolidation chemotherapy and
autologous stem cell infusion.

STEM CELL HARVESTING (stage 4a or 4b disease only): Peripheral blood stem cells (preferred)
or bone marrow cells are collected after at least 1 course of induction chemotherapy.

HIGH-DOSE CONSOLIDATION CHEMOTHERAPY (stage 4a or 4b disease only): Patients receive
carboplatin IV over 4 hours on days -8 to -6 and thiotepa IV over 3 hours and etoposide IV
over 3 hours on days -5 to -3.

AUTOLOGOUS STEM CELL INFUSION (stage 4a or 4b disease only): Patients undergo autologous
stem cell infusion on day 0. Patients then receive G-CSF SC beginning on day 1 and
continuing until blood counts recover.

RADIOTHERAPY: Patients with stage 2 or 3 disease (orbital and/or regional involvement)
undergo radiotherapy to sites that were initially involved beginning within 42 days after
the start of course 4 of induction chemotherapy. Patients with stage 4a or 4b disease
undergo radiotherapy to sites initially involved based on response beginning approximately
42 days after autologous stem cell infusion. Patients with stage 4a disease who achieve a
complete response to induction chemotherapy or with less than 5 mm of residual tumor at the
time of planned irradiation, or patients with stage 4b disease who achieve a complete
response to induction chemotherapy do not undergo radiotherapy.

After completion of study therapy, patients are followed every 3 months for 1 year and then
annually thereafter.