This is a dose-escalation study aimed to assess the toxicity (and marginally the activity) of periocular topotecan in patients with relapsed-resistant retinoblastoma.

Patients with bilateral retinoblastoma who have relapsed after attempts of conservative therapy with standard regimens such as carboplatin, etoposide, vincristine and external beam radiotherapy who face immediate enucleation of their single remaining eye are eligible for this protocol. Starting dose of topotecan will be 0.5 mg and dose escalation will be done by the accelerated titration method. Any Grade 3 ocular toxicity or grade 4 non ocular toxicity will be designed as the dose limiting toxicity. Grade 2 scleral toxicity will be considered for DLT. In case of grade 2 ocular toxicity or grade 3 systemic toxicity, the escalation dose will be 0.25 mg. Maximal dose will be 2 mg.

Inclusion Criteria:

• Group Vb (Reese Ellsworth)
• Relapsed or progressed after carboplatin-based regimens and external beam radiotherapy
• Enucleation of the contralateral eye
• Normal renal and liver function

Exclusion Criteria:

• Presence of glaucoma, rubeosis iridis, anterior chamber extension
• Extraocular disease
• Adequate follow up impossible for social reasons