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Potentially active levels of melphalan after SSOAI were achieved in the vitreous of animals. Low systemic exposure was found in animals and children. Doses greater than 0.48 mg/kg, given for bilateral tandem infusions, were associated with significantly higher plasma levels and increased risk of neutropenia. Synergistic in vitro cytotoxicity between melphalan and topotecan favors combination treatment.

Superselective OAI resulted in significantly higher vitreous concentrations and exposure and a trend toward lower systemic exposure than POI.

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Topotecan alone or in combination is active against retinoblastoma. It shows a favorable passage to the vitreous when given intravenously and intraarterially, and ocular toxicity is minimal by all routes of administration. However, its clinical role, optimal dose, and route of administration for the treatment of retinoblastoma are to be determined.

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