Intra-arterial chemotherapy for retinoblastoma. Challenges of a prospective study.

To report the efficacy and complications of intra-ophthalmic artery melphalan (IAM) for treatment of patients with advanced intra-ocular retinoblastoma.Patients with newly diagnosed, unilateral, group D retinoblastoma were included in a phase II protocol. Children with relapsed-refractory disease after systemic chemoreduction were later treated under the same guidelines.Melphalan (3–5 mg/procedure) was injected through a 1.2 F microcatheter placed into the ophthalmic artery every 21 days.Eleven patients (12 eyes, eight as primary treatment) received 33 IAM procedures. The phase II protocol closed prematurely because of low accrual. The IAM technique was overall safe and could be performed successfully in 31 of 33(94%) attempts. After the second administration of IAM, very good partial response was achieved in all treated eyes. With a median follow-up time of 29.5 months (range 6–57), ocular salvage was achieved in 7 of 12 (58%) eyes. No systemic adverse events were observed. Two patients developed diffuse arteriolar sclerosis, hyperpigmentation of the retinal pigment epithelium and partial retinal atrophy after the second IAM. Both eyes were preserved with no tumour activity, good motility and perception of light, 56 and 30 months after the last IAM treatment. Multinucleated macrophages with intracytoplasmic foreign material were found in the choroid and the retina in 2 of 5 enucleated eyes.Our study reports the activity and reproducibility of IAM in advanced retinoblastoma but also underlines the challenges of performing prospective studies on this treatment modality. Toxicity was limited to only ocular vascular events.