Combined Intravitreal Melphalan and Topotecan for Refractory or Recurrent Vitreous Seeding From Retinoblastoma

Abstract

IMPORTANCE Demonstrating the usefulness and complications of multiagent intravitreal chemotherapy is necessary for successful treatment in patients with recalcitrant vitreous seeding of retinoblastoma.OBJECTIVE To determine the efficacy and complications of combined intravitreal chemotherapy (melphalan hydrochloride and topotecan hydrochloride) for viable vitreous seeding from retinoblastoma. DESIGN, SETTING, AND PARTICIPANTS This retrospective study was conducted in a hospital setting. Trans-pars plana intravitreal injection of melphalan hydrochloride (40 μg in 0.04 mL of diluent) combined with topotecan hydrochloride (8-20 μg in 0.04 mL of balanced salt solution) was performed in 9 eyes, followed by injection site cryotherapy. MAIN OUTCOMES AND MEASURES Complete regression of vitreous seeds of retinoblastoma.RESULTS Nine eyes, initially classified as group D (n = 6) or E (n = 3) according to International Classification of Retinoblastoma categorization, received a standard 6 cycles of intravenous chemotherapy and/or intra-arterial chemotherapy and subsequently developed recurrent viable vitreous seeds. Intravitreal administration of melphalan combined with topotecan produced complete control of vitreous seeds in all 9 eyes following a mean of 1.9 injections (median, 2; range, 1-3 injections). In 3 cases (33%), tumor control was achieved with a single injection, whereas in 6 (67%) cases, 2 or 3 injections were necessary. Three patients (33%) subsequently underwent enucleation because of recurrent tumor and persistent anterior chamber lesions. During a mean 15.2 months of follow-up (median, 16; range, 7-25 months), there was no recurrence of new tumor or vitreous seeds in the remaining 6 eyes. Complications included temporary hypotonia of 2 weeks or less (2 [22%]), temporary epithelial defect (1 [11%]), and vitreous hemorrhage (1 [11%]). There was no case of episcleral or orbital retinoblastoma extension or remote retinoblastoma metastasis. There was no change in the a and b waves of bright-flash electroretinograms.CONCLUSIONS AND RELEVANCE Administration of combined intravitreal melphalan and topotecan in eyes not subsequently enucleated appears to be safe and effective for resistant or recurrent vitreous seeds from retinoblastoma. In 3 of the cases (33%), tumor control was achieved with a single injection.

Intravitreal topotecan in the management of refractory and recurrent vitreous seeds in retinoblastoma

“…Rabbit eyes injected with four-weekly doses of up to 5 µg/0.1 mL of intravitreal topotecan showed no significant retinal or systemic toxicity 25. Ghassemi et al 16 used intravitreal topotecan at a dose of 8–20 µg/0.04 mL in combination with melphalan for vitreous seeds, and observed no changes on ERG.…”

“…As a periocular injection, topotecan has been used in patients with recurrent tumour and in those not amenable to systemic chemotherapy 14. Intravitreal topotecan injection in combination with melphalan has been reported to achieve complete vitreous seed regression with no change observed on electroretinogram (ERG) 16. Herein, we analysed the efficacy and safety of three-weekly intravitreal topotecan injection in the management of focal and diffuse refractory or recurrent vitreous seeds.…”

Secondary and tertiary intra-arterial chemotherapy for massive persistent or recurrent subretinal retinoblastoma seeds following previous chemotherapy exposure: long-term tumor control and globe salvage in 30 eyes

“…There were 3 eyes in our series with persistent or recurrent VS that came to enucleation, but more current methods of intravitreal chemotherapy could possibly have been beneficial. [23][24][25] The most important goal of retinoblastoma management is salvage of the child's life. In the present series, there were no serious sequelae of IAC, including stroke, neurologic impairment, or vascular insufficiency.…”

Update on Ocular Oncology

“…Intra-vitrealchemptherapeutic agents melphalan 21 , or combination of melphalan and topetecan 22 have been used with good response. Limitation of this includes excessive retinal pigment epithelial atrophy with diminution in the ERG responses.…”