Integrated Treatment during the Intravitreal Melphalan Era: Concurrent Intravitreal Melphalan and Systemic Chemoreduction

Abstract

Background: Intravitreal injection of melphalan (IVM) is safe and effective for the treatment of seeding in retinoblastoma. Current protocols require weekly injections during examination under anesthesia (EUA). To avoid additional anesthesia exposure for these children, IVM was initiated at the EUA concurrent with the 4th cycle of systemic chemoreduction in a series of 6 patients with persistent seeding. Methods: A retrospective review was completed to assess treatment response compared to all patients at our center treated with IVM and systemic chemotherapy. Overall, 6 eyes of 6 patients were included; salvage therapy included systemic chemoreduction with vincristine, etoposide, and carboplatin and IVM for persistent seeding. Results: IVM was initiated in all eyes at cycle 4 of their chemotherapy. Success in eradicating vitreous seeds was 100%; overall salvage rate was 67%. Anterior toxicity was observed in 2 out of 6 eyes and posterior toxicity in 4 out of 6 eyes. Conclusion: The concurrent chemoreduction and IVM protocol demonstrated a similar efficacy of globe salvage while sparing children additional EUAs. However, the increased rates of observed melphalan-related toxicities for concurrent therapy are concerning. Further clinical experience is necessary to define the best initiation time and dosing schedule for IVM.

Intravenous Chemotherapy for Retinoblastoma in the Era of Intravitreal Chemotherapy: A Systematic Review

“…Incorporation of iVitc can potentially improve ocular survival rates to 71% (500 + 66/797) from 63% (without use of iVitc), which seems to be comparable to results reported with IAC [15]. In fact, a few recent studies have shown improved ocular survival (70-80%) with use of concurrent or subsequent administration of iVitc for refractory or recurrent vitreous seeding [13,[36][37][38][39][40]. Similar enhancing effect on ocular survival has also ■ Control ■ Recurrence: Other ■ Recurrence: Vitreous seeding Fig.…”

Intravitreal HDAC Inhibitor Belinostat Effectively Eradicates Vitreous Seeds Without Retinal Toxicity In Vivo in a Rabbit Retinoblastoma Model

“…Several recent clinical treatment protocols for intravitreal injections with melphalan have decreased the frequency even further, to every 2 weeks or every 3 weeks, while maintaining good efficacy. 9 , 17 , 45 Less frequent belinostat dosing might likewise maintain the same excellent efficacy-to-toxicity ratio and therapeutic window seen here. Our protocol of three weekly injections did not eliminate 100% of tumor cells quantified in the vitreous.…”

A single‐arm study of systemic and sub‐Tenon chemotherapy for Groups C and D intraocular retinoblastoma: A Children's Oncology Group study (ARET 0231)

“…Intravitreal chemotherapy with melphalan and/or topotecan is increasingly used in conjunction with IA therapy for better and durable control of vitreous seeds. The integration of intravitreal melphalan with systemic chemotherapy with carboplatin, etoposide, and vincristine has also been shown to be promising 25 …”