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)

Abstract

Background Eyes with Group D intraocular retinoblastoma have low salvage rates. A pilot study showed safety and efficacy of sub‐Tenon's fascia carboplatin with systemic chemotherapy supporting further study. Methods Children with newly diagnosed bilateral intraocular retinoblastoma with at least one remaining Group C or D eye were treated with six courses of carboplatin/etoposide/vincristine (CEV) with sub‐Tenon's fascia carboplatin for Group C/D eyes during courses 2‐4. Local ophthalmic therapy started at course 3. The primary study objective was to determine the 1‐year failure rate of Group D eyes. Results The study closed prematurely due to poor accrual and 22 of 30 patients were evaluable for failure rate, contributing 25 Group D and four Group C eyes. Among the 25 Group D eyes, there were 13 failures within the first year of study enrollment including eight needing external beam radiotherapy (EBR) and five needing enucleation, resulting in 1‐year failure rate of 52%. The failure rate was significantly lower than the historical rate of 70% (P = .039). The 1‐year eye preservation rate for Group D eyes was 80% (20/25). One‐year failure rate for Group C eyes was 25% (1/4); 1‐year preservation rate was 100% without need for EBR. Systemic toxicity included Grade 3 hearing loss in two subjects, infections, neutropenia, and thrombocytopenia. Ocular toxicities included periorbital fat atrophy (13/29 = 45% eyes), optic nerve atrophy (1/29 = 3% eyes), and restrictive fibrosis (1/29 = 3% eyes). Conclusions Sub‐Tenon's fascia carboplatin plus CEV was partially effective in Group D intraocular retinoblastoma but had unacceptable ocular toxicities.

A single‐blinded, randomized controlled trial of standard versus higher dose carboplatin‐based intravenous chemotherapy for group D and E retinoblastoma

“…The studies on higher dose carboplatin-based chemotherapy for advanced intraocular or extraocular retinoblastoma are summarized in Table 4. [5][6][7]11,[15][16][17][18] As is apparent, the prevailing evidence is largely from single-arm or retrospective studies. It prompted us to study a head-to-head compar- group E retinoblastoma undergoing enucleation following neoadjuvant chemotherapy are treated with a total of six cycles of standard-dose chemotherapy in the authors' unit.…”

“…However, evidence is scarce for the role of higher dose carboplatin‐based chemotherapy in improving ocular and vision salvage for group D or E retinoblastoma. The studies on higher dose carboplatin‐based chemotherapy for advanced intraocular or extraocular retinoblastoma are summarized in Table 4 5–7,11,15–18 . As is apparent, the prevailing evidence is largely from single‐arm or retrospective studies.…”

“…Carboplatin is considered to be the most effective agent for retinoblastoma 4 . Uncontrolled, single‐arm studies on small cohorts of patients with advanced IORB have demonstrated satisfactory control of the primary tumor, vitreous seeds, and optimized globe and vision salvage with higher dose carboplatin‐based intravenous chemotherapy 5–7 . However, there is a paucity of randomized controlled trials (RCTs) comparing the efficacy of standard versus higher dose regimens for IORB.…”

A multi‐institutional feasibility study of intra‐arterial chemotherapy in children with retinoblastoma. A Children's Oncology Group study (COG ARET12P1)

“…Attempts to salvage the globe with systemic intravenous chemotherapy were successful in approximately 50% of patients with group D disease 1–7 . Increasingly, efforts to cure the child and save the globe have rapidly evolved to local delivery techniques like periocular carboplatin in conjunction with systemic chemotherapy as well as IA therapies 5,8,9 . At the time of initiation of this study, retrospective data from single institutions had reported promising results of the intra‐arterial technique of delivering chemotherapy to the eyes of children with retinoblastoma via the ophthalmic artery 9–12 .…”

“…[1][2][3][4][5][6][7] Increasingly, efforts to cure the child and save the globe have rapidly evolved to local delivery techniques like periocular carboplatin in conjunction with systemic chemotherapy as well as IA therapies. 5,8,9 At the time of initiation of this study, retrospective data from single institutions had reported promising results of the intra-arterial technique of delivering chemotherapy to the eyes of children with retinoblastoma via the ophthalmic artery. [9][10][11][12] This technique is a variation of the original intra-arterial technique used by Japanese investigators.…”