A number of large centers in Europe and North America have published trial results using systemic chemotherapy for patients whose intraocular tumors are not initially amenable to local management.[2,20,23,24,30,31,41,42,43,44,45,46,47,48,49]; [Level of evidence: 3iiDiv] Examples of such tumors are those that are too large to be treated with either cryotherapy, laser therapy, or plaque brachytherapy, or those located adjacent to visually sensitive areas such as the optic nerve and macula. Chemotherapy may shrink the tumors (chemoreduction) allowing greater efficacy of subsequent focal therapy.[2,33] Most centers have limited this approach to patients with bilateral disease, reasoning that for patients with unilateral disease, the morbidity of enucleation is modest. Also, most centers use one of two staging systems. Treatment strategies often differ in terms of chemotherapy regimens and local control measures.
Centers using the R-E classification have demonstrated the goal to save eyes may be achievable for tumors that are R-E Group IV or lower. The backbone of the chemoreduction protocols has generally been carboplatin, etoposide, and vincristine (CEV). Studies from The Children's Hospital of Philadelphia and Wills Eye Hospital reported that enucleation or EBRT may be avoided in R-E Group I, II, and III eyes when patients were treated for six cycles.[1,2,21] Other available data have been published in abstract form, and larger studies with more mature data are still required to make definitive conclusions. Group V tumors, particularly those with vitreous seeding, have proven problematic. Subretinal microscopic tumor has a recurrence rate of 5% following chemotherapy.[24,50]; [Level of evidence: 3iiDiv] Local control was often transient in patients with vitreous seeding or very large tumors (R-E Group V), and fewer than half of patients were treated successfully without requiring EBRT and/or enucleation.[1,2]
Other researchers reported the use of nine courses of CEV with the addition of high-dose cyclosporine A (a modulator of the p-glycoprotein) for eight R-E Group V eyes with an 88% (7 out of 8 eyes) success rate without the use of EBRT or enucleation.[44,45] However, conflicting results were seen in another study using the cyclosporine regimen in ten R-E Group V eyes, which reported only a 20% (2 out of 10 eyes) success rate.
A pilot study evaluated the delivery of chemotherapy via ophthalmic artery cannulation as initial treatment of advanced unilateral and bilateral intraocular retinoblastoma.
The International Classification system for staging intraocular retinoblastoma has also been used in combination with local control. (Refer to the Treatment Options Under Clinical Evaluation section of this summary for a more complete description of the International Classification system.) The addition of carboplatin and etoposide (CE) [22,51] or CEV [52,53] have been used in combination with local control. All of these studies are single institution studies that report some salvage of Group C and Group D eyes.[22,53]; [Level of evidence: 3iiDiv] However, in another study with carboplatin, etoposide, and local ophthalmic treatment, Group D eyes were at high risk for enucleation.; [Level of evidence: 3iiDiii] The question of whether eyes classified as Group E can be salvaged is under study.