Randomized Control Trial Comparing Carboplatin 560mg/m2 With 750mg/m2 for Ocular Salvage in Groups C and D Intraocular Retinoblastoma

Chemoreduction has become an important method in management of retinoblastoma. This technique has been employed in an effort to avoid enucleation and external beam radiotherapy (EBRT) for children with intraocular retinoblastoma, especially those with bilateral disease. Although an ideal regimen for chemoreduction has not been determined, most authors use a combination of vincristine, etoposide and carboplatin for 2- 6 cycles along with local treatment including cryotherapy, laser photocoagulation, thermotherapy and plaque radiotherapy. Chemoreduction along with local treatment has been shown to have high treatment success in groups A and B of retinoblastoma allowing globe salvage without need of EBRT. But globe salvage rates remain low in groups C and D, which mostly need enucleation, or EBRT in a large number of cases.

In bilateral retinoblastoma where one eye is already lost owing to enucleation or both the eyes have advanced retinoblastoma (group C/D) globe salvage assumes a significant role in the overall treatment. Recurrences of the vitreous seeds or the sub retinal seeds are the main causes of treatment failure with chemoreduction and local treatment, ultimately requiring enucleation or EBRT.

The recurrence of vitreous or subretinal seeds do not necessarily mean a tumor resistance, it may reflect an inadequate penetration of the chemotherapeutic agents in these relatively avascular sites i.e the vitreous cavity or the subretinal space.

The penetration to these sites could be enhanced by (a) increase in the dose of the intravenous chemotherapeutic agents. The IInd Toronto protocol that was started in 2000 explores this option. The initial reports are encouraging but they have used high doses chemotherapy in combination with cyclosporin A. Therefore the effect of high dose chemotherapy on the globe salvage rates in groups C and D cannot be evaluated as an independent factor. (b) Periocular carboplatin injection has proven to deliver much higher levels of the drug in to the vitreous cavity, but several studies have revealed local side effects of this apparently harmless technique.The National Collaborative Retinoblastoma Study funded by the Children's oncology group plans to carry out a single arm trial of 6 cycles of systemic high dose chemotherapy and subtenon carboplatin injections in groups C and D of retinoblastoma. (c) Use of Cryotherapy/thermotherapy along with chemotherapy, has shown to increase the penetration of the chemotherapeutic agents into the vitreous cavity probably by disrupting the blood retinal barrier.

Shield's et al has already shown that the 6 cycle chemotherapy regimen achieves better long-term control of vitreous and subretinal seeds as compared to a 2 cycle regimen.