An Open, Single-centre Non-randomized Phase II Clinical Trial on Intra-arterial Chemotherapy With Melphalan for the Treatment of Retinoblastoma (RTB) in Advanced Intraocular Stage
Retinoblastoma (RTB) is the most frequent tumour of the eye in early childhood and the
commonest cancer in the first year of life. Approximately 60% of cases are sporadic and
unilateral. Unilateral tumours are usually diagnosed in the advanced intraocular stage and
the most frequent treatment prescribed is enucleation. This prevents disease progression but
has an important visual risk, and also constitutes a mutilation, with potentially
devastating psychological effects on patients and their relatives.
At diagnosis, patients affected with RTB and their relatives are faced with the important
effects of this disease, such as a threat to life, although rare in developed countries, and
the risk of losing their sight, which depends on the uni- or bilateral nature of the tumour,
the topography of the tumour or tumours, and the still prevalent need for enucleation as a
treatment. In fact, almost all advanced stage unilateral RTBs are treated with enucleation.
In addition to the risk to life and the patient's sight associated with this treatment, it
is also important to take into account the risk to the eye itself. For selected cases with
advanced intraocular involvement (stage V of the Reese-Ellsworth classification) in which
enucleation would usually be the standard therapeutic approach, in this project we propose
an alternative conservative treatment using intra-arterial chemotherapy with melphalan, via
direct administration by catheterization of the ophthalmic artery.
The treatment aims to preserve the eye ball and visual acuity as much as possible in these
patients, and has been demonstrated to be extremely effective at achieving volumetric
reduction of tumours, which permits, if necessary, the subsequent conservative treatment,
mainly with brachytherapy for anterior tumours or thermotherapy with laser diode for
posterior tumours. In cases of retinal detachment, significant volume reduction, such as
that achieved after injection with melphalan would, in most cases, permit retinal
reapplication that would favour visual prognosis.
This technique was first described by David H. Abramson in the Sloan-Kettering Cancer Center
Memorial Hospital of New York (A Phase I/II Study of direct Intra-arterial (Ophthalmic
Artery) Chemotherapy with Melphalan for Intraocular Retinoblastoma). Here, in this study we
propose using this technique for the first time outside New York city, in our own clinical
setting (Retinoblastoma Unit, affiliated to the Oncology Development Department and the
Ophthalmology Department of the Sant Joan de Déu Hospital in Barcelona).
The attainment of positive results, in addition to those previously obtained by the New York
project, could consolidate this treatment as an alternative to enucleation in most cases of
advanced intraocular RTB, and open the way for the future indication of this technique in
other stages of RTB.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To assess the saving of eyes affected with RTB for patients who would have been candidates for enucleation.
The primary endpoint will be the objective response to treatment determined by funduscopy and RetCam explorations, recorded as a percentage of partial response (PR) or complete response (CR) to the treatment administered.
From V1 (Baseline) to V14 (1+ year after last treatment)
Andreu Parareda, MD
Hospital Sant Joan de Déu
Spain: Agencia Española de Medicamentos y Productos Sanitarios