Program Book

4. Fluoroscopy for cannula placement was needed in all cases. Radiation
exposure was far below toxic levels in all cases.
5. Complications mainly involved retinal vascular pruning, often
subclinical and only detected on fluorescein angiography. Occlusion of
ophthalmic/retinal artery (5%) or choroidal vessels (10%) was noted.
Conclusions. IAC provides satisfactory control for less advanced
eyes with retinoblastoma. Retinal detachment often shows complete
resolution. Complications of vascular occlusion should be monitored.
Financial disclosure. None
1527 RB21
COMPARATIVE PHARMACOKINETICS OF TOPOTECAN
AND MELPHALAN AFTER INTRA-ARTERIAL ADMINIS-
TRATIONS IN THE SWINE MODEL
Paula Schaiquevich, PhD, Emiliano Buitrago, Bsc, Ana Torbidoni PhD,
Alejandro Ceciliano, MD, Adriana Fandino, MD, Javier Opezzo, PhD,
Marcelo Asprea, DVM, Sergio Sierre, MD, Flavio Requejo, David H.
Abramson, MD, Guillermo F. Bramuglia, PhD, Guillermo L. Chantada,
MD. (gchantada@yahoo.com)
Hospital JP Garrahan
Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET)
Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires,Agencia
de Promocion Cientifica y Tecnologica, Argentina
Memorial Sloan Kettering Cancer Center, New York, NY, USA
Purpose. To compare the vitreous and plasma pharmacokinetics of
topotecan and melphalan after ophthalmic artery infusion (OAI) following
super-selective artery catheterization.
Methods. The ophthalmic artery of 8 Landrace pigs was super-selectively
catheterized and 1 mg of topotecan in one group and 7 mg of melphalan in
the other group were infused over 30 minutes. Serial vitreous specimens
were obtained by microdialysis with simultaneous plasma samples. Drug
levels were measured by HPLC and pharmacokinetic analysis was carried
out with the obtained data. IC50 for each drug were estimated in vitro from
retinoblastoma cell line Y79.
Results. Maximum median vitreous (Cmax) topotecan concentration in
the vitreous was 288 nM, (range 247-303) and that of melphalan 650 nM,
(range 160-1360). The ratio between the vitreous and plasma Cmax and area
under the curve were 15.4 versus 3.4 and 29 versus 3.2 for topotecan and
melphalan respectively. Systemic exposure was low for both drugs (median
plasma Cmax: 0.018 and 0.2 uM for topotecan and melphalan respectively).
The IC50 for topotecan was 10 nM and for melphalan 1000 nM. Topotecan
levels higher than the IC50 were detected for up to 4 hours.
Conclusions. Super-selective OAI resulted in vitreous concentrations of
topotecan that exceeds the IC50, while melphalan levels are slightly below
that range. Topotecan vitreous/plasma concentration is almost 10 times
higher than of melphalan.
Financial disclosure. Universidad de Buenos Aires, CONICET, Agencia de Promocion Cientifica y
Tecnologica, (Argentina). Fund for Ophthalmic Knowledge, New York, USA. Fundacion Natali
Flexer, Buenos Aires, Argentina, Hospital JP Garrahan, Buenos Aires, Argentina
539 RB22
RELAPSES FOLLOWING INTRA-ARTERIAL CHEMO-
THERAPY WITH MELPHALAN
T. Hadjistilianou1, S. De Francesco1, S. Bracco2, P. Galluzzi2, P. Toti3,
P. Gennari2, A. D’Ambrosio4, M. Caini4, D. Galimberti4, A. Cerase2, C.
Venturi2 (hadjistilian@unisi.it)
RETINOBLASTOMA
Abstracts
42
1. Ophthalmology Unit, Retinoblastoma Referral Center
2. Neuroradiology Unit
3. Dept.of Pathology
4. Dept.of Pediatrics
AOUS-Azienda Ospedaliera Universitaria Senese.
Purpose. To report the incidence of relapses following intra-arterial
chemotherapy with melphalan for advanced retinoblastoma at diagnosis
and after systemic neoadjuvant chemotherapy.
Methods. From may 2008 to may 2011, 41 patients (45 eyes, 25 eyes
with relapses and 20 at first diagnosis) have been treated at the Referral
Center for Retinoblastoma (University of Siena) with intra-arterial
chemotherapy using melphalan alone. All patients had an advanced
stage of disease (VB Reese Classification, D ABC Classification). Twenty
eyes were at first diagnosis and twenty five eyes were relapses after
systemic neoadjuvant chemotherapy. All patients had received 3 to 6
infusions of Melphalan. The dose varied from 3 to 7 mg. Five out of 41
had “tandem” therapy for bilateral relapses. All patients received focal
therapy (argon laser, thermotherapy, cryotherapy, and plaques).
Results. Six out of 20 (30%) eyes at first diagnosis had relapses
following intra-arterial chemotherapy with melphalan. Six out of 20 (30%)
underwent enucleation for progressive disease. Six out of 20 (30%)
obtained complete remission; two were lost to follow up. Fifteen out of
25 eyes (60%) which relapsed after systemic neoadjuvant chemotherapy
had new relapses following intra-arterial chemotherapy with melphalan;
one out of 15 eyes (6%) has been successfully treated with focal therapy
alone, fourteen out 15 required one more cycle (3 infusions) of melphalan
and focal therapy. Nine out of 25 eyes (36%) obtained complete remission
with one cycle of melphalan; 1 patient was lost to follow-up.
Conclusions. Intra-arterial chemotherapy with melphalan may represent
a potential treatment option for advanced retinoblastoma, but more
investigations with new chemotherapeutic agents are necessary when
diffuse vitreous and/or subretinal seeding are present.
Financial disclosure. None
2257 RB23
FACTORS INFLUENCING RESPONSE RATE FOLLOWING
INTRA-OPHTHALMIC ARTERY MELPHALAN SALVAGE
THERAPY FOR RELAPSE AFTER PRIMARY TREATMENT
OF RETINOBLASTOMA
John Hungerford1, Judith Kingston2,3, Stefan Brew4, Ashwin Reddy2,
Mandeep Sagoo1,2, Fergus Robertson4, Jane Herod5 (john.hungerford@
btopenworld.com)
1. Oncology Service, Moorfields Eye Hospital
2. Retinoblastoma Service, St Bartholomew’s and the London Hospital
3. Paediatric Oncology Service, Great Ormond Street Hospital
4. Interventional Neuroradiology Service, Great Ormond Street Hospital
5. Anaesthetics Service, Great Ormond Street Hospital, London, UK
Purpose. To evaluate intra-ophthalmic artery Melphalan (IAM) as a
salvage treatment.
Methods. Consecutive, retrospective chart review.
Results. Between December 2008 and May 2011, 39 treatment episodes,
each comprising 1-3 infusions of intra-ophthalmic artery Melphalan
(IAM), were undertaken in 36 eyes of 34 patients for relapsed (34) or
refractory (5) retinoblastoma. Of 34 treatment episodes for relapse,
7 were for vitreous relapse alone whilst a further 10 were for patients
with vitreous disease associated with recurrence of the primary tumour.