Local carboplatin and radiation therapy in the treatment of murine transgenic retinoblastoma.
BACKGROUND
Combined modality therapy in the treatment of retinoblastoma may decrease treatment-related morbidity and second tumor-associated mortality, while maintaining excellent tumor control rates.


OBJECTIVE
To evaluate tumor control and potential synergy between intravitreally delivered carboplatin and external beam radiation therapy (EBRT), using a transgenic murine model of spontaneous heritable retinoblastoma.


METHODS
Sixty-six mouse eyes from 4-week-old transgenic mice positive for the simian virus 40 large T antigen were evaluated. Thirty-three mice were treated with 5 intravitreal injections of carboplatin (ranging from 0.1-4.0 micrograms) combined with concurrent bilateral EBRT (ranging from 10-30 Gy) delivered in twice daily 5-Gy fractions. All eyes were followed up for treatment complications. Twelve weeks following final treatment, all eyes were enucleated, serial histologic sections obtained, and the eyes examined for the presence of retinoblastoma.


RESULTS
No eye treated with 0.1 microgram of carboplatin and EBRT exhibited tumor control. Three (75%) of 4 mice receiving 1.0 microgram of carboplatin combined with 10-Gy EBRT had complete tumor control. Four (100%) of 4 mice receiving 1.0 microgram of carboplatin combined with 30-Gy EBRT had complete tumor control. Nine (100%) of 9 mice receiving 4.0 micrograms of carboplatin in combination with EBRT had complete tumor control. The chemotherapeutic enhancement ratio ranged from 1.07 to 3.24.


CONCLUSIONS
Combined administration of intravitreal carboplatin and EBRT enhances local tumor control in murine retinoblastoma. Combining these treatment modalities may allow tumor control in selected patients with retinoblastoma while decreasing treatment-related morbidity and the mutagenic risks associated with radiation and systemic chemotherapy.
Department of Ophthalmology, University of Miami, Fla, USA.
T G
TG
Murray
D B
DB
Roth
J M
JM
O'Brien
W
W
Feuer
N
N
Cicciarelli
A M
AM
Markoe
E
E
Hernández
B J
BJ
Smith
J J
JJ
Windle
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005134:Eye Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D016161:Genes, Retinoblastoma / Q000235:genetics; D007267:Injections; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D011859:Radiography; D011879:Radiotherapy Dosage; D011882:Radiotherapy, High-Energy; D012175:Retinoblastoma / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D014822:Vitreous Body
D000952:Antigens, Polyomavirus Transforming; D000970:Antineoplastic Agents; D016190:Carboplatin