Local carboplatin and radiation therapy in the treatment of murine transgenic retinoblastoma

Timothy G. Murray, Daniel B. Roth, Joan M. O'Brien, William J Feuer, Nicole Cicciarelli, Arnold Markoe, Eleut Hernández, Barbara J. Smith, Jolene J. Windle

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Abstract

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 μg) 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 μg of carboplatin and EBRT exhibited tumor control. Three (75%) of 4 mice receiving 1.0 μg of carboplatin combined with 10-Gy EBRT had complete tumor control. Four (100%) of 4 mice receiving 1.0 μg of carboplatin combined with 30-Gy EBRT had complete tumor control. Nine (100%) of 9 mice receiving 4.0 μg 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.

Original languageEnglish
Pages (from-to)1385-1389
Number of pages5
JournalArchives of Ophthalmology
Volume114
Issue number11
StatePublished - Nov 1 1996

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Retinoblastoma
Carboplatin
Radiotherapy
Neoplasms
Therapeutics
Morbidity
Combined Modality Therapy
Intravitreal Injections
Simian virus 40
Viral Tumor Antigens
Transgenic Mice
Radiation
Drug Therapy
Mortality

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Murray, T. G., Roth, D. B., O'Brien, J. M., Feuer, W. J., Cicciarelli, N., Markoe, A., ... Windle, J. J. (1996). Local carboplatin and radiation therapy in the treatment of murine transgenic retinoblastoma. Archives of Ophthalmology, 114(11), 1385-1389.

Local carboplatin and radiation therapy in the treatment of murine transgenic retinoblastoma. / Murray, Timothy G.; Roth, Daniel B.; O'Brien, Joan M.; Feuer, William J; Cicciarelli, Nicole; Markoe, Arnold; Hernández, Eleut; Smith, Barbara J.; Windle, Jolene J.

In: Archives of Ophthalmology, Vol. 114, No. 11, 01.11.1996, p. 1385-1389.

Research output: Contribution to journalArticle

Murray, TG, Roth, DB, O'Brien, JM, Feuer, WJ, Cicciarelli, N, Markoe, A, Hernández, E, Smith, BJ & Windle, JJ 1996, 'Local carboplatin and radiation therapy in the treatment of murine transgenic retinoblastoma', Archives of Ophthalmology, vol. 114, no. 11, pp. 1385-1389.
Murray TG, Roth DB, O'Brien JM, Feuer WJ, Cicciarelli N, Markoe A et al. Local carboplatin and radiation therapy in the treatment of murine transgenic retinoblastoma. Archives of Ophthalmology. 1996 Nov 1;114(11):1385-1389.
Murray, Timothy G. ; Roth, Daniel B. ; O'Brien, Joan M. ; Feuer, William J ; Cicciarelli, Nicole ; Markoe, Arnold ; Hernández, Eleut ; Smith, Barbara J. ; Windle, Jolene J. / Local carboplatin and radiation therapy in the treatment of murine transgenic retinoblastoma. In: Archives of Ophthalmology. 1996 ; Vol. 114, No. 11. pp. 1385-1389.
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abstract = "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 μg) 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 μg of carboplatin and EBRT exhibited tumor control. Three (75{\%}) of 4 mice receiving 1.0 μg of carboplatin combined with 10-Gy EBRT had complete tumor control. Four (100{\%}) of 4 mice receiving 1.0 μg of carboplatin combined with 30-Gy EBRT had complete tumor control. Nine (100{\%}) of 9 mice receiving 4.0 μg 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.",
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AU - Cicciarelli, Nicole

AU - Markoe, Arnold

AU - Hernández, Eleut

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N2 - 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 μg) 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 μg of carboplatin and EBRT exhibited tumor control. Three (75%) of 4 mice receiving 1.0 μg of carboplatin combined with 10-Gy EBRT had complete tumor control. Four (100%) of 4 mice receiving 1.0 μg of carboplatin combined with 30-Gy EBRT had complete tumor control. Nine (100%) of 9 mice receiving 4.0 μg 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.

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