Subconjunctival carboplatin in retinoblastoma: impact of tumor burden and dose schedule.

Abstract

OBJECTIVE:

To evaluate the impact of tumor burden and chemotherapy dose scheduling on the response to subconjunctival carboplatin treatment in a murine transgenic retinoblastoma model.

METHODS:

Eighty simian virus 40 T antigen-positive mice were treated at age 5 or 10 weeks. Six control animals received placebo treatment. Twenty-four 5-week-old mice received 6 subconjunctival carboplatin injections at doses of 30 to 300 microg delivered at 72-hour intervals. Fifty 10-week-old mice received either 6 or 12 subconjunctival carboplatin injections at doses of 30 to 300 microg delivered at 72-hour intervals. All eyes were obtained at age 16 weeks for histopathologic examination. Eyes were graded as positive if any tumor was present.

RESULTS:

All simian virus 40 T antigen-positive control eyes contained large tumor foci throughout the retina. Subconjunctival carboplatin injections controlled tumors in a dose-dependent manner. Tumor control was observed in 50% of treated eyes at 138.3 microg for the 10-week-old 6-injection group, 94.3 microg for the 5-week-old 6-injection group, and 85.9 microg for the 10-week-old 12-injection group.

CONCLUSION:

Increased tumor burden requires an increase in subconjunctival carboplatin dose scheduling to maintain local tumor control in this murine model of retinoblastoma.

CLINICAL RELEVANCE:

This study documents the efficacy of subconjunctival carboplatin in the treatment of an animal model of retinoblastoma. These data establish a framework for further human clinical trials. Arch Ophthalmol. 2000;118:1549-1554

• Authors: B H Hayden, T G Murray, I U Scott, N Cicciarelli, E Hernandez, W Feuer, L Fulton, J M O'Brien
• Journal: Archives of ophthalmology (Chicago, Ill. : 1960) (Arch Ophthalmol) Vol. 118 Issue 11 Pg. 1549-54 (Nov 2000) ISSN: 0003-9950 [Print] United States
• PMID: 11074812 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Ophthalmic Solutions
• Carboplatin

Topics

• Animals
• Antineoplastic Agents (administration & dosage)
• Carboplatin (administration & dosage)
• Conjunctiva
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Injections
• Mice
• Mice, Transgenic
• Ophthalmic Solutions
• Retinal Neoplasms (drug therapy, pathology)
• Retinoblastoma (drug therapy, pathology)