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Brenda L. Gallie, MD; Andrew Budning, MD; Gerrit DeBoer, PhD; Jake J. Thiessen, PhD; Gideon Koren, MD; Zul Verjee, PhD; Victor Ling, PhD; Helen S. L. Chan, MB, BS

Arch Ophthalmol. 1996;114(11):1321-1328.

Abstract
Background
External beam radiotherapy is standard treatment for medium and large, or visually threatening, intraocular retinoblastoma but markedly increases the risk of cosmetic deformities and second malignant neoplasms in children with germline RB1 mutations. Large tumors and those with vitreous seeds do poorly despite radiotherapy. Chemotherapy traditionally is ineffective for intraocular retinoblastoma, perhaps because many retinoblastomas overexpress the multidrug resistance protein, P-glycoprotein.

Objective
To avoid radiotherapy in the management of intraocular retinoblastoma by using chemotherapy and focal therapy.

Interventions
We shrank retinoblastomas in 40 eyes of 31 patients that conventionally should be enucleated or receive radiotherapy by using chemotherapy (ie, vincristine-teniposide, 8 eyes; additional carboplatin, 32 eyes) combined with the administration of cyclosporine, a known multidrug—resistance-reversal agent. We then consolidated these responses to chemotherapy by subsequent 532- and 1064-nm laser therapy and cryotherapy.

Results
At the median follow-up of 2/8 years (range, 1/10-43/4 years), the results of treatment were excellent. The actuarial relapse-free rate was 89% in patients not previously treated (91% for 28 eyes) and 67% in patients treated after relapse from previous therapy (70% for 12 eyes). For the eyes with the worst prognosis (ie, vitreous seeds), the relapse-free rate was 88%, better than previously reported. Cyclosporine is nontoxic and did not enhance the expected toxic effects of chemotherapy. Most eyes required laser therapy, cryotherapy, or both for consolidation of tumor control.

Conclusions
This pilot study suggests that most retinoblastomas are curable by combining chemotherapy with cyclosporine therapy, laser therapy, and cryotherapy, without requiring external beam radiotherapy. We propose a randomized trial to clarify the role of cyclosporine.

Author Affiliations
From the Departments of Ophthalmology (Drs Gallie and Budning), Molecular and Medical Genetics (Dr Gallie), Pediatrics (Drs Chan and Koren) and Medical Biophysics (Dr DeBoer), Faculty of Pharmacy (Dr Thiessen), the University of Toronto; Divisions of Clinical Pharmacology and Toxicology (Dr Koren), Hematology and Oncology (Dr Chan), Immunology and Cancer Research of the Research Institute (Drs Gallie and Chan), and Clinical Biochemistry (Dr Verjee), Hospital for Sick Children; Division of Clinical Trials and Epidemiology, Toronto-Sunnybrook Regional Cancer Center (Dr DeBoer), Toronto, Ontatio; British Columbia Cancer Agency, University of British Columbia, Vancouver (Dr Ling).

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