Chemoplaque therapy for retinoblastoma: A potentially novel more accessible treatment approach

The early results from a phase II study on the use of the topotecan episcleral chemoplaque (Targeted Therapy Technologies LLC) for treating retinoblastoma showed that this new treatment method was generally well accepted by patients.

The preliminary results achieved mixed responses, and further investigation is needed, according to the investigators from the Department of Ophthalmology, Columbia University Medical Center, New York. Lauren Yeager, MD, an ocular oncology fellow, and Brian Marr, MD, director of ocular oncology, reported the preliminary study data at the 51^st annual meeting of the American Association for Pediatric Ophthalmology and Strabismus in Boston from March 18-22.

While there are several treatment options for retinoblastoma, a globe-salvaging therapy that is readily accessible and effective on a global scale is not yet available. “This is an interesting trial, because for retinoblastoma, that type of treatment access is unavailable worldwide. In the US and developed countries, there is intraarterial chemotherapy that requires a robust medical network with interventional radiologists and expensive equipment. This trial offers an alternative using a chemotherapy plaque, a small device that delivers chemotherapy after surgical placement on the eye,” Marr explained.

This approach negates the need for the intra-arterial background and support that is not readily available worldwide. In addition, he pointed out, the use of chemoplaque therapy may offer different chemokinetics to kill ocular tumors more efficiently.

“If successful, this could change the way retinoblastoma is managed around the world,” he stated.

Phase II chemoplaque study

All patients enrolled in the study had new or recurrent retinoblastoma. They all received 1.2 mg of topotecan delivered via chemoplaques (0.6 mg x 2) over 56 days. Follow-up examinations were conducted with the patients under anesthesia on days 0, 28, 56, and 84 after surgical implantation of the delivery system.

The chemoplaque, which is about 8 mm in size, is placed using a tissue adhesive on the sclera under the conjunctiva. A small dose of topotecan is released slowly from the device over weeks, Yeager explained.

“The drug delivery system is unique in that the medication is sequestered and delivered directly into the eye with no systemic absorption of the drug,” she commented. This is in contrast to the injection of chemotherapeutic drugs in the periorbital space that are toxic to ocular tissue and muscles, and it also avoids the side effects associated with intravenous and intraarterial treatments.

“The potential benefit of this drug device is the ease of its application. Many of the available retinoblastoma treatments require highly specialized centers and multidisciplinary care. The costs of creating these centers are high. The chemoplaque is accessible, easy to place, and easy to use,” Yeager emphasized.

What did the preliminary results of chemoplaque therapy show?

Three patients were included in the study. All had Group D refractory retinoblastoma, according to the International Classification of Retinoblastoma, which is defined as an advanced, high-risk, or diffuse intraocular disease that fails to respond adequately to or relapses after initial treatment, chemotherapy, and laser/cryotherapy.

The patients had been treated previously with intravenous and intra-arterial chemotherapy and focal laser.

The phase I data showed that the treatment was safe with minimal side effects.

Yeager and Marr reported, “At the final follow-up, one patient had resolution of disease, one patient demonstrated a partial response to therapy, and one patient had disease progression. One patient received adjuvant laser therapy, and two patients required further treatment after treatment with the topotecan chemoplaque.”

The investigators emphasized that the phase II trial is important to provide the treatment’s effectiveness and that the effectiveness requires further evaluation.

“We are excited to be on this path and to help patients with this disease,” Yeager said.

Marr expressed excitement about patients from distant residences traveling to New York for treatment with the chemoplaque.