Retinoblastoma requires strategy

Philadelphia-Several modalities currently exist for the delivery of chemotherapy for retinoblastoma in children, said Carol L. Shields, MD. She reviewed the advantages and disadvantages of each of these.

"It's a game of strategy," said Dr. Shields, associate director and attending surgeon on the Ocular Oncology Service at Wills Eye Hospital, Philadelphia. "It's up to you to make the right treatment choice."

Options include the following modalities:

IV chemotherapy is used as standard therapy in children with retinoblastomas, said Dr. Shields, who is also professor of ophthalmology at Thomas Jefferson University and consultant at Children's Hospital of Philadelphia.

This therapy incurs only few complications, and has been shown to be remarkably effective. In 1996, researchers from four centers worldwide (London, Toronto, Los Angeles, and Philadelphia) demonstrated good response using six cycles of three chemoreductive agents, including vincristine (Oncovin), etoposide (Eposin, Etopophos, Vepesid, VP-16), and carboplatin (Paraplatin, Paraplatin-AQ).

After the first cycle, the tumors were shown to shrink dramatically, and then each tumor was consolidated with thermotherapy, Dr. Shields said. Protocol calls for six cycles with consolidation at each cycle.

"We have learned that chemotherapy with only two agents is typically not sufficient. One report showed a 90% recurrence rate with two agents," she said. "We use three agents; this allows tumor control, particularly if there is partial resistance to one drug."

When chemoreduction is evaluated according to the stages of retinoblastoma (Group A being small tumors, Group D large tumors), there was complete tumor control in 90% or more of eyes in Groups A, B, and C. Of eyes in Group D, there was only a 50% success rate. These eyes often need other therapies such as enucleation, intra-arterial chemotherapy, or external beam radiotherapy, she said.

Chemoreduction also has been recognized to prevent pinealoblastoma.

"We rarely see this tumor anymore due to the influence of chemoreduction, and 25 years ago, pinealoblastoma occurred in 8% to 10% of children with bilateral disease," she said.

"One secret of chemoreduction is the tumor is controlled, [often with] preservation of visual acuity," Dr. Shields said. "We are witnessing better visual acuity in children who receive chemotherapy rather than radiotherapy. In fact, if you study the children who are successfully treated with chemoreduction for retinoblastoma, 50% see 20/20 to 20/40 after treatment.

"Even after a history of macular involvement, some children still have potential for vision with patching," she added.

Researchers from Toronto have shown that with patching for amblyopia, eyes with treated retinoblastoma can recover 1 to 2 lines of vision, she explained.

Sub-Tenon's chemotherapy

Sub-Tenon's chemotherapy is used in conjunction with chemoreduction for advanced cases of retinoblastoma, Dr. Shields continued. For this type of therapy, a small dose of carboplatin is used.

"We have found that using sub-Tenon's carboplatin alone for retinoblastoma does not do the trick," she said. "We believe it is most effective in conjunction with systemic chemoreduction."

Dr. Shields related that at the Wills Eye Institute, three cycles of sub-Tenon's carboplatin injection are used for eyes with advanced Group D or Group E retinoblastoma that are also receiving IV chemoreduction. Currently, a depot that delivers carboplatin is under investigation.