Booster approach helps stabilize vision in AMD patients

Winter Haven, FL-Combination therapy using bevacizumab (Avastin, Genentech) as a "booster shot" in conjunction with pegaptanib sodium (Macugen, OSI/Eyetech/Pfizer) to treat exudative age-related macular degeneration (AMD) appears to work very well in both the short term and the long term, according to Michael Tolentino, MD.

Dr. Tolentino, director of the Research Center for Retina and Macular Disease, Winter Haven, FL, has tried this combination on more than 40 eyes. "I have several cases where it works phenomenally well," he said. "There seems to be a synergy between bevacizumab and pegaptanib."

Pegaptanib is a VEGF-165 selective inhibitor, and bevacizumab is a pan-VEGF isoform inhibitor. Dr. Tolentino hypothesized that the two agents are effective in combination because the selective inhibition of pegaptanib leads to upregulation of the other VEGF family members. The others will not be as powerful or as important but can still cause damage.

"It is like a one-two punch," Dr. Tolentino explained. "First you get the leader, then the smaller guys. They are not going to be as important, but you can knock them out with just one or two shots of the pan-isoform."

His technique is to inject the pegaptanib once every 6 weeks and administer a booster of 1.25 mg/0.05 ml bevacizumab injected intravitreally between the doses of pegaptanib if the condition is not improving. Snellen visual acuity and optical coherence tomography (OCT) are measured prior to and 1 week after each injection of bevacizumab and immediately before subsequent pegaptanib injections.

"What that does is minimize the amount of bevacizumab usage, which is important because we don't know what its effects are over the long term," Dr. Tolentino said.

The bevacizumab booster helps maintain the gains achieved with pegaptanib, whose safety profile and long-term effects are better known. Pegaptanib received FDA approval in December 2004.

Bevacizumab, in combination with intravenous 5-fluorouracil-based chemotherapy, is indicated for first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum. It has not been approved for use in macular degeneration. However, studies using bevacizumab off-label have had positive results and indicated that the drug is relatively safe.

A form of bevacizumab known as ranibizumab (Lucentis, Genentech) that was specifically formulated as an AMD treatment received FDA approval on June 30.

Dr. Tolentino described early results of his combination therapy approach. At that time, he had treated 26 eyes in 23 patients but has continued to add new patients to this therapeutic regimen. He added that he is aware of other physicians who have begun to try this approach, although none to his knowledge are conducting a formal study.

"The advantage of this for a retina specialist is that a lot of us are still conservative," Dr. Tolentino said. "If you are conservative and don't want to use off-label drugs, for example, or are worried about possible deleterious side effects but also want to garner their power, then this combination allows a couple of things.

"One is that it allows you to feel comfortable using a questionable, possibly long-term toxic type of drug because you can keep the dose to a minimum. It also allows you to individualize the therapy."

The booster approach

He explained that he devised the booster approach when some patients complained their vision began to deteriorate during the 6 weeks between the pegaptanib injections. However, nothing could be done for them until the next scheduled treatment session.

Now, if an examination with OCT reveals worsening between injections, he administers a booster of bevacizumab. It is not yet known how frequently the booster would be needed or how often it could be safely administered.

"I believe that one or two injections per year may be adequate, but the patients will dictate that," Dr. Tolentino said. "So far I have given repeat booster shots in only a few patients."