Short-term follow-up of intravitreal bevacizumab indicates drug is safe in study

Short-term results show that bevacizumab (Avastin, Genentech) seems to be safe and effective for neovascular age-related macular degeneration (AMD), reported Philip Rosenfeld, MD, PhD, during Retina Subspecialty Day.

Bevacizumab is approved for treatment of colorectal and lung cancers but not for injection into the eye. Intravitreal injections of the drug are an off-label use of the drug that is being performed worldwide because of its availability, perceived safety and efficacy, and low cost, Dr. Rosenfeld commented. He is professor of ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine.

"We do not know the long-term ocular and systemic safety profile of bevacizumab," Dr. Rosenfeld said. "However, we are beginning to gather more and more information about the drug."

No toxicity associated with the drug has been detected from in vivo and in vitro studies in a number of recently published studies; no ocular toxicity was detected in studies using multifocal electroretinograms, he said.

In addition, no inflammation has been detected in association with bevacizumab in a study of 61 patients; interestingly, flare measurements decreased in these patients, according to Dr. Rosenfeld.

The projected systemic complications of bevacizumab treatment include hypertension and increased risk of heart attack and stroke. With these concerns in mind, an Internet safety survey was established that included short-term results from 7,000 intravitreal injections in more than 5,000 patients worldwide.

"No significant inflammation or safety signals were identified," he said. "However, the follow-up was limited and we really don't know the long-term effects of bevacizumab."

The combined results from five studies with a total of 350 patients treated with bevacizumab indicated that there was a modest improvement in visual acuity that corresponded to a decrease in central retinal thickness measured on optical coherence tomography. Two prospective studies of bevacizumab also showed decreased retinal thickness and no ocular or systemic toxicity.

"Bevacizumab appears to be nontoxic in tissue-culture and animal studies and appears safe and effective in short-term prospective and retrospective studies," Dr. Rosenfeld said. "The optimal dosing regimens are not known but will be studied prospectively in a head-to-head trial with ranibizumab (Lucentis, Genentech) sponsored by the National Eye Institute to begin in early 2007."