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Fenretinide slows lesion growth


Oral fenretinide slowed the growth of geographic atrophy and reduced the incidence of choroidal neovascularization in patients who were treated over a 2-year period with a daily dose of the drug.

Key Points

Fenretinide, a derivative of vitamin A, is advantageous because it is chemopreventive, apoptotic, anti-angiogenic, anti-inflammatory, and is available in an oral form. The drug has been studied extensively in pediatric and adult patients in doses ranging from 100 to 7,200 mg daily. Its safety is well known and it has been shown to have fewer side effects compared with other retinoids.

The drug has a long history of clinical use. Fenretinide has been used clinically for three decades in large clinical trials to treat breast cancer, bladder cancer, leukoplakia, prostate cancer, and neuroblastoma as well as in smaller studies of ovarian cancer, cervical cancer, solid tumors, and lung cancer. Other conditions studied include rheumatoid arthritis, cystic fibrosis (preclinical with clinical trials under way), obesity, acne, psoriasis, malignant gliomas, renal carcinoma, and leukemia.

Jason S. Slakter, MD, participated in a study in which the efficacy of fenretinide to slow the progression of geographic atrophy in patients with age-related macular degeneration (AMD) was evaluated. Dr. Slakter is clinical professor of ophthalmology, New York University School of Medicine, New York.

He explained that in a normal eye, vitamin A (retinol) is necessary for vision. The retinol is recycled and regenerated by the retinal pigment epithelium (RPE). However, in individuals who are predisposed to the development of AMD, that recycling process becomes compromised, resulting in the build-up of vitamin A waste products that subsequently damage the RPE, ultimately causing cell death.

In autofluorescence photographs, Dr. Slakter showed the accumulation of toxic byproducts of vitamin A that precedes atrophy of the ocular tissue. Retinol comes to the eye bound to retinol binding protein (RBP) and transthyretin (TTR), which is the preferred form of uptake by the RPE.

Fenretinide, the structure of which is similar to retinol, competes with retinol for binding to RBP and prevents an interaction with TTR. The drug is effective in the eye because the fenretinide that is bound to RBP, according to Dr. Slakter, "is eliminated from the circulation due to its small size, thereby reducing delivery of vitamin A to the eye and the accumulation of toxins in the RPE."

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