BETHESDA, Md--Delta-amino-levulinic acid (ALA), a compound found in cells throughout the body, holds potential as an active drug in photodynamic therapy and could provide an alternative to surgery for patients with basal and squamous cell carcinomas, R. Rox Anderson, MD, said at the General Motors Cancer Research Foundation conference.
ALA is currently in advanced clinical testing for use in treating actinic keratosis, a precancerous sun-induced thickening of the skin. "These are very superficial lesions, and they are very responsive to ALA," said Dr. Anderson, associate professor of dermatology, Harvard Medical School.
Initial trials of ALA at Massachusetts General Hospital have also shown good results with skin carcinomas. "We find that for superficial tumors, with two treatments of ALA photodynamic therapy, efficacy is close to 100%," Dr. Anderson told Oncology News International. "The deeper the tumor, the lower the efficacy." ALA is not seen as a likely treatment for melanoma.
Cutaneous basal and squamous cell carcinomas, which rarely metastasize, are "almost always surgically curable," he noted, "but the cost, disfigurement, and high incidence argue strongly for developing alternative treatments."
ALA is among a half dozen drugs currently in testing as photodynamic agents in cancer, Dr. Anderson said. Such agents accumulate preferentially in certain cells but become active only when exposed to certain wavelengths of light.
Porfimer sodium (Photofrin), used in the photodynamic treatment of esophageal cancer, is the only such drug approved as a cancer therapy. It is given intravenously and induces sun intolerance for 6 to 8 weeks. "For dermatology, that's a major problem. We like agents that can be given topically or orally," he said, noting that ALA can be delivered topically in a cream.
ALA is a precursor of protoporphyrin, a naturally occurring photosensitive compound in cells. ALA given topically accumulates preferentially in skin tumors, epidermis, and hair follicles, all of which synthesize excessive amounts of protoporphyrin.
Dr. Anderson and his colleagues then use the red and yellow portions of visible light to kill the skin cancers.
Clinically, one treatment using 630 nanometers of red light, given 3 to 24 hours after applying 20% ALA, eradicates about 60% of basal cell and squamous cell carcinomas.
Alternative to Surgery
"We have shown that the low efficacy is due to a combination of failure of the tumor to express protoporphyrin synthesis and insufficient ALA delivery," he said. However, he added, for basal cell and squamous cell carcinomas less than 2 mm thick, efficacy appears to be almost 100% after two treatments, and cosmetic appearance is excellent.
In Dr. Anderson's view, ALA is a viable alternative to surgery for two groups of cancer patients--those with superficial skin carcinomas and people prone to multiple skin cancers as a result of immunosuppression, radiation exposure, or genetic disorders.
But, he said, "for photodynamic therapy to become a preferred skin cancer treatment, we still need reliable ways to deliver both ALA and adequate light exposure deeply, at low cost."
