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
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
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
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
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."