|
Although PDT
remains an investigational treatment modality in dermatology, several important areas of
development may ultimately lead to official and practical acceptance of PDT for the skin.
Indeed the skin is usually the first organ in which many of the newer second generation
photosensitizers are evaluated. The modern era of PDT began in the 1970s with the
pioneering work by Dougherty et al at the Roswell Park Memorial Cancer Institute in
Buffalo using hematoporphyrin derivative.1 It
is perhaps somewhat ironic that although the skin was the first organ in which PDT was
systematically evaluated, as of mid 1997 the only official regulatory approvals for PDT
are for the treatment of internal malignancies involving the lung, genitourinary system,
and gastrointestinal tract using porfimer sodium (Photofrin®), the first generation
photosensitizer.
For treating diseased tissue, PDT, like PUVA, involves the sequential administration of
drug followed by light. However, PDT involves the photochemical generation of reactive
singlet oxygen that interacts with tissue components, whereas PUVA’s effects appear
to depend more on reactions independent of O2.
New photosensitizers
Persistent generalized cutaneous photosensitivity due to photosensitizer retention in
the skin has been the main limitation of porfimer sodium, which is administered
parenterally. This has led to the development of second generation photosensitizers, some
of which appear to be cleared far more rapidly from the skin than porfimer sodium (Table). With topically active agents such as 5-aminolevulinic acid
(5-ALA) and ATMPn, skin photosensitivity is restricted to areas of direct drug
application. 5-ALA is unique in that it is actually a low molecular weight porphyrin
precursor that is metabolized in situ within the skin to protoporphyrin IX, which
possesses significant PDT activity.
Are lasers essential for PDT?
PDT has become synonymous with the use of porphyrins and lasers for treating skin
cancer. While lasers are indispensable for delivering light to internal organs via
fiberoptic endoscopy, they are relatively expensive and inefficient light sources for
photosensitizer activation in the skin. The critical property for any PDT light source is
that its spectral output provides sufficient power at an activation wavelength that is
appropriate for the photosensitizer being used.
In the future, non-coherent, broad or narrow band light sources such as
incandescent bulbs, arc lamps, fluorescent tubes, and light-emitting diodes may prove to
be the light sources of choice for dermatologic PDT. These latter devices are usually
cheaper to operate, more compact, and more effective for irradiating large surfaces than
lasers.
Does PDT work?
- Skin cancer Although the literature documents an extensive collective
experience for PDT of skin cancer (reviewed in Reference 2) there is a
dearth of either long term follow-up data (i.e. more than 2-5 years of reported follow up)
or histologic evaluation of treated sites. Moreover, in dermatology, there is only one
published, controlled trial of PDT. In treating Bowen’s disease, the combination of
ALA and a broad band lamp was felt to be as effective as cryotherapy, but with fewer
adverse effects.3 More studies such as
this will be needed in order to more precisely define the role of PDT for skin cancer
management.
Novel indications for PDT
- Non-hypertrophic actinic keratoses of the face and scalp In a
vehicle-controlled study, topical ALA and red laser light have recently been shown to
clear up to 91% of these keratoses.4 Multicenter
phase III studies of topical ALA for this indication are currently underway in the US.
- Psoriasis PDT has been shown to demonstrate significant immunomodulatory
effects in animal models of arthritis.5
Thus there is a rationale for using PDT in treating inflammatory disorders such as
psoriasis. One potential advantage of PDT over PUVA is that PDT may not be
intrinsically carcinogenic. Pilot studies have demonstrated clearing of psoriasis
using topical6 and systemic
photosensitizers.7
- Removal of unwanted terminal hair Topical ALA selectively photosensitizes
pilosebaceous structures and Grossman et al have used ALA-PDT to remove unwanted terminal
hair with some degree of success.8 How
this modality will compare to the current generation of hair removal lasers will await
controlled clinical studies.
| If the potential therapeutic advantages of using PDT to
treat actinic keratoses, non-melanoma skin cancers, psoriasis and hair removal continue to
be demonstrated in clinical trials, Dermatologists would welcome PDT as an effective, safe
and cheaper treatment alternative to current therapy, including lasers. Photodynamic
therapy should no longer be looked upon as a procedure looking for a disease to treat. |
Dr. Stuart Maddin, Editor |
|
|
