Photodynamic Therapy for the
Treatment of Nonmelanomatous
Cutaneous Malignancies
Ron R. Allison, Thomas S. Mang, and B. Dale Wilson
Photodynamic therapy (PDT) is a modality whose
concept is not new to dermatologists. PDT has
gained regulatory approval in the United States for
the treatment of esophageal a n d lung malignan-
cies. The field has grown over the last d e c a d e , a n d
now phase II/III clinical trials using second genera-
tion drugs for the treatment of nonmelanoma skin
cancers, palliation of metastases to the skin, a n d
Kaposi's sarcomas have been introduced. These
new sensitizers tend to reduce the one side effect
of PDT, namely persistent generalized cutaneous
photosensitivity. PDT has shown efficacy in (1)
patients who have failed conventional therapies,
and for whom local treatment options are limited
(2) patients in whom surgery would result in cos-
metic disfigurement, a n d (3) patients prone to
developing multiple lesions as in Godins syn-
drome. Dosimetry is based on well-understood
treatment matrices that have optimized light deliv-
ery with known photosensitizer administrations.
The advantages of PDT for cutaneous malignan-
cies include the ability to treat numerous lesions in
one setting, in a noninvasive manner without any
apparent concern for the development of carcino-
genicity.
Copyright 9 1998 by W.B. Saunders Company
EW MEDICAL CONDITIONS are as obvious
F as those that affect the skin. All too often
these lesions, particularly malignant and premalig-
nant ones, cause physiological and psychological
distress. Furthermore, the myriad of treatment
options and techniques available for cutaneous
disorders are almost as numerous as the length of
the differential diagnosis. Mohs micrographic
surgery is the recognized standard for the exci-
sion and treatment of primary and recurrent
nonmelanoma skin cancers. 1 Other treatment
modalities include surgical resection, cryosurgery,
electrodessication, chemosurgery, topical treat-
ment with chemotherapeutic agents, and radia-
tion therapy. 2 Only recently has photodynamic
therapy (PDT) come of age to be considered as a
therapeutic option. Although this review is not
intended to be all inclusive, it is intended to give a
clear picture of the state-of-the-art practice of
Seminars in Cutaneous Medicine and Surgery, Vol 17, No 2 (June). 1998:pp 153-163
PDT today. In this review, we will examine the
current results of PDT on a wide variety of
cutaneous findings.
PDT is a treatment modality with unique
properties that make it an appealing therapy for
the local treatment of nonmelanoma skin cancers.
PDT uses photoactive drugs that concentrate in
tumors and hyperproliferating tissues. These pho-
tosensitizers can be activated by low-power non-
thermal light specifically directed to sites to
selectively destroy diseased cells and tissues. PDT
has the ability to treat many lesions simulta-
neously, in an outpatient setting.
Historically, PDT has been available since an-
cient times with reference made to treat wounds
and tumors by light activated substances. 3 The
first known use of a chemical-light interaction in
oncology was in 1903. In that particular applica-
tion, eosin and light were combined to treat skin
cancer. 4,s Experiments in 1911 showed the tumor
localizing capabilities of porphyrin-based photo-
sensitizers. The emergence of porphyrin mixtures
in the treatment of cancer was described in a
series of studies by Dougherty et al, during the
1970s and 1980s. 6 These studies investigated the
application of hematoporphyrin derivative (HPD)-
induced PDT in a broad range of malignancies in
preclinical and clinical trials. They were focused
on determining the sites of action, toxicity, drug
and light dosimetry, and efficacy of HPD-PDT.
Through their success, PDT has become an emerg-
ing modality for the treatment of cancer today
From the State University of New York at Buffalo School of
Biomedical Sciences and Dental Medicine, Buffalo, NY,, and The
Photodynamic Therapy Center, Buffalo General Hospital, Buf-
falo, NY.
Address reprint requests to Thomas S. Mang, PhD, State
University of New York at Buffalo, School of Dental Medicine,
Dept of Oral Surgery, Squire 112, 3435 Main St, Buffalo, NY
14214.
Copyright 9 I998 by WB. Saunders Company
1085-5629/98/I 702-000858.00/0
153
154
PHOTOSENSITIZERS
PDT has three main components: a photosensi-
tizer, intense light, and molecular oxygen, the
combination of which creates a photodynamic
reaction. There has been significant interest re-
cently, as a result of the FDA approval of Photo-
frin (porfimer sodium; QLT Phototherapeutics,
Vancouver, B.C., Canada)-induced PDT in the
treatment of esophageal cancer, in the develop-
ment of new photosensitizers for the treatment of
malignancies. Some of these may be shown to
have a specific niche in the treatment of disease,
whereas others may ultimately have a broad
applicability, as has Photofrin, the only photosen-
sitizer currently approved for PDT.
The properties that are essential for photosensi-
tizer use in humans are (1) low toxicity; (2)
photophysically efficient, or in other words, show
a high yield of singlet oxygen or some other
cytotoxic species; (3) can be activated by light in
the electromagnetic spectra >600 nm for signifi-
cant tissue penetration; and (4) have a pharmaco-
kinetic profile that results in selective retention/
uptake in tumors and relatively rapid clearance
from normal tissues. Other properties that are
highly desirable in photosensitizers include (1)
easily formulated; (2) low cost; and (3) have
strong absorption in the red or near infrared
portion of the electromagnetic spectrum.
Currently, Photofrin is the only drug that is
approved for use in the treatment of cancer.
However, there has been recent emergence in the
development of new photosensitizers. The design
of these new drugs is along the lines of the
properties listed above. The sensitizers that are
currently in clinical trials and their wavelength of
absorbance used in treatment are: Purlytin, 664
nm (SnET2; Miravant Medical Technologies, Santa
Barbara, CA); Lutetium texaphrin, 732 nm (Phar-
macyclics, Sunnyvale, CA); Benzoporphyrin de-
rivative, 692 nm (BPD; Quadra Logic Photothera-
peutics, Vancouver, B.C., Canada); and Foscan,
652 nm (m-THPC; Scotia Pharmaceuticals, Sur-
rey, England). One of the defining characteristics
of these various photosensitizers is a ring struc-
ture with multiple unsaturated double bonds.
These bonds act as resonators to accept the light
energy to create the photochemical reaction.
As alluded to earlier, tumor selectivity in PDT
is achieved through selective photosensitizer re-
tention and selective light direction. The therapeu-
ALLISON, MANG, AND WILSON
tic ratio as well as favorable photobleaching
kinetics of the photosensitizers in normal tissue,
can lead to a highly selective therapy for most
patients/ It is the differential cytotoxicity that
distinguishes PDT from other chemically based
forms of cancer therapy.
To achieve greater selectivity without the unde-
sired side effect of systemic cutaneous photosensi-
tivity, there have been recent developments in the
photosensitization of cutaneous diseased sites by
topical application of photosensitizers. Chief
among the photosensitizers developed for this
purpose is 5-aminolevulinic acid (ALA).s-ll ALA
is a precursor of protoporphyrin IX (PplX) in the
heme biosynthetic pathway. ALA is not photody-
namically active; however, PpIX, the endogenous
end product of ALA application, is highly photo-
reactive. Once ALA is applied to a site and enters
the pathway the production of sufficient levels of
PplX to induce a photodynamic reaction, once
illuminated, can be achieved.
LIGHT SOURCE
The light source for PDT is generally derived
from a laser and delivered via a fiberoptic device
designed for that specific application. The wave-
length of light that activates the photosensitizer is
dictated by the absorbance characteristics of the
sensitizer to a greater degree and by the spectral
characteristics of the target tissue to a lesser
degree. Nonlaser light sources have also been
used as illumination devices in PDT. The critical
factor in activation is generally the appropriate
wavelength of the light, which is selectively
absorbed by the sensitizer. Because it is used as an
activating source for a photochemical reaction,
and not a device to coagulate or vaporize tissue,
the laser may not be essential. This is a unique
difference because lasers, particularly in the disci-
pline of dermatology, are usually used to perform
functions such as skin resurfacing and tattoo
removal among others, therefore utilizing photo-
thermal or photomechanical effects. The primary
lasers used in the treatment of patients with PDT
consist of argon-dye or potassium-titanyl-phos-
phate (KTP)-dye lasers. The argon-dye laser has
been a mainstay for PDT for most of its recent
history, and is an example of a continuous wave
laser system. This laser has two distinct advan-
tages in PDT. The first is that of tunability. This
means that by adjusting the optical components
PDT FOR CUTANEOUSMAUGNANCIES
within the cavity of the dye laser, one can use the
laser at various wavelengths. This can also be
achieved by changing the dye that is used in the
laser, because different dyes have characteristic
wavelengths at which one can achieve maximal
output. Characteristically, because Photofrin has
been the photosensitizer that has been used in
most clinical trials to date, lasers have been used
at 630 nm. The second advantage is that the
argon-dye systems generated high output powers.
The high power allowed for the coupling of the
laser power to multiple fiberoptics, which facili-
tated treating up to four tumor sites at one setting.
Hence, many tumors could be treated in a rela-
tively short period of time. Since the approval of
Photofrin, argon-dye systems are commercially
available and relatively easy to use.
KTP-dye laser systems have only become avail-
able recently. They are also capable of achieving
relatively high power outputs. Unlike the argon-
dye laser, the KTP-dye is a pulsed system. How-
ever, because the pulse repetition is rapid, the
effect on tissues is essentially equivalent to a
continuous wave laser operating at the same
wavelength. It is for this reason that the KTP-dye
system has been referred to as a quasi-continuous
wave laser.
Diode lasers are now being tested in various
clinical trials with specific photosensitizers. These
lasers are compact and can be inexpensively
produced as the technology evolves. Currently, a
diode laser has not been produced for use at 630
nm in the United States. Diode lasers do exist,
however, at longer wavelengths, ie, 652 nm and
664 nm, and are used in clinical trials for other
photosensitizers.
GENERAL PROCEDURES
Laser Preparation
One of the pitfalls of using lasers in patient
procedures is the potential for technological fail-
ure. For this reason and to ensure proper opera-
tion of the laser, the system should be checked
before the injection of the patient with a photosen-
sitizer. The system should also be checked again
before its use on the day of treatment. Generally,
the system should be checked to ensure that there
is adequate power to carry out the intended
procedure, for the stability of the output, and that
the proper wavelength is being emitted.
155
Fiber Preparation
The fiber that is generally used for superficial
light application is a lens fiberoptic. Before using
the fiberoptic, it should be examined for transmis-
sion defects by checking first, the output power
through the lens, and second, that the illumina-
tion pattern from the fiber is even. The latter can
be accomplished by shining the output from the
fiber onto a wall or other fiat object. The output is
evaluated with the power meter that is usually
supplied with the laser system.
MECHANISMS
Information regarding the mechanisms of ac-
tion for PDT has been ascertained from in vitro
and preclinical data on experimental tumors.
Regardless of the problematic relevance of these
studies for cancers in humans, certain conclu-
sions correlate to what has been observed in
human trials. The photodynamic mechanism for
the biological inactivation of target tissues appar-
ently proceeds via a photochemical reaction in-
volving singlet oxygen. 12 In this reaction, the
photodynamic process produces an excited state
of ground state oxygen. This species, called
singlet oxygen, is generated via a so-called Type II
mechanism of photosensitized oxidation. The
photosensitizing molecule, on absorption of a
photon, is brought to an excited singlet state.
From this singlet state, the photosensitizer can
decay back to the ground state and emit light in
the form of fluorescence. For the photodynamic
process, however, the photosensitizer should un-
dergo intersystem crossing to the excited triplet
state. This triplet state has a long half-life, and
therefore, has a high probability of interacting
with ground state oxygen. The energy transfer
from the triplet photosensitizer generates the
reactive singlet oxygen species. Singlet oxygen
seems to be the essential cytotoxic agent for
Photofrin and most other photosensitizers tested
to date. 13 It is the electrophilic nature of singlet
oxygen that makes it very efficient at producing
oxidized forms of biomolecules. This process can
result in irreversible oxidation of critical cellular
components, as well as tumor microvasculature. 14
Photosensitizers such as Photofrin are lipophilic,
and therefore, can be found concentrated in
membranous structures, is Oxidation of the outer,
mitochondrial, lysosomal, and nuclear mem-
156
branes may result because of the photodynamic
action.
in vivo, the response to photodynamic therapy
can be rapid, At least part of the response to PDT
in tissues results from an effect on the microvascu-
lature in and around the tumor, 14,16 The ultimate
result is a loss of blood flow to the area and
subsequent oxygen nutrient depletion. Direct
cellular effects are evident within hours after light
therapy as well, The effects at the cellular level
range from apoptosis to nonspecific autoantibody
response, resulting in deposition of factors such
as igM, C3, and fibrin in a Cascade fashion.
Multiple studies, which continue to explore the
relationship between metabolic and vascular ef-
fects, have been published on the various effects
of PDT.
CLINICAL APPLICATIONS
Photodynamic therapy has the potential to
treat a wide variety of cutaneous lesions, both
benign and malignant. Malignancies involving
the skin that have been treated with PDT include
basal and squamous cell carcinomas~ such as
basal cell nevus syndrome, Bowen's disease, myco-
sis fungoides, human immunodeficiency virus
(HIV) associated Kaposi's sarcoma, and recurrent
metastatic breast carcinoma2 7-~2 As long as the
photosensitizer can accumulate in the tumor in
question and light activation can be achieved,
therapeutic reaction may occur, We will discuss
the histology of each individually,
Basal Cell Carcinomas
AS in the case of other pathologies, a wide
variety of photosensitizing agents have been used,
along with many different light sources and
treatment schedules. However, all have proven
rather effective~ but the optimal PDT is yet to be
determined,
For these studies, patients with biopsy-proven
basal cell carcinoma, either primary or recurrent,
generally in multiple sites, were entered into the
treatment protocol. Most of the patients had
previous therapies, which included surgical exci-
sion, cryosurgery, ionizing radiation, or electrodes-
sication. Recurrent tumors were either too exten-
sive for excision or not candidates for Moh's
surgery. Primary tumors could be easily excised
or treated by subsequent Moh's surgery if PDT
failed. Patients for whom excision of their tumors
ALLISON, MANG, AND WILSON
would result in signifcant disfigurement requir-
ing reconstructive or plastic surgery were also
offered PDT as an option in lieu of undergoing
surgical excision at that time. Finally, patients
who had been diagnosed with basal cell nevus
syndrome were also offered PDT as part of their
overall management strategy.
For both practical and theoretical reasons,
early protocols were designed to establish the
lowest possible drug dose (to reduce normal skin
effects and decrease overall photosensitivity) and
the maximum light dose (to achieve maximum
tissue penetration for depth effect). 7 A drug dose
of 1.0 mg/kg body weight of Photofrin was
injected intravenously, as a bolus over a period of
10 minutes; Two days later, the patient would
return to the clinic for laser/light treatment. In the
treatment of skin lesions, the laser is often fitted
with a multiple fiber coupler, which allows the
use of 2 to 4 fibers for the simultaneous treatment
of multiple lesions. In all cases, the power density
(dose rate) was approximately 150 mW/cm 2 per
fiber. The total dose of light (energy density)
given to each lesion was 215 J/cm 2. When pos-
sible, a margin of normal tissue, equal to approxi-
mately 1 cm greater than the greatest bidimen-
sional measurement of the tumor, was included
within the treated volume. When a larger tumor
was encountered (>1 cm in the largest bidimen-
sional measurement), an interstitial method of
light illumination was often used. In a case such
as this, a fiberoptic with a small cylindrical
diffusing tip was used. Dosimetry for a diffusing
tip consists of the use of 400 mW/lin.cm (power
output) and a total dose of 300 J/lin.cm When
possible, the interstitial method was combined
with the superficial technique.
Wilson et al reported an 88% complete re-
sponse on 151 lesions treated in a series of 37
patients with 29-month follow-up, z In this series,
125 of the sites were primary basal cell carcino-
mas and 26 sites were recurrent. This study was
conducted as a drug and light dose ranging study,
and consequently, some tumors received what is
now known to be subtherapeutic treatment. There
was an approximately 18% recurrence rate in this
group (for all treatment combinations). Interest-
ingty, retreatment of recurrences resulted m a
100% complete response rate. Patients who have
multiple lesions or large surface areas that are
affected are particularly suited for PDT (Fig i).
PDT FOR CUTANEOUSMALIGNANCIES 157
t i t

The response of the lesion is quite selective in that

only the lesion is irreversibly damaged. The
normal tissue undergoes some response, yet does
not undergo necrotic change. The healing process
occurs over approximately 4 to 8 weeks, depend-
ing on the size of an individual lesion. Some
response of large treated areas shows temporary
hypertrophic scarring that usually resolves with-
out further intervention (Figs 2 and 3). The
treatment involves only one outpatient session.
There were no nonresponders in this series of
patients. It was clear from this study that lesions
in different anatomic locations responded differ-
ently. Of note, a majority of the recurrences were
on the nose (particularly in the folds of the nose). Fig 2. Patient in Fig I, 4 months post-PDT. Com-
This may be due in part to the multiple treatment plete healing of the lesion is noted. Some residual
angles required to obtain adequate light dose hypertrophic scarfing is evident from the treat-
delivery, superficially, for this anatomy. The sug- ment of this large surface area. (Reprinted with
gestion from this report is to include an intersti- permission. ~3)
tial treatment of these lesions in addition to the
treatment from the surface, to achieve complete showing that lesions greater than 2 mm in depth
response on the first exposure. Svanberg, as well treated by ALA-PDT had only a 45% complete
as Hintschich, reported a 100% complete re- response rate compared with 90% for lesions less
sponse on a total of 36 lesions with excellent than 2 mm in depth. ~l When used, dimethyl
cosmesis, using Photofrin.l~ sulfoxide increases skin penetration of ALA, and
Studies involving topical ALA report complete
clinical responses in the 90% to 100% range from
superficial lesions to a bit less for nodular tu-
mors. 1~ This was well defined by Warloe's report

Fig I. Multiple basal cell carcinoma on the

forehead of patient before PDT. The patient had
previously been treated by multiple surgical exci-
sions and liquid nitrogen over a period of approxi-
mately 7 years. The entire area was treated with Fig 3. Patient in Fig I, 9 months post-PDT. Hyper-
PDT in one outpatient session. She experienced trophic scarring caused by PDT is no longer evi-
facial edema, persisting for several days after PDT, dent, and patient was free of disease. (Reprinted
which resolved. (Reprinted with permission. 13) with permission. 13)
158
response rates may increase. In addition, retreat-
ment (fractionation) for lesions with incomplete
response is often fruitful as shown by Svanberg's
report on 100% complete response rates for those
patients undergoing two PDT sessions on the
same lesions. 1~
Of note is that both topical and systemic PDT
agents often have excellent response and cosme-
sis. To determine the optimal modality for PDT of
basal cell lesions would require a randomized
study, which is lacking at this time. An important
concept to remember is that topical sensitizers
may not penetrate deeply enough to allow for a
photodynamic reaction in nodular lesions, n and
as such, systemically injected sensitizers may be
more versatile in the clinical study. An important
application for PDT is in Gorlins syndrome (basal
cell nevus syndrome) in which the multiple
lesions can be clinically and cosmetically con-
trolled in a very effective and minimally morbid
fashion.18 Wilson, reporting on 588 lesions treated
by IV Photofrin, found a 95% clinical complete
response, with mean follow-up of 28 months, r
Squamous Cell
Squamous lesions in the skin respond to PDT,
but apparently at a slightly lower rate than basal
cell carcinomas. This is compensated for by
increasing the light dose to the lesion by approxi-
mately 20%. Generally, the normal tissue reaction
is more severe; however, cosmetic results after 23
the higher light dose are basically the same as
those obtained for the treatment of basal cell
carcinomas.
Hernnijton used systemic HPD and treated 32
lesions, resulting in a 81% complete response
rate. 24 Several series, reporting on more than 700
lesions treated, showed an outstanding 100%
complete response rate with superb cosmesis. 25-2r
Both topical and systemic agents had been used in
these reports. A large series by Robinson using
Photofrin intravenous had a 100% complete re-
sponse rate with a minimum 6 month follow-up
with 500 lesions treated; cosmetic results were
excellent. 28
An interesting application of PDT was reported
by Petrelli. 19 In this series, PDT was exceptionally
useful in treating squamous cell lesions of the
perianal region in which rather extensive surgery
ALLISON,MANG, AND WILSON
would have been required, as well as potentially
greater morbidity.
Bowen's disease (intraepidermal squamous cell
carcinoma) responds to PDT. Jones et al have
reported a series of six patients with biopsy-
proven Bowen's disease who were treated with
PDT. 22 Patients were given an intravenous injec-
tion of Photofrin (1.0 mg/kg). Approximately 48
hours after injection, the areas were exposed to
630 nm light for a total dose of 215 to 250 J/cm 2.
The reported follow-up time ranged from 14 to 24
months. The lesion sites included areas of the
head and neck as well as buttock and perianal
lesions. All the patients treated in this series were
reported to be disease free at the longest fol-
low-up period. Perhaps in situ disease (Bowen's
disease) will be the most common diagnosis for
squamons cell lesions to be treated with PDT.
Kaposi's Sarcoma
Kaposi's sarcoma (KS) is the most common
malignancy in AIDS patients. 29 Despite a wide
variety of therapeutic approaches, effective pallia-
tive treatment is still difficult to achieve. 3~ The
multifocal nature of KS often makes local treat-
ment by radiation or surgery difficult and time-
consuming. Furthermore, cosmetic results are
generally unacceptable with these modalities.
PDT offers a possible solution in that multiple
lesions are treated in a single session, and no
immune compromise is noted from the photosen-
sitizer, as is seen from chemotherapy and immune
therapy. The cosmetic results in KS patients
treated with PDT are usually excellent.
Patients with biopsy-proven acquired immuno-
deficiency syndrome (AIDS)-associated KS have
been treated in various PDT trials. Experience has
been gained in the treatment of this disease with
two photosensitizers, Photofrin and SnET2.
In a series of patients reported by Bernstein et
al, patients were treated with 1.0 mg/kg of Photo-
frin and escalating surface length doses of 100 to
400 J/cm 2 via lens fiberoptics. The study con-
sisted of 26 patients with 348 lesions. In this
study, 94 lesions (32.5%) were rated as complete
responses. A total of 183 lesions (63.3%) showed
a partial response, and 12 lesions (4.2%) were
classified as clinical failures. These response rates
were consistent with studies performed on other
skin malignancies, in that there was a clear light
PDT FOR CUTANEOUSMALIGNANCIES 159

dose dependent effect of PDT. 33 There did not,

however, seem to be any correlation between
peripheral blood CD4 § counts and treatment
response. In this study, the m a x i m u m tolerable
light dose was found to be 300 J/cm 2. Patients
treated in this fashion show similar wound devel-
opment and healing characteristics as those treated
with other cutaneous (basal or squamous cell)
malignancies. Initial response includes erythema
and edema of the treated site. Breakdown and
necrosis of the lesion usually follows within 1 to 2
weeks. This is usually selective for the lesion
versus normal surrounding skin treated within
the fields volume. After 4 to 8 weeks, again ~k
depending on the size of the lesion and field
Fig 5. Patient from Fig 4, 12 weeks post-PDT
dimensions, the lesions heal. treatment. Treatment sites show no evidence of
Hebeda reported on eight HIV-positive patients diesease or pigmentation. The patient continues I
with a total of 83 lesions. 34 Overall response rates year postfreatment with no evidence of disease in
were very good in this study; however, the cos- treated sites.
metic results were unsatisfactory. In that study,
there was a prevalence of scars and long lasting
quently activated, 24 hours postinjection, by
hyperpigmentation. Severe side effects as a result
664 +__ 3 nm light delivered via fiberoptic from a
of treatment were also seen, including intense
diode laser light source. The total light dose
pain and blistering. This was likely because of the
delivered was 300 J/cm 2 at a power density of 150
combination of a high dose of sensitizer (2 mg/kg
mW/cm 2. Patients were administered 1.2 mg/kg
Photofrin) and high laser dose (up to 120 J/cm2).
(IV) Purlytin. Outcome analysis reported excel-
In a recent study, 35 Purlytin-PDT was per-
lent cosmesis and an overall 75% complete re-
formed on 9 patients with biopsy-proven KS
sponse rate on 121 lesions. Those individuals
lesions. The total number of lesions treated was
with a partial response to the first PDT session
121. All patients were HIV-positive. The drug
had a 95% complete response after a second
SnET2 was intravenously injected and subse-
treatment session. Morbidity was limited to pho-
tosensitivity for 2 weeks. Cosmesis was superb in
areas treated on the face (Figs 4 and 5).

Fig 4. Patient with multiple Kaposi's sarcoma
lesion. Two lesions on the eyelids were treated with
PDT. The eye was protected from exposure using
an eye cup.
Chest Wall R e c u r r e n c e
Various treatment modalities are used in treat-
ing recurrent breast cancer. 36"38 Treatment of
primary disease may include lumpectomy, mastec-
tomy, radiation therapy, chemotherapy, or hor-
mone manipulation therapy. Often, several meth-
ods are used in combination to manage systemic
and local cutaneous disease resulting from metas-
tases. However, following mastectomy, chemother-
apy, and radiation, chest wall recurrence of breast
cancer is devastating in that few palliative options
remain. Further, breast cancer that is metastatic to
the chest wall/skin is usually seen in advanced
cases, and these patients have normally failed
other therapies. Uninhibited, the recurrent chest
wall nodules cause the patient extreme pain.
160 ALLISON, MANG, AND WILSON

Twenty-four percent of patients who have been

treated for advanced breast cancer have been
reported to develop cutaneous lesions. 39
A phase II trial of Purlytin-PDT was conducted
to assess the response of patients with advanced
breast cancer metastases to the chest wall. A total
of 86 lesions (2.4 cm mean diameter) were treated
on eight patients who had biopsy-proven chest
wall recurrence despite mastectomy, chemother-
apy, and radiation. Each patient underwent a
single photodynamic therapy session in which
the drug Purlytin (1.2 mg/kg) was injected.
followed 24 hours later by laser light treatment at
660 + 3 nm (@ 150 mW/cm 2, for a total light dose
of 200 J/cm2). With a minimum &month follow- Fig 6. Large recurrent breast cancer in patient
up, the objective response rates after PDT were previously treated with radiation and chemother-
apy. Patient received PDT in four separate fields to
complete response (CR) 92%, partial response
provide adequate dosimetry to the tumor site.
(PR) 8%, no response (NR) 0%, for a total of
100% response rate overall. Patients who undergo
infection that responded to oral antibiotics. No
this therapy show wound healing characteristic of
photosensitivity reactions were reported in this
the previously described treatments. There are.
set of patients. Posttreatment pain, which could
however, some discernable differences in the
be treated with medication and application of
response of these lesions to PDT. Generally, as
cold compresses, was reported.
many of the patients treated by PDT at various PDT appears to offer an excellent local control
institutions have previously received other thera- rate of chest wall recurrence after multimodality
pies, the response to PDT is more exuberant. treatment failure with minimal morbidity. The
Frequently, during the treatment sessions in pa- treatment is given in a single session and on an
tients with multiple lesions that are in close outpatient basis. In patients who may register a
proximity to each other, pain is associated with PR or have recurrence or the incidence of further
the light illumination itself. This is generally chest wall nodules post-PDT, the treatment is
controlled with an analgesic given patients before repeatable. At 6-month follow-up, some of these
therapg as well as during the course of the
treatments themselves. Occasionally, stronger
medications are necessary. Overall. the lesions
respond with very good selectivity. The light dose
used is generally 25% less than that which is used
to treat other cutaneous lesions. This again is
because of the apparent greater sensitivity of
these lesions to PDZ Lesions generally undergo
necrotic change within 2 weeks after treatment
and form eschars over the treated lesion within 2
to 4 weeks after treatment (Figs 6 and 7).
Complete healing of the lesion is slower and may
require 12 to 16 weeks to reepithelialize com-
pletely (Fig 8). This is generally attributed to the
fact that the lesion is in a previous radiation
therapy field. Lesions less than 0.5 cm in diameter
Fig 7. Patient from Fig 6, at 16 weeks post-PDT.
had a 100% CR. Morbidity was minimal with no Small eschar remained over the treated site, which
systemic toxicity. One patient developed a wound was left untreated,
PDT FOR CUTANEOUS MALIGNANCIES
Fig 8. Patient from Fig 6, 20 weeks post-PDT.
Eschar resolved without intervention. Site was free
of disease. Patient remained free of disease in
treated site I year post-PDT.
patients developed new lesions outside the prior
PDT field. As such, fractionation of PDT sessions
for those individuals with new or recurrent le-
sions may offer the best chance of an extended
palliation. This seems to be a much higher
response rate than Lapes' report using topical
TPPS4 (Porphyrin Products, Logan, UT), in which
only a 33% complete response rate was re-
ported. 4~
ADVERSE REACTIONS
The one side effect of concern to patients
receiving the photosensitizer is prolonged cutane-
ous photosensitivity to bright, visible light (eg,
sunlight). 41 Patients are therefore instructed to
avoid such light for 2 to 6 weeks after injection.
The length of the photosensitivity period is highly
dependent on the specific photosensitizer used
and the total dose of the drug. Generally, the light
precaution that a patient needs to take consists of
protecting exposed skin with appropriate cloth-
ing. This clothing should be a tightly woven
material, so as not to let sunlight or intense visible
light through. The patients are instructed to wear
a broad brimmed hat and gloves. Sunscreens are
not of value in protecting the skin from a photo-
sensitivity reaction, as it is the visible wavelengths
of the sun that cause the reaction and not the
ultraviolet. The patient is not in danger from
normal indoor lighting. Further, low level expo-
161
sure to light is of help in the elimination process.
Low level exposure will photobleach residual
drug in the skin and ultimately shorten the
photosensitivity period.
The drug application and the light treatment
are generally well tolerated and undertaken as an
outpatient procedure. In a minority of individu-
als, some topical pain is noted during the laser
procedure, at the site being treated. This is well
controlled with the application of a cold com-
press for 10 to 15 minutes while the treatment is
held.
SUMMARY
Over the last two decades, PDT has gone from
an interesting laboratory observation to an excit-
ing and useful therapy for the treatment of
malignant, premalignant, and benign disease. To
date, enough patients and lesions have been
treated to begin to define and refine the role of
PDT. Clearly, PDT offers promising results for in
situ manifestations such as Bowen's disease. Squa-
mous cell and basal cell carcinomas also have
been rigorously shown to be candidates for treat-
ment with PDT, as clinical and cosmetic results
are excellent. PDT also offers local palliative
therapy for breast cancer patients who have
recurrent cutaneous manifestations. The therapy
is tolerated well and can be combined with some
forms of concomitant chemotherapy for the effec-
tive treatment of these patients.
Finally, the treatment of HIV-associated KS
lesions has also been shown to be efficacious in
these patients, and again the treatment is well
tolerated. Furthermore, the injection of either
Photofrin or purpurins does not adversely affect
the patient's immune status.
With only a limited number of photosensitiz-
ing agents and a wide variety of application
techniques, PDT has already shown superb clini-
cal promise. As new agents are introduced and
applications optimized, the future for PDT looks
bright.
ACKNOWLEDGMENT
The authors are grateful to Wendy L. Snider
and Gretchen Hewson, RN, for their contribu-
tions in the preparation of this manuscript.
162
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