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PHOTO
DYNAMIC THERAPY (PDT)
The
operation of photo dynamic therapy is simple in theory. The patient is given a
substance (the photo sensitizer) that is absorbed by cells and makes the cells
sensitive to damage by light. PDT has been used for many years to treat skin cancer
and other tumours that are near enough to the surface of the skin to be affected
by light. The question is whether a tumour in the prostate gland can be treated
effectively by this means.
There are two primary points to be considered:
1.
How can light be introduced into the prostate gland?
2. How can PDT be used
to treat systemic disease, since there is a widespread view that prostate cancer
may be systemic by the time it is capable of diagnosis?
In a discussion
in 2008 on the PPML
Mailing List, Dr Luis Garcia-Bunuel had this to say regarding the first of
these items:
"In well confined, non-superficial lesions, PDT would
be administered using same approach as with brachytherapy. For the prostate, it
could be called interstitial PDT. As the light has relatively low penetration,
multiple light-emitting probes would have to be placed within the prostate itself
to cover the entire gland. The good side of PDT is that it is a non-ionizing radiation
--and therefore non-carcinogenic-- and it can be repeated as frequently as necessary
with less damage to surrounding tissues than with other methods. It will probably
become an additional weapon, particularly for salvage therapy and for lesions
confined to the prostate.
Although the results of this phase
1 trial are not very encouraging, the two most important conclusions to be
derived from it, IMO, are that the preferred wavelength is in the near infrared
and that the light delivery is through optical fibres inserted using a transperineal
brachytherapy template in the same manner as for pellet-delivering probes for
traditional brachytherapy. The infrared wave length is convenient because it still
is in the photosensitizer range and with much better penetration of tissues than
its close neighbour in the red visible range. Although these techniques will probably
undergo refinements, they are likely to be the preferred ones in future trials.
It also appears likely from this trial that interstitial PDT can become a good
additional weapon, but not particularly superior to some of the existing ones,
and only for site-confined deep-seated lesions. For more superficial lesions,
both cutaneous and intraluminal, PDT has already been proved of help, but it is
very unlikely that it will ever be of value in metastatic spreads, as claimed
by some people..
…….[there would be a] necessity for a substantial number
of light-emitting probes to reach all prostate areas. If too few, the effective
distribution will be uneven, with some areas receiving insufficient doses. …….
Even if infrared penetration is much greater than in the red visible range, the
number of probes still has to be sufficient to cover the entire prostate adequately.
I don't get a good idea from my readings of how many probes that would be, and
the answer may await further clinical trials."
As to the treatment
of a systemic or metastasised disease, Dr Luis Garcia-Bunuel had this to say about
claims that using light in the red and infrared range, PDT could reach deep-seated
metastases by surrounding the entire patient with light-emitting diodes (LEDs)
to the tune of 48 thousand of them (!!).
"At the longer wavelengths
of red and infrared, they claim the light can penetrate twelve inches into the
body. That's where scientific facts end and fantasy begins. The reason why non-interstitial
PDT has been mostly used in skin and other superficial lesions is that even at
the longer wavelengths, the penetration of soft tissues is relatively shallow.
From short to long wavelengths, we have the following spectrum:
Short
waves--> ultraviolet --> [visible spectrum (violet through red)]--> near infrared-->
far infrared-->microwaves--> radio. The longer the wavelength, the deeper the
penetration.
[The suggested] methodology appears to rely on red and near
infrared. It is doubtful that those wavelengths would penetrate deeper than one
or two centimetres Even microwaves don't go as deep as the twelve inches claimed
….That's why one can roast small game birds in a microwave oven, but would have
trouble roasting a regular chicken.
The medical spectrum could be defined
as: Facts--> Sound but unproven theories--> Unsound theories--> Quack claims.
It looks like the theories of advocates of SPDT are moving from the factual end
of the spectrum towards the other end."
So, theoretically, PDT looks
as if it might be a good option for the treatment of prostate cancer where the
disease is confined to the gland, although clearly it will be some time before
studies are concluded and approval gained from the authorities.
An aspect
that must be considered for any prostate cancer treatment is the question of side
effects or collateral damage. To quote Dr Luis Garcia-Bunuel again:
"As
for potential collateral damage, that ought to be a concern, as is with cryotherapy
and other procedures. It is a misconception to think that only cancer cells collect
the photosensitizer. They do to a greater degree than more mature and less vascularized
tissues, but the normal tissues also absorb the photosynthesizer and still are
vulnerable. "
As Luis says, part of the issue here is the selectivity
of the photosensitizer and another is how long it remains in the body. Normally
patients using PDT have to be very careful to avoid light, especially sunlight.
Skin exposed to light will get a reaction and will be damaged severely by the
sun , or have rashes and blisters.
In theory, the newer substances being
used in trials are designed to home in on cancer cells (and certain other kinds)
in preference to normal tissue, but this selectivity is not absolute. The possibility
of selectivity being enhanced by chemically combining the photosensitizer with
certain antibodies is being actively pursued. In this way the selectivity of the
photosensitizer is combined with the localized introduction of light to improve
the attacking of just the cells that it is intended to attack. If this is achieved
it would greatly reduce the potential for damaging the cells in the erectile nerves
and the bladder.
Newer applications are also being developed that have
a very short 'life' in the patients' bodies. The aim is to have the photosynthesizer
out of the patients' bodies by the time they leave the recovery room and thus
minimise potential damage.
J
Environ Pathol Toxicol Oncol. 2006;25(1-2):373-87.
Updated results of a
phase I trial of motexafin lutetium-mediated interstitial photodynamic therapy
in patients with locally recurrent prostate cancer.
Verigos K, Stripp DC,
Mick R, Zhu TC, Whittington R, Smith D, Dimofte A, Finlay J, Busch TM, Tochner
ZA, Malkowicz S, Glatstein E, Hahn SM.
Department of Radiation Oncology,
University of Pennsylvania, 3400 Spruce Street, 2 Donner, Philadelphia, PA 19104,
USA.
Locally recurrent
prostate cancer after treatment with radiation therapy is a clinical problem with
few acceptable treatments. One potential treatment, photodynamic therapy (PDT),
is a modality that uses laser light, drug photosensitizer, and oxygen to kill
tumor cells through direct cellular cytotoxicity and/or through destruction of
tumor vasculature. A Phase I trial of interstitial PDT with the photosensitizer
Motexafin lutetium was initiated in men with locally recurrent prostate cancer.
In this ongoing trial, the primary objective is to determine the maximally tolerated
dose of Motexafin lutetium-mediated PDT. Other objectives include evaluation of
Motexafin lutetium uptake from prostate tissue using a spectrofluorometric assay
and evaluation of optical properties in the human prostate. Fifteen men with biopsy-proven
locally recurrent prostate cancer and no evidence of distant metastatic disease
have been enrolled and 14 have been treated.
Treatment plans were developed
using transrectal ultrasound images. The PDT dose was escalated by increasing
the Motexafin lutetium dose, increasing the
732 ran light dose, and decreasing
the drug-light interval. Motexafin lutetium doses ranged from 0.5 to 2 mg/kg administered
IV 24, 6, or 3 hr prior to 732 ran light delivery. The light dose, measured in
real time with in situ spherical detectors was 25-100 J/cm2. Light was delivered
via optical fibers inserted through a transperineal brachytherapy template in
the operating room. Optical property measurements were made before and after light
therapy. Prostate biopsies were obtained before and after light delivery for spectrofluorometric
measurements of photosensitizer uptake.
Fourteen patients have completed protocol
treatment on eight dose levels without dose-limiting toxicity. Grade I genitourinary
symptoms that are PDT related have been observed. One patient had Grade II urinary
urgency that was urinary catheter related. No rectal or other gastrointestinal
PDT-related tox-icities have been observed to date. Measurements of Motexafin
lutetium demonstrated the presence of photosensitizer in prostate tissue from
all patients. Optical property measurements demonstrated substantial heterogeneity
in the optical properties of the human prostate gland which supports the use of
individualized treatment planning for prostate PDT.
Publication Types:
a.. Clinical Trial, Phase I
