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What is SPDT/SDT?
 Overview
This report describes two therapies to treat cancer. They are:·
- Systemic Photodynamic therapy (SPDT). Used both systemically (to treat
the whole body) and semi-locally ( to treat reasonably large but local
areas of the body). PDT is a 100 year old therapy which has recently
benefited from greatly improved technology.
- Sonodynamic therapy (SDT). This is a very new therapy which
is complementary to SPDT. Its major uses are for treating deeper tumours,
and for amplifying the benefits of SPDT. The two therapies in combination
are more effective than either alone.
These treatment modes used in combination are called SPDT/SDT.
The therapy is carried out in the Opal Clinic on an outpatient basis.
There are no injections, no pain, no anaesthetics. Except for late stage
patients, the only common side effect is tiredness, which is treated with
plenty of rest and by slowing down the treatment as necessary. Later stage
patients may experience very significant tiredness and other symptoms
such as moderate pain in the tumours and nausea. These symptoms are easily
controlled, mainly by slowing down the treatment and controlling the resulting
inflammation. There are no known long term side effects. Some patients
experience side benefits not related to their cancer, and this is believed
to be due to the therapy also attacking microbes (bacteria, viruses, fungi
and parasites) and atherosclerotic plaque.
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Why
do we need SPDT /SDT?
Successful treatment for cancer requires a four-step process:
- Diagnose the condition.
- Surgically remove the primary tumour, providing this can be safely
done with limited damage to function.
- Kill any remaining metastases.
- Shift to an 'anti-cancer' life style: to attack the underlying conditions
that caused the disease and to reduce the risk of recurrence/further
cancers.
Current medical practice does reasonably well with diagnosing and surgically
removing the primary tumour. The greatest weakness of current therapies
is in killing remaining metastases. The best time to eliminate them is
as early in the disease process as possible, before they have had time
to grow and damage vital tissue. However, there are problems:
- The main tools currently used to attack metastases: chemotherapy and
radiation therapy may not work at all for many people, may not work
enough to completely solve the problem, and may only work with only
some of the tumours present. They may cause side effects which are completely
unacceptable to the patient. When the treatment provides little or no
benefit, the patient is likely to be net loser. The damage to quality
and quantity of life can easily outweigh whatever benefits are achieved.
- Small metastases are hard to find. Tumors less than about 5 millimeters
in size are hard to detect with conventional scanning techniques. They
may not be detected at all by blood tests (until much later in the disease
process). The net result is that the doctor often does not know if the
patient needs additional treatment after surgery, does not know if any
therapy actually used is working, and may not be able to accurately
decide how much (if any) treatment to give. Lack of accurate knowledge
of treatment effects is a very important issue when using toxic therapies,
because the margin for error may be low. Even if effective, too little
treatment may not be enough to complete the job; too much may cause
severe side effects.
- Conventional therapies may be too dangerous to use with patients who
might have cancer remaining after surgery.
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Photodynamic
Therapy
PDT was first used medically in 1904 to cure skin cancer. It is now a
thoroughly studied therapy in reasonably common use. A Google search of
PubMed (find PubMed using the Google search, then in the PubMed web site,
search the database "PubMed" for "Photodynamic therapy
" ) will yield over 8,600 references to medical journal articles.
In a 2000 review, Hopper (6) states that, "PDT can
achieve control rates similar to those achieved with the standard techniques
of surgery and radiotherapy. The real advantages of PDT are the lower
morbidity rates, improved functional and cosmetic outcomes and simplicity
of the technique." This comment is based on the use of earlier sensitizers
and light equipment. There have been significant improvements in the therapy
since then.
PDT has been approved in countries such as Canada, Netherlands, France,
Germany, Japan and U.S. for the first-line treatment of various cancers
(10). The Peter McCallum Institute in Melbourne, Australia,
recently completed a trial on using PDT to treat a skin cancer. The purpose
of the trial was to seek regulatory approval for this application.
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How SPDT works:
The therapy is illustrated in Figure 1.
Step 1 - The patient ingests a photosensitizer (PS),
Step 2 - The PS is selectively absorbed
by cancer cells.
Step 3 - Exposure to light activates the PS, producing a high-energy
molecule PS*.
This in turn gives up the energy it has acquired in two
ways:
- By reacting with oxygen in the body to produce free radical oxygen
and other free radicals. These are powerful oxidants, so powerful that
they immediately attack nearby organic material - the cancer cell.
- By emitting fluorescent radiation that can be detected and used to
locate cells that have taken up the PS, once again - the cancer cells.
Figure 1
Dougherty et al (4) report that SPDT destroys cancer cells
using a number of different mechanisms:
- Direct cytolytic (cell destroying) effect.
- Induction of apoptosis (programmed cell death)
- Induction of an immune response to tumour (non-specific as well as
specific response, which may lead to long term control of the tumour).
- Induction of micro vascular damage, which may lead to tumour nutrient
deprivation.
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Limitations
of Classical PDT
Despite the safety and efficacy of the treatment (3), PDT
is only used on a limited scale in Western countries, mainly to treat
skin cancer. The limiting factors are cultural and technical:
Cultural
- Chemotherapy, radiation therapy and hormone therapy are well entrenched.
In China, where there is much less acceptance of toxic therapies, PDT
is reported to be used in 1,100 clinics·
- The medical fraternity is very slow to take up new therapies. "In
medicine there is a 15 year rule. It takes about 15 years for a new,
non-controversial therapy to be widely accepted by the medical community.(7)"
Technical
There a number of limitations with earlier photosensitizers:
- Inadequate selectivity for cancer cells, limiting PDT to treating
only local tumours. Use of a not very selective sensitizer results in
much sensitizer present in healthy cells, and the healthy cells will
be damaged by light. Treating large areas of the body results in excessive
damage to healthy cells.·
- Not enough free radicals are produced, i.e. the cancer cell killing
capacity is limited;
- Some sensitizers are activated using blue light where the body is
not very transparent. This makes the therapy ineffective with deeper
tumours.
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What
has changed to make SPDT a more attractive therapy option?
The development of new sensitizers with the following characteristics:·
- Increased selectivity; they are taken up almost exclusively by cancer
cells. This allows treatment of the whole body, rather than limiting
the therapy to small, local areas ( with the risk of not treating some
metastases at all)·
- Less toxicity·
- Oral administration (as opposed to intramuscular or intravenous injection)·
- Rapid clearance from normal cells, thus avoiding sensitivity to ambient
light.·
- Increased potency-greater oxygen radical production·
- Increased penetration depth, because they absorb at longer (red and
infra-red) wavelengths. ·
- Greater understanding of mechanisms of action(3),(10)
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Sonodynamic
therapy (SDT)
This is a much newer therapy. A PubMed search will only show about 30
references. It is very similar to SPDT except that the sensitizer is activated
by ultra sound rather than by light.
SDT is complementary to SPDT. It provides further vital advantages:·
- We use sensitizers which are activated by both ultra sound and red
light.· ]
- The body is very transparent to ultra sound (that is why it can be
used to visualize the fetus developing in the womb). This makes SDT
particularly useful for treating deeper tumours.·
- Safety. To the best of our knowledge, there has never been a law suit
in the U.S. claiming damages as a result of ultra sound treatment.
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Opal
Clinic's systemic photodynamic therapy and sonodynamic therapy
The Clinic uses new, highly selective sensitizers and light equipment
to:
- Treat the whole body with light i.e. give systemic therapy. We use
a light treatment bed fitted with 48,000 light-emitting diodes to expose
the whole body to red and infra red light. Systemic therapies are the
only ones that can treat undetected cancer. If the cancer can be anywhere,
we have to treat everywhere.
- Treat semi-localized areas with intense SPDT. We typically know the
general area where cancer is mainly present, or where it could be, and
then give these areas more intense therapy.
- We then treat these areas with ultra sound radiation, thereby attacking
the cancer a different way, using a different mechanism to activate
the sensitizer, and an activating medium (sound) which behaves differently
to light.
Some useful characteristics of the Opal therapy
- Knowledge of type of tumour and the exact tumour location are not
required. We only need a general idea where the tumours are, or are
likely to be. Compare this with radiation therapy and surgery, which
require accurate knowledge of tumour size and location. Chemotherapy
and hormone therapy require accurate knowledge of the type of tumour
present. Systemic PDT does require any knowledge at all about any cancer
present.
- There are no known disease transmission processes associated with
this therapy. With surgery and biopsies, cutting into tumours may result
in the growth of the smaller tumours at distant sites, or along the
surgical wounds (9).
- The therapy can be repeated as often as required. This is because
the sensitizer has very low or no toxicity before it is exposed to light
or sound. The body treats it as a foodstuff. Once activated, it is toxic,
but only to the cells it is in, i.e. the cancer cells. Thus the sensitizer
acts as a 'Trojan horse', and the body does not develop resistance to
it. Compare this with chemotherapy and radiation therapy, where the
larger the dose, the greater the damage to normal cells as well as to
cancer cells. Also, with chemotherapy, the body correctly treats these
drugs as toxins. It may learn to resist them, resulting in the drugs
no longer being effective.
- The two therapies together are more effective than either alone(17)
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How
good is SPDT/SDT?
Let us start by looking at the medical literature, (actually using
earlier and less effective sensitizers and light equipment):
- Hopper(6) has reviewed the field and reports that trials
with many cancers have shown that PDT can achieve control rates similar
to those achieved with the standard techniques of surgery and radiotherapy.
The advantages of PDT are: fewer side-effects; improved functional and
cosmetic outcomes and simplicity. He reports many complete responses
with various skin cancers and oral cancers. There were impressive results
for early stage lung cancer (85 % complete response), early bronchial
and esophageal cancers (83 % showed no recurrence after an average follow
up time of 15.3 months) and early gastric cancer (complete response
in 80 % of patients with intestinal cancer). As expected, best results
are obtained with early stage cancers, but unlike radiation therapy
and surgery, PDT can be repeated many times(6).
- Okunaka and Kato(12) reported on the PDT treatment of
145 patients with a total of 191 early lung cancer lesions. Complete
remission was obtained with 86.4 % of the total number of lesions.
- Kato et al(8) reported a complete response with 83% of
patients treated with PDT for early squamous cell carcinoma of the lung.
- Sheleg et al(13) used PDT to treat 14 patients with skin
metastases from melanoma. All skin melanoma metastases showed complete
regression with no recurrence during the study period.
- These results are so good that cancer specialists should be reporting
them to patients as part of a full disclosure of treatment options.
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SPDT
plus surgery
Hopper(6) makes the point that in a large number of solid
tumours, surgery leaves behind residual microscopic disease that may lead
to local recurrence or metastatic disease. SPDT is an ideal adjuvant therapy
especially when the risk of local failure is high, as in gastrointestinal
and prostate surgery. A review of the treatment of more than 310 brain
cancer patients concluded that there is a clear trend towards improved
survival when PDT is used along with surgery.
SPDT/SDT for early-stage breast cancer SPDT, usually in conjunction with
a lumpectomy or a mastectomy is expected to be particularly effective
with early-stage breast cancer. Why? Because the cancer is near the surface
where the light can easily reach it and where photodynamic diagnosis can
be used to map the cancer spread. In early stage disease, there will not
be much cancer to kill.
While we have not found reports in the medical literature regarding the
use of PDT for early-stage breast cancer, there are studies reporting
good results with later-stage breast cancer. Wyss et al(16)
treated chest wall recurrences in patients treated by mastectomy for breast
cancer. They treated 7 patients with a total of 89 metastatic skin nodes.
They achieved a complete response in all cases.
Allison et al (1) carried out a similar study of 9 patients
at a total of 102 chest wall sites, with lesions up to 9 cm. Despite the
fact that all patients had failed surgery, full dose radiation and multi-agent
chemo-hormonal therapy, chest wall lesions healed with no scarring after
SPDT was used. Clearly, if doctors can get such good results with metastatic
breast cancer, it is reasonable to expect even better results earlier
in the disease process.
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Opal
treatment outcomes with SPDT/SDT
Please read the material in Treatment Outcomes.
This information is rapidly developing, so please get the latest report
from our clinic.
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Where
is SPDT/SDT now?
SPDT/SDT is a new and very rapidly improving technology. The use of chlorin
e6 based photosensitizers is only about 10 years old, use of whole body
light treatment is about 4 years old, and use of sonodynamic therapy is
less than two years old.
Since these therapies are so new, we lack long term patient outcome data.
This will eventually come. What we do know at present is that we can produce
remarkable short term benefits. It is reasonable to assume that these
short term benefits will translate into long term benefits, but we do
not yet know much about this. It would be better to have more certainty,
but unfortunately people with cancer usually cannot wait. They have to
make decisions based on whatever evidence is available.
If SPDT/SDT can get good results with patients with later stage cancer,
it is reasonable to assume that it will do even better with early stage
patients. A good time to begin therapy is during the "window of opportunity"
after surgery. This is the time when the patient has least cancer. Surgery
may have completely removed the cancer, (we never know) in which case
SPDT/SDT may be a waste of time and money. If there is cancer remaining,
whether it has been detected or not, we believe that SPDT/SDT is likely
to remove it.
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Side
effects of SPDT/SDT Cancer Treatment
- SPDT/SDT often provides immediate symptomatic relief. Patients often
experience reduced pain and nausea, as well as a halting of weight loss
and an improvement in their appetite levels.
- The treatment process itself is health enhancing, not negative to
patients' health.
- Side effects are only due to cancer breakdown, which means the more
cancer the more side effects. These are fairly easily managed.
- Although some side effects may be uncomfortable, they are mild in
comparison to those experienced after some other cancer treatments.
- SPDT/SDT has shown no evidence of long-term damage.
- Even if the cancer does recur, SPDT/SDT can be repeated as many times
as required and still have full effect.
- There is no risk of disfigurement. Successful SPDT/SDT will leave a
hole where the cancer was. That is all.
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The
limiting factors in treating larger tumour loads
Amount of treatment needed
SPDT/SDT (like all other cancer treatments except surgery), can only kill
cancer at a limited rate. If surgical de-bulking is not possible, then
two or more rounds of therapy, each taking 2 weeks or more, are likely
to be necessary.
Tumour breakdown symptoms
Patients receiving SPDT/SDT therapy may experience symptoms associated
with tumour breakdown. The therapy induces cell death, releasing the cell
contents and cell fragments into the blood. The most common symptom of
tumour breakdown is tiredness. This could range from modest tiredness,
requiring a few extra hours sleep each day, to complete exhaustion, requiring
stopping the therapy until the symptoms subside. The more cancer present,
the greater the likelihood and severity of tumour breakdown symptoms.
For this reason our doctor has to design an individual therapy plan for
each patient, and carefully monitor patient condition during the therapy.
In general, the more cancer present, the slower the therapy, and the more
that is done to control these symptoms. There is no point in overloading
the patients detoxification organs- liver, kidneys, etc.
Please note these important points about tumour breakdown :
- These symptoms are very mild by cancer treatment standards, and are
easily managed by slowing down the treatment, by taking anti-inflammatory
drugs, by taking supportive foods and herbs such as cod liver oil and
St Mary's thistle, and by drinking plenty of water.
- This problem is rarely noticed with mainstream therapies. It is not
a problem with surgery, because the tumour is removed rather than killed
in situ. Tumour breakdown will rarely be noticed with chemotherapy because
the therapy may not kill cancer at all, it may kill cancer slowly enough
for the body to easily detoxify breakdown products, or the breakdown
symptoms may be masked by more severe symptoms due to drug toxicity.
- With a large tumour load, tumour breakdown symptoms are likely to
be the limiting factor in SPDT/SDT treatment intensity. Our strategy
is to give whole body light therapy to attack cancer everywhere in the
body. We give intense light treatment to areas where cancer is known
or expected to be present. The length of treatment is increased each
day until the patient (usually) experiences tumour breakdown. We then
back off and treat at the maximum comfortable light dosage. Ultra sound
therapy is usually added when any tumour breakdown symptoms have abated.
- If tumour breakdown symptoms are not present or easily manageable,
a round of treatment will be completed in two weeks. If symptoms are
significant, three weeks may be required. If symptoms are severe, a
round may take even longer to complete.
- Presence of "tumour breakdown symptoms" does not guarantee
that we are killing cancer, however we believe that it is a reasonably
reliable indicator that the treatment is working.
- Note that these side effects are (usually ) the result of successfully
killing cancer. They are not the result of any inherent treatment toxicity.
Given that we have cancer present, tumour breakdown symptoms are good
symptoms to have.
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New
developments
Opal Clinic has been treating patients for cancer for several years.
The original technology was based on a chlorin e6 type sensitizer with
whole body systemic photodynamic therapy (SPDT). This technology is new, and new
technologies often rapidly improve. We have made a number of improvements;
using a better sensitizer, adding sonodynamic therapy (SDT), etc.
In August, 2006, we acquired a very much better light sources and a better
designed rectal probe, and we simultaneously increased treatment times
to about 1 ½ hours per session. We have only a few months experience
with this new protocol, but results so far have been spectacular. We believe
these changes have fundamentally altered the nature of the therapy. We
are rapidly developing information on treatment results with this new
development, please contact us for the most recent information. Click here
to email us for up to date information.
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References:
1. Allison R, Mang T, Hewson G, Snider W, Dougherty D, Photodynamic therapy
for chest wall progression from breast carcinoma is an underutilized treatment
modality. Cancer 2001; 91 (1); 1-8.
2. Baum M, Demicheli R, Hrushesky W, Retsky M. 2005. Does surgery unfavourably
perturb the "natural history" of early breast cancer by accelerating
the appearance of distant metastases? Eur J Cancer. 41(4):508-15.
3. Collection of abstracts from medical journals on PDT efficacy in treating
specific cancers. Opal Clinic_PDT_ Scientific_Statement.doc. www.opalclinic.com.au
4. Dougherty T.J., Gomer C.J., Henderson B.W., Jori G., Kessel D., Korbelik
M., Moan J., Peng Q., 1998. Photodynamic Therapy Review. Journal of the
National Cancer Institute 90 (12), 889-905.
5. Galbraith RA, Drummond GS, Kappas A, Suppression of bilirubin production
in the Crigler-Najjar type I syndrome: studies with the haeme oxygenase
inhibitor tin-mesoporphyrin, Pediatrics, 89,175- 181, 1992.
6. Hopper Colin, Photodynamic therapy: a clinical reality in the treatment
of cancer. The Lancet Oncology 2000 (1), 212- 19.
7. Hyman, Mark and Liponis, Mark, Ultra-prevention. Scribner, 2003.
8. Kato H, Sato M, Okunaka T, Yusunoki Y, Kawahara M, Fukuoka M, Miyazawa
T, Yana T, Matsui K, Shiraishi T and Horinouchi H. Phase II clinical study
of photodynamic therapy using mon-L-aspartyl chlorine e6 and diode laser
for early superficial squamous cell carcinoma of the lung. Lung Cancer
2003; 42(1): 103 -11.
9. Kumar V, Cotran R S, Robbins S L. Robbins Basic Pathology (7th ed).
Philadelphia, 2003.
10. Lane, N New light on medicine. Scientific American, January 2003.
11. Moan J, Peng Q., 2003. An outline of the hundred-year history of
PDT. Anticancer Res. 23 (5A), 3591-600.
12. Okunaka T and Kato H, Nippon Photodynamic therapy for lung cancer:
state of the art and expanded indications. Geka Gakkai Zasshi 2002, 103(2):
258- 62.
13. Sheleg SV, Zhavrid EA, Khodina TV, Kochubeev GA, Istomin YP, Chalov
VN, Zhuravkin IN, Photodynamic therapy with chlorine e (6) for skin metastases
of melanoma. Photodermatol Photoimmunol Photomed 2004; 20(1); 210-6.
14. Whelan HT, Houle JM, Whelan NT, Donohue DL, Cwiklinski J, Schmidt
MH, Gould L, Larson D, Meyer GA, Cevenini V, and Stinsen H, The NASA light-emitting
diode medical program- progress in space flight and terrestrial applications,
1997.
15. Woolams Chris, Everything you need to know to help you beat cancer.
Health Issues Ltd. United Kingdom, 2003.
16. Wyss P, Schwarz D, Dobler-Girdziunaite D, Hornung R, Walt H, Degen
A and Fehr M, Photodynamic therapy of loco-regional breast cancer recurrences
using a chlorine - type sensitizer. Int J Cancer 2001; 93(5); 720-4.
17. Zhao-hui Jin et al, The combined effect of photodynamic and sonodynamic
therapy on experimental skin squamous cell carcinoma in C3H/HeN mice,
J Dermatology, 27,294-306,2000
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IMPORTANT DISCLAIMER
This article is intended for informational purposes only. Nothing in this
article is intended to be a substitute for professional medical advice.
This document may not be modified, and derivative works of it may not
be created.
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