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Integrative Cancer Therapies
http://ict.sagepub.com/content/8/3/283
The online version of this article can be found at:
DOI: 10.1177/1534735409343693
2009 8: 283Integr Cancer Ther
Xiaohuai Wang, Weimin Zhang, Zhiyong Xu, Yifan Luo, Doug Mitchell and Ralph W. Moss
Sonodynamic and Photodynamic Therapy in Advanced Breast Carcinoma: A Report of 3 Cases
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2. Sonodynamic and PhotodynamicTherapy in
Advanced Breast Carcinoma:A Report of
3 Cases
Xiaohuai Wang,Weimin Zhang, Zhiyong Xu,Yifan Luo,
Doug Mitchell, and Ralph W. Moss1
Abstract
Photodynamic therapy (PDT) is an established therapeutic method, first approved by the FDA for certain kinds of cancer
in 1998. There are also increasing data to show that a related procedure, sonodynamic therapy (SDT), is a promising new
modality for cancer treatment. Here, the authors report clinical results in 3 advanced refractory breast cancer patients who
were treated using a combination of sonodynamic and photodynamic therapy (SPDT), along with conventional therapies.All
3 patients had pathologically proven metastatic breast carcinoma.These widely disseminated carcinomas had ultimately failed
to respond to conventional therapy.A new sensitizing agent, Sonoflora 1™ (SF1) was administered sublingually; then, after a
24-hour delay, patients were treated with a combination of light and ultrasound.All patients had significant partial or complete
responses. SPDT is a promising new therapeutic combination for the treatment of breast cancer.
Keywords
sonosensitizer, photosensitizer, sonodynamic therapy, photodynamic therapy, chlorophyll derivatives, breast cancer
1
Liu Hua Qiao Hospital, Guangzhou 510010, People’s Republic of China,
Chemistry and Environment College, Southern China Normal University,
Guangzhou, People’s Republic of China, Science Group, Melbourne,
Australia, Cancer Decisions, Inc, Lemont, PA, USA
Corresponding Author:
Xiaohuai Wang, Department of Oncology, Liu Hua Qiao Hospital, 111 Liu
Hua Road, Guangzhou 510010, People’s Republic of China.
Email: wangxhgz@163.com
Introduction
Since the 1990s, photodynamic therapy (PDT) has been
increasingly used for the treatment of various human tumors.
However, the successful application of this method has been
limited to superficial lesions because of the limited penetra-
tion of laser light into tumor tissues.1,2
Sonodynamic therapy
(SDT) has been developed as a complementary or alternative
therapy to PDT.3-9
There are data to show that an additive
effect might be obtained if SDT is combined with PDT.10
There are also data showing that PDT is synergistic with che-
motherapeutic agents.11
In SDT treatment, patients first ingest
a sonosensitizer, a drug that can be activated by ultrasound.
This drug is then activated through the use of low-intensity
ultrasound, producing a cascade of endogenous cytotoxic
agents. The therapy is thus similar to PDT, except that the
sensitizer is activated by ultrasound rather than by light. The
body transmits ultrasound much more efficiently than light,
and this is a decisive advantage when treating deeper tumors.
So far, not much clinical data on SDT have been pub-
lished. One reason is the difficulty in finding a drug suitable
for clinical use. Such a drug would need the following 5
characteristics:
1. No significant toxicity
2. High tumor selectivity
3. High clearance rate from normal tissues
4. High sonosensitivity
5. A stable chemical composition
In recent years, a novel sonosensitizer was developed by the late
Donald Burke, MD, of Advanced Technologies, Boston, USA.
He named this Sonoflora 1™ (SF1). This agent is a chlorophyll
derivative with very high sonodynamic as well as photodynamic
activity. The absorption peak is a wavelength of 636 nm. SF1
basically fulfills all the above desiderata. Embryonic zebra fish
assay data provided by Advanced Technologies show no
evidence of toxicity. Our own animal studies demonstrate that
SDT with SF1 inhibits the growth of mouse S-180 sarcoma,
even when the tumor is covered by a bone.12
Here, we report initial clinical data using SF1 for sonody-
namic and photodynamic therapy (SPDT) in advanced breast
Integrative Cancer Therapies
8(3) 283–287
© The Author(s) 2009
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3. 284 Integrative CancerTherapies 8(3)
carcinoma. For this study, SF1 was supplied by Advanced
Technologies, Boston, MA, and by its successor company,
SonneMed LLC, Marlborough, NH.
Case Presentation
Treatment Method
From 2005 to 2007, we consecutively treated 3 advanced
breast carcinoma patients using SPDT. All these carcinomas
were pathologically proven, and all patients had failed con-
ventional therapies. SF1 was given to patients through lin-
gual absorption for 2 or 3 days. Then, 24 h after taking the
last dose of agent, a red LED light, 630 nm and 20 mW/cm2
,
was used to irradiate the tumor area or the whole body for
30 minutes (Figures 1A and 1B, and Figure 2). After this, a
portable ultrasound device was applied to treat each tumor
area for 20 minutes at a 1 MHz frequency and power of 2.0
W/cm2
(Figure 2 and Figure 3B). The light and ultrasound
treatments were performed daily for 3 days. Based on each
patient’s situation, 1 or 2 weeks later, the next cycle of
treatment was carried out. Two light designs were used in
this study—a handheld device and a light bed. The handheld
light was for local treatment (Figure 1A and Figure 2), and
the light bed was for whole body treatment, provided that
the patient was strong enough to get in the device (Figure
1B). Cases 1 and 2 were given SDT using a conductive gel
on the skin (Figure 2). Case 3 was given SDT in a water
bath (Figure 3B). Water conducts ultrasound almost as well
as gel, but it is much easier to carry out SDT under water,
and this can be used for whole body treatment.
Case 1, woman, aged 43. She had a resection of her left
breast carcinoma in March, 1997. Pathological examination
confirmed this to be carcinoma, T2N2M0, with Her-2[++],
P53[-], ER[+++], PR[+++], EGFR[−]. After surgery, she
received 6 cycles of chemotherapy (cyclophosphamide +
doxorubicin + 5-fluorouracil, CAF), radiation therapy (DT:
50 Gy/25F), and then tamoxifen. The cancer recurred in
1999 and spread throughout her body. She then had radia-
tion therapy and 6 cycles each of paclitaxel and
5-fluorouracil (TF), vinorelbine + trastuzumab, capecitabine,
and hormonal therapy with goserelin and letrozole. She also
had 2 courses of 89Sr treatment. All these treatments ulti-
mately failed.
A PET/CT scan in March 2005 showed that the tumor had
spread to the bones, lungs, liver, and abdomen. The metastases
in the neck had already destroyed the cervical vertebra and had
involved the spinal cord (Figure 4A). By May 2005, the patient
had high-level paraplegia, respiratory failure, heart failure, lung
infections, high fever, and no feeling in the limbs. Her heart rate
was 150 to 170 per minute, and she was put on a respirator to
Figure 1. Case 1, breast carcinoma, further treatment:A, the picture shows her second cycle of treatment with sonodynamic and
photodynamic therapy (SPDT) in the ICU. She was able to stop the use of the respirator that had been necessary to maintain breath. B,
the picture shows the third cycle of treatment of SPDT in a LED red light bed. Her symptoms were already much improved. C, comparison
of PET/CT scans before and after 3 cycles of SPDT treatment: PET/CT on August 4, 2005, shows positive partial response, especially in
the neck
Figure 2. Case 2, woman, 49 years.The picture shows case 2 in
treatment by light for axillary lymph nodes and by ultrasound for
primary breast tumor
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4. Wang et al 285
Figure 3. Case 3, woman, 36 years.A, PET/CT taken before
sonodynamic and photodynamic therapy treatment showing right
breast cancer with multiorgan metastases, including lung, bones,
liver, and abdominal lymph nodes. B, the picture of a water bath
used for ultrasound treatment in case 3
Figure 4. Case 1, breast carcinoma, woman, 42 years:A, PET/CT
scan on March 25, 2005, showed that the tumor had spread widely
in the patient’s body, and the metastases in the neck had already
destroyed the cervical vertebra and involved the spinal cord (see
arrow). B, a picture showing case 1 treated in the ICU.The patient
was unable to talk, move, feel, eat, or even breathe. She had to use
a respirator to maintain breath
maintain her breath. The patient was deemed terminally ill, and
her tumors could no longer be treated with conventional meth-
ods. She was transferred from the ICU of another hospital to
our hospital for SPDT on May 16, 2005 (Figure 4B). The next
day, she was treated with SPDT using 30 mg of SF1 plus a half
dose of chemotherapy consisting of dicycloplatinum (DCP)
and hydroxycamptothecin. DCP, which is little known in the
West, is approved in China for use in clinical trials. After 1
cycle of treatment, the patient’s breathing was much improved
and feeling in the limbs was restored (Figure 1A). After
2 cycles, the tumor in the patient’s neck had shrunk from
13 × 6 cm2
to 5 × 3 cm2
. The heart rate was now <100 per
minute, and she could breathe without a respirator (Figure 1B).
After 3 cycles, her symptoms further improved, and her limbs
could be moved with aesthesis. The respiratory, gastric, and
urine catheters were all removed. PET-CT scans in August
2005 showed a partial response, especially in the neck (Figure
1C). She only had reversible grade 2 hematological toxicities.
She was moved out of the ICU into a general ward. However,
from 3 to 6 months after the treatments, the patient’s neck
gradually shortened by about 5 cm because of the destruction
wrought by her cancer. In November 2005, the patient died from
respiratory failure, heart failure, and lung infections.
Case 2, woman, aged 49. The patient found a small mass on
her left breast in July 2005. A needle biopsy proved this to be
a breast carcinoma, which was ER− and PR+. The PET/CT
scan showed left breast carcinoma with multiorgan metasta-
ses to the axillary lymph nodes, bones, liver, and abdominal
lymph nodes (Figure 5A). From July to August, 2005, the
patient was treated with 3 cycles of chemotherapy (first 2
cycles with taxol 240 mg + hydroxycamptothecin 30 mg +
DCP 600 mg and the third cycle with 4-epi-adriamycin
80 mg, cyclophosphamide 0.8 mg, and DCP 600 mg). In
September 2005, a PET/CT scan showed no significant
change in the primary tumor, with new metastases suspected.
Immediately thereafter, high-intensity-frequency ultrasound
(HIFU) was used to destroy a large mass in the patient’s left
liver lobe, and 125
I radioactive seeds were implanted into
masses in the right liver lobe and in the breast primary tumor.
In October and November 2005, she had 2 cycles of SPDT
with SF1 60 mg per cycle (Figure 2). A PET/CT scan in
December 2005 showed a very positive PR. This included
improvement in the tumors in the vertebra, sternum, and
abdominal lymph nodes. These had not been treated by HIFU
and radio seeds (Figure 5B). A PET/CT taken 28 months after
SPDT treatment failed to detect any tumor activity whatso-
ever (Figure 5C).
Case 3, woman aged 36. In April, 2003, the patient’s right
breast and axillary lymph nodes were surgically removed.
Pathology confirmed a T1N1M0 carcinoma with ER++,
PR+++, P53+, PCNA+++, C-erbB2−. After surgery, she had
radiotherapy (TD: 60 Gy/F30) and chemotherapy (3 cycles
of CAF and 3 cycles of TAX/EPI). Her hematological toxici-
ties were grade 2 to 4. Then she started hormone therapy. A
March 2007 PET/CT scan showed metastases in the liver,
lungs, and in many bones (Figure 3A). She was considered
too ill to receive conventional chemotherapy. She was then
admitted to this hospital, where she received 3 cycles of 125I
radio-seed implantation combined with local chemotherapy
for the tumors in her chest, liver, lumbar vertebra, sacrum,
and pelvis. Her CEA (carcinoembryonic antigen) dropped
from 39.7 µg/L to 4.90 µg/L and CA153 from 5000 U/L
to 1500 U/L. However, her marrow function deteriorated,
presumably as a result of radioactive seeds and local
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5. 286 Integrative CancerTherapies 8(3)
chemotherapy in the lumbar vertebra, sacrum, and pelvis. On
April 22, 2007, her white blood cell count was 2.0 × 109
/L;
HGB (hemoglobin), 72 × 109
/L; and PLT (platelet) 48 ×
109
/L. In May, she received 2 cycles of SPDT with SF1 60 mg
per cycle. The ultrasound treatment was performed in a water
bath (Figure 3B). After this treatment, her symptoms were
much improved. She had less pain, a more active lifestyle, and
better appetite. A PET/CT scan in June 2007 showed signifi-
cant tumor inhibition in both the tumors treated with radio
seeds and local chemotherapy as well as in those only treated
with SPDT (Figure 6B). Tumor markers and blood routine
tests had improved to CEA, 5.81 µg/L; CA153, 306.05 U/L;
white blood cell count, 3.9 × 109
/L; HGB, 98 × 109
/L; and
PLT, 80 × 109
/L. They were even better than before SPDT.
Discussion
From 2005 to 2007, we consecutively treated 3 patients with
advanced breast carcinoma using SPDT along with conven-
tional therapies.
Case 1 was safely and effectively treated with SPDT plus
a small dose of chemotherapy. Although chemotherapy was
used, in our opinion, the good response in this case was
mainly a result of SPDT. The patient had 24 cycles of chemo-
therapy, but all chemotherapy ultimately failed. During the
first 3 cycles, the patient was so ill that we had to treat her in
the ICU and give the SPDT mainly on her neck tumors,
which were the most dangerous manifestation of the cancer.
After 2 cycles of treatment, the tumors in her neck shrank
very significantly (from 13 × 6 cm2
to 5 × 3 cm2
), and PET/
CT scan after 3 cycles showed a positive response, especially
on the neck.
We obtained positive results in case 2 and case 3 using
2-step therapy—first the debulking of larger tumors and then
SPDT. To debulk larger tumors we used 125
I radio-seed
implantation and HIFU. Both these methods have few adverse
effects and are able to destroy local tumors very efficiently.
In general, the above local treatment reduces the tumor load
but cannot effectively treat widespread metastases. For a
given amount of sensitizer, the fewer living tumor cells will
absorb more sensitizer, enhancing the SPDT therapeutic
effect. In case 2 we mainly used SPDT to treat undebulked
tumors in the vertebra, sternum, and abdominal lymph nodes
and obtained very good results. In case 3, the patient still had
many untreated metastases in her cervical and thoracic verte-
brae and elsewhere after tumor debulking. We used a water
bath for SDT treatment for almost her whole body (Figure
6B). Ultrasound conducts very quickly and effectively in
water. We believe that SDT delivery through water contrib-
uted to this patient’s excellent results, and we now routinely
use this method of ultrasound delivery.
In all 3 cases, SPDT with SF1 was well tolerated. Unlike
chemotherapy and radiation therapy, SPDT has almost no
toxic effects, nor has it affected marrow and gastrointestinal
function, or damaged important organs such as the spinal
cord, heart, lungs, liver, or kidney. All 3 patients had metas-
tases in the spine, and for case 1, tumors in the neck had
already involved the spinal cord. In our experience, SPDT is
even safer than conventional PDT. The 3 cases did not have
photosensitive dermatitis and did not require interventional
procedures to introduce optical fibers into the body or
tumors, as is often necessary with conventional PDT.
Pain in the tumor regions was the main side effect
of SPDT. If the handheld ultrasound probe is left in one
Figure 5. Case 2, PET/CT scans:A, before sonodynamic and
photodynamic therapy (SPDT); B, after SPDT—PET/CT shows a
highly satisfactory outcome of therapy; C, after SPDT—PET/CT
taken 28 months later shows no signs of tumor in the body
Figure 6. Case 3. PET/CT scans:A, before sonodynamic and
photodynamic therapy (SPDT); B, after SPDT—PET/CT on June
27, 2007, shows a highly satisfactory outcome of therapy
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6. Wang et al 287
position, the energy can accumulate in the deep organs, espe-
cially in the bone. This causes pain. The problem can be
largely avoided by using pulsed ultrasound or by constantly
moving the ultrasound probe. SPDT-induced tumor break-
down can also induce local pain and make patients feel weak
and tired. This is not a severe problem, and in our experience,
patients recover in a few days.
In case 1, 3 to 6 months after SPDT treatments, the
patient’s neck gradually shortened by about 5 cm, but her
neck tumors did not enlarge. We believe that cervical vertebra
collapse, resulting in repression of the respiratory center on
the cervical spine caused or contributed to her death. Before
SPDT, her cervical vertebra had already been seriously
destroyed by tumor (Figure 4A). The SPDT shrank the
tumors, but the bone could not be adequately restored.
In summary, SPDT with Sonoflora is well tolerated and
had significant therapeutic benefits for some patients with
advanced breast cancer. SPDT with Sonoflora has significant
merit for further investigation.
Acknowledgments
The authors wish to acknowledge the scientific contributions
and intellectual leadership of the late Don Burke, MD, in the con-
duct of this research. Lucy Qing Li, PhD, and Mr Jiangan Su, as
officers of EEC Bio-Tech (Guangzhou) Co, Ltd, supported this
project in providing funding, equipment, information, and organiza-
tional skills.
Declaration of Conflicting Interests
The authors declared no conflicts of interest with respect to the
authorship and/or publication of this article.
Funding
The authors received no financial support for the research and/or
authorship of this article.
References
1. Dolmans DE, Fukumura D, Jain RK. Photodynamic therapy for
cancer. Nat Rev Cancer. 2003;3:380-387.
2. Brancaleon L, Moseley H. Laser and non-laser light sources for
photodynamic therapy. Lasers Med Sci. 2002;17:173-186.
3. Umemura S, Kawabata K, Sasaki K, Yumita N, Umemura K,
Nishigaki R. Recent advances in sonodynamic approach to can-
cer therapy. Ultrason Sonochem. 1996;3:S187-S191.
4. Lane N. New light on medicine. Sci Am. 2003:288:38-45.
5. Kinoshita M, Hynynen K. Mechanism of porphyrin-induced
sonodynamic effect: possible role of hyperthermia. Radiat Res.
2006;165:299-306.
6. Yumita N, Umemura S. Sonodynamic antitumour effect of
chloroaluminum phthalocyanine tetrasulfonate on murine solid
tumour. J Pharm Pharmacol. 2004;56:85-90.
7. Huang D, Okada K, Komori C, Itoi E, Kawamura K,
SuzukiT.Ultrastructureofsarcoma180cellsafterultrasoundirra-
diation in the presence of sparfloxacin. Anticancer Res. 2004;24:
1553-1559.
8. Apkarian VA. Chemistry: a pixellated window on chemistry in
solids. Science. 2006;313:1747-1748.
9. Yumita N, Han QS, Kitazumi I, Umemura S. Sonodynamically-
induced apoptosis, necrosis, and active oxygen generation by
mono-l-aspartyl chlorin e6. Cancer Sci. 2008;99:166-172.
10. Jin ZH, Miyoshi N, Ishiguro K, et al: Combination effect of
photodynamic and sonodynamic therapy on experimental
skin squamous cell carcinoma in C3H/HeN mice. J Dermatol.
2000;27:294-306.
11. Crescenzi E, Chiaviello A, Canti G, et al. Low doses of cisplatin
or gemcitabine plus Photofrin/photodynamic therapy: disjointed
cell cycle phase-related activity accounts for synergistic out-
come in metastatic non–small cell lung cancer cells (H1299).
Mol Cancer Ther. 2006;5:776-785.
12. Wang X, Lewis TJ, Mitchell D. The tumoricidal effect of son-
odynamic therapy (SDT) on S-180 sarcoma in mice. Integr
Cancer Ther. 2008;7:96-102.
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