INSULIN POTENTIATION THERAPY (IPT) COMBINED WITH ULTRASONIC ASSISTANT CHEMOTHERAPY WITH TONGUE TUMOURS A CASE FROM THE PRACTICE

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INSULIN POTENTIATION THERAPY COMBINED WITH
ULTRASONIC ASSISTANT CHEMOTHERAPY OF TONGUE
TUMOURSA CASE REPORT
Dr. Christo Damyanov, Dr. Ivan Maslev, Dr.
Desislava Gerasimova, Dr. Veselinka Yankova, Dr.
Vladislav Tashev Medical Center of Integrative
Medicine, Sofia, Bulgaria
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TONGUE CANCER

• The average age of tongue cancer patients is 61,
  the diagnosed cases represent about 25 per cent
  of the oral cavity tumors. Total survival rate of
  the patients for 5 and 10 years is 61 and 51
  percent respectively. Mortality from the disease
  has not significantly changed during the last 40
  years. Annually in Europe there die about 8,000
  tongue cancer patients. The main reason for the
  increased mortality is the late cancer diagnosis.
  
• In the early stages treatment is operative
  (partial glossectomy) while in the advanced
  stages the combined treatment includes surgery,
  radiotherapy and chemotherapy.
• The problems of the late stage treatment are the
  increased recurrent rate, the seriously
  compromised quality of life and the reduced
  survival rate.
• In the current report we present a case from our
  practice of loco-regional advanced tongue tumor
  treated with IPTLD in combination with local
  chemotherapy and ultrasonic irradiation.

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A CASE REPORT

• A 60-year-old man of was admitted for treatment
  progressively complaining of speech and eating
  disturbances, a swelling and ulceration on the
  left halve of the tongue. For these complaints
  he consulted in Oral and Maxillofacial surgery
  department on December 2011, following which a
  biopsy was performed with a histological result
  a squamous cell carcinoma. The case was
  considered as a locally advanced tumor and
  radical surgical treatment was proposed or radio
  and chemotherapy, which were declined by the
  patient.

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EXAMINATION BEFORE TREATMENT

• Tumor nodular lesion and ulceration in the left
  side of the tongue with a diameter 4/3 cm.
  Submandibulary to the left a lymph node
  palpitated of about 2,5 cm in size.
• PET/CT (01.2012) A metabolically active tumor
  process in the area of the tongue, without
  defining the size due to available artifacts in
  the oral cavity (teeth dentures). Dissemination
  of the process in the left submental lymph node
  17 mm size, submandibular lymph nodes of 14 and
  11 mm sizes as well as other two behind the left
  sternocleidomastoid muscle of 14 and 12 mm sizes.

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Macroscopic findings before treatment
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TREATMENT

• IPT treatment with Cisplatin/5-FU (Four IPT
  applications)
• Alternating treatment with a new chemotherapy
  scheme Epirubicin, Methotrexat, Carboplatin in
  four consecutive applications, once a week.
• Length one scan treatment 4 applications in
  every 5 days interval, then sustaining treatment
  in gradual increasing intervals (four
  applications in 10 days, 2, 3 and more weeks).
• In the interval an vitamin therapy, immune
  therapy and ozone therapy.
• IPT therapy was combined with a local DMSO and
  5-FU application and a local ultrasonic
  (sonodynamic) treatment of the tongue and left
  cervical area two time weekly.

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ULTRASOUND DEVICE

• The ultrasonic treatment (1 watt/cm2 and
  frequency 1 Mhz) is applied ten minutes after the
  local 5-Fu application with a duration 10
  minutes.

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RESULTS

• In the course of the treatment the patients
  complaints of speech and eating disturbances
  phased out. The Beretta symptomatic index of 12
  points went down to 1 point. Right now the
  patient is stabilized and with a totally restored
  to a working capacity. Treatment continues to the
  present.
• Examination after the treatment a tumor nodular
  lesion and ulceration in the left side of the
  tongue with a diameter about 15 mm.
  Submandibulary to the left a lymph node
  palpitated of about 5 mm in size.
• Control investigation with MRI (03.2012) A
  slight asymmetry of the tongue. With the applied
  native and post contrast MRI techniques also
  including dynamic evaluations could not
  categorically verify the tumor formation in the
  tongue. The lesions described in the lymph nods
  from the preceding PET/CT underwent a negative
  development in quantity.

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RESULTS
Macroscopic findings 1 months after treatment
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RESULTS
Macroscopic findings 2 months after treatment
Macroscopic findings 3 months after treatment
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SIDE EFFECTS

• No serious side effects were observed excluding
  increasingly growing thrombocytopenia of up to 76
  g/l which was medically treated. Following the
  treatment the thrombocytes values steadied within
  112-118 g/l. The thrombocytopenia was explained
  by the available hypersplenism before the
  treatment and a side effect of the chemotherapy
  applied.

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DISCUSSION

• Searching for a possibility of lowering the side
  effects from the treatment and maintaining the
  functional capacities of the tongue, we applied a
  combined treatment on a patient with a locally
  advanced tongue tumor who had declined
  conventional treatment.
• Treatment started by an IPTLD combined with
  Cisplatin/5-FU. Aiming at increasing the local
  anti tumor effect, after the third application
  the chemotherapy scheme was changed and the
  treatment included a local chemotherapy with a 20
  percent solution of 5-Fluorouacil in DMSO and
  ultrasonic therapy of the tongue lesion in the
  left cervical area.
• The ultrasonic treatment (1 watt/cm2 and
  frequency of 1 Mhz) is applied ten minutes after
  the local 5-FU application with a duration of 10
  minutes. The local treatment is applied at the
  same time with IPTLD as well as in the interval
  of twice weekly.

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DISCUSSION

• DMSO
• The idea of applying locally a 5-FU dissolved in
  DMSO is based on experimental and clinical
  researches demonstrating the potentiation effect
  of the organic solvent DMSO on the chemotherapy.
• On 1968 it was discovered that dimethyl sulfoxide
  (DMSO) had a very high affinity for cancer cells
  so DMSO targeted cancer cells.
• DMSO could bind to other substances, and still
  target cancer cells. It would bind to certain
  types of molecules, and then DRAG these molecules
  inside cancer cells.
• In later studies DMSO was found to bind to
  Adriamycin, Cisplatin, 5 Fluorouracil,
  Methotrexate, and others.

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DISCUSSION

• Resistance to chemotherapy is the important
  reason for treatment failure in patients with
  cancer. Current methods which focus on the
  identification of more selective and potent drug
  resistance reversing agents are not satisfying.
  It is an urgent need for development of new
  approaches to overcoming drug resistance. The use
  of low power ultrasound in cancer therapy is a
  developing field. Recently, it was found that
  some anticancer drugs, upon ultrasonic
  irradiation, could create active oxygen species
  and effectively destruct cancer cells. This means
  that, in addition to cytotoxicity, these
  chemotherapeutic agents may be used as
  sonosensitizers and kill cancer cells by another
  mechanism. Moreover, local hyperthermia induced
  by ultrasound could enhance drug cytotoxicity.
  For the unique advantage of ultrasound, which are
  quite different from current therapy, we
  hypothesize that ultrasound assistant
  chemotherapy may be a new strategy to block drug
  resistance, which might enhance the efficacy of
  chemotherapeutic drugs, and reduce undesired side
  effects.
• Med Hypotheses. 2009 Oct73(4)526-7. Epub 2009
  Jul 1.
• Ultrasound assistant chemotherapy may be a novel
  modality for solid tumors
• HuiXuan Pan, XiaoPeng Ma MingZhong Li., JunZhang
  Chen, Hong Jiang, Summary Department of
  Medicine, Clinic
• Medical College of Yangtze University, Jingzhou
  434000, China.

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CONCLUSION
In the presented case, complementing the standard
IPT with local chemotherapy and sonodynamic
therapy demonstrates an increased therapeutic
efficiency and alludes to potential possibilities
for the successful combination of IPTLD with
other methods in the treatment of metastatic
tumors.