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18.7.200418.7.2004Internationales Forum zur Internationales Forum zur Anwendung von TaheeboAnwendung von Taheebo

Osaka / JapanOsaka / Japan

ZENTRUM NOSOMIZENTRUM NOSOMIALLGEMEINMEDIZIN, ONKOLOGIE, NATURHEILVERFAHRENALLGEMEINMEDIZIN, ONKOLOGIE, NATURHEILVERFAHREN

ÄRZTLICHE LEITUNG: Dr.Dr. HELMUT BACOWSKYÄRZTLICHE LEITUNG: Dr.Dr. HELMUT BACOWSKY

1200 Wien, Sachsenplatz 9/301200 Wien, Sachsenplatz 9/30Tel.: +43 1 330 85 62, Fax: +43 664 507 81 82Tel.: +43 1 330 85 62, Fax: +43 664 507 81 82

E-Mail: E-Mail: nosomi@nosomi.atnosomi@nosomi.at www.nosomi.atwww.nosomi.at

Short Report on Intratumoral Application

of Taheebo Extract in Combination with ECT

(Electro-Chemical-Therapy) in 18 Patients suffering from Cancer of

the Prostate

Bacowsky H.www.nosomi.at

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CCancerancer of the of the prostateprostate Incidence:Incidence:

Austria 2000:Austria 2000: 4.925 4.925 patients patients EU:EU: 42,6142,61 cases / cases / 100.000100.000 inhabitants inhabitants

Mortality:Mortality: 14,6514,65 / /100.000 100.000

(Statistic Austria, (Statistic Austria, Gesundheitsbuch 2002).Gesundheitsbuch 2002).

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Purpose of investigation:Purpose of investigation: Are there Are there side side

effectseffects when when Taheebo-extract is Taheebo-extract is injectedinjected directly directly into the prostate? into the prostate?

Are there Are there risksrisks for for incontinence ? incontinence ? impotence ? impotence ? reoccurrence ? reoccurrence ? metastasismetastasis ??

Is Is prolongation of prolongation of remissionremission possible? possible?

Is there a Is there a positivepositive influence on influence on quality of life?quality of life?

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This investigation is based on This investigation is based on individual cases, no exclusions individual cases, no exclusions have been performedhave been performed

Each patient was informed thoroughly Each patient was informed thoroughly and in detail about risks concerning and in detail about risks concerning side effects, prognosis, relapse and side effects, prognosis, relapse and possibility of metastasis compared with possibility of metastasis compared with established therapies like operation, established therapies like operation, radiation, brachytherapy, radiation, brachytherapy, hormonblockade.hormonblockade.

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Methode:Methode:

18 patients, mean age 18 patients, mean age 70,270,2 yearsyears (max.96 (max.96 min. 51years ) with min. 51years ) with prostate cancer, prostate cancer, verified by biopsyverified by biopsy

Gleason score, mean Gleason score, mean 5,15,1 ranging from 3 to 7 ranging from 3 to 7

Bone metastasis Bone metastasis present before present before treatment (3)treatment (3)

Male hormone blockage Male hormone blockage before ECT+Taheebo before ECT+Taheebo application (3)application (3)

being continued after being continued after treatment (3)treatment (3)

male hormone male hormone blockage after blockage after ECT+Taheebo, new ECT+Taheebo, new application (3) application (3)

Chemotherapy, Chemotherapy, operation and operation and radiation before radiation before ECT+Taheebo ECT+Taheebo application (0). application (0).

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n = 18 Age Gleason

mean 70,2 5,1

min. 51 3

max. 96 7

Hormonblockage

Metastasis

Chemotherapy

Operation/Radiation

3 3 0 0

Status before treatment

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ECT (Electro-Chemical-Therapy)

ECTECT:: In the case of initial or progressed cancer of In the case of initial or progressed cancer of the prostate ECT provides a possible the prostate ECT provides a possible effective effective minimal invasive  treatmentminimal invasive  treatment using electricity using electricity provided by a DC-device. After local anaesthesia 2 provided by a DC-device. After local anaesthesia 2 electrodes made out of platin are inserted via the electrodes made out of platin are inserted via the perineum into the prostate. Then a perineum into the prostate. Then a currency of 7-currency of 7-7.5 Volt7.5 Volt is administered for about is administered for about 40-50 minutes40-50 minutes depending on the size of the prostate. At the end of depending on the size of the prostate. At the end of treatment the electrodes are removed. treatment the electrodes are removed. SideeffectsSideeffects like mild haematuria or impairment of urination can like mild haematuria or impairment of urination can be possible, but as we have seen in more than 57 be possible, but as we have seen in more than 57 patients so far, these side effects happened only in patients so far, these side effects happened only in 2 cases.2 cases.

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TaheeboTaheebo-extract-extract was prepared by was prepared by boiling downboiling down 30g30g Tabebuia av. powderTabebuia av. powder

(provided by Taheebo Japan Co.)(provided by Taheebo Japan Co.) with with 500 ml water500 ml water in a in a glass jarglass jar for for 40 minutes40 minutes. Decoct and sediment was . Decoct and sediment was transferred into transferred into 10 ml vials10 ml vials, which were then , which were then sterilisedsterilised at 120ο C for 2 hours. at 120ο C for 2 hours. Probes were tested on bacterial Probes were tested on bacterial contaminationcontamination (ARGE Graz) and (ARGE Graz) and analysed for content of analysed for content of Furan-NaphtochinonFuran-Naphtochinon (Laboratories of Kyoto Prefectural (Laboratories of Kyoto Prefectural University of Medicine). Each University of Medicine). Each 10 ml vial contained10 ml vial contained 25mg25mg Furan-NaphtochinonFuran-Naphtochinon

Immediately after ECTImmediately after ECT platin electrodes were removed platin electrodes were removed and via syringe and via syringe 5-10ml Tabebuia-extract was injected 5-10ml Tabebuia-extract was injected directly into the prostatedirectly into the prostate

PSAPSA-levels were determined before treatment and -levels were determined before treatment and every 6-8 months after therapy, sonographic and every 6-8 months after therapy, sonographic and physical examination were done and Quality of life physical examination were done and Quality of life assessed by using a standard questionnaire (TOC)assessed by using a standard questionnaire (TOC)

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Results:Results:

N=18 33% 17% 6%

days afterTreatment

allergic reaction

mild sensation

mild fever

urinationblockage inflammation

days of necessarytreatment

0-1 0 6 0 1 10

1 to 2 0 3 0 0

≥ 2 0 0

total 0 6 3 0 1 10

side effects

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ResultsResults//結果結果

3 patients out of 18 died3 patients out of 18 died, two patients , two patients due to additionaldue to additional chemotherapychemotherapy performed in another clinic, 25 months and performed in another clinic, 25 months and 30 months after ECT/Taheebo, one died of old age. 30 months after ECT/Taheebo, one died of old age.

１８　症例中３人死亡１８　症例中３人死亡。。そのうち２人は、他の病院で化学療法を受そのうち２人は、他の病院で化学療法を受けたことが原因。通電治療とタヒボ注入後、２５ヶ月と３０ヶ月けたことが原因。通電治療とタヒボ注入後、２５ヶ月と３０ヶ月生存。もう１人は、老衰による。生存。もう１人は、老衰による。

6 patients6 patients underwent therapy withunderwent therapy with male hormone blockingmale hormone blocking agentagent

６症例はホルモン遮断剤の治療を受けた。６症例はホルモン遮断剤の治療を受けた。

33 already some timealready some time before treatmentbefore treatment,, becausebecause 2 out of 32 out of 3 hadhad bone metastasisbone metastasis

３症例は通電治療とタヒボ注入前にホルモン遮断剤を受けた。そ３症例は通電治療とタヒボ注入前にホルモン遮断剤を受けた。そのうちの２人は既に骨転移が認められていた。のうちの２人は既に骨転移が認められていた。

30 months Observation30 months Observation//経過観察期間３０ヶ月経過観察期間３０ヶ月

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ResultsResults//結果結果 3 received hormone blockade immediately after ECT/Taheebo.3 received hormone blockade immediately after ECT/Taheebo. ３症例は、通電治療とタヒボ注入直後、予防としてホルモン療法を行った。３症例は、通電治療とタヒボ注入直後、予防としてホルモン療法を行った。

15 patients are still alive, no relapse or bone metastasis15 patients are still alive, no relapse or bone metastasis in those in those patients who had patients who had none beforenone before treatment, treatment, no marked progressionno marked progression in those in those 2 patients with bone metastasis2 patients with bone metastasis who were treated by who were treated by hormone blockade and biphosphonate infusion at regular interval. hormone blockade and biphosphonate infusion at regular interval. One patientOne patient with bone metastasis before ECT/Taheebo therapy is with bone metastasis before ECT/Taheebo therapy is stable with only slow progress observed, neither treated with a stable with only slow progress observed, neither treated with a hormone blocking agent nor receiving biphosphonate infusions. hormone blocking agent nor receiving biphosphonate infusions.

１５症例　全て生存中、治療前に再発、骨転移のなかった患者は、その状１５症例　全て生存中、治療前に再発、骨転移のなかった患者は、その状態を保っている。骨転移のあった２人の患者は治療後、顕著な進行を認め態を保っている。骨転移のあった２人の患者は治療後、顕著な進行を認めていない。ていない。

12 patients without new metastasis during 30 months of 12 patients without new metastasis during 30 months of observationobservation..

１２症例では、新たな骨転移は認められない。１２症例では、新たな骨転移は認められない。

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Results:Results:Mean PSA level

before/after ECT+Taheebo injection

0,00

5,00

10,00

15,00

20,00

25,00

t=months

psa PSA

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Results:Results:

Individual PSA-levelsIndividual PSA-levels differ in a wider range, differ in a wider range, elevationelevation can be observed can be observed 4-6 months4-6 months after after treatment, due to manipulation of the treatment, due to manipulation of the prostate, prostate, dropping thendropping then or also or also rising againrising again after 6-8 months, though after 6-8 months, though no visible no visible metastasismetastasis are detectable are detectable in bonesin bones by by szintigraphy. szintigraphy.

In those cases an examination by PET and In those cases an examination by PET and molecular genetic evaluation of minimal molecular genetic evaluation of minimal residual cancer cells in peripheral blood will residual cancer cells in peripheral blood will be done in a next step. be done in a next step.

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Results:Results:

ECT/Taheebo 10ml 11.12.01Androgenblockage since 5/02

32,70

68,0051,50

34,10

0,19 0,10 0,10 1,40 5,1510,10 11,29

0,00

20,00

40,00

60,00

80,00

t

PSA

Individual PSA level performance

ECT/Taheebo 5ml19.11.01

11,00

17,00 14,8015,3018,0012,00

0,00

5,00

10,00

15,00

20,00

Sep

01No

v 01

Jan 0

2M

rz 02

Mai

02

Jul 0

2Se

p 02

Nov 0

2Ja

n 03

Mrz

03M

ai 0

3Ju

l 03

Sep

03No

v 03

Jan 0

4M

rz 04

Mai

04

t

psa

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Results:Results:

ECT/Taheebo 10ml 11.12.01 Change in Prostate-Volume

39

24

4847

0102030405060

Jan 0

2

Mrz

02

Mai

02

Jul 0

2

Sep 0

2

Nov 0

2

Jan 0

3

Mrz

03

Mai

03

Jul 0

3

Sep 0

3

Nov 0

3

Jan 0

4

Mrz

04

Mai

04

t

ml

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SummerySummery//結論結論ECT/Taheebo ECT/Taheebo をを

手術、化学療法、放射線治療と比較手術、化学療法、放射線治療と比較

Nearly pain free treatmentNearly pain free treatment No severe side effectsNo severe side effects No allergic reactionsNo allergic reactions No impairment of libido No impairment of libido

and sexual functionand sexual function No incontinenceNo incontinence No hospitalisationNo hospitalisation Patient is mobile Patient is mobile

immediately after immediately after treatmenttreatment

able to work within the able to work within the next daynext day

low cost compared to low cost compared to operation, radiationoperation, radiation

ほとんど痛みを伴わない治療ほとんど痛みを伴わない治療 ほとんど副作用を伴わないほとんど副作用を伴わない アレルギー反応なしアレルギー反応なし 性欲、性機能を損なわない 性欲、性機能を損なわない 失禁がない失禁がない 外来治療のみ外来治療のみ 治療後、即、動ける治療後、即、動ける 翌日から仕事　復帰可能翌日から仕事　復帰可能 治療費が安価治療費が安価

ECT/Taheebo ECT/Taheebo 利利点点

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SummerySummery//結論結論ECT/Taheebo ECT/Taheebo をを

手術、化学療法、放射線治療と比較手術、化学療法、放射線治療と比較

Not yet approved Not yet approved methodmethod

Too small number of Too small number of patients with only 30 patients with only 30 months of observation months of observation

Further investigations Further investigations necessary necessary

公に認可された治療法で公に認可された治療法ではないはない

症例が少なく、経過観察症例が少なく、経過観察の期間も短い、３０ヶ月の期間も短い、３０ヶ月のみのみ

今後も研究が必要 今後も研究が必要

ECT/Taheebo ECT/Taheebo 考慮考慮点点

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Conclusion:Conclusion:

Prospective follow ups of patients of this pilot study are Prospective follow ups of patients of this pilot study are planned planned

Data will be compared with patient´s treated with other Data will be compared with patient´s treated with other methodsmethods

Future investigations are planned to see, wether a Future investigations are planned to see, wether a combination combination of one or multiple injections in a certain interval combined with of one or multiple injections in a certain interval combined with oral administered Taheebooral administered Taheebo can be helpful can be helpful to suppress cancerto suppress cancer growth in the prostate. growth in the prostate.

Further Investigations will be directed using Further Investigations will be directed using Taheebo extractTaheebo extract in in cell cultures cell cultures onon different wild type human cancer celldifferent wild type human cancer cell strainsstrains to to

show a possible direct show a possible direct cytostatic effectcytostatic effect To elucidateTo elucidate the potential of the potential of Taheebo extract Taheebo extract as anas an apoptosis apoptosis

inducing agentinducing agent on a moleculargenetic level on a moleculargenetic level enhancing enhancing BAX proteinBAX protein reducing reducing Bcl2 Bcl2 gene expressiongene expression reducingreducing MDR-RNA MDR-RNA levels levels in vivoin vivo, minimising drug resistance, , minimising drug resistance,

implementing the possibility of lower dosage of toxic chemo implementing the possibility of lower dosage of toxic chemo therapeutics.therapeutics.

ZENTRUM NOSOMIZENTRUM NOSOMIALLGEMEINMEDIZIN, ONKOLOGIE, NATURHEILVERFAHRENALLGEMEINMEDIZIN, ONKOLOGIE, NATURHEILVERFAHREN

ÄRZTLICHE LEITUNG: Dr.Dr. HELMUT BACOWSKYÄRZTLICHE LEITUNG: Dr.Dr. HELMUT BACOWSKY

1200 Wien, Sachsenplatz 9/301200 Wien, Sachsenplatz 9/30Tel.: +43 1 330 85 62, Fax: +43 664 507 81 82Tel.: +43 1 330 85 62, Fax: +43 664 507 81 82

E-Mail: E-Mail: nosomi@nosomi.atnosomi@nosomi.at, , www.nosomi.atwww.nosomi.at