OncothermiaOncothermiaOncothermiaOncothermia L o c oL o c oL o c oL o c o ---- r e g i o n a l h y p e r t h e r m i a w i t hr e g i o n a l h y p e r t h e r m i a w i t hr e g i o n a l h y p e r t h e r m i a w i t hr e g i o n a l h y p e r t h e r m i a w i t h

Medical Results h i g h t e c h m e d i c i n eh i g h t e c h m e d i c i n eh i g h t e c h m e d i c i n eh i g h t e c h m e d i c i n e

■ First year survival

■ Median survival

■ Efficacy and safety

40

7176

17 16

36

89

68

45

59

8287

72

51

65

97

85 83

68

114

92

25

99

258

103

39

24

0

20

40

60

80

100

120

0

20

40

60

80

100

120

Stomach Colon Rectum Liver Pancreas Lung andbronchus

Breast Kidney andrenal pelvis

Brain GBMStomach Colon Rectum Liver Pancreas Lung andbronchus

Breast Kidney andrenal pelvis

Brain GBM0

50

100

150

200

250

300

0

50

100

150

200

250

300

Oncothermia dataOncothermia data

Oncothermia patient’s numberOncothermia patient’s number

# p

ati

en

ts (

n)

SEERSEER

1st

yea

r s

ur

viv

al

(%)

First year survival comparison Challenge – Oncothermia is taken only in a small fraction of the overall survival. Its effect on the long overall survival could be negligible, even if it is very effective. The aggressive disease with short survival is a chance to indicate the efficacy. In this sense oncothermia is indicated as a feasible, effective method. (A. Szasz, A. Dani, et.al.: Retrospective analysis of 1180 oncological patients treated by electro-hyperthermia, DEGRO 11. Jahreskongress der Deutschen Gesellschaft für Radioonkologie, 26-29 Mai 2005, Kongresszentrum, Karlsruhe)

Studies are single arm, open label, observational for intention-to-treat (ITT) population, dominantly for the patients in late/advanced stages, where the conventional methods have fallen.

A comparison with large databases* was done. The survival rate was the studied endpoint. Inclusion criteria were the inoperable and/or in progression after chemo- and/or radio-therapy. Exclusions were the well known contraindications of oncothermia. The possible negative biases were connected to the missing randomization and the historical arm comparison and the voluntary basis (ITT population). Positive bias is the selected advanced patient-population, the missing “trial attention” and the entirely regular treatment conditions (no extra care is given). The treatment had minor number of erythema (<8%), and rarely subcutaneous fibrosis was observed; no other toxicity was observed except the usual toxic reactions of the complementarily applied

conventional treatments (radio- and/or chemo-therapies). Patients reported (subjective) decrease of adverse effect of parallel conventional therapies, decrease of pain and other subjective symptoms. Most patients reported improvement of their general well-being.

(*) Surveillance, Epidemiology, and End Results (SEER), National Cancer Institute, April 2000, www.seer.cancer.gov; EUROCARE-3, European Cancer Database, www.eurocare.org/profiles/index.html

40

7176

17 16

36

89

68

45

59

8287

72

51

65

97

85 83

68

114

92

25

99

258

103

39

24

0

20

40

60

80

100

120

0

20

40

60

80

100

120

Stomach Colon Rectum Liver Pancreas Lung andbronchus

Breast Kidney andrenal pelvis

Brain GBMStomach Colon Rectum Liver Pancreas Lung andbronchus

Breast Kidney andrenal pelvis

Brain GBM0

50

100

150

200

250

300

0

50

100

150

200

250

300

Oncothermia dataOncothermia data

Oncothermia patient’s numberOncothermia patient’s number

# p

ati

en

ts (

n)

SEERSEER

1st

yea

r su

rviv

al

(%)

Median survival comparison Median survival comparison Median survival comparison Median survival comparison

Oncothermia is applied for liver metastases from colorectal cancer primarily together with chemotherapy (n=30) and as monotherapy, after the failure of the conventional therapies (n=50).

The median survival rate was increased remarkably compared to the historical control.

(Hager ED, Dziambor H,

Hohmann D, Gallenbeck D,

Stephan M, Popa C.et al.: Deep hyperthermia with radiofrequencies in patients with liver metastases from colorectal

cancer. Anticancer Res. 19(4C):3403-3408, 1999)

Definite and impressive results were achieved for brain glioma patients. The median survival was increased by more than 75%, while in the case of the most advanced cohort (Glioblastoma multiforme, WHO IV) the results shows also excellent (more than 50%) gain.

(Szasz A, Sahinbas H: Presentation on the Annual Congress of Hungarian Oncologists, Budapest, 2004)

The retrospective data could be convincingly controlled by comparison of independent clinics, having the same device and treatment protocols for brain gliomas.

(HTT Clinic – Varkonyi A: Brain tumor

treatment by electro-hyperthermia, Annual User’s conference of OncoTherm, St. Istvan University, Godollo, 2003, BioMed Clinic – D.

Hager, H. Dziambor, E. M. App et all. The treatment of patients with high-grade malignant

gliomas with RF-hyperthermia. 39th ASCO Annual Meeting. 2003 (Abstract No. 470); Groenemeyer Clinic – Sahinbas H, Groenemeyer D, Boecher E, Szasz A: Retrospective clinical study of adjuvant electro-

hyperthermia treatment for advanced brain-gliomas, Deutsche Zeitschrift fuer Onkologie, 39:154-160, 2007)

Oncothermia study

Brain gliomas,

Dr. Sahinbas et. al.

Oncothermia study

Brain gliomas,

Dr. Sahinbas et. al.

Average median survival from data-banks

11.35 month

Average median survival from data-banks

11.35 month

74.5%

Patient n

um

ber

12.1

14.6

9.5

12.1

14.6

9.5

19.8

296 287 339 335

140

296 287 339 335

140

296 287 339 335

140

296 287 339 335

140200

400

600

800

1000

1200

1400

1600

200

400

600

800

1000

1200

1400

1600

12.1

14.6

9.5 1011.3

12.1

14.6

9.5

12.1

14.6

9.5

12.1

14.6

9.5

296 287 339 335

140

296 287 339 335

140

1578

296 287 339 335

140

296 287 339 335

140

0

5

10

15

20

25

Me

dia

n s

urv

iva

l(m

)

0

5

10

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20

25

Me

dia

n s

urv

iva

l(m

)

0

5

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25

Me

dia

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l(m

)

SEER (Surveillance, Epidemiology, and End Results) by the National Cancer Institute USA, April 2000MRC (Medical Research Council, Brain Tumor Working Party)RTOG(Radiation therapy Oncology Group, EORTC(European Organization for Research and Treatment of Cancer)

RT = Radiotherapy,

PCV= Procarbazine+CCNU(Lomustine)+Vincristine, TMZ= Temizolomide

SEER (Surveillance, Epidemiology, and End Results) by the National Cancer Institute USA, April 2000MRC (Medical Research Council, Brain Tumor Working Party)RTOG(Radiation therapy Oncology Group, EORTC(European Organization for Research and Treatment of Cancer)

RT = Radiotherapy, RT = Radiotherapy,

PCV= Procarbazine+CCNU(Lomustine)+Vincristine, PCV= Procarbazine+CCNU(Lomustine)+Vincristine, TMZ= TemizolomideTMZ= Temizolomide

0

5

10

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20

25

Me

dia

n s

urv

iva

l(m

)

EORTC RT EORTC RT+TMZ MRC RT total MRC RT+PCV

total

RTOG total

Clinical study

0EORTC RT EORTC RT+TMZ MRC RT total MRC RT+PCV

total

RTOG total

Clinical study

0

200

400

600

800

1000

1200

1400

1600

200

400

600

800

1000

1200

1400

1600Brain-gliomas (all grades)Brain-gliomas (all grades)Brain-gliomas (all grades)Brain-gliomas (all grades)Brain-gliomas (all grades)Brain-gliomas (all grades)Brain-gliomas (all grades)Brain-gliomas (all grades)

Brain glioma median survival [month]

11.49 11.3

23.63 23

19.8

n=140n=28970 n=35n=29n=1578

5

15

25

SEER RTOG HTT Clinic BioMed Clinic Groenemeyer

Clinic

Brain glioma median survival [month]

11.49 11.3

23.63 23

19.8

n=140n=28970 n=35n=29n=1578

5

15

25

SEER RTOG HTT Clinic BioMed Clinic Groenemeyer

Clinic

Efficacy and safetyEfficacy and safetyEfficacy and safetyEfficacy and safety

The 3E+3S philosophy of oncotherm together with the scientific and technical solutions is also present in the medical studies. The 3E efficacy is well shown on the Kaplan-Meyer plots for advanced pancreatic and advanced non-small-cell lung cancer results. (The control arms are the historical data form the same physician.) (Dani A, Varkonyi A, Nyiro I, Osvath M.: Clinical experience of electro-hyperthermia for advanced pancreatic tumors, ESHO Conference, Munich, June 2003) and (Dani A.: Electro-hyperthermia for advanced NSCLC tumors, Deutscher Kongress für

Radioonkologie, Strahlenbiologie und Medizinische Physik , Erfurt 10-13 June 2004)

p=0.023

0

0.2

0.4

0.6

0.8

1

0 20 40 60 80 100 120 140

Overall Survival (months)

Pro

ba

bilit

y

Censored

Historical control

Oncothermia

Control arm (n=43)

Median (m) = 11.0

Control arm (n=43)

Median (m) = 11.0

Active arm (n=132)Median (m) = 14.7Active arm (n=132)Median (m) = 14.7

Advanced non-small-cell lung cancer (III+IV)

The 3S safety is well demonstrated on the combination of oncothermia with platinum derivatives and applying it second line with great success, without remarkable toxicity. (Fiorentini G, deGiorgi U, Turrisi G, Rossi S, Dentice P, Bernardeschi P: Deep electro-hyperthermia with radiofrequencies combined with thermoactive drugs in patients with liver metastases from colorectal cancer (CRC): a Phase II clinical study, ICACT 17th, Jan30-Feb2, Paris, France) and (Panagiotou P, Sosada M, Schering S, Kirchner H,: Siloah Clinic, Hannover, Irinotecan plus capecitabine with

regional electrohyperthermia of the liver as second line therapy in patients with metastatic Colorectal Cancer; European Society for Hyperthermic Oncology, June 8-11, 2005 Graz, Austria )

Comaprison of platinum derivatives completed with oncothermia

6 611

44

60

22

11

0

42

58

67

100

8

17

0 00.0

10.0

20.0

30.0

40.0

50.0

60.0

70.0

80.0

90.0

100.0

Res

ponse

CEA re

duct

ions

Red

uctio

n ana

lgesi

cs

Bette

r qua

lity o

f life

Burns G

2

Leuko

peni

a G2

Nau

sea &

V. G

3

Nef

roto

xicity G

2

Neu

roto

xicity

G3

clinical response oncothermia related toxicity chemotherapy related toxicity

pe

rce

nta

ge

[%

]

Carboplatine (n=18) [%]

Oxaliplatine (n=12) [%]

Liver metastasis of colerectal CA

response rate [%]

50.7

80

0

30

60

90

First line

(Oxalyplatine+

+folicacid+5-FU)

Second line

(Irinotecan+

+capecitabine+oncothermia)

Our principle, the 3E+3S, makes values for the patients and for their doctors, keep the oncothermia method an excellent weapon against cancer.

__________________________________________________________________________________________________________

Oncotherm Kft. Ibolya u. 2. H-2071 Páty Tel: +36 (0) 23/555-510 Fax: +36 (0) 23/ 555-515 info@oncotherm.org www.oncotherm.org

Hot Oncotherm GmbH Bonnerstr. 40. D-53842Troisdorf Tel: +49 (0) 2241/31992-0 Fax: +49 (0) 2241/31992-11 info@oncotherm.de www.oncotherm.de

Pancreas CA average survivals

7.1

8.33

11.9

0

2

4

6

8

10

12

14

classical chemotherapy* Gemzar+5FU+LV** classical plus oncothermia

Ave

rag

e s

urv

iva

l [m

on

ths]