2. Ärztlicher Direktor Dr. Ursula Jacob Köln 2011

3. Therapiekonzepte in der Onkologie

4. ONCOTRACE

5. ONCOTRAIL

6. ONCOCOUNT

7. TU profile +

16. Case studies

17. Case report for hypertheramia treatment and sensitivity testing: Patient C.O., born 13.10.72 Diagnosis:01/00 Hodgkin’s disease (nodular sclerotic). Until 08/00 multiple chemotherapies and radiation with partial remission. 10/00recurrence right axilla. No therapy. 02/01progressive disease, chemotherapy with ESHAP. Progressive disease. 03/01change of chemotherapy. 06/01progressive disease, high dosage chemotherapy, full remission. 02/02progressive disease lymph node right axillary region. Radiotherapy. 08/03progressive disease mediastinal, hilar lymph nodes, bilateral. CD30 antibody treatment, without effect. 05/04massive progressive disease in PET CT and clinically. Start of Gemzar mono without effect. High-dosed Prednisolone. 08/04in our treatment – chemosensitivity test showed Vinblastin in combination with Procarbazin in combination with CD20 antibody Mabthera until 12/04. Start of local chemotherapy plus systemic chemo, whole-body hyperthermia every few months until now. PET scan and MRI: full remission until now. 12/08microtumor testing showed cells under the norm. 11/10microtumor test: again cells under the normal limit. Full remission

18. 2007 ONCOTRACE

19. 2008 ONCOTRACE

20. 2010 ONCOTRACE

21. History Patient female D.F. dob.: 28.01.1947 2006: Abnormal mammogram then MRI diagnosed stage IV breast cancer with bone, liver and lymph node metastases. Therapy – bilateral mastectomy (ER+, HER2 –ve) then monthly Zometa, Femara 2008:Hepatic recurrence, therapy changed from Femara to Xeloda plus Herceptin (now HER2 +) 2009:Progressive disease. Xeloda increased. Tycarb commenced with initial beneficial effect but then further progression. Therapy changed to Abraxane plus Carboplatin (but reduced blood count) 9/2010Markedly progressive disease on CT with massive increase in hepatic tumour mass, therapy changed to Abraxane, Zometa and Herceptin with partial remission

23. 29.9.10-4.11.10 Treatment in the clinic Chemosensitivity test performed Local therapy – chemoperfusion/chemoembolisation (Prof Vogl, Uniklinik Frankfurt), x3 (28.9.2010 Mitomycin C + Avastin, 12.10.2010 Mitomycin C + Avastin, 29.10.2010 Gemcitabine + Avastin) Systemic chemotherapy – 2.10.2010 Navelbine 50 mg (together with whole body hyperthermia ) Antibody therapy – Thalidomide Anti-hormone therapy – Faslodex Other therapies – Zometa, Bondronate Supportive therapies – whole body hyperthermia (2.10.2010 [39.0], 8.10.2010 [39.1], 1.11.2011 [39.1]), photophoresis

24. Given Medication Oral – quercetin, Immune plus, vitamin D Infusion – HepaMerz, vitamin C, selenium, Neurium, ProNeuroplus, Tationil Parenteral – thymus/spleen extract, mesenchymal growth factors

25. Ongoing therapy at home Chemotherapy – Navelbine 50 mg 2-3 weekly (dependent on blood picture) Antibody therapy – Thalidomide Anti-hormone therapy – Faslodex 250 mg fortnightly Oral – quercetin, vitamin D, Bondronate, Immune plus, Kwai (garlic extract), Chlorella, selenium, Hepamerz, CoQ10, probiotics, fish oil, B complex, Viromax Parenteral – Lektinol, thymus, mesenchymal growth factors

27. 25.1.2011-7.2.2011 Treatment in the clinic Local therapy – chemoembolisation/chemoperfusion (Prof Vogl, Uniklinik Frankfurt) with Mitomycin C + Avastin (31.1.2011) Systemic chemotherapy 27.1.2011 Navelbine 50 mg (together with whole body hyperthermia ) Antibody therapy – Thalidomide (ceased 25.1.2011) replaced with Herceptin (3 weekly) Anti-hormone therapy – Faslodex Other therapies – Zometa, Bondronate Supportive therapies – whole body hyperthermia (27.1.2011 [39.7], 3.2.2011 [39.0], photophoresis

28. Given Medication Oral – quercetin, Immune plus, vitamin D plus Vayara (Boswellia), CoQ10, melatonin, Bactoflor, Infusion – HepaMerz, vitamin C, selenium, Neurium, ProNeuroplus, Tationil plus Artemesinin, Agaricus phalloides D4 Parenteral – thymus/spleen extract, lektinol

29. Ongoing therapy at home Chemotherapy – Navelbine 50 mg 2-3 weekly (dependent on blood picture) Antibody therapy – Herceptin 3 weekly Anti-hormone therapy – Faslodex 250 mg fortnightly Oral – vitamin D, Bondronate, Immune plus, selenium, Hepamerz, CoQ10, probiotics, fish oil, B complex plus Detoxolite, Agaricus phalloides D4, melatonin, Vayara (Boswellia), Aniflazyme, Nattokinase Parenteral – Lektinol, thymus, mesenchymal growth factors

31. 10.3.2011- 8.4.2011 Treatment in the clinic Local therapy – chemoembolisation/chemoperfusion (Prof Vogl, Uniklinik Frankfurt) with Mitomycin C + Avastin (14.3.2011) Antibody therapy – Removab 16.3.2011 (5 mcg), 21.3.2011 (10 mcg), 28.3.2011 (10 mcg) Anti-hormone therapy – Faslodex Other therapies – Zometa,

32. Given Medication Oral – Immune plus, vitamin D, Vayara (Boswellia), CoQ10, melatonin, Bactoflor, Detoxolite Infusion – HepaMerz, vitamin C, selenium, Neurium, ProNeuroplus, Tationil plus Artemesinin, Agaricus phalloides D4 Parenteral – thymus/spleen extract, lektinol, mesenchyme growth factors

33. Staging – PET CT – 6.4.2011 total remission in bones and lungs, good partial remission in liver

34. Ongoing therapy at home Chemotherapy – Navelbine 50 mg 2-3 weekly (dependent on blood picture) Antibody therapy – Herceptin 3 weekly Anti-hormone therapy – Faslodex 250 mg fortnightly Oral – vitamin D, Immune plus, Hepamerz, CoQ10, fish oil, B complex, Agaricus phalloides D4, Vayara (Boswellia), Aniflazyme, Nattokinase Parenteral – Lektinol, mesenchymal growth factors

39. 20.5.2011-28.5.2011 Treatment in the clinic Local therapy – chemoembolisation/chemoperfusion (Prof Vogl, Uniklinik Frankfurt) with Mitomycin C + Avastin (19.5.2011) Systemic chemotherapy 27.1.2011 Navelbine 50 mg (together with whole body hyperthermia ) tumour specific targeted antibody therapy on 22.5.11 Anti-hormone therapy – Faslodex Other therapies – Zometa, Bondronate Supportive therapies – whole body hyperthermia (23.5.2011), photophoresis

40. Given Medication Oral –Immune plus, vitamin D, Vayara (Boswellia), CoQ10, melatonin plus Biobran Infusion – HepaMerz, vitamin C, selenium, Neurium, ProNeuroplus, Tationil, Artemesinin, Agaricus phalloides D4 Parenteral – mesenchymal growth factors, lektinol

41. Ongoing therapy at home Chemotherapy – Navelbine 50 mg 2-3 weekly (dependent on blood picture) Antibody therapy – Herceptin 3 weekly Anti-hormone therapy – Faslodex 250 mg fortnightly Oral – vitamin D, Bondronate, Immune plus, Hepamerz, CoQ10, fish oil, Agaricus phalloides D4, melatonin, Vayara (Boswellia), Aniflazyme, Nattokinase Parenteral – Lektinol, mesenchymal growth factors

42. 10.09.2011 – 06.10.2011 Treatment in the clinic Local therapy – chemoembolisation/chemoperfusion (Prof Vogl, Uniklinik Frankfurt) with Mitomycin C + Avastin (13.9.2011) and 23.9.11 (with Gemcitabine) – initial MRI shows progressive hepatic disease Antibody therapy – Removab (5 mcg 18.9.11, 10 mcg 28.9.11) tumour specific targeted antibody therapy 7/11 and 09/11 Anti-hormone therapy – Faslodex, changed to Tamoxifen 22.9.11 Other therapies – Zometa, Bondronate, Pantozol Supportive therapies – whole body hyperthermia (15.9.2011 [38,7], 26.9 [39,2]),

43. Given Medication Oral –Immune plus, vitamin D, Vayara (Boswellia), CoQ10, Nattokinase, Aniflazyme, Arcoxia (changed to Arthrotec), Membrain, glycine, Venalot, Cimetidine Infusion – HepaMerz, vitamin C, selenium, Neurium, ProNeuroplus, Tationil, Artemesinin, Agaricus phalloides D4, DCA, zinc Parenteral – thymus extract, lektinol, methylcobalamin, Iecur growth factors

44. Staging PET CT (5.10.11) full remission

45. 22.11.2010*01.12.2010*13.12.2010*03.01.2011*12.1.11*26.01.201109.02.2011* 119107121132149197107 285286 385369341309298265 14.03.201120.04.2011*09.05.2011*24.05.201101.06.2011*10.06.201120.06.2011 169137167243164163195 288379 299355378364 13,813,6 11.07.201127.07.201113.09.2011 208235369 676 433421 17,7 Tumour markers CEA CA15-3 CA27,29 CA125 Tumour markers CEA CA15-3 CA27,29 CA125 Tumour markers CEA CA15-3 CA27,29 CA125 Tumour markers CEA CA15-3 CA27,29 CA125 05.01.2010*22.07.2010*04.08.2010*21.09.2010*02.11.201017.11.2010* 510494676943360130 181215162394951524 1222104014371927377 24,1

48. CST comparisons (Antibody therapy 22.5.11) Genes16.09.201003.06.201128.06.201120.09.2011 CES1&2 (carboxylase)Normal E2F1Normal p18030% over control 25% over control p2735% over control 30% over control DPDNormal UPNormal NPNormal TPNormal Gamma GCNormal p5335% over control40% over control p1650% over control65% over control VEGF60% over control 45% over control65 % over control FGF45% over control40% over control25% over control30% over control PDGF40% over control55% over control40% over control30% over control COX2Normal 5-LOXNormal MMP60% over control40% over control45% over control40% over control TSNormal DHFRNormal SHMTNormal GARFTNormal NFκB30% over control 35% over control IκB (a,d,e)35% below control 45% below control50% below control Ribonuclease reductaseNormal DNA methyltransferase I30% over control 15% over control20% over control DNA methylase20% below control25% below control20% below control O6-methylguanin-DNA-tran.Normal TGF-b35% over control40% over control25% over control30% over control EGF45% over control50% over control40% over control55% over control IGFNormal Histone deacylase-dispeptideNormal Bcl-2Normal KISS-1-r45% below control65% below control25% below control30% below control Nm2320% below control40% below control15 % below control10% below control Ras/Raf/MEK/Erk50% over control40% over control30% over control35% over control mTORNormal c-erb-B2Normal c-erb-B1Normal Bcr-ablNormal h-TERT (Human telomerase)20% over control15% over control 10% over control

49. 16.09.201003.02.201103.06.201128.06.201120.09.2011 CTC (cells/7,5 ml) 6,15,86,64,84,5 ONCOTRACE

51. History Patient female V.B. dob.: 18.12.1957 11/2010: Diagnosed with ovarian cancer with peritoneal carcinomatosis (Figo IIc). Treated with debulking surgery and hysterectomy (with reduction in CA125) followed by 6 cycles of Taxol plus carboplatin with further reduction of tumour marker. 1/2011 Chemosensitivity test performed

52. ONCOCOUNT 14.06.2011

56. 16.06.2011 – 06.07.2011 Treatment in the clinic Staging PET CT 15.6.2011. ‘discrete residual activity of the peritoneal carcinosis’ and 2 small liver metastases in left liver lobe’ Antibody therapy – Thalidomide, Removab (5 mcg 17.6.11, 10 mcg 22.6.2011 and 28.6.2011) Supportive therapies – whole body hyperthermia (13.6.2011 [39.7]), photophoresis

57. Given Medication Oral – quercetin, Immune plus, vitamin D, Boswellia, CoQ10, Detoxylite, Nattokinase, Aniflazyme Infusion – HepaMerz, vitamin C, selenium, Neurium, ProNeuroplus, Tationil, Faktor AF2, Viromax, B12/folate. Pantozol, Periplasmal Parenteral – thymus extract, mesenchymal growth factors, bone marrow extract, Abnoba pini, filgastrim, erythropoetin Ongoing therapy at home Antibody therapy – Thalidomide Oral – quercetin, Boswellia, vitamin D, Immune plus, selenium, Hepamerz, fish oil, Nattokinase, Aniflazyme, chlorella, Detoxylite, Ribomunyl, Delimmun Parenteral –mesenchymal growth factors, Faktor AF2, Abnoba pini Intravenous- vitamin C, glutathione

58. ONCOCOUNT 16.09.2011

59. 13.09.2011 – 06.10.2011 Treatment in the clinic Remains well Noted to have elevated TSH (4.70) and subsequently elevated TPO (141), though vitamin D levels optimised Staging PET CT 16.9.2011. ‘previously described peritoneal and hepatic changes are no longer traceable. Present activity level does not differ from the surrounding, so that one can speak of a complete remission’ Antibody therapy – Thalidomide, Removab (5 mcg 17.9.2011, 10 mcg 26.9.2011) Dendritic cell vaccination – 22.9.2011 Supportive therapies – whole body hyperthermia (14.9.2011 [40.2]), photophoresis

60. Given Medication Oral – quercetin, Immune plus, vitamin D, Boswellia, CoQ10, Detoxylite, Nattokinase, Aniflazyme, glycine, Membrain, Kreon Infusion – HepaMerz, vitamin C, selenium, Neurium, ProNeuroplus, Tationil, zinc, Agaricus, Artesunate, Periplasmal Parenteral – thymus extract, mesenchymal growth factors, thyroid extract, Abnoba pini, filgastrim, erythropoetin

61. Ongoing therapy at home Antibody therapy – Thalidomide Oral – quercetin, Boswellia, vitamin D, Immune plus, selenium, Hepamerz, fish oil, Nattokinase, Aniflazyme, glycine, Membrain, Delimmun, Labolife 2HERP, Labolife 2EBV Parenteral –mesenchymal growth factors, thyroid extract, Abnoba pini, Zylexis

62. RGCC ONCOTRAIL 28.01.201108.06.201114.09.2011 CTC (cells/ml)5,74,83,6

63. Viral activity and cancer What can we learn from this?

64. CFS Test

66. History Patient male M.M. dob.: 29.07.1968 Diagnosis:.07/08 Lennert’s lymphoma (Hodgkin’s disease), stage IV, diagnosed through a lymph node biopsy left cervical region, with multiple mediastinal, abdominal and retroperitoneal lymph nodes, as well as hepato- and splenomegaly. (Histologically lymphoma Popema-Lennert, CD 20 positive, CD 30 negative.) 04/2009:Full remission in PET CT. Thalidomide from 04-06/09.

71. Treatment in the clinic 10/08-12/08 chemotherapy with BEACOPP-14 plus Mabthera with full remission ( 4 cycles ) 12/08 consolidation therapy with Mabthera until 03/09 03/09 Thalidomide until 08/09 08/09 Finished Thalidomide and Mabthera Microtumor test showed an decrease of the tumor cell amount CFS Panel showed an increased RT-PCR for EBV virus in the cell The autoimmune panel showed no signs of autoimmune disease

72. Tumour markers15.09.200818.11.200827.02.200909.12.200905.11.2010 Thymidine kinase (<7)8,912,4137,94,7 β-2 microglobulin (0,7- 1,8)22,22,31,11,6

75. 09.03.200917.08.200930.09.200911.05.201010.11.201018.08.2011 CTC (cells/ml) 3,72,92,200<1

76. 24.08.2009

84. CLINICAL RESULTS The scientific base of micro-arrays analysis of gene expression is confirmed by the clinical data that we collect from our patients. This information has been organized into DATA TABLES OF CANCER PATIENTS’ RESPONSE TO SUGGESTED SCHEMES THROUGH CHEMO- SENSITIVITY – CHEMO-RESISTANCE TESTING