Optimal preparation for cancer treatment. Dr Jann Arends Tumor Biology Center Freiburg Germany

Transcription

1 Optimal preparation for cancer treatment Dr Jann Arends Tumor Biology Center Freiburg Germany

2 Introduction Nutritional problems follow the cancer patient.. everywhere.. 2 major elements: Metabolism Immunology

3 Development of cancer Immunesurveillance Inflammatory progression D. Progression E. Metastasis

4 Immune activity and cancer D. Progression Johansson et al., 2008

5 Immune surveillance - inflammatory progression DeNardo & Coussens, 2007

6 Patient journey Malnutrition Diagnosis D. Progression E. Metastasis Fatigue Loss of appetite Weight loss Complications Reduced QoL Catabolism Immune defects Therapy Recovery

7 Patient Clinical problems Catabolism Chronic inflammation Immune defects

8 Immune cells in tumours DeNardo & Coussens, 2007

9 Chronic inflammation in cancer CRP increased at diagnosis in 50% (pancreatic cancer) CRP correlated with weight loss Wigmore 1997 Deans 2004, Barber 1999, Falconer 1995 increased energy expenditure decreased caloric intake decreased survival Falconer 1994 Wigmore 1997 Deans 2004

10 Immune defects Susceptibility to infections Post-operative complications Death by infection

11 Prognostic factors in cancer activity QoL inhibit improve psychol. stress nutritional state systemic inflammation cancer therapies immune competence TUMOUR

12 Goals for oncology-specific nutrition Reduce inflammation Improve muscle function (strength and endurance) Improve immunity

13 New nutritional supplement Reduce inflammation Improve muscle function Improve immunity Eicosapentaenoic acid - EPA High protein/leucine content Oligosaccharides - FOS/GOS

14 Plasma fatty acids with supplement % of total FA 13% 10% 7% 6% 5% 4% 3% 2% 1% 0% day no. EPA DHA DPA AA Significantly different from baseline p < Data presented as mean ± standard deviation. All FAs increase/decrease significantly at all time points.

15 Plasma fatty acids with supplement n-3 n-6 % of total FA 40% 30% 20% 10% ratio n-3/n-6 0% day no. 0.0 Significantly different from baseline p < Data presented as mean ± standard deviation. All FAs increase/decrease significantly at all time points.

16 Tumour-induced cachexia: In vivo model Syngenic CD2F1 mice Day 0: s.c.-inoculation of 5x10 5 colon adenocarcinoma cells A and B: test for contact hypersensitivity to oxazolone (Th1-response) Bodyweight (gram) Pre-cachectic phase Cachectic phase Control Tumor-bearing Tumor B A Days after tumor inoculation Tumor weight (gram) Faber et al. Br J Cancer 2008 Growth of the tumor and effect of tumor inoculation on body weight. p<0.01 vs Control group.

17 Significant reduction in Th1-immune function prior to weight loss Pre-cachectic phase Cachectic phase A 125 B % of Control C TB 0 C TB Effect of tumour inoculation on in vivo Contact Hypersensitivity measured by ear swelling in a pre-cachectic state on day 14 (A) and in mice already suffering from cachexia on day 22 (B). p<0.001 between groups. Van Helvoort et al., 2007

18 New supplement: Effects on inflammatory mediators TNF-α in plasma 30 TNF-α (pg/ml) # 0 Control TB-con TB-SUPPL p< vs Control, ^ 0.001<p<0.01 vs Control, # 0.01<p<0.05 vs Control and TB-con Faber et al. Br J Cancer 2008

19 New supplement: Effects on Th1-immune function Oxazolone contact hypersensitivity 300 Ear thickness (µm) # 50 0 Control TB-con TB-SUPPL Faber et al. Br J Cancer 2008 p< vs Control, # p< vs TB-con

20 New supplement: Effects on opportunistic infections post Ctx Pseudomonas infection model 6 Faecal colonization 6 Liver translocation Pseudomonas Log 10 [cfu/g feces] Pathogens Control SUPPL Time (days) Nutritional intervention Infections Pseudomonas Log 10 [cfu/liver] CTRL SUPPL Translocation incidence 95% 60% p=0.02 Sepsis

21 New supplement: Improvement muscle function Maximal muscle force Daily activity (day 19) Force (mn) ,#,#,#,#,#,#,# Control ctrl-tb SUPPL Frequence (Hz) 0 C C-TB TB-SUPPL Van Norren et al. Br J Cancer 2009

22 Dual mode of action Anticatabolic and immune-preserving Actives Mechanism of action Dual mode of action Leucine High Protein Anabolism + Leucine High Protein Muscle function Fish oil Fish oil Daily activity Quality of Life - Catabolism FOS GOS Improved Nutritional status Decreased inflammatory status + FOS GOS Immune function

23 Dawn of a new era of cancer therapies Tlsty & Coussens, 2006

24 Conclusions Cancer is associated with nutritional, metabolic and immunological deterioration. This makes the patients susceptible to complications or delay of treatment. The New Supplement (EPA, Oligosaccharides, Protein, Leucine mixture) clearly demonstrated in pre-clinical studies: - improvement in immune activity - reduction in inflammation - improvement in muscle function The improvement of the immune function, already in an early phase, will help to reduce the risk for infectious complications. This will increase the chances of an optimal execution of cancer therapies.

25 Imbalance of anabolism vs catabolism 13 C-Casein 13 C-Whey Leucine concentration (µm) During catabolic stress Cancer First pass extraction normal time

26 Optimal preparation for cancer treatment Dr Jann Arends Tumor Biology Center Freiburg Germany