O ρόλος της διατροφής κατά τη θεραπεία του καρκίνου

Transcription

1 O ρόλος της διατροφής κατά τη θεραπεία του καρκίνου I. Gioulbasanis MD, PhD Dept. of Chemotherapy Larissa General Clinic E. Patsidis

2 INTRODUCTION Καρκινογένεση Ενεργός Νόσος Επιβιώσαντες με καρκίνο (cancer survivors)

3 INTRODUCTION

4 INTRODUCTION Baracos VE et al. Nat Rev Dis Primers 2018

5 INTRODUCTION BMI <= % Overweight or obese = 41.9% Patients with metastatic primaries Penman AD et al. Prev Chronic Dis 2006; 3(3): A74; WHO 2008, Prev Chronic Dis. 2006, Gioulbasanis et al. Ann Oncol 2014

6 MECHANISMS OF WEIGHT LOSS Martin L et al. Abstract: 4 th cancer cachexia conference, Philadelphia, PA, USA, 2018

7 MECHANISMS OF WEIGHT LOSS Cancer Cachexia: Terminology Kakos = Bad Hexis = Condition Hippocrates (Kos 460 BC - Larissa 377 BC) Definition Cancer cachexia is defined as a multifactorial syndrome characterised by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. The pathophysiology is characterised by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism. Fearon K, et al., Lancet Oncol. 2011

8 MECHANISMS OF WEIGHT LOSS Baracos VE et al. Nat Rev Dis Primers 2018

9 MECHANISMS OF WEIGHT LOSS The effect of tumor mass Reduced food intake Energy consumption (by the tumor) Fearon KC et al. Nat Rev 2012

10 MECHANISMS OF WEIGHT LOSS Secondary causes of malnutrition Obstruction of the GI track Dysphagia Uncontrolled symptoms Pain Dyspnoea Depression Anxiety Insomnia Side-effects of anticancer therapies Smell / taste alterations Anorexia Mucositis Nausea - vomiting Diarrhea Constipation Medications for symptom management Nausea Constipation Shoemaker LK et al. Cleve Clin J Med 2011

11 MECHANISMS OF WEIGHT LOSS Schakman O et al. Int J Biochem Cell Biol 2013 Barreto R et al. Oncoterget 2016 Smith MR, et al. J Clin Oncol Fearon KC et al Cell Metab 2012

12 MECHANISMS OF WEIGHT LOSS Gene polymorphisms Gene IL-1B IL-10 IL-6 IL-8 SELP TNF ACE gene Polymorphism rs16944, rs rs , rs rs rs rs6136 rs rs4291 Tan BHL and Fearon KC. Curr Opin Support Palliat Care 2010;4(4): ; Tan BH et al. EMBO Mol Med 2012;4(6): Cur Op in Supp and Pal Care 2010 Johns N et al. J Cachexia sarcopenia and muscle, 2016, DOI: /jcsm.12138

13 MECHANISMS OF WEIGHT LOSS Sarcopenia (other contributing factors) Biolo G, et al. Clin Nutr 2014

14 Dodds RM et al. Clin Densitom 2015 MECHANISMS OF WEIGHT LOSS Sarcopenia (other contributing factors)

15 MECHANISMS OF WEIGHT LOSS Body composition... Schock et al. 1984

16 CLINICAL ASSESSMENT Fearon K et al. Nat Rev Clin Oncol 2013

17 BMI (kg/m 2 ) CLINICAL ASSESSMENT d x2 SMI 29.8 cm²/m², BMI 40.2 kg/m² d x2 d 3 SMI 29.8 cm²/m², BMI 28.1 kg/m² 1440 x2 SMI 29.7 cm²/m², BMI 15.3 kg/m² d 4 d 5 L3 Skeletal Muscle Index (cm 2 /m 2 ) SMI 33.7 cm²/m², BMI 29.5 kg/m² SMI 46.3 cm²/m², BMI 29.4 kg/m² SMI 58.3 cm²/m², BMI 29.4 kg/m² d 6 Martin et al. JCO 2013

18 CLINICAL ASSESSMENT % weight loss Nutritional screening In depth nutritional assessment Dewys WD et al. Am J Med 1980, Nutrition and the Cancer Patient, Edited by Del Fabbro e, et al., Oxford University press 2010

19 CLINICAL ASSESSMENT Stages of cachexia Pre-cachexia Cachexia Refractory cachexia Normal Death Weight loss 5% Anorexia and metabolic change Weight loss >5% BMI <20 and weight loss >2% or sarcopenia and weight loss >2% Often reduced food intake/ systemic inflammation Variable degree of cachexia Cancer disease both procatabolic and not responsive to anticancer treatment Low performance score <3 months expected survival Fearon K, et al.lancet Oncol 2011

20 CLINICAL ASSESSMENT Pre diagnosis Post Diagnosis Co-morbidities Early symptoms and/or signs Biopsy / Surgery Recovery Diagnostic distress Chemotherapy Palliative care Uncontrolled symptoms Pre-cachexia ----> Cachexia ----> Refractory Cachexia

21 DIAGNOSIS Development of new grading systems Martin L, et al. J Clin Oncol 2015

22 DIAGNOSIS Development of grading systems Martin L, et al. J Clin Oncol 2015

23 DIAGNOSIS Development of grading systems Obesity Paradox (?) Martin L, et al. J Clin Oncol 2015

24 DIAGNOSIS Development of grading systems Fearon K et al. Nat Rev Clin Oncol 2013; Martin L et al. Lancet Oncol 2009 Gioulbasanis et al. Ann Oncol 2014

25 TREATMENT

26 TREATMENT Effective antineoplastic therapy Sten GB et al. Acta Oncologica 2015

27 TREATMENT Targets for potential treatment interventions Fearon K et al. Nat Rev Clin Oncol 2013

28 TREATMENT Nutritional Care Plane Timely identification of nutritional defects and initiation of nutritional support (Regular) nutritional screening Brief and casual nutritional advice Identify all reversible causes of weight loss Treatment of symptoms impairing food intake Nutrition assessment (Professional) Nutritional counseling Oral nutritional supplements Artificial nutrition Via enteral tubes (enteral nutrition) Parenteral infusions (parenteral nutrition ) Arends J, et al, Clinical Nutrition 2016

29 TREATMENT Nutritional Care Plane (determining nutritional deficits and goals) Weight-losing advance cancer patients Caloric deficiency 200 kcal/day Protein deficiency g/kg/day Goals of nutritional intervention energy intake kcal/day protein intake +50% Average nutritional requirements Energy intake: kcal/kg/day Protein intake: >1 g/kg/day (if possible up to 1.5 g/kg/day) Arends J, et al, Clinical Nutrition 2016

30 TREATMENT Nutritional support (evidence from clinical trials) Nutritional therapy in cancer patients improves body weight and energy intake but not survival Neither nutritional counselling nor oral nutritional supplements had a clear positive effect on patient s quality of life Combination of both dietary advice and oral nutritional supplements may be more effective! Heterogeneity: cancer sites and stages antineoplastic therapies length and type of dietary interventions Arends J, et al, Clinical Nutrition 2016

31 TREATMENT Nutritional support (specific considerations) For short-term nutritional support there is no need any specifically formulated amino acids mixture An increase ratio of energy from fat to energy from carbohydrates maybe used to reduce the glycemic load No evidence that glutamine or branched-chain amino acids improve clinical outcomes in cachectic patients Vitamins and minerals be supplied in amounts close to the RDA Dietary provisions that restrict energy intake in patients with or at risk of malnutrition should not be used No evidence supports that nutrients feed the tumour Arends J, et al, Clinical Nutrition 2016

32 TREATMENT Pharmaconutrients and other drugs used in common practice Laviano A, et al, NEJM 2014

33 TREATMENT Pharmaconutrients and other drugs used in common practice Arends J, et al, Clinical Nutrition 2016

34 TREATMENT Science 2008

35 TREATMENT Drug - food interactions none With food Empty stomach grapefruit Anastrazole Capecitabine Abiraterone Axitinib Axitinib Regorafenib Afatinib Crizotinib Bicalutamide Erlotinib Erlotinib Cyclophosphamide Estramustine Etoposide Enzalutamide Lapatinib Gefitinib Lenalidomide Pazopanib Lapatinib Letrozole Sorafenib Pazopanib Methotrexate Temozolamide Regorafenib Tamoxifen Thalidomide Sunitinib Topotecan Vemurafenib

36 TREATMENT Drugs used in common practice Drug Mechanism of action (Strength of) Recommendation LoE Dronabinol Appetite ( - :) Insufficient consistent clinical data Low Amino acids (Leucine, HMB) Progestins Corticosteroids Anti-catabolic ( - :) Insufficient consistent clinical data Low Appetite Appetite (Weak:) In anorectic patients be aware of serious side effects (Weak:) For a restricted period (1-3 weeks) be aware of side effects High High NSAIDs Cytokines ( - :) Insufficient consistent clinical data Low Prokinetics Gastric emptying (Weak:) Insufficient consistent clinical data Moderate Arends J, et al, Clinical Nutrition 2016

37 TREATMENT Novel drugs Agent Mechanism of action Physiological effects References Anamorelin Ghrelin receptor agonist Appetite-enhancing and anabolic activity Bimagrumab Clazakizumab Enobosarm Anti-ActRII monoclonal antibody Anti-IL-6 monoclonal antibody Selective androgen receptor modulator Prevent skeletal muscle atrophy Garcia et al Lach-Trifilieff et al Anti-inflammatory activity Bayliss et al Anabolic activity Dobs et al IP-1510 IL-1 receptor antagonist Anti-inflammatory activity Paspaliaris et al MABpl REGN1033 Anti-IL-1α monoclonal antibody Myostatin antagonising antibody Anti-inflammatory and anti-neoplastic activity Prevents skeletal muscle atrophy Hong et al Ebner et al Petruzzelli M, et al. Genes Dev 2016

38 TREATMENT Exercise Lira FS, et al. Appl Physiol Nutr Metab 2014

39 TREATMENT Conclusion: Despite a strong rationale for the use of exercise, there is insufficient evidence to determine safety and effectiveness in patients with cancer cachexia. Findings from ongoing studies are awaited. Strength of recommendation: STRONG Level of evidence Strength of recommendation: WEAK Level of evidence We recommend maintenance or an increased level of physical activity in cancer patients to support muscle mass, physical function and metabolic pattern High We suggest individualised resistance exercise in addition to aerobic exercise to maintain muscle strength and muscle mass Low Grande AJ, et al. Journal Cachexia, Sarcopenia and Muscle 2015, Arends J, et al. Clinical Nutrition 2016

40 TREATMENT Exercise Drawbacks Anemia Compromised immune function Fatigue Radiotherapy Indwelling catheters and feeding tubes Peripheral neuropathy or ataxia Multiple - uncontrolled co-morbidities Intervention Delay until anemia improved Avoid public gyms and public pools 10 of light exercises daily Avoid chlorine exposure to irradiated skin (swimming pools) Avoid pool, lake, ocean and other microbial exposures Prefer stationary reclining bicycle Individualised exercise program C A Journal 2012

41 TREATMENT Multimodal approach The MENAC Study Patients with advanced lung, pancreatic and bile duct primaries Standard care R Standard care + nutritional counselling + oral nutritional supplements + 2 grams of EPA + home-based physical exercise program (strength and aerobic activity) mg of ibuprofen ClinicalTrials.gov. NCT

42 TREATMENT Artificial nutritional support Hui D et al. Curr Opin Support Paliat Care 2015

43 TREATMENT End of life care: When to stop nutritional support (?) Strength of recommendation: STRONG Level of evidence We recommend offering and implementing nutritional interventions in patients with advanced cancer only after considering together with the patient the prognosis of the malignant disease and both the expected benefit on quality of life and potentially survival as well as the burden associated with nutritional care Low Strength of recommendation: STRONG Level of evidence In dying patients, we recommend that treatment be based on comfort. Artificial hydration and nutrition are unlikely to provide any benefit for most patients. However, in acute confusional states, we suggest to use a short and limited hydration to rule out dehydration as precipiting cause Low Arends J, et al, Clinical Nutrition 2016

44 CONCLUSIONS Malnutrition in a cancer patients is multifactorial Muscle wasting is the most striking event of the cancer associated weight loss Obese patients may also be sarcopenic (sarcopenic obesity) Timely diagnosis of malnutrition / cachexia is important Treatment of malnutrition - Multidisciplinary approach

45 The 1953 Mount Everest team

46