* P< 0.01 for each comparison; P< for all groups combined. ! During anticancer therapy, involuntary weight loss is

Transcription

1 COMMON Head and Neck Esophagus Stomach Pancreas Lung INTERMEDIATE Colorectal Ovarian Lymphoma UNCOMMON Breast Prostate Leukemia M Schattner, MSKCC, ASPEN 2008 Retrospective review of QOL (EORTC QLQ C-30) in patients with weight loss at presentation. 75 QOL Score * * * N = 1555 Patients with weight loss Patients without weight loss 0 Esophageal Gastric Pancreatic Colorectal Type of cancer * P< 0.01 for each comparison; P< for all groups combined Andreyev et al. Eur J Cancer 34: ; 1998 Lung Pancreatic Bachmann. J GI Surg, 2008 Esophageal! During anticancer therapy, involuntary weight loss is associated with:! Poorer survival! Poorer treatment response! Increased adverse events Tewari N et al. Lung Cancer 2007; 57: F Bozzetti, ESMO Symposium, 2009 Maltoni M et al. Hem Onc Clin North Am 2002;16:715-29; J Clin Oncol 2005;23: Stahl M, et al.. J Cancer Res Clin Oncol 2004 Tammemagi CM, et al. Cancer 2004;101: Argiris A et al. Cancer 2004;10 A Laviano, ESMO Symposium on Nutrition in Cancer, Mar

2 Cancer patients with stabilized weight during chemotherapy show significantly longer incidence-free and overall Andreyev survival HJN rates et al. Eur J Cancer 1998 Lancet Oncol, %, Anorexia, Metabolic Changes Survival >6-9 months? 3-9 months? <3months? Fearon KCH. Eur J Cancer, 2008 Early diagnosis, early treatment Early, active, multimodal intervention Supportive and palliative care Personal discussion Prof M Muscaritoli Recognized consequences of sarcopenia Respiratory failure Asthenia, fatigue Impaired physical function Increased risk of falls/fractures Reduced tolerance to treatments Impaired quality of life (QoL) Reduced survival 2

3 Age-associated loss of skeletal muscle mass & strength Less-than-expected muscle mass in an individual of a specified age, gender and race Baumgartner RN, Waters DL, 2006 Liver Muscle Adipose tissue Losses of muscle & fat reflect tumor progression Roubenoff R, J Gerontol Med Sci 2003; 58: A viscerally driven cachexia syndrome in patients with advanced colorectal cancer Lieffers, Am J Clin Nutr, 2009; 89: Body composition and 5-FU-related toxicity in stage II and III colon cancer patients- Gender Toxicity absent Toxicity present p = Toxicity absent Toxicity present p <0.001 p = p = Lower lean body massà greater toxicity Prado MM, et al. Clin Cancer Res 2007 p <0.001 Lower lean body massà greater toxicity Prado MM, et al. Clin Cancer Res 2007 p =0.05 p = Higher dose-limiting toxicity with sarcopenia Shorter time to tumor progression with sarcopenia Prado MM, et al. Clin Cancer Res 2009 Prado MM, et al. Clin Cancer Res

4 Cancer patients for major abdominal surgery Patients with malnutrition + advanced cancer + chemo- or radiotherapy with impaired GI function p<0.02 p= Perioperative nutrition support Early goal-directed nutrition therapy More dose-limiting toxicity with sarcopenia Prado MM, et al. Cancer Chemother Pharmacol 2011 Therapeutic goals for PN in cancer patients are the improvement of function and outcome by: Preventing and treating under-nutrition/cachexia Enhancing compliance with anti-tumor treatments Controlling adverse effects of anti-tumor therapies Improving quality of life ESPEN PN Guidelines for Non-Surgical Oncology, Clin Nutr, Aug 2009! Glucose is the primary metabolic substrate of tumors! Consider glucose deprivation during chemotx! Fat is an ideal energy substrate but utilization by tumors is poor (lack enzymes for FFA & ketone degradation)! Increase lipids, esp. during chemotx (Up to 50%- ESPEN Guidelines for Oncology) Bongaerts et al. Medical Hypotheses. 67, , 2006 Daly, J.M.; JPEN 14(5), 1990, DeBlaauw, I Clin. Nutr., 1997 Laviano, A. Nutrition, 1996 Holm, E.: Karger Verlag, Basel, 1991, Rossi-Fanelli, F JPEN, 1991! Glucose is the primary metabolic substrate of tumors! Consider glucose deprivation during chemotx! Fat is an ideal energy substrate but utilization by tumors is poor (lack enzymes for FFA & ketone degradation)! Increase lipids, esp. during chemotx (Up to 50%- ESPEN Guidelines for Oncology) Bougnoux, P. Expert Mtg Oncology, Paris 2012 ESPEN PN Guidelines for Nonsurgical Oncology, Aug 2009 Bongaerts et al. Medical Hypotheses. 67, , 2006 Daly, J.M.; JPEN 14(5), 1990, DeBlaauw, I Clin. Nutr., 1997 Laviano, A. Nutrition, 1996 Holm, E.: Karger Verlag, Basel, 1991, Rossi-Fanelli, F JPEN, 1991 Using a higher than usual percentage of lipid (e.g. 50% of non-protein energy), may be beneficial for those with frank cachexia needing prolonged parenteral nutrition (PN) ESPEN PN Guidelines for Non-Surgical Oncology, Clin Nutr, Aug

5 EN is the preferred route of delivery PN is used to supplement inadequate EN Specific nutrients exert specific effects I Bosaeus, ESMO Symposium, 2009 Intern Emerg Med, 2010! Prevent/ treat weight loss, malnutrition, cachexia! Maintain/ improve muscle mass and function! Improve immunity! Enhance quality of life! Reduce inflammation! Improve compliance with anti-cancer therapies! Reduce side effects of anti-cancer therapies! Enhance efficacy of multimodal therapies Andreyev HJN et al: Eur J Cancer 1998;34(4):503. Baracos V. ESPEN Symposium, Gothenberg, 2011 Muscaritoli et al. Crit Rev Hema Onco. Jan

6 ! Prevent/ treat weight loss, malnutrition, cachexia! Maintain/ improve muscle mass and function! Improve immunity! Enhance quality of life! Reduce inflammation! Improve compliance with anti-cancer therapies! Reduce side effects of anti-cancer therapies! Enhance efficacy of multimodal therapies Correction of malnutrition (risks) Preservation of muscle mass & function Modulation of pharmacologic and/or physiologic effects of chemotherapy +/- radiotherapy Andreyev HJN et al: Eur J Cancer 1998;34(4):503. Baracos V. ESPEN Symposium, Gothenberg, 2011 Muscaritoli et al. Crit Rev Hema Onco. Jan 2012 Goldwasser F, Expert Mtg Onco, Paris 2012! Multimodal treatment combines surgery, chemotherapy, radiotherapy -----> multiplying nutritional risk! Systemic antineoplastic agents have characteristic toxicities, limiting the dose and duration of therapy! Nutrition (incl specific nutrients) may improve the therapeutic index of cancer treatments by increasing efficacy, reducing toxicity, or both V Baracos, ESPEN 2011, Gothenburg, Sweden! Patients experience limitations in their chemotherapy treatment:! dose reductions! delays in therapy! discontinuation of therapy! Toxicities also worsen malnutrition and wasting V Baracos, ESPEN 2011, Gothenburg, Sweden Ø Fish oils Ø Glutamine! Inhibit PIF proteolysis-inducing factor/ LMF lipid mobilizing factor! Preserve or increase lean body mass! Decrease fatigue and improve quality of life! Decrease inflammatory cytokine production! Inhibit carcinogenesis & cancer growth! Increase efficacy of chemo-radiotherapy! Reduce adverse effects of chemo-radiotherapy X X X August D. JPEN Sep-Oct;33(5): ; Grimble R.F. Clin Nutr Highlights 2007; 3: 2-7 MacDonald et al, JACS, July 2003; Swails, W; JPEN 21(5), , 1997 Barber, M.D; J. Nutr. 129, , 1999; Wigmore, S.J.; Nutrition & Cancer 36(2), , 2000 Colomer et al. Br J Nutr May;97(5):

7 25/4/13 Influence of ω-3 fatty acids on the efficacy of doxorubicin in nude mice with breast cancer xenografts: Tumor size Days after therapy with Doxorubicin vs. all other groups: ω-3 fatty acids may slow down tumor growth ω-3 fatty acids enhance the efficacy of chemotherapeutic agents Ramos et al, J Am Coll Surg 2004; 199: Hardmann et al 2001 *Study details excluded pending study publication Cytokine results suggest that ω-3 FA are likely to reduce new tumour growth and metastases *Study details excluded pending study publication Improved disease control, progression-free survival, and over-all toxicity A Dennison, Leicester. Presented at Oncology Mtg, Paris M Metcalfe, Leicester. Presented at Oncology Mtg, Paris Cytokines Cytokines Complement Complement Prostaglandins Prostaglandins (Ostrand-Rosenberg S, Nat Biotech 2008) (Ostrand-Rosenberg S, Nat Biotech 2008) M Metcalfe, Leicester. Presented at Oncology Mtg, Paris M Metcalfe, Leicester. Presented at Oncology Mtg, Paris

8 !... pharmacologically acting nutrients - are a potentially important approach to modulate the therapeutic index of antineoplastic therapy.! Glutamine, ω-3 FAs... hold promise to prevent or treat GI toxicities related to cancer chemotherapy. Glutamine! Preferred energy fuel for enterocytes! Precursor for GSH biosynthesis! Modulation of heat shock response! Regulation of apoptotic/proliferative signaling! Modulating intestinal and systemic immunity Xue H, Sawyer M, Wischmeyer P, Baracos VE. J Parenteral Enteral Nutr. Vol 35 No 1, Jan breast cancer patients receiving CT (cyclophosphamide/epirubicin/5-fu); oral glutamine vs. placebo 3 x 10 g/day; from beginning of CT for at least 12 days 326 breast cancer patients developing WHO grade 2 oral mucositis during anthracycline-based CT. Oral glutamine 3 x 2.5 g/day vs. placebo % Placebo Glutamine Placebo Glutamine Intestinal permeability after CT was significantly increased in placebo group (p<0.05) Li Y et al. Tumori 2006, 92: Percentage of patients with oral mucositis (WHO gr 2) during treatment with oral glutamine vs. placebo. Oral glutamine consistently reduced mucositis, thereby increasing the proportion of patients able to eat solid foods. Peterson DE et al. Cancer 2007, 109: Effects on mucositis & other outcomes 29 patients with head and neck cancer treated with CRT, randomised to receive Ala-Gln ( g/kg b.w./day) vs. saline over a 60 day- period on the days of CT (14 x). Patients free of severe mucositis (WHO score 3), Kaplan-Meier survival curve. More patients remained free of severe mucositis in Ala-Gln group vs. placebo (p<0.05, Cox-test) Cerchietti LCA et al., Int. J. Radiation Oncology Biol. Phys. 2006, 65: Grade of mucositis Pain intensity Need for analgesics International Journal of Radiation Oncology Biology Physics, Volume 65, Issue 5, Pages

9 53 leukaemia pts undergoing Allo-SCT randomised to receive Ala-Gln (Dipeptiven g/kg bw/day) vs. standard PN during 1st wk of transplantation. Cumulative survival on D 180. Survival improved significantly on D100 & D 180 with Dipeptiven (GI-PN) vs. standard PN (p<0.05, log rank test). Assessment of tumor growth: Flow cytometry 3H-Thymidine labelling index Bromodeoxyuridine labelling index Evidence: Nutrition therapy does not stimulate tumor growth Bossola, M. ESMO Symposium, March 2009 There is evidence that nutrition support (EN & PN) does not stimulate tumor proliferation Survival data seem to show a benefit of nutrition support or, at least, no deterioration of prognosis Bossola, M. ESMO Symposium, March 2009 Although PN supplies nutrients to the tumor, there is no evidence that this has deleterious effects on the outcome. This consideration should therefore have no influence on the decision to feed a cancer patient when PN is clinically indicated ESPEN PN Guidelines for Non-Surgical Oncology, Clin Nutr, Aug

10 10