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Anemia: a major challenge in cancer patients Anemia is a common problem in cancer,

Anemia: a major challenge in cancer patients Anemia is a common problem in cancer, too often under-recognised and under-treated. Anemia is common in patients with cancer. n = 13 412 ECAS: anaemia defined as Hb <12.0 g/dl. Ludwig et al. Eur J Cancer 2004;40:2293–306.

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Anemia: a major challenge in cancer patients Anemia is a common problem in cancer,

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  1. Anemia: a major challenge in cancer patients Anemia is a common problem in cancer, too often under-recognised and under-treated

  2. Anemia is common in patientswith cancer n = 13 412 ECAS: anaemia defined as Hb <12.0 g/dl Ludwig et al. Eur J Cancer 2004;40:2293–306

  3. Anemia is under-recognised in patients with cancer • Affects 35–95% of those receiving chemotherapy1 • 52% of patients had anaemia (Hb 12 g/dl)Only 22% of patients were considered anaemic by their physician Hb <10 g/dl 20%(n = 603) Hb >12 g/dl 48%(n = 1497) 32%(n = 967) Hb 10–12 g/dl 1Groopman & Itri. Natl Cancer Inst 1999;91:1616–34 Courtesy of M. Aapro, ESO

  4. Patients with anaemia are under-treated Transfusion*14.9% ECAS survey (n = 9118) Iron alone6.5% No treatment 61.1% Epoetin** 17.4% ECAS data *With or without iron**With or without iron or transfusions Ludwig et al. Eur J Cancer 2004;40:2293–306

  5. Management of cancer-related anemia: evidence-based guidelines

  6. Two out of 3 patients suffer without anemia treatment 100 80 60 40 20 0 Patients NOT receiving treatment (%)* Total 10.0–11.9 8.0–9.9 <8.0 Hb category (g/dl) *Patients anemic at least once during the surveyn=9118 Ludwig et al. Eur J Cancer 2004;40:2293–306

  7. Treatment options for cancer patients with anemia • RBC transfusions • Transient increase in Hb (not sustained)1 • Potential unwanted effects (e.g. excess iron)2,3 • Function of transfused erythrocytes may be defective • Limited blood supply,4 demanding administration • rHuEPO • Smooth and sustained increase in Hb and Ht5–7(Ht ≥6%; Hb ≥2 g/dl) • Significant reduction in requirement for transfusion (9–45% according to the literature)8 • Stimulation of normal erythrocyte function9 • Generally well tolerated • Assured availability and accessibility, easy administration 5: Ludwig et al. N Engl J Med 1990;322:1693–9 6: Procrit Study Group. Glaspy, et al. J Clin Oncol 199;15(3):1218–34 7: Procrit Study Group. Demetri GD, et al. J Clin Oncol 1998;16(10):3412–25 8: Rizzo JD J Clin Oncol 2002;20(19):4083–107 9: Ludwig et al. Hematol J 2002;3:121–30 1. Österborg. Med Oncol 1998;15(Suppl. 1):S47–9 2 :Williamson et al. BMJ 1999;319:16–9 3. Jensen et al. Blood 2003;101:91–6 4. Brittenham et al. Hematology (Am Soc Hematol Educ Program) 2001:422–32

  8. Evidence-based guidelines • Current guidelines were developed by • ASCO / ASH1 • EORTC2 • Aim of guidelines • to encourage physicians to adopt consistent practice patterns • to improve patient outcomes • These guidelines were published after the time of data collection for ECAS (2001)3 1. Rizzo et al. J Clin Oncol 2002;20:4083–102 2. Bokemeyer et al. Eur J Cancer 2004;40:2201–16 3. Ludwig et al. Eur J Cancer 2004;40:2293–306

  9. Guideline recommendations forepoetin treatment ASCO/ASH1 • Recommend epoetin for patients with Hb <10 g/dl (and Hb 10–12 g/dl based on clinical circumstances) • Advocate target Hb level ~12 g/dl EORTC2 • Recommend epoetin for patients with Hb 9–11 g/dl • Advocate target Hb level 12–13 g/dl • EORTC guidelines likely to be updated in 2006 1. Rizzo et al. J Clin Oncol 2002;20:4083–107 2. Bokemeyer et al. Eur J Cancer 2004;40:2201–16

  10. Transfusion avoidance is a major goalof epoetin therapy • According to EORTC guidelines, the major goals of erythropoietic protein therapy are • Improvement of QoL and • Prevention of transfusions • Transfusion avoidance is important as • Transfusions should be reserved for the emergency setting • Blood supplies are increasingly limited • Transfusions are associated with several risks Bokemeyer et al. Eur J Cancer 2004;40:2201–16

  11. Blood is getting more expensive to transfuse safely • Donor supply is declining — each unit takes more effort to collect • Screening tests needed — each new test costs more and rejects more donors Patient screening: • Reduces risk of exposure to infection (e.g. variant CJD*) Blood screening: • Blood groups —minor compatibility antigens • Diseases —new variants of hepatitis and HIV • Screening for variant CJD becoming necessary *Creutzfeldt–Jakob disease

  12. Adverse events associated withblood transfusions Transfusion-transmitted infections 3% Post-transfusion purpura 6% Acute lung injury Incorrect blood/component transfused 8% Graft vs host disease (2%) 52% Delayed transfusion reaction 14% 15% Acute transfusion reaction Williamson et al. BMJ 1999;319:16–9

  13. rHuEPO yields a smoother and more sustained increase in Hb rHuEPO 14 12 Transfusions 10 Hb (g/dl) 8 6 4 0 30 60 90 120 150 180 210 Treatment (days) Transfusion Österborg. Med Oncol 1998;15(Suppl. 1):S47–S49 Ludwig et al. N Engl J Med 1990;322:1693–9

  14. EPO: a specific treatment of anemia

  15. Erythropoietins • rapidly increase Hb • reduce transfusions • treat fatigue and improve QoL

  16. 1.2 1.25 Standard care 1.1 1.0 1.00 0.75 Hb change by week 4 (g/dl) 0.50 0.3 0.25 0 0 0.2 –0.25 Platinum-based chemotherapy Non platinum-based chemotherapy All Epoetin beta is effective in patients with solid tumours: a meta-analysis of three trials Epoetin beta‡ Boogaerts et al. Anticancer Res 2006; In press ‡30 000–60 000 IU per week (three divided doses)

  17. Epoetin betaOnce Weekly is as effective as three times weekly (TIW) – NOW study 13 EORTC-recommendedtarget Hb 1213 g/dl 12 Mean Hb (g/dl) 11 Epoetin beta 30 000 IU Once Weekly Epoetin beta 10 000 IU TIW 10 0 4 8 12 16 Δ Hb +1 g/dl Time (weeks) Patients with non-Hodgkin’s lymphoma, chronic lymphocytic leukaemia, multiple myeloma Cazzola et al. Br J Haematol 2003;122:386–93

  18. 100 80 60 40 20 0 75% 72% Hb response* (%) Once weekly Three times weekly Efficacy of epoetin beta Once Weekly:Hb response and transfusion-free patients 100 80 60 40 20 0 91% 86% Transfusion-free patients (%) Once weekly Three times weekly *Hb2 g/dl vs baseline without transfusion in the previous 6 weeks Adapted from Cazzola et al. Br J Haematol 2003;122:386–93

  19. Epoetin beta: Hb response in 67% of transfusion-dependent patients Patients with haematological malignancies 100 Epoetin beta 30 000 IU weekly 67% 80 p<0.0001 60 Patients with Hb increase ≥2 g/dl* (%) ~ 40% improvement 40 20 Placebo27% 0 4 6 8 10 12 14 16 Time (weeks) Österborg et al. J Clin Oncol 2002;20:2486–94 *Without blood transfusion in previous 6 weeks

  20. p=0.001* p=0.01* p=0.001* p=0.068* Improving QoL‡ (FACT-An) Improving QoL‡ (FACT-F) Improving QoL‡ (SF-36) Improving QoL‡ (VAS) 7.5 1.5 15 5.0 Epoetin beta Epoetin beta 1.0 5.0 10 Control Control 2.5 0.5 5 2.5 0.0 0 0.0 0.0 –2.5 –5 –0.5 Week 12 Week 12 Week 12 Week 12 Weeks 6–8 Weeks 6–8 Weeks 6–8 Weeks 6–8 Weeks 3–4 Weeks 3–4 Weeks 3–4 Weeks 3–4 *p-value is for median change from baseline to study end (epoetin beta vs control) ‡Mean (SD) change in score from baseline Epoetin beta improves QoL of anaemic patients with cancer Improvements in QoL seen in first 4 weeks of epoetin beta treatment in patients with solid or lymphoid malignancies Boogaerts et al. Br J Cancer 2003;88:988–95

  21. 65 Improving QoL (LASA, mm) Open-label study of epoetin 30 000 IU/week in patients with non-myeloid malignancy undergoing chemotherapy (n = 1575) 60 55 6.7 mm 50 3.7 mm 45 11 12 13 14 7 8 9 10 Hb level (g/dl) Optimal QoL improvement followsearly intervention LASA = Linear Analogue Scale Assessment Crawford et al. Cancer 2002;95:888–95

  22. Epoetin beta provides an effective treatment of anaemia in patients with cancer • Epoetin beta is superior to standard care in managing anaemia1–3 • In accordance with the EORTC guidelines4 • Epoetin beta increases Hb levels in patients with solid1 or lymphoid malignancies2 • Regardless of chemotherapy type1 • Epoetin beta improves QoL3 • Epoetin beta reduces the need for emergency transfusions2,3 1. Boogaerts et al.Anticancer Res 2006; In press 2. Österborg et al. J Clin Oncol 2002; 20: 2486–94 3. Boogaerts et al. Br J Cancer 2003; 88: 988–995 4. Bokemeyer et al. Eur J Cancer 2004; 40: 2201–16

  23. Anemia: importance to the patient

  24. Impact of anemia in oncology patients Fatigue Cognitive function Anemia Disrupts daily activities Affects physical, mental, and emotional health Cytokine mediated: eg, IL-6 May persist months post-CT Subjective: mechanisms poorly understood – CNS effect of CT? Hormonal milieu? Psychological factors? Roles and relationships Social activities Anxiety, Depression Sexual function Appearance Quality of life Ahlberg K, et al. Lancet. 2003;362:640–50Beggs VL, et al. Proc Am Soc Clin Oncol. 2003;22:733 Abstract 2484Cella D, et al. Cancer. 2002;94:528–38Curt GA, et al. The Oncologist. 2000;5:353–60Phillips KA, Bernhard J. J Natl Cancer Inst. 2003;95:190–7 CT = chemotherapy Adapted from Corey J. Langer

  25. Fatigue is the most frequently reported symptom in cancer patients 100 76 80 54 60 Patients (%) 40 23 20 20 0 Fatigue Nausea Depression Pain n = 379 Curt et al. Oncologist 2000;5:353–60

  26.          Anemia: importance to the patient • 9 out of 10 cancer patients say treatment of fatigue is important to them • Treating anemia treats fatigue Vogelzang et al. Semin Hematol 1997;34(3 Suppl 2):4–12

  27. What is fatigue? • Fatigue is one of the most prevalent and distressing symptoms of cancer and is also one of the most prevalent and distressing symptoms of anemia • Chronic form of tiredness, perceived by the patient as being unusual/abnormal and disproportionate to the amount of exercise/activity • Not relieved by rest or sleep • Confounded by other factors such as cancer treatment or the cancer itself Ahlberg et al. Lancet 2003;362:640–50

  28. n=301 50 Preparing food 51 Concentrating 56 Climbing stairs Socialising 59 Lifting things 60 67 Exercising 68 Household chores Cleaning house 69 Walking distances 69 0 10 20 30 40 50 60 70 80 Patients (%) Ordinary household tasks become difficult with fatigue – 70% of patients struggle Curt et al. Oncologist 2000;5:353–60

  29. 61 Fatigue 37 19 Pain 61 Patients 5 Both Oncologists 2 Physicians’ underestimate the effectof fatigue on their patients Differences between patient and physician perceptions Effect on daily life 0 10 20 30 40 50 60 70 Response (%) Vogelzanget al. Semin Hematol 1997;34(Suppl 2):4–12

  30. Fatigue – can treatment work? What impact does an improvementin fatigue have on the patient?

  31. Recormon-induced Hb increases= improved fatigue scores 12 8 weeks * Hb increase ³2 g/dl† 10 Hb increase <2 g/dl 8 6 * Score (points) * Improved QoL 4 2 0 FACT-An FACT-G FACT-F FACT-An = Anaemia; FACT-G = General; FACT-F = Fatigue *p<0.05 vs Hb increase <2 g/dl †Without transfusion in previous 6 weeks Österborg et al. J Clin Oncol 2002;20:2486–94

  32. Who should receive erythropoietic proteins fortheir anemia? EORTC guideline recommendations CT = chemotherapy; RT = radiotherapy Bokemeyer et al. Eur J Cancer 2004;40:2201–16

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