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Cancer og trombose Tromboseprofylakse Morten Schnack Rasmussen Overlæge

Cancer og trombose Tromboseprofylakse Morten Schnack Rasmussen Overlæge Kirurgisk Gastroenterologisk K Bispebjerg Hospital. Disposition. Primær profylakse Kemoterapi og anti-hormonel behandling Central Vene Katetre Stråle behandling Postoperative venøs tromboemboliske komplikationer

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Cancer og trombose Tromboseprofylakse Morten Schnack Rasmussen Overlæge

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  1. Cancer og trombose Tromboseprofylakse Morten Schnack Rasmussen Overlæge Kirurgisk Gastroenterologisk K Bispebjerg Hospital

  2. Disposition • Primær profylakse • Kemoterapi og anti-hormonel behandling • Central Vene Katetre • Stråle behandling • Postoperative venøs tromboemboliske komplikationer • Sekundær profylakse • Øger LMWH overlevelsen hos cancer patienter?

  3. Concurrent VTE and cancer increases the risk of death Probability of death within 183 days of initial hospital admission 1.00 0.80 0.60 0.40 0.20 0.00 DVT/PE and malignant disease Probability of death Malignant disease alone 0 40 80 120 180 Number of days Levitan et al Medicine 1999

  4. Kemoterapi og anti-hormonel behandling

  5. Incidence of VTE in malignancy: Breast cancer 17.6% 9.6% 1.6% VTE incidence 0.9% 0.2% 0.2% 0.1% Prevention (1) Node –ve (2) Node +ve (3) Advanced (4) • 1:Fischer et al J Natl Cancer Inst 1997;89:1673; 2:Fischer et al New Eng J Med 1989; 320: 479; 3: Pritchard J Clin Oncol 1996: 14; 4:Goodnough et al Cancer; 1984: 54

  6. LAVDOSIS Warfarin BEHANDLING ved C. MAMMAE 5 4.4 % 4.5 • 311 kvinder, stage 3 and 4 mamma cancer. Kemoterapi. • 6 week 1mg Warfarin dagligt. • INR 1.3–1.9 • Median behandlingstid 181 dage 4 3.5 3 2.5 p=0.03 Thrombosis (%) 2 1.5 1 0.7% 0.5 0 Placebo Warfarin 85% VTE reduction Levine M et al. Lancet 1994;886:886–9

  7. Kemo terapi og VTE komplikationer • Mangler evidensbaserede rekommandationer • Ingen fra ACCP • Kun et enkelt randomiseret studie med peroral AK behandling.

  8. Central venøse katetre og venøse tromboemboliske komplikationer

  9. Central Venous CatheterVTE complications Author VTE P value control n/N treatment n/N Monreal et al. 1996 Veno 8/13 1/16 Reitchard et al 2002 Symp n.s Couban et al 2002 Symp 5/125 6/130 n.s Diagnosis 4/42 Veno Warfarin 15/40 < 0.001 Bern et al. 1992 0.002 LMWH 3.4% LMWH 3.7% Warfarin LMWH=low-molecular-weight heparin

  10. Stråle behandling og venøse tromboemboliske komplikationer

  11. VTE og strålebehandling Author VTE P value control Stråle- behandling Holm et al. 1996 Goldberg et al. 1994 3.0% 13.0% Silvani et al 2003 Rectum cancer 7.5% 3.6% 0.001 <0.001 Rectum cancer 19.0% Malignt Glioma

  12. Postoperative venøs tromboemboliske komplikationer

  13. The ENOXACAN II studydesign Surgery Randomization Phlebography control prophylaxis Day 30 Prophylaxis 6-10 days Bergqvist et al. N Engl J Med 2002;346:975-80

  14. Incidence of venous thromboembolic events:The ENOXACAN II study p = 0.02 12 Percentage of patients • ns 4.8 • ns 1.8 0.6 0.6 Bergqvist et al. N Engl J Med 2002;346:975-80

  15. FAME study design 21 days 7 days R Dalteparin (5,000 IU sc od) Dalteparin(5,000 IU sc od) + TED No further prophylaxis Major abdominal surgery Bilateral venography(assessor-blinded) TED: graduated compression stockings

  16. Incidence of all VTE 28 days after major abdominal surgery p = 0.01 RRR: 55% (95% CI: 15% - 76%) NNT: 12 (7 – 44)

  17. Incidence of proximal DVT 28 days after major abdominal surgery RRR: 77% (95% CI: 22% – 93%) p = 0.009 NNT: 17 (10 – 59)

  18. Conclusions • Cancer patients undergoing surgery: High risk patients • TP: LMWH in combination with TED. In selected high risk patients, including those operated for cancer, we suggest post hospital discharge prophylaxis with LMWH The 7th ACCP Guidelines. Chest 2004; 126 (3 suppl): 410S

  19. Anti-koagulations behandling hos cancer patienter

  20. Øget risiko for recidiv og blødning

  21. VTE recidiv Blødning * * : Fatal, hjerne, retroperitoneum. ≥ 2 transfusioner, fald i Hb ≥ 2 mmol/L AK-behandling: Effekt, risiko Hutten BA, et al. J Clin Oncol 2000; 18: 3078-83

  22. Lavmolekylært heparin ved VTE • Veldokumenteret til behandling og profylakse af VTE • Bedre end UFH • Pålidelig biotilgængelighed og kinetik, få interaktioner • Vægtbaseret dosering. Ingen monitorering • Bedre effekt, færre blødninger • Sikkert i langtidsbehandling (HIT, osteoporose) • Selvadministration, behandling i hjemmet

  23. Long-term treatment of cancer patients with VTE: LMWH versus warfarin Outcome Warfarin LMWH* 3 months n=71 (%) n=67 (%) Major bleed 12 (16.9) 5 (7.5) VTE 3 (4.2) 2 (3.0) Total 15 (21.1) 7 (10.5)† *Enoxaparin 1.5 mg/kg; †P=0.09 Meyer G et al. Arch Intern Med. 2002;162:1729–35.

  24. LITE trial Event Tinzaparin (n=369) OAC (n=368) Recurrent VTE (%) 4.9 5.7 Major bleeding (%) 3.3 4.6 Subgruppe - analyse : Cancer n=80 n=87 * Recurrent VTE (%) 6.3 11.5 * =0.03 P LITE trial: Hull et al. ASH 2002 14 14

  25. CLOT in cancer Dalteparin • Acute VTE • 5-7 days • Dalteparin • 200 IU/kg R Oral anticoagulant Lee A et al. N Engl J Med 2003;349:146-153

  26. CLOT trial

  27. Recurrent VTE 25 20 15 Probability of recurrent VTE (%) 10 5 0 0 30 60 90 120 150 180 210 Days post-randomisation Risk reduction=52% p=0.0017 OAC Dalteparin

  28. Recidiv af VTE 8,0% 15,8% Absolut risikoreduktion 7,8% 1 event sparet pr. 13 behandlede (NNT 13)

  29. CLOT-studiet ”For patients with DVT and cancer, we recommend LMWH for the first 3 to 6 months of long-term anticoagulant therapy (Grade 1A)”. ”For these patients, we recommend anticoagulant therapy indefinitely or until the cancer is resolved (Grade 1C)”. The 7th ACCP Guidelines. Chest 2004; 126 (3 suppl): 410S

  30. LMWH AND SURVIVAL Dalteparin 5000 units once daily for up to 1 year FAMOUS 385 patients with solid tumour malignancy R Placebo Up to 1 year Chemotherapy plus dalteparin 5000 IU od 18 weeks SCLC study 84 patients with Small cell lung cancer (SCLC) R Chemotherapy (cyclophosphamide, epirubicin, vincristine) 18 weeks MALT Nadroparin 2 weeks therapeutic dose 4 weeks 1/2 therapeutic dose 302 patients with solid tumor malignancy R Placebo 6 weeks

  31. LMWH and Survival Data *% surviving at 1 year D = dalteparin; N = nadroparin; OAC = oral anticoagulant; P = placebo; HR = hazard ratio

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