Cancer og trombose

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)
1Fischer et al J Natl Cancer Inst 1997891673
2Fischer et al New Eng J Med 1989 320 479 3
Pritchard J Clin Oncol 1996 14 4Goodnough 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 1.31.9
• Median behandlingstid 181 dage

4
3.5
3
2.5
p0.03
Thrombosis ()
2
1.5
0.7
1
0.5
0
Placebo
Warfarin
85 VTE reduction
Levine M et al. Lancet 19948868869
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
Diagnosis
4/42
15/40
lt 0.001
Warfarin
Veno
Bern et al. 1992
0.002
LMWH
3.4
LMWH
3.7
Warfarin
LMWHlow-molecular-weight heparin
10
Stråle behandling og venøse tromboemboliske
komplikationer
11
VTE og strålebehandling
Rectum cancer
7.5
0.001
3.6
lt0.001
Rectum cancer
19.0
Malignt Glioma
12
Postoperative venøs tromboemboliske
komplikationer
13
The ENOXACAN II study design
Surgery Randomization Phlebography
control
prophylaxis
Day 30
Prophylaxis 6-10 days
Bergqvist et al. N Engl J Med 2002346975-80
14
Incidence of venous thromboembolic eventsThe
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 2002346975-80
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
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 n71 () n67 ()
• 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 P0.09 Meyer G et al.
Arch Intern Med. 2002162172935.
24
(No Transcript)
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 2003349146-153
26
CLOT trial
Treatment group Initial treatment (5-7 days) Long-term therapy (180 days)
OAC Dalteparin 200 IU/kg sc once-daily Warfarin or acenocoumarol (target INR 2.5)
LMWH Dalteparin 200 IU/kg sc once-daily Day 30 dalteparin 200 IU/kg Day 31 to 180 75-80 of full dose
27
Recurrent VTE
Risk reduction52 p0.0017
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
Treatment Outcomes Results
Long-term LMWH Recurrent VTE
Long-term LMWH Bleeding No increase
Long-term LMWH Quality of life
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
31
LMWH and Survival Data
Year LMWH Survival (months) Median (95 CI) Survival (months) Median (95 CI)
Year LMWH Overall population Good prognosis population
FAMOUS 2002 Dalteparin D 10.80 P 9.14 43.5 24.3

CLOT 2003 Dalteparin D 62 OAC 61 (HR 1.0) 80 64 (HR 0.5)
SCLC study 2003 Dalteparin D 13.0 P 8.0 16.0 10.0
MALT 2003 Nadroparin N 8.0 P 6.6 (HR 0.75) 15.4 9.4 (HR 0.64)
surviving at 1 year
D dalteparin N nadroparin OAC oral
anticoagulant P placebo HR hazard ratio