1. A Systematic Analysis of VTE Prophylaxis in the Setting of Cancer
Innovation ● Investigation ● Application
A Systematic Analysis of VTE Prophylaxis in the Setting of Cancer
Linking Science and Evidence to Clinical Practice—
What Do Trials Teach?
Program Chairman
Craig Kessler, MD MACP
Director, Division of Coagulation
Lombardi Comprehensive Cancer Center
Georgetown University Medical Center
Washington, DC

2. VTE and Cancer: Epidemiology
Of all cases of VTE:
About 20% occur in cancer patients
Annual incidence of VTE in cancer patients ≈ 1/250
Of all cancer patients:
15% will have symptomatic VTE
As many as 50% have VTE at autopsy
Compared to patients without cancer:
Higher risk of first and recurrent VTE
Higher risk of bleeding on anticoagulants
Higher risk of dying
Lee AY, Levine MN. Circulation. 2003;107:23 Suppl 1:I17-I21

3. DVT and PE in Cancer Facts, Findings, and Natural History
VTE is the second leading cause of death in hospitalized cancer patients1,2
The risk of VTE in cancer patients undergoing surgery is 3- to 5-fold higher than those without cancer2
Up to 50% of cancer patients may have evidence of asymptomatic DVT/PE3
Cancer patients with symptomatic DVT exhibit a high risk for recurrent DVT/PE that persists for many years4
Let’s continue examining the association between DVT/PE and cancer.
Consider these statistics. DVT/PE is the second leading cause of death in hospitalized cancer patients. Up to twenty percent of all DVT/PE cases occur in cancer patients and up to fifty percent of cancer patients may have evidence of asymptomatic DVT/PE.
As I previously mentioned, surgery is a well-known risk factor; however cancer patients undergoing surgery compound that risk to 3 to 5-times greater than surgery patients without cancer.
Finally, cancer patients are at higher risk of developing a recurrent DVT or PE following a primary experience than patients without cancer.
Ambrus JL et al. J Med. 1975;6:61-64
Donati MB. Haemostasis. 1994;24:
Johnson MJ et al. Clin Lab Haem. 1999;21:51-54
Prandoni P et al. Ann Intern Med. 1996;125:1-7

4. Clinical Features of VTE in Cancer
VTE has significant negative impact on quality of life
VTE may be the presenting sign of occult malignancy
10% with idiopathic VTE develop cancer within 2 years
20% have recurrent idiopathic VTE
25% have bilateral DVT
Bura et. al., J Thromb Haemost 2004;2:445-51

5. Thrombosis and Survival Likelihood of Death After Hospitalization
0.00
0.20
0.40
1.00
0.80
0.60
DVT/PE and Malignant Disease
Malignant Disease
DVT/PE Only
Nonmalignant Disease
Number of Days
Probability of Death
Levitan N, et al. Medicine 1999;78:285

6. Incidence of VTE and Colon Cancer Stage
Days after Cancer Diagnosis
Incidence of VTE (%) 7% 6% 5% 4% 3% 2% 1% 0%
Local Regional Remote
White RH et al. Thrombosis Research 120 Suppl. 2 (2007) S29-40

7. Symptomatic VTE in Cancer Reduces Survival Counterintuitively, Magnitude of Effect on Survival is Greatest with Local Stage Disease
Cancer type
Hazard ratio (95% CI) for death within one year, cases with VTE diagnosed in year 1 vs. no VTE, by stage
Local
Regional
Remote
Prostate
5.6 ( )‡
4.7 ( ) ‡
2.8 ( ) †
Breast
6.6 ( ) ‡
2.4 ( ) ‡
1.8 ( )*
Lung
3.1 ( ) ‡
2.9 ( ) ‡
2.5 ( ) ‡
Colon/rectum
3.2 ( ) ‡
2.2 ( ) ‡
2.0 ( ) ‡
Melanoma
14.4 ( ) ‡
N/A
2.8 ( ) †
Non-Hodgkin’s lymphoma
3.2 ( ) ‡
2.0 ( ) †
2.3 ( ) ‡
Uterus
7.0 ( ) ‡
9.1 ( ) ‡
1.7 ( )*
Bladder
3.2 ( ) ‡
3.3 ( ) ‡
3.3 ( ) ‡
Pancreas
2.3 ( )*
3.8 ( ) ‡
2.3 ( ) ‡
Stomach
2.4 ( )*
1.5 ( )*
1.8 ( ) ‡
Ovary
11.3 ( ) †
4.8 ( )*
2.3 ( ) ‡
Kidney
3.2 ( )*
1.4 ( )
1.3 ( )
R.H. White et al. Thombosis Research 120 Suppl. 2 (2007) S29-S40
* p<0.05; †p<0.01); ‡ p<0.001)

8. VTE Associated with Accelerated Death in Breast Cancer Does Symptomatic VTE Reflect Presence or Emergence of Metastatic, Aggressive Cancer?
White, et al. Thromb Res,120 suppl. 2 (2007)

9. Recurrent Ovarian Cancer
• 7% symptomatic VTE ( % in primary ovarian Cancer) • 78% of VTE in ROC occur within 2 months of second line chemo regimen: cisplatin-related • Ascites is the only independent risk factor for VTE (HR=2.2)
Fotopoulou C et al. Thromb Res 2009

10. Hospital Mortality With or Without VTE
N=66,016
N=20,591
N=17,360
Khorana, JCO, 2006

11. Thrombosis Risk In Cancer
Primary Prophylaxis
Medical Inpatients
Surgery
Radiotherapy
Central Venous Catheters

12. Risk Factors for Cancer-Associated VTE
Type
Men: prostate, colon, brain, lung
Women: breast, ovary, lung
Stage
Treatments
Surgery
10-20% proximal DVT
4-10% clinically evident PE
0.2-5% fatal PE
Chemotherapy
Central venous catheters (~4% generate clinically relevant VTE)
Patient
Prior VTE
Comorbidities
Genetic background

13. Cancer and Thrombosis
Medical Inpatients

14. Antithrombotic Therapy: Choices
Pharmacologic
(Prophylaxis & Treatment)
Nonpharmacologic
(Prophylaxis)
Low Molecular Weight Heparin (LMWH)
Intermittent
Pneumatic
Compression
Elastic
Stockings
Unfractionated
Heparin (UH)
Inferior
Vena Cava
Filter
Several classes of agents have been used for prophylaxis and treatment of VTE
Nonpharmacologic approaches to prophylaxis include: intermittent pneumatic compression (IPC), elastic stockings, and inferior vena cava filter
Most commonly used pharmacologic agents for thromboprophylaxis and treatment of VTE include: unfractionated heparin (UH) (standard, low-dose, or adjusted-dose), oral anticoagulants such as warfarin, and low molecular weight heparins (LMWHs)
Oral
Anticoagulants
New Agents: e.g.
Fondaparinux, Direct anti-Xa inhibitors, Direct anti-IIa, etc.?

15. Prophylaxis Studies in Medical Patients
Relative risk reduction 47%
Relative risk reduction 63%
Rate of VTE (%)
Relative risk reduction 44%
Placebo Enoxaparin
MEDENOX Trial
Placebo Dalteparin
PREVENT
Placebo Fondaparinux
ARTEMIS
Francis, NEJM, 2007

16. ASCO Guidelines 1. SHOULD HOSPITALIZED PATIENTS WITH
CANCER RECEIVE ANTICOAGULATION FOR
VTE PROPHYLAXIS?
Recommendation. Hospitalized patients with cancer should be considered candidates for VTE prophylaxis with anticoagulants in the absence of bleeding or other contraindications to anticoagulation.
Lyman GH et al. J Clin Oncol (25) 2007; 34:

17. Cancer and Thrombosis
Surgical Patients

18. Incidence of VTE in Surgical Patients
Cancer patients have 2-fold risk of post-operative DVT/PE and >3-fold risk of fatal PE despite prophylaxis:
No Cancer
N=16,954
Cancer
N=6124
P-value
Post-op VTE
0.61%
1.26%
<0.0001
Non-fatal PE
0.27%
0.54%
<0.0003
Autopsy PE
0.11%
0.41%
Death
0.71%
3.14%
Kakkar AK, et al. Thromb Haemost 2001; 86 (suppl 1): OC1732

19. Natural History of VTE in Cancer Surgery: The @RISTOS Registry
Web-Based Registry of Cancer Surgery
Tracked 30-day incidence of VTE in 2373 patients
Type of surgery
• 52% General
• 29% Urological
• 19% Gynecologic
82% received in-hospital thromboprophylaxis
31% received post-discharge thromboprophylaxis
Findings
2.1% incidence of clinically overt VTE (0.8% fatal)
Most events occur after hospital discharge
Most common cause of 30-day post-op death
Agnelli, Ann Surg 2006; 243: 89-95

20. Prophylaxis in Surgical Patients
LMWH vs. UFH
Abdominal or pelvic surgery for cancer (mostly colorectal)
LMWH once daily vs. UFH tid for 7–10 days post-op
DVT on venography at day 7–10 and symptomatic VTE
Study N
Design
Regimens
ENOXACAN 1
631
double-blind
enoxaparin vs. UFH
Canadian Colorectal DVT Prophylaxis 2
475
1. ENOXACAN Study Group. Br J Surg 1997;84:1099–103
2. McLeod R, et al. Ann Surg 2001;233:

21. Prophylaxis in Surgical Patients
Canadian Colorectal DVT Prophylaxis Trial
16.9%
P=0.052
13.9%
Incidence of Outcome Event
N=234
N=241
1.5% 2.7%
VTE Major Bleeding
(Cancer) (All)
McLeod R, et al. Ann Surg 2001;233:

22. Extended Prophylaxis in Surgical Patients
12.0%
ENOXACAN II
P=0.02
Incidence of Outcome Event
N=167
4.8%
5.1%
N=165
3.6%
1.8%
NNT = 14
0.6%
0% 0.4%
VTE Prox Any Major
DVT Bleeding Bleeding
Bergqvist D, et al. (for the ENOXACAN II investigators) N Engl J Med 2002;346:

23. Major Abdominal Surgery: FAME Investigators—Dalteparin Extended
A multicenter, prospective, assessor-blinded, open-label, randomized trial: Dalteparin administered for 28 days after major abdominal surgery compared to 7 days of treatment
RESULTS: Cumulative incidence of VTE was reduced from 16.3% with short-term thromboprophylaxis (29/178 patients) to 7.3% after prolonged thromboprophylaxis (12/165) (relative risk reduction 55%; 95% confidence interval 15-76; P=0.012).
CONCLUSIONS: 4-week administration of dalteparin, 5000 IU once daily, after major abdominal surgery significantly reduces the rate of VTE, without increasing the risk of bleeding, compared with 1 week of thromboprophylaxis.
Rasmussen, J Thromb Haemost Nov;4(11): Epub 2006 Aug 1.

24. ASCO Guidelines: VTE Prophylaxis
All patients undergoing major surgical intervention for malignant disease should be considered for prophylaxis.
Patients undergoing laparotomy, laparoscopy, or thoracotomy lasting > 30 min should receive pharmacologic prophylaxis.
Prophylaxis should be continued at least 7 – 10 days post-op. Prolonged prophylaxis for up to 4 weeks may be considered in patients undergoing major surgery for cancer with high-risk features.
Lyman GH et al. J Clin Oncol (25) 2007; 34:

25. Central Venous Catheters
Thrombosis is a potential complication of central venous catheters, including these events:
Fibrin sheath formation
Superficial phlebitis
Ball-valve clot
Deep vein thrombosis (DVT)
Geerts W, et al. Chest Jun 2008: 381S–453S

26. Prophylaxis for Venous Catheters
Placebo-Controlled Trials
Study
Regimen N
CRT (%)
Reichardt* 2002
Dalteparin 5000 U daily
placebo
285
140
11 (3.7)
5 (3.4)
Couban*
2002
Warfarin 1mg daily
130
125
6 (4.6)
5 (4.0)
ETHICS†
2004
Enoxaparin 40 mg daily
155
22 (14.2)
28 (18.1)
*symptomatic outcomes; †routine venography at 6 weeks
Reichardt P, et al. Proc ASCO 2002;21:369a; Couban S, et al, Blood 2002;100:703a; Agnelli G, et al. Proc ASCO 2004;23:730

27. WARP: Prophylactic Warfarin Does Not Reduce Catheter-Associated Thrombosis in CA
Thrombotic Events
Warfarin evaluation
Dose evaluation
No warfarin (n=404)
Warfarin (n=408)
Relative risk
(95% CI, p value)
Fixed-dose warfarin (n=471)
Dose-adjusted warfarin (n=473)
Relative risk (95% CI, p value)
Catheter-related thrombotic events 24
(6%)
0.99
( , 0.98) 34
(7%) 13
(3%)
0.38
( ,0.002)
No catheter-related event
370
(92%)
372
(91%) -
433 (92%)
448 (95%)
Not known 10
(2%) 12 4
(<1%)
All thrombotic events 38
(9%) 30
0.78
( ), 0.30 37
(8%) 26
0.70
( , 0.15)
Young AM et al. Lancet 2009;373:567

28. WARP: Prophylactic Warfarin Does Not Reduce Catheter-Associated Thrombosis in CA
Bleeding and Raised INR
Warfarin evaluation
Dose evaluation
No warfarin (n=404)
Warfarin (n=408)
Relative risk
(95% CI, p value)
Fixed-dose warfarin (n=471)
Dose-adjusted warfarin (n=473)
Relative risk (95% CI, p value)
Major bleeding and no reported raised INR
1 (<1%)
3 (<1%) -
5 (1%)
7 (1%)
Major bleeding and raised INR
4 (<1%)
2 (<1%)
9 (2%)
Total major bleeding
7 (2%)
6.93
( , 0.07)
16 (3%)
2.28
( , 0.09)
Moderate and severe raised INR and no major bleeding
12 (3%)
Minor bleeding
14 (3%)
21 (4%)
24 (5%)
Young AM et al. Lancet 2009;373:567

29. WARP: Prophylactic Warfarin Does Not Reduce Catheter-Associated Thrombosis in CA
Combined thrombosis and major bleeding events
Warfarin evaluation
Dose evaluation
No warfarin (n=404)
Warfarin (n=408)
Relative risk
(95% CI, p value)
Fixed-dose warfarin (n=471)
Dose-adjusted warfarin (n=473)
Relative risk (95% CI, p value)
Total catheter-related thrombosis and major bleeding events
25 (6%)
31 (8%)
1.23
( , 0.51)
41 (9%)
29 (6%)
0.84
( , 0.17)
All thrombotic and major bleeding events
39 (10%)
37 (9%)
0.94
( , 0.87)
44 (9%)
42 (9%)
0.95
( , 0.89)
Young AM et al. Lancet 2009;373:567

30. Central Venous Catheters: Warfarin
Tolerability of Low-Dose Warfarin
95 cancer patients receiving FU-based infusion chemotherapy and 1 mg warfarin daily
INR measured at baseline and four time points
10% of all recorded INRs >1.5
Patients with elevated INR
2.0– %
3.0– %
> %
Masci et al. J Clin Oncol. 2003;21:

31. Influence of Thrombophilia on Thrombotic Complications of CVADs in Cancer
In 10 studies involving more than 1250 cancer patients with CVADs vs CA controls:
The attributable risk of catheter associated thrombosis conferred by:
CA + FVL OR=5.18 (95% confidence interval: )
CA + G20210A OR=3.95 (95% confidence interval: )
FVL 13.5%
G20210A 3.6%
Dentali F et al. JTH 2007; 5(Suppl 2):P-S-564

32. 8th ACCP Consensus Guidelines
No routine prophylaxis to prevent thrombosis secondary to central venous catheters, including LMWH (2B) and fixed-dose warfarin (1B)
Revised 2009 NCCN guidelines diverge from this philosophy
Chest Jun 2008: 454S–545S

33. Primary Prophylaxis in Cancer Radiotherapy The Ambulatory Patient
No recommendations from ACCP
No data from randomized trials (RCTs)
Weak data from observational studies in high risk tumors (e.g. brain tumors; mucin-secreting adenocarcinomas: Colorectal, pancreatic, lung, renal cell, ovarian)
Recommendations extrapolated from other groups of patients if additional risk factors present (e.g., hemiparesis in brain tumors, etc.)

34. Risk Factors for VTE in Medical Oncology Patients
Tumor type
Ovary, brain, pancreas, lung, colon
Stage, grade, and extent of cancer
Metastatic disease, venous stasis due to bulky disease
Type of antineoplastic treatment
Multiagent regimens, hormones, anti-VEGF, radiation
Miscellaneous VTE risk factors
Previous VTE, hospitalization, immobility, infection, thrombophilia

35. Independent Risk Factors for DVT/PE
Risk Factor/Characteristic
O.R.
Recent surgery with institutionalization
21.72
Trauma
12.69
Institutionalization without recent surgery
7.98
Malignancy with chemotherapy
6.53
Prior CVAD or pacemaker
5.55
Prior superficial vein thrombosis
4.32
Malignancy without chemotherapy
4.05
Neurologic disease w/ extremity paresis
3.04
Serious liver disease
0.10
Dr. John Heit and colleagues have provided some interesting information regarding the risk factors associated with developing DVT/PE based on a very thorough epidemiological study.
This study, part of the Rochester Epidemiology Project, looked at all residents in Olmsted County, 90 miles southeast of Minneapolis, Minnesota. The study collected information on every patient that underwent a diagnostic test looking for DVT/PE over a 25 year period. The investigators also looked at all death certificates and autopsy reports to gather further data.
Obviously, this was a large study covering a considerable period of time. Over 9,000 patients were included.
What you see here are the relative odds ratios of various risk factors or risk characteristics from this study for developing either DVT or PE.
Notice that malignancy with chemotherapy carried an odds ratio of 6.53 and malignancy without chemotherapy, an odds ratio of In comparison to other well known risk factors, such as surgery alone, these data indicate malignancy with and without chemotherapy are frequently associated with the development of a DVT or PE.
Heit JA et al. Thromb Haemost. 2001;86:

36. VTE Incidence In Various Tumors
Oncology Setting
VTE Incidence
Breast cancer (Stage I & II) w/o further treatment
0.2%
Breast cancer (Stage I & II) w/ chemo 2%
Breast cancer (Stage IV) w/ chemo 8%
Non-Hodgkin’s lymphomas w/ chemo 3%
Hodgkin’s disease w/ chemo 6%
Advanced cancer (1-year survival=12%) 9%
High-grade glioma
26%
Multiple myeloma (thalidomide + chemo)
28%
Renal cell carcinoma
43%
Solid tumors (anti-VEGF + chemo)
47%
Wilms tumor (cavoatrial extension) 4%
Otten, et al. Haemostasis 2000;30:72. Lee & Levine. Circulation 2003;107:I17

37. Primary VTE Prophylaxis
Recommended for hospitalized cancer patients
Not universally recommended for outpatients, but there are exceptions
New data for certain agents
Heterogeneous population
Need for risk stratification

38. VTE Risk with Bevacizumab in Colorectal Cancer
Approaches Risk of Antiangiogenesis in Myeloma
All-Grade Venous Thromboembolism, No./Total No.
Tumor Type
No. of Studies
Bevacizumab
Control
Incidence (95% CI), %
RR (95% CI)
Overall 6
155/1196
107/1083
11.9
( )
1.29
( )
Colorectal cancer 3
108/564
85/532
19.1
( )
1.19
( )
NSCLC 1
10/66
3/32
14.9
( )
1.59
( )
Breast cancer
17/229
12/215
7.3
( )
1.30
( )
Renal cell carcinoma
20/337
6/304
3.0
( )
3.00
( )
Naluri SR et al. JAMA. 2008;300:2277

39. Bevacizumab Increases Risk of Symptomatic VTE by 33% vs Controls
Naluri SR et al. JAMA. 2008;300:2277

40. Incidence of VTE: USA and Canada Greater than Israel, Australia, and Europe
rEPO used more in USA and Canada
L+Dex: 23% VTE with EPO vs 5% w/o EPO
Placebo + Dex: 7% VTE with EPO vs 1% without EPO
Multivariate Analysis of the Risk of Thrombosis Associated with Lenalidomide plus High-Dose Dexamethasone and Concomitant Erythropoietin for the Treatment of Multiple Myeloma
Treatment Odds Ratio P Value
(95% CI)
Lenalidomide plus 3.51 ( ) <0.001
High-dose dexamethasone
Concomitant erythropoietin ( ) <0.001
Knight: N Engl J Med.2006,354:2079 40

41. Oral Anticoagulant Therapy in Cancer Patients: Problematic
Warfarin therapy is complicated by:
Difficulty maintaining tight therapeutic control, due to anorexia, vomiting, drug interactions, etc.
Frequent interruptions for thrombocytopenia and procedures
Difficulty in venous access for monitoring
Increased risk of both recurrence and bleeding
Is it reasonable to substitute long-term LMWH for warfarin ? When? How? Why?

42. CLOT: Landmark Cancer/VTE Trial
Dalteparin
Dalteparin
CANCER PATIENTS WITH
ACUTE DVT or PE
Randomization
Dalteparin
Oral Anticoagulant
[N = 677]
Primary Endpoints: Recurrent VTE and Bleeding
Secondary Endpoint: Survival
Lee, Levine, Kakkar, Rickles et.al. N Engl J Med, 2003;349:146

43. Landmark CLOT Cancer Trial
Reduction in Recurrent VTE 5 10 15 20 25
Days Post Randomization 30 60 90
120
150
180
210
Probability of Recurrent VTE, %
Risk reduction = 52%
p-value =
Dalteparin
OAC
Recurrent VTE
Lee, Levine, Kakkar, Rickles et.al. N Engl J Med, 2003;349:146

44. Bleeding Events in CLOT
Dalteparin
N=338
OAC
N=335
P-value*
Major bleed
19 ( 5.6%)
12 ( 3.6%)
0.27
Any bleed
46 (13.6%)
62 (18.5%)
0.093
* Fisher’s exact test
Lee, Levine, Kakkar, Rickles et.al. N Engl J Med, 2003;349:146

45. Treatment of Cancer-Associated VTE
Study
Design
Length of Therapy
(Months) N
Recurrent VTE
(%)
Major Bleeding
Death
CLOT Trial
(Lee 2003)
Dalteparin
OAC 6
336 9 17 4 39 41
CANTHENOX
(Meyer 2002)
Enoxaparin 3 67 71 11 21 7 16 23
LITE
(Hull ISTH 2003)
Tinzaparin 80 87 8 22
ONCENOX
(Deitcher ISTH 2003)
Enox (Low)
Enox (High) 32 36 34
3.4
3.1
6.7 NS
0.002 NS
0.09
0.09
0.03
0.03 NS NS NS NS NR

46. Treatment and 2° Prevention of VTE in Cancer – Bottom Line
New Development
New standard of care is LMWH at therapeutic doses for a minimum of 3-6 months (Grade 1A recommendation—ACCP)
NOTE: Dalteparin is only LMWH approved (May, 2007) for both the treatment and secondary prevention of VTE in cancer (NCCN preferred agent)
Oral anticoagulant therapy to follow for as long as cancer is active (Grade 1C recommendation—ACCP)
Chest Jun 2008: 454S–545S

47. CLOT 12-month Mortality All Patients Dalteparin10 20 30 40 50 60 70 80 90
100
120
180
240
300
360
Dalteparin
OAC
HR 0.94 P-value = 0.40
Days Post Randomization
Probability of Survival, %
Lee AY et al. J Clin Oncol. 2005; 23:

48. Anti-Tumor Effects of LMWH
CLOT 12-month Mortality
Patients Without Metastases (N=150) 10 20 30 40 50 60 70 80 90
100
Dalteparin
OAC
Probability of Survival, %
HR = P-value = 0.03 30 60 90
120
150
180
240
300
360
Lee AY et al. J Clin Oncol. 2005; 23:
Days Post Randomization

49. LMWH Influences Survival of Patients with Advanced Solid Tumor Malignancies
6 wks LMWH immediately post diagnosis of CA-no initial chemo
>6 mos anticipated survival
<6 mos anticipated survival
Klerk, C. P.W. et al. J Clin Oncol; 23:

50. LMWH for Small Cell Lung Cancer Turkish Study
84 patients randomized: Chemo +/- LMWH (18 weeks)
Patients balanced for age, gender, stage, smoking history, ECOG performance status
Chemotherapyplus Dalteparin
Chemo alone
P-value
1-y overall survival, %
51.3
29.5
0.01
2-y overall survival, %
17.2
0.0
Median survival, m
13.0
8.0
CEV = cyclophosphamide, epirubicin, vincristine;
LMWH = Dalteparin, 5000 units daily
Altinbas et al. J Thromb Haemost 2004;2:1266.

51. VTE Prophylaxis Is Underused in Patients With Cancer
[1/Kakkar. Oncologist.2003/ p381/c1/line A1-A24; p383/c1/line 44-46, c2/line 1-3]
[2/Stratton. ArchInternMed. Feb.2000/ p336/c2/line 7-11]
[3/Bratzler. ArchInternMed. Sept.1998/ p1909/c1/line A10-A15, c2/line A1-A3]
[4/Rahim.ThrmbRes. 2003/p3/c2/line 1-5]
[5/Goldhaber. AmJCardiol.Jan.2004/ p261/c2/line 6-8]
Cancer:
FRONTLINE Survey1— 3891 Clinician Respondents
Major Surgery2
Cancer: Surgical
Major Abdominothoracic Surgery (Elderly)3
Confirmed DVT (Inpatients)5
Rate of Appropriate Prophylaxis, %
Medical Inpatients4
Cancer: Medical
VTE prophylaxis is underused in patients with cancer
The Fundamental Research in Oncology and Thrombosis (FRONTLINE) survey was a questionnaire distributed globally to clinicians involved in cancer care and accessible on a dedicated Web site1
Data from 3891 completed questionnaires were available for analysis1
The results indicated that 52% of respondents would routinely utilize thromboprophylaxis for surgical oncology patients, and that most respondents only considered thromboprophlyaxis in approximately 5% of their medical oncology patients1
These results can be compared with prophylaxis rates in other patient groups as determined by other recent studies
A retrospective record review in 10 US teaching or community-based hospitals of patients undergoing major surgeries (major abdominal surgery, total hip replacement, hip fracture repair, or total knee replacement) showed VTE prophylaxis was used in 89% of patients2
A retrospective record review of patients aged 65 and older in 20 Oklahoma hospitals undergoing major abdominothoracic surgery indicated that prophylaxis was used in 38% of patients3
A retrospective record review at 2 Canadian hospitals of medical inpatients indicated that prophylaxis was used in 33% of patients4
In the DVT-FREE prospective registry of patients with ultrasound-confirmed DVT, among 5451 patients, 42% had received prophylaxis5
[1/Kakkar.Oncologist. 2003/p381/c1/ line A5-A22]
[1/Kakkar/p381/c1/ line A23-A24]
[1/Kakkar/p383/c1/ line 44-46, c2/line 1-3]
[2/Stratton.ArchIntern Med.Feb.2000/ p334/c1/line A14-A19, c2/line A1-A2; p336/c2/line 7-11]
[3/Bratzler.ArchIntern Med.Sept.1998/ p1909/c1/line A10-A15, c2/line A1-A3]
[4/Rahim.ThrmbRes. 2003/p1/line A1-A12; p3/c2/line 1-5]
[5/Goldhaber.AmJ Cardiol.Jan.2004/ p259/c1/line A1-A10; p261/c2/line 6-8]
1. Kakkar AK et al. Oncologist. 2003;8:
2. Stratton MA et al. Arch Intern Med. 2000;160:
3. Bratzler DW et al. Arch Intern Med. 1998;158:
4. Rahim SA et al. Thromb Res. 2003;111:
5. Goldhaber SZ et al. Am J Cardiol. 2004;93:
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52. Conclusions and Summary
Risk factors for VTE in the setting of cancer have been well characterized: solid tumors, chemotherapy, surgery, thrombocytopenia
Long-term secondary prevention with LMWH has been shown to produce better outcomes than warfarin
Guidelines and landmark trials support administration of LMWH in at risk patients
Cancer patients are under-prophylaxed for VTE
Health system pharmacists can play a pivotal role in improving clinical outcomes in this patient population