Page 327 - Haematologica March 2020

Prevention of VTE in cancer patients
Table 1. Main features of randomized studies on the role of anticoagulants in ambulatory cancer patients receiving chemotherapy with VTE as primary outcome.
Author, year
Levine, 199419
Mitchell, 200320
Agnelli, 200921
Perry, 201022
Larocca, 201123
Haas, TOPIC-1 201224
Haas, TOPIC-2 201224
Agnelli, 201225
Maraveyas, 201226
Levine, 201210
D-B patients
Yes
No
Yes
Yes
No
Yes
Yes
Yes
No
Yes
N. of
311
85
1150
186
342
351
532
3212
121
122
Eligible cancers
Metastatic breast carcinoma
Newly diagnosed acute lymphoblastic leukemia
Metastatic or locally advanced lung, GI, pancreatic, breast, ovarian, or head and neck cancer
Newly diagnosed, pathologically confirmed WHO grade 3 or grade 4 glioma
Newly diagnosed multiple myeloma
Objectively proven, disseminated
metastatic breast carcinoma
Objectively proven,
stage III or IV,
non-small cell lung carcinoma
Metastatic or locally advanced cancer of the lung, pancreas, stomach, colon or rectum, bladder, and ovary
Non-resectable, recurrent or metastatic pancreatic adenocarcinoma(histological or cytological diagnosis)
Advanced or metastatic lung, breast, colon, rectum, pancreas, stomach, bladder, cancer
of unknown origin, ovarian
or prostate cancer, myeloma
or selected lymphomas
Histologically confirmed advanced pancreatic cancer
Adenocarcinoma of pancreas (locally advanced or metastatic), or stomach (unresectable or metastatic), colorectal stage IV, non-small cell lung cancer
stage III or IV, relapsed
or stage IV ovarian
Main inclusion criteria
First-line or second-line CHT for 4 weeks or less
Age >6 months and <18 years, at the beginning of the induction CHT, a functioning CVL placed <2 weeks of initiating
induction CHT
Receiving CHT, age> 18 years
Age >18 years
Previously untreated patients; age >18 and <65 years
Adult patients receiving first- or second-line CHT
Adult patients receiving first- or second-line CHT
Patients >18 years of age and planned to receive a course of CHT
Age >18 years, life expectancy >12 weeks, KPS of 60%; evaluable disease in baseline CT, adequate hematologic function, and bilirubin <1.5 UNL
Receiving first-line or second- line CHT; able to begin study medication within 6 weeks of starting CHT; expected course of CHT >90 days; age > 18 years.
No previous RT or CHT, KPS
of 60%, measurable tumor lesion confirmed by CT or MR <14 days, age >18 years
Histologically confirmed malignancy with no curative therapies,
<4 weeks of first or second line CHT, life expectancy >6 months, ECOG ≤ 2; neutrophil count ≥1.0×109, platelet count
Study treatments
Warfarin (INR 1.3-1.9) vs. Placebo
Antithrombin (plasma levels 3.0 - 4.0 U/mL) vs. No antithrombin
Nadroparin (3800 IU o.d.) vs. Placebo
Dalteparin (5000 IU o.d.) vs. Placebo
Primary outcome of prophylaxis
DVT or PE and arterial thrombosis (myocardial infarction, stroke, or peripheral-artery thrombosis)
Clinically symptomatic or asymptomatic TE in any location. TE categorized as not clinically significant
or clinically significant
Composite of symptomatic venous or arterial TE
Symptomatic DVT or PE
Duration
6 weeks
4 weeks
For the duration of CHT (maximum
120 ±10 days)
6 months
During the
4 cycles of Rd therapy and the 6 cycles of MPR consolidation
6 months
6 months
3 months, then discontinued
when CHT was stopped or regimen changed
12 weeks
12 weeks
Until disease progression *
60-day
First objectively confirmed symptomatic DVT, PE,
Enoxaparin
(40 mg o.d.)
vs. ASA (100 mg o.d.)arterial thrombosis, any acute
Pelzer, No 312 201527
Certoparin (3000 IU o.d.)
vs. Placebo
Certoparin (3000 IU o.d.) vs. Placebo
Semuloparin (20 mg o.d.) vs. Placebo
Dalteparin (200 IU/Kg o.d. for 4 weeks then 150 IU/Kg)
vs. No prophylaxis Apixaban (5mg,
10mgor20mgo.d.) vs. Placebo
Enoxaparin (40 mg o.d.) vs.
No prophylaxis
Enoxaparin (40 mg o.d.) vs. No enoxaparin
cardiovascular event or sudden, otherwise unexplained death
First objectively confirmed symptomatic or asymptomatic DVT, symptomatic PE, thrombosis of the jugular or subclavian veins; and superficial thrombophlebitis
First objectively confirmed symptomatic or asymptomatic
DVT, symptomatic PE, thrombosis of the jugular or subclavian veins; and superficial thrombophlebitis
Any symptomatic DVT in lower or upper limbs, any non-fatal PE, or death related to VTE (fatal PE
or unexplained death)
All types of DVT/PE, all arterial events and all visceral TE
Major bleeding event
or a clinically relevant non-major bleeding event
First symptomatic VTE
Symptomatic or proximal VTE, based on levels of tissue factor-bearing microparticles
Zwicker, No 201528
34
≥100×109/L
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