A prospective, randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC): Results of the CONKO 004 trial

Riess, H.; Pelzer, Uwe; Deutschinoff, G.; Opitz, Bernhard; Stauch, Martina; Reitzig, P; Hahnfeld, S.; Hilbig, A.; Stieler, Jens; Oettle, Helmut

doi:10.1200/jco.2009.27.18s.lba4506

Cited by 24 publications

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“…Despite clear association between the development of VTE in APC patients and the risk of death, neither CONKO 004 nor FRAGEM had shown any improvement in overall survival [6,7]. This is certainly due to the competing risk of death in APC which precludes the beneficial survival impact from VTE prevention being observed [9].…”

Section: Editorialmentioning

confidence: 99%

“…These studies randomized over 400 APC patients equally into LMWH or placebo. CONKO 004 showed that the use of enoxaparin at an unconventionally (high) primary prophylaxis dose of 1 mg/kg reduced the incidence of symptomatic (DVT and PE combined) from 9.87 to 1.25% [6]. FRAGEM had a broader primary endpoint of all-type VTE (i.e.DVT/PE but also incidental PE and arterial and splanchnic VTE), [2] and an "even higher" dose of LMWH (dalteparin at 150-200 u/kg) was used.…”

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confidence: 99%

“…Similar trend was seen in the early analysis of the EPIPHANY trial which is an observational study of cancer patients developing PE and treated in the outpatient settings. In the first 3 months, 56% deaths were related to cancer progression but PE related (PE and other causes) deaths were observed in 47% patients [8].Despite clear association between the development of VTE in APC patients and the risk of death, neither CONKO 004 nor FRAGEM had shown any improvement in overall survival [6,7]. This is certainly due to the competing risk of death in APC which precludes the beneficial survival impact from VTE prevention being observed [9].…”

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confidence: 99%

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Thromboprophylaxis in Pancreatic Cancer: Why isnt Prime Time Here Compared to Multiple Myeloma?

Maraveyas¹

2015

Pancreat Disord Ther

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EditorialHypercoagulability and the clinical manifestation of VTE are shared by most cancers and the use of chemotherapy canfurther increase this risk. VTE in cancer patients results in increased morbidity and mortality [1]. Patients with advanced pancreatic cancer (APC) have one of the worst prognoses of all malignancies and the highest incidence of disease provoked venous thromboembolism (VTE) [2]. Given the prominence of VTE in APC, it is not surprising that data on VTE prevention for APC have been generated from subgroup analysis of non-APC targeted placebo-controlled randomized trials of cancer patients treated with chemotherapy. Further data is derived from trials dedicated to evaluate VTE prophylaxis in APC patients. These studies have been rather homogeneous in that only low molecular weight heparins (LMWH) have been investigated for anticoagulation. The choice of LMWH was partly industry driven (e.g. study of new agent such as the semi-synthetic LMWH semuloparin) and partly due to the established superiority of LMWH over vitamin K analogues in terms of safety and efficacy both in VTE prophylaxis when given in nononcologic settings and in the therapeutic (treatment) settings of malignancy associated established VTE [3]. SAVE-ONCO and PROTECHT are the largest trials that enrolled between them more than 4000 patients with non-selected solid cancers using LMWH for the variable length of palliative chemotherapy. Both studies showed similar reduction in the symptomatic venous thrombosis (DVT) and non-fatal pulmonary embolism (PE) and in the case of SAVE-ONO, arterial thromboemoblic events were also decreased. There was a subgroup of around 300 APC patients in both of these trials but benefit in APC subgroup was only seen in SAVE-ONCO study. While the VTE reduction for the whole patient population (primary aim of the study) was from 3.9% to 2%, it went from 10.9% in the placebo arm to 2.4% in the LMWH arm for the APC subgroup [4,5]. Two trials evaluated VTE prevention by enrolling APC patients only who were receiving gemcitabine based first line palliative chemotherapies. These studies randomized over 400 APC patients equally into LMWH or placebo. CONKO 004 showed that the use of enoxaparin at an unconventionally (high) primary prophylaxis dose of 1 mg/kg reduced the incidence of symptomatic (DVT and PE combined) from 9.87 to 1.25% [6]. FRAGEM had a broader primary endpoint of all-type VTE (i.e.DVT/PE but also incidental PE and arterial and splanchnic VTE), [2] and an "even higher" dose of LMWH (dalteparin at 150-200 u/kg) was used. It showed a significant 85% risk reduction in all-type VTE in the dalteparin arm as compared to placebo (3.4% vs. 23%) over the 3 months of thromboprophylaxis [7]. None of these studies increased risk of major bleeding significantly and no fatalities were noted in APC due to haemorrhage in either of these RCTs. Subsequent meta-analysis of these trials have verified the significant impact of thromboprophylaxis on APC related VTE [1].Up to a quarter of APC patients die within the fir...

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Section: Editorialmentioning

confidence: 99%

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Thromboprophylaxis in Pancreatic Cancer: Why isnt Prime Time Here Compared to Multiple Myeloma?

Maraveyas¹

2015

Pancreat Disord Ther

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“…Several studies have assessed the use of LMWH or ultra-LMWH for thromboprophylaxis in outpatients undergoing chemotherapy (Table 2) [Agnelli et al 2011[Agnelli et al , 2009Haas et al 2005;Maraveyas et al 2011;Perry et al 2010;Reiss et al 2009]. Whereas some studies have showed a significant difference in overall or symptomatic VTE between the treatment groups, others have not.…”

Section: Outpatients Undergoing Chemotherapymentioning

confidence: 99%

“…Whereas some studies have showed a significant difference in overall or symptomatic VTE between the treatment groups, others have not. The CONKO-004 trial and the FRAGEM study have both showed a significant relative risk reduction of VTE in patients with advanced pancreatic adenocarcinoma [Maraveyas et al 2011;Reiss et al 2009]. The PROTECHT study has also shown that thromboprophylaxis using nadroparin significantly decreases the risk of venous and arterial thrombosis in patients with locally advanced or metastatic cancers [Agnelli et al 2009].…”

Section: Outpatients Undergoing Chemotherapymentioning

confidence: 99%

Prevention and treatment of venous thromboembolism in patients with cancer

Hogg¹,

Carrier²

2011

Therapeutic Advances in Hematology

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Venous thromboembolism (VTE) is the second leading cause of death and a major cause of morbidity in patients with cancer. Pharmacologic thromboprophylaxis is recommended in all hospitalized cancer patients without contraindications to anticoagulants. The role of thromboprophylaxis in outpatients undergoing chemotherapy is less certain because of the diversity of the tumor types and their associated risks of VTE and bleeding. Thromboprophylaxis should only be considered in patients at high risk for VTE. Cancer patients with a newly diagnosed VTE should be preferably treated with low-molecular-weight heparin for a minimum of 3-6 months. Treatment duration should be individualized based on the clinical status and stage of the cancer, the risk of recurrent VTE, the risk of bleeding, and personal preference of the patient. Further research is required to assess the role of the new oral anticoagulants (direct Xa and thrombin inhibitors) for this high-risk population.

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Oral anticoagulation in people with cancer who have no therapeutic or prophylactic indication for anticoagulation

Kahale

Hakoum

Tsolakian

et al. 2017

Cochrane Database of Systematic Reviews

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The existing evidence does not show a mortality benefit from oral anticoagulation in people with cancer but suggests an increased risk for bleeding.Editorial note: this is a living systematic review. Living systematic reviews offer a new approach to review updating in which the review is continually updated, incorporating relevant new evidence, as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.

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A prospective, randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC): Results of the CONKO 004 trial

Cited by 24 publications

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Thromboprophylaxis in Pancreatic Cancer: Why isnt Prime Time Here Compared to Multiple Myeloma?

Thromboprophylaxis in Pancreatic Cancer: Why isnt Prime Time Here Compared to Multiple Myeloma?

Prevention and treatment of venous thromboembolism in patients with cancer

Oral anticoagulation in people with cancer who have no therapeutic or prophylactic indication for anticoagulation

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A prospective, randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC): Results of the CONKO 004 trial

Cited by 24 publications

References 0 publications

Thromboprophylaxis in Pancreatic Cancer: Why isnt Prime Time Here Compared to Multiple Myeloma?

Thromboprophylaxis in Pancreatic Cancer: Why isnt Prime Time Here Compared to Multiple Myeloma?

Prevention and treatment of venous thromboembolism in patients with cancer

Oral anticoagulation in people with cancer who have no therapeutic or prophylactic indication for anticoagulation

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Product

Resources

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Thromboprophylaxis in Pancreatic Cancer: Why isnt Prime Time Here Compared to Multiple Myeloma?

Thromboprophylaxis in Pancreatic Cancer: Why isnt Prime Time Here Compared to Multiple Myeloma?