International Good Clinical Practices Guidelines (GCPG) for Antithrombotics in CANCER Patients

Heterogeneity in clinical practices worldwide for Venous Thromboembolism (VTE) is a major challengs. This concern led us to establish international good clinical practices guidelines (GCPG) for the management VTE in cancer patients (pts).

Twenty-four international experts (WG) worked with the methodological support of the French Cancer institute (INCa). All studies on cancer, venous thromboembolism (VTE, pulmonary embolism PE), and anticoagulant drugs (AC) published from 1996 to 2011 were searched using MEDLINE^®database. Studies quality was evaluated double-blind manner by the methodologists using the GRADE appraisal grids. Main study outcomes were rates of VTE, major and minor bleeding, thrombocytopenia and death. Extracted data were entered in evidence tables and validated by the WG. High A, Moderate B, Low C, Very low D levels of evidence depended on study design, limitations, inconsistency, indirectness, imprecision and publication bias. Guidelines were classified as Strong (Grade 1) or Weak (Grade 2) based on GRADE. If absence of scientific evidence, the WG consensus judgement was defined as Best Clinical Practice (BCP). The GCP were then evaluated by 45 independent experts worldwide and 3 pt representatives using a specific grid.

Results in cancer pts A) For initial treatment of established VTE: low molecular weight heparin (LMWH) is recommended [1B], Fondaparinux and unfractionated heparin (UFH) can be also used [2D]. Thrombolysis may be considered on a case-by-case basis, with attention to contraindication (bleeding risk) [BCP], Vena Cava Filters (VCF) may be considered if contraindication to AC of PE recurrence under optimal AC with periodic reassessment of contraindications to AC.VCF are not recommended for primary VTE prophylaxis [BCP]. For early maintenance (10 days-3 mths) and long-term treatment (>3 mths) of established VTE: LMWH are preferred over vitamin K antagonist (VKA) [1A]; LMWH should be used at least 3 mths After 3–6 mths, continuation of LMWH or VKA should be based on individual benefit-risk ratio [BCP]. If VTE recurrence, 3 options: switch from VKA to LMWH; increase in LMWH dose in pts treated with LMWH; VCF insertion [BCP].

B) To prevent postoperative VTE: LMWH once a day or low dose UFH 3 times a day are recommended; AC prophylaxis should start 12 to 2 hrs preoperatively and continued at least 7 to 10 days [ 1A]. No evidence support fondaparinux as an alternative to LMWH [2C]. The highest prophylactic dose of LMWH is recommended [ 1A]. Extended prophylaxis (4 weeks) after major laparotomy may be indicated if high VTE and low bleeding risks [2B]. For laparoscopic surgery, LMWH may be recommended as for laparotomy [BCP]. External compressions devices (ECD) are not recommended as monotherapy except if AC is contraindicated [ 2C].

C) In hospitalized medical cancer pts with reduced mobility, prophylaxis with LMWH UFH or fondaparinux [1B] is recommended. For ALL children and adults treated with L-asparaginase, depending on local policy and each pt prophylaxis may be considered [BCP]. In pts receiving chemotherapy, prophylaxis is not recommended routinely [1B]. Primary VTE prophylaxis VTE may be indicated for locally advanced or metastatic pancreatic [1B] or lung [2B] cancer pts treated with chemotherapy and having low bleeding risk. In pts treated by IMiDs with steroids and/or anthracycline, VTE prophylaxis is recommended: low or therapeutic VKA doses, LMWH at prophylactic doses and low-dose aspirin have shown similar effects [2C].

D) A brain tumor per se is not a contraindication to AC for established VTE [2C], for which we prefer LMWH [BCP]. LMWH or UFH are recommended postoperatively to prevent VTE in neurosurgery cancer pts [1A]. If creatinine clearance <30 mL/min, we suggest UFH followed by VKA (from day 1) or LMWH adjusted to anti-Xa level to treat established VTE [BCP]; ECD may be applied and UFH used on a case-by-case basis [BCP]. If platelets >50 G/L and no bleeding, full doses AC can be used for established VTE; if platelet < 50 G/L, treatment and dose depend on a case-by-case basis [BCP ]; if platelet >80 G/L, AC prophylaxis may be used and if < 80 G/L, only on a case-by-case basis [BCP]. In pregnant cancer pts, standard treatment for established VTE and prophylaxis should be implemented [BCP].

Dissemination and implementation of international GCPG for the management of VTE, the second cause of death in cancer pts, is a major public health priority.

No relevant conflicts of interest to declare.