PO-39 - Primary thromboprophylaxis for ambulatory patients with advanced metastatic pancreatic cancer. A practical...

The efficacy and safety of primary prophylaxis in advanced pancreatic cancer (APC) has been demonstrated in randomized controlled studies. Current guidelines suggest use of primary prophylaxis in high risk ambulatory cancer patients. The VTE in cancer working group in our centre reviewed our experience with FRAGEM and relevant literature.

(1) Dose: (a) conventional prophylactic dosing is not established in APC (b) 200IU/kg followed by 150IU/kg dalteparin may be superior to 1mg/kg followed by 40mg enoxaparin. (2) Duration of treatment: (a) FRAGEM observed a rapid increase in VTE events after the 3-month treatment period. Transfer to 40mg enoxaparin in CONKO-04 after 3months also demonstrated reduced efficacy. (3) Recognition that bleeding in metastatic incurable pancreatic cancer is not uncommon even without anticoagulation. Cumulative incidence rates of major bleeding over the first 3months were: 4.5% vs. 3.4% (NS) in CONKO-04 and 3.4% vs. 3.1 % (NS) in FRAGEM (treatment vs observation arms respectively).

This abstract describes our interpretation and experience on implementing available evidence for primary prophylaxis in ambulatory APC patients.

A simplified body weight-adjusted schedule for thromboprophylaxis with Dalteparin for the ambulant APC patient was agreed as follows: <50kg: 7500IU, 50 -80kg: 10,000IU, >80kg: 12,500IU. Eligible patients: All patients with advanced / metastatic pancreatic cancer undergoing palliative chemotherapy. Dalteparin treatment was initiated at least one day prior to the first administration of chemotherapy and continued until death or unacceptable toxicity (bleeding). This guideline was implemented in May 2009. A departmental audit was conducted for patients treated till December 2012 to assess efficacy and safety.

Results of the audit have been presented in an analysis including 67 patients. The compound adverse outcome (CAE) in this cohort was 24% (VTE: 13%, bleeding: 11%). For patients with no prior exposure to anticoagulation CAE rate was 18% (VTE: 7%, bleeding: 11%) with a median duration of LMWH treatment of 8months. The majority of the bleeding events observed were due to cancer related lesions (duodenal infiltration or varices). VTE and bleeding rates were similar to published experience with extended duration therapeutic LMWH in cancer-related VTE. VTE risk appeared improved compared to the 3-month regimen of FRAGEM.

In our opinion, thromboprophylaxis in ambulatory APC is a pragmatic evidence-based approach trying to deal with a serious cancer related complication that affects these patients. It is expected that data from further randomised trials (e.g SELECT-D and CASSINI) will provide further evidence in this area.