Gemcitabine with or without prophylactic weight-adjusted Dalteparin (WAD) in patients with advanced or metastatic pancreatic cancer (APC): a multicentre, randomised phase IIB trial (the UK FRAGEM study)


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Anthony Maraveyas1, Justin Waters2, Rajarshi Roy3, David Propper4, David Fyfe5, Fiona Lofts6, Eric Gardiner1, Joseph Sgouros1, Kevin Wedgwood1

1The Queens Centre for Oncology & Hematology, Hull, UK, 2Kent Oncology Centre, Maidstone Hospital, UK, 3Diana Princess of Wales Hospital, Grimsby, UK, 4St Bartholomews Hospital,, London, UK, 5Royal Lancaster Infirmary, UK, 6St. Georges Hospital Medical School, London, UK

Abstract

Background
The incidence of vascular thromboembolism (VTE) in advanced pancreatic cancer (APC) is high (17-30%) and has been shown to confer a worse prognosis. Nullifying VTE therefore could have beneficial effects for APC patients. The study hypothesis is that the use of weight-adjusted Dalteparin dosing (WAD) in a prophylaxis setting may eliminate VTE and its impact in APC patients.

Method
Patients, aged 18 years, with histologically/cytologically-confirmed APC, Karnofsky performance status KPS 60-100, with adequate haematological, hepatic and renal function, no baseline VTE, no hemorrhagic risk, no recent VTE (<6 months) and not on anticoagulants were randomised to either Gemcitabine 1000 mg/m2 (Burris schedule) (Arm A) or same with WAD (CLOT schedule) for 3 months (Arm B) stratified by extent of disease (LA vs. M), and KPS (90-100 vs. 80-60). Primary end point was the reduction of all-type VTE and lethal VTE during study period (<100days). (FRAGEM, EUDRACT No:111-111111-11, Sponsored by HEYNHST-University of Hull).

Results
From April 2003 to January 2009, 123 (A/B 64/59) pts were randomised from 6 institutions in the UK. Pre-planned analysis of the primary endpoint of overall reduction of VTE and reduction of VTE during WAD treatment period <100days) is presented. Overall VTE was 31% (A) Vs 12% (B) (p=0.019) with RR=0.38 (95% CI =0.17,0.84). VTE during treatment period (<100days from randomisation): 25% (A) vs. 3.5% (B) (p=0.002) with RR =0.14 (95%CI 0.03,0.58). Secondary endpoints, lethal VTE and sudden death were seen only in (A) 9%Vs 0% (B) (p=0.028) RR=0.08 (95% CI=0.005,1.45) and Early Death Burden was