title: Intensified chemotherapy and simultaneous treatment with heparin in outpatients with pancreatic cancer - the CONKO 004 pilot trial.
abstract: BACKGROUND
  Advanced pancreatic cancer (APC), beside its high mortality, causes the highest rates of venous thromboembolic events (VTE). Enoxaparin, a low molecular weight heparin (LMWH), is effective in prevention and treatment of VTE. Some small studies indicated that this benefit might extend to patients with cancer and probably prolong survival due to independent mechanisms. We initiated this safety investigation to get feasibility information on intensified chemotherapy combined with LMWH in outpatients with APC treated in 1st line.
  
  
  METHODS
  The trial was a prospective, open-label, single center investigation in outpatients with inoperable pancreatic cancer who were treated with intensified first-line chemotherapy along with concomitant application of subcutaneous LMWH. The combined chemotherapy consisted of gemcitabine 1 g/m2 (30 min), 5-FU 750 mg/m2 (24 h), folinic acid 200 mg/m2 (30 min), and Cisplatin 30 mg/m2 (90 min) on day 1 and 8; q3w for the first 12 weeks (GFFC) followed by gemcitabine alone in patients without cancer progression. The simultaneous application of prophylactic enoxaparin started on day 1 of chemotherapy with a fixed dose of 40 mg daily. Statistical analyses were performed using R 3.01 with software package CMPRSK and SPSS software v19.0.
  
  
  RESULTS
  The investigation was stopped after recruitment of 19 patients. At this time 15 patients had completed the required 12 weeks of treatment. Based on 71 cycles of GFFC + enoxaparin (median 4/pt [range: 2-4]) and 108 cycles of single-agent gemcitabine + enoxaparin (median 4/pt [range: 0-18]) the cumulative frequency of NCI-CTC toxicities grade 3/4 was below 10%. One case (5%) of a symptomatic non-lethal thromboembolic event was observed while receiving LMWH treatment. No severe bleeding event as defined in the protocol has been observed. The median overall survival was 10.05 [95% CI: 8.67-18.14] months.
  
  
  CONCLUSIONS
  The addition of enoxaparin to GFFC chemotherapy is feasible, safe and does not appear to affect the efficacy or the toxicity profile of the chemotherapy regimen in patients with advanced pancreatic adenocarcinoma. Based on these findings we have initiated the randomized CONKO-004 trial to examine whether enoxaparin reduces the incidence of thromboembolic events or increases overall outcome.
  
  
  BACKGROUND
  Clinical Trials NCT01945879.
authors.affiliation: Department of Hematology/Oncology, CharitéCentrum für Tumormedizin, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin 13353, Germany. uwe.pelzer@charite.de.
authors.forename: Uwe
authors.initials: U
authors.lastname: Pelzer
authors.forename: Andreas
authors.initials: A
authors.lastname: Hilbig
authors.forename: Jens M
authors.initials: JM
authors.lastname: Stieler
authors.forename: Marcus
authors.initials: M
authors.lastname: Bahra
authors.forename: Marianne
authors.initials: M
authors.lastname: Sinn
authors.forename: Bernhard
authors.initials: B
authors.lastname: Gebauer
authors.forename: Bernd
authors.initials: B
authors.lastname: Dörken
authors.forename: Hanno
authors.initials: H
authors.lastname: Riess
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D017984:Enoxaparin / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000150:complications / Q000188:drug therapy*; D010865:Pilot Projects; D011446:Prospective Studies; D013923:Thromboembolism / Q000517:prevention & control*; D000093542:Gemcitabine
chemical_list: D000925:Anticoagulants; D000970:Antineoplastic Agents; D017984:Enoxaparin; D003841:Deoxycytidine; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil; D000093542:Gemcitabine