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Randomized Controlled Trial
. 2014 Mar 19:14:204.
doi: 10.1186/1471-2407-14-204.

Intensified chemotherapy and simultaneous treatment with heparin in outpatients with pancreatic cancer - the CONKO 004 pilot trial

Uwe Pelzer  1 , Andreas Hilbig, Jens M Stieler, Marcus Bahra, Marianne Sinn, Bernhard Gebauer, Bernd Dörken, Hanno Riess
Affiliations
Randomized Controlled Trial

Intensified chemotherapy and simultaneous treatment with heparin in outpatients with pancreatic cancer - the CONKO 004 pilot trial

Uwe Pelzer et al. BMC Cancer. .

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.

Trial registration: Clinical Trials NCT01945879.

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Figures

Figure 1
Figure 1
Hematological and non-hematological toxicities (no. out of 179 cycles). Numbers represent the count of treatment cycles with corresponding toxicity.
Figure 2
Figure 2
Kaplan-Meier plot for overall survival.
Figure 3
Figure 3
Forest plot of prognostic factors.
See this image and copyright information in PMC

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