Effect of low-molecular-weight heparin on survival in patients with advanced pancreatic adenocarcinoma

Summary

This retrospective analysis aimed to identify whether low-molecular- weight heparins (LMWH) might improve survival in patients receiving chemotherapeutic treatment for advanced pancreatic adenocarcinoma.Two hundred forty-three patients who had received chemotherapy for advanced pancreatic adenocarcinoma were identified from a prospectively maintained database. Of these, 30 patients had to be excluded from analysis due to insufficient documentation. Of the remaining 213 patients 94 patients had been treated with LMWH, whereas 119 patients served as controls. Outcome was assessed in relation to overall survival, which was calculated from the date of initiation of chemotherapy to the date of death.There was no significant difference (hazard ratio, 0.8; 95% confidence interval (CI), 0.6 to 1.1; P=0,2) between the two groups in terms of overall survival. The median survival was 7.1 months (95% CI,5.8–8.4 months) in the LMWH group and 5.9 months (95% CI, 5.1–6.7 months) in the non-LMWH group. A positive effect of LMWH was seen in patients with metastatic disease (hazard ratio for LMWH vs. non-LMWH, 0,6; 95% CI, 0,4 to 0,8; P=0,006) in contrast to those without metastatic disease (hazard ratio for LMWH vs. non-LMWH, 1; 95% CI, 0.6 to 1.7; P=0,96).The median survival of patients with metastatic disease was 6,6 months (95% CI, 5–8,2 months) and 3.8 months (95% CI, 2.5–5.1 months) for the LMWH group and the non-LMWH group, respectively. In conclusion, we found for metastatic pancreatic adenocarcinoma a survival advantage for patients receiving LMWH. Nevertheless, our observations need confirmation by prospective randomized studies.

Keywords

Low-molecular-weight heparin - pancreatic adenocarcinoma - metastasis - survival

• References

• 1 Jemal A, Murray T, Ward E. et al. Cancer statistics, 2005. CACancer J Clin 2005; 55: 10-30.
• 2 Schneider G, Siveke JT, Eckel F. et al. Pancreatic cancer: basic and clinical aspects. Gastroenterology 2005; 128: 1606-1625.
• 3 Ogren M, Bergqvist D, Wahlander K. et al. Trousseau’s syndrome - what is the evidence? A population-based autopsy study. Thromb Haemost 2006; 95: 541-545.
• 4 Khorana AA, Fine RL. Pancreatic cancer and thromboembolic disease. Lancet Oncol 2004; 5: 655-663.
• 5 Lee AY, Levine MN, Baker RI. et al. Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer(CLOT) Investigators.. Low-molecular-weight heparin versus acoumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003; 349: 146-153.
• 6 Lee AY, Rickles FR, Julian JA. et al. Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thromboembolism. J Clin Oncol 2005; 23: 2123-2129.
• 7 Kakkar AK. Low-molecular-weight heparin and survival in patients with malignant disease. Cancer Control 2005; 12 (Suppl. 01) 22-30.
• 8 Eckel F, Lersch C, Lippl F. et al. Phase II trial of cyclophosphamide, leucovorin, 5-fluorouracil 24-hour infusion and tamoxifen in pancreatic cancer. J Exp Clin Cancer Res 2000; 19: 295-300.
• 9 Eckel F, Lersch C, Lippl F. et al. Monitoring of tumourglucose metabolism by PET in aphase I study evaluating hormonal therapy in advanced pancreatic cancer. Sc and JG astroenterol 2002; 37: 972-977.
• 10 Richards DA. Chemotherapeutic gemcitabine doublets in pancreatic carcinoma. Semin Oncol 2005; 32 (04) (Suppl. 06) S9-13.
• 11 Zacharski LR. Anticoagulants in cancer treatment: malignancy as as olid phase coagulopathy. Cancer Lett 2002; 186: 1-9.
• 12 Kakkar AK, Lemoine NR, Scully MF. et al. Tissue factor expression correlates with histological grade in human pancreatic cancer. Br J Surg 1995; 82: 1101-1104.
• 13 Borsig L, Wong R, Feramisco J. et al. Heparin and cancer revisited: mechanistic connections involving platelets, P-selectin, carcinomamucins, and tumor metastasis. Proc Natl Acad Sci USA 2001; 98: 3352-3357.
• 14 Kakkar AK, Levine MN, Kadziola Z. et al. Low molecular weight heparin, therapy with dalteparin, and survival in advanced cancer: the fragmin advanced malignancy outcome study (FAMOUS). J Clin Oncol 2004; 22: 1944-1948.
• 15 Klerk CP, Smorenburg SM, Otten HM. et al. The effect of low molecular weight heparin on survival in patients with advanced malignancy. J Clin Oncol 2005; 23: 2130-2135.
• 16 Altinbas M, Coskun HS, Er O. et al. A randomized clinical trial of combination chemotherapy with and without low-molecular-weight heparin in smallcell lung cancer. J Thromb Haemost 2004; 2: 1266-1271.
• 17 Icli F, Akbulut H, Utkan G. et al. Low molecular weight heparin (LMWH)increases the efficacy of cisplatinum plus gemcitabine combination in advanced pancreatic cancer. J Surg Oncol 2007; 95: 507-512.
• 18 von Tempelhoff GF, Heilmann L, Hommel G. et al. Impact of rheological variables in cancer. Semin Thromb Hemost 2003; 29: 499-513.