Benefit and risk of primary thromboprophylaxis in ambulatory patients with advanced pancreatic cancer receiving chemotherapy: a systematic review and meta-analysis of randomized controlled trials.

As vascular thromboembolism (VTE) is a leading cause of death in cancer patients, it has been postulated that primary thromboprophylaxis (PTP) in cancer patients might improve survival by reducing VTE occurrence. We performed a systemic review and meta-analysis of randomized controlled trials (RCTs) to investigate the benefit and risk of PTP with low-molecular-weight heparins (LMWHs) in ambulatory advanced pancreatic cancer (APC) patients receiving chemotherapy. We undertook a literature search using MEDLINE and EMBASE databases through May 2015. RCTs with reduction in symptomatic VTE as a primary or secondary endpoints were included. Mantel-Haenszel method was used to estimate the pooled event-based risk ratio as well as the pooled absolute risk difference with 95% confidence interval (CI). Seven hundred and thirty-eight APC patients were eligible for analysis. PTP lasted 3-6 months. The crude VTE incidence was 2.1 and 11.2% in LMWH and in control groups, respectively (risk ratio, 0.18; 95% CI, 0.083-0.39; P < 0.0001). The absolute risk difference in VTE was -0.092 (95% CI, -0.127 to -0.057; P < 0.0001), with an estimated number needed to treat of 11 patients to prevent one symptomatic VTE event. The pooled risk ratio for major bleeding was 1.25 (95% CI, 0.48-3.3, P = 0.65). Although these findings are encouraging to deploy PTP in APC patients receiving chemotherapy, uncertainties remain as to its survival benefit, optimal PTP duration, type and dose of LMWH, and costs of care. Therefore, adequately powered randomized phase III studies are warranted to address these questions.