The Impact of Thromboprophylaxis on the Survival of Patients with Advanced Pancreatic Cancer. The Pancreatic Cancer and Tinzaparin (PaCT) Study

Abstract

Pancreatic cancer (PaC) induces a prothrombotic and hypercoagulable state. The aim of this study was to investigate the effect of tinzaparin in combination with chemotherapy. The PaCT (pancreatic cancer and tinzaparin) study was a retrospective observational study that collected data regarding progression free survival (PFS) in advanced or metastatic PaC patients who received thromboprophylaxis with tinzaparin during chemotherapy with nab-paclitaxel (N) and gemcitabine (G). The primary end point was to compare, from already published data, the PFS of patients receiving thromboprophylaxis with tinzaparin with the PFS of patients receiving chemotherapy with N–G but no thromboprophylaxis. Secondary end points were efficacy and safety of anticoagulation. In total, 110 PaC patients, 93% with advanced or metastatic disease, treated with N–G and tinzaparin (10,291 ± 1176 Anti-Xa IU, OD, median duration 8.7, IQR: 5.6–11.9 months) were enrolled. Of these, 52% were males and; the median age was 68 (40–86 years). The tumor was located to in the pancreatic head at in 45% of the patients. The median PFS was 7.9 months (IQR: 5.0–11.8 months). Out of 14 similar studies (involving 2994 patients) identified via systematic search, it was determined that the weighted PFS of patients receiving N–G but no anticoagulation was 5.6 months. Therefore, patients receiving tinzaparin had 39.54% higher PFS than patients without thromboprophylaxis (p < 0.05). During the follow-up period of 18.3 ± 11.7 months, three (2.7%) thrombotic events were recorded while two clinically relevant non-major bleeding events occurred (1.9%). In conclusion, PFS in advanced PaC patients undergoing chemotherapy is positively impacted by anticoagulation. Thromboprophylaxis with tinzaparin in treatment dose is efficient and safe.

The Role of Injectables in the Treatment and Prevention of Cancer-Associated Thrombosis

“…Preincubation of the chemoresistant A2780cis cell line led to sensitization to cisplatin [ 132 ] possibly through the Wnt signaling pathway [ 133 ]. Karamouzis et al demonstrated in a recent meta-analysis that the administration of tinzaparin in patients diagnosed with advanced pancreatic cancer increased the disease-free period by 39.5% compared to the population that did not receive the drug [ 134 ]. Enoxaparin was found to inhibit the CXCL12-driven proliferation, adhesion, and colony formation of human colon cancer HCT-116 cell line and suppressed the formation of metastases in Balb/C mice [ 135 ].…”

Cancer-Associated Thrombosis: Not All Low-Molecular-Weight Heparins Are the Same, Focus on Tinzaparin, A Narrative Review

“…In addition, PaCT (Pancreatic Cancer and Tinzaparin) is a retrospective observational study conducted in 110 patients with advanced or metastatic pancreatic cancer with the aim of examining the anticancer effect of tinzaparin. The patients receiving “hyper-prophylactic” dose of tinzaparin (10000 anti-Xa IU/die) during chemotherapy with nab-paclitaxel and gemcitabine had 39.5% higher progression-free survival compared to patients without tinzaparin ( P < 0.05) [ 51 ]. However, overall, evidence on the antitumoral activity of LMWH is still contradictory and not conclusive.…”

Tumour cell-activated platelets modulate the immunological activity of CD4+, CD8+, and NK cells, which is efficiently antagonized by heparin

“…Reasoned by the elevated incidence, low molecular weight heparins (LMWH) are the guideline based drug for prevention and therapy of venous thromboembolism in cancer patients [ 19 ]. Since some clinical trials observed additional survival benefits for LMWH treated patient subgroups, while others did not, there is an ongoing debate whether LMWH exerts anti-metastatic effects beside its anticoagulant properties [ 20 – 22 ]. Thus, several metastasis-related targets of heparin have been postulated and are currently in debate [ 23 ].…”