Rationale and design of PROSPECT-CONKO 004: a prospective, randomized trial of simultaneous pancreatic cancer treatment with enoxaparin and chemotherapy)

Abstract

Background: Advanced pancreatic cancer, in addition to its high mortality, is characterized by one of the highest rates of venous thromboembolic events (VTE) as compared to other types of cancer. Enoxaparin, a low molecular weight heparin (LMWH), has proven to be effective for the prevention and treatment of VTE in surgical and general medical patients. Results of some small studies suggest that this benefit might extend to patients with cancer, however, enoxaparin is not currently indicated for this use. This phase IIb study was designed to analyze the efficacy of enoxaparin in patients with locally advanced or metastatic pancreatic cancer undergoing systemic chemotherapy.

Thromboembolic events in patients with urothelial carcinoma undergoing neoadjuvant chemotherapy and radical cystectomy

“…However, the risk of thromboembolism among patients in our cohort receiving NCT (19%) was much higher than the baseline risk of the untreated patients in these studies (3.9% and 3.4%, respectively), suggesting that prophylaxis may yield a larger benefit in patients with urothelial carcinoma. This suggestion is supported by 2 randomized studies in patients with pancreatic cancer, whose baseline risk of VTE is similar to the risk reported in our study, which showed absolute risk reductions of 9.5% and 19.6% with enoxaparin and dalteparin prophylaxis, respectively [24,25]. Furthermore, an incidence of 19% is higher than the baseline risk of VTE in many groups in which VTE prophylaxis is recommended by the American College of Chest Physicians, including surgical patients without cancer [26].…”

Cancer and Venous Thromboembolic Disease: From Molecular Mechanisms to Clinical Management

“…Despite the relatively low incidence of vte in the control arm (3.4%), the study demonstrated a significant reduction in the incidence of vte in patients receiving semuloparin (1.2%), with no apparent increase in the incidence of major bleeding 60 . Similarly, the fragem and conko 004 trials explored thromboprophylaxis in patients with locally advanced pancreatic cancer undergoing systemic chemotherapy and demonstrated a combined vte risk reduction of 12.5% 61,62 .…”

Suppression of pancreatic cancer by sulfated non-anticoagulant low molecular weight heparin

“…When the dose of S-NACH was increased to 20 mg/kg, there was still no difference in mean bleeding time. Further, clinical studies have demonstrated that prolonged administration of heparin derivatives can result in improved survival in certain patient populations but with risk of bleeding [33,34]. …”