Low molecular weight heparin (LMWH) increases the efficacy of immunotherapy in metastatic renal cell carcinoma patients with abnormal coagulation

Abstract

15591 Background: Antitumor effects of LMWH are unclear. Heparin can bind with fibroblast-growth factor, other heparine-binding angiogenic factors, their receptors, and/or impact on coagulation system which induces angiogenesis. We previously revealed hypercoagulation is a frequent symptom in metastatic renal cell carcinoma (MRCC) patients (pts) and clinically correlates with progression of the disease. Methods: Pts with MRCC and high level of fibrinogen, D-dimer or fibrin, antithrombin III and prothrombin were stratified by MSKCC prognostic criteria and included to receive immunotherapy plus LMWH (IL-2, 1 MIU, i.v, 3 tiw + IFN alpha, 5 MU, s.c, 3 tiw ± 5-FU 500 mg/m2, i.v. once a week, and Dalteparin, LMWH, 5000 IU, s.c, every day, for 3 weeks) or immunotherapy alone. Demographic and treatment characteristics were similar between both arms. The primary endpoint was cancer-related overall survival (OS). Results: Flu-like syndrome, hypotension, anorexia were most common side effects (CTC grade 1). There were no bleedings in LMWH group. Conclusions: These results demonstrate that Dalteparin significantly improves cancer specific overall survival and decreases disease progression rate in combination with immunotherapy in MRCC pts with abnormal coagulation. Phase II randomized multicenter open-label discontinuation trial will be conducted. [Table: see text] No significant financial relationships to disclose.

The effect of low molecular weight heparin on survival in cancer patients: an updated systematic review and meta‐analysis of randomized trials

“…Nine studies were included in the meta-analysis [4,5,16,[23][24][25][26][27][28]. We fully evaluated 28 studies that met the criterion for inclusion in our meta-analysis, but excluded 19 of these because of unavailable data on 1-year survival outcomes [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47]. For one of the studies, the 1-year survival data were extracted from the Kaplan-Meier survival curves [27].…”

“…As in our previous study, data available from individual studies lacked uniformity, and information was missing. Nineteen of the studies that we retrieved for data extraction did not report 1-year mortality, and we were unable to include these in our meta-analysis [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47]. We attempted to contact the corresponding authors of these studies to obtain 1-year mortality data, but either these were unavailable or we received no response.…”