Circulating D‐dimer levels are better predictors of overall survival and disease progression than carcinoembryonic antigen levels in patients with metastatic colorectal carcinoma

Abstract

BACKGROUND Fibrin formation is required for tumor angiogenesis, metastasis, and invasion. D‐dimer, a fibrin degradation product, is produced when crosslinked fibrin is degraded by plasmin. The current study prospectively examined D‐dimer levels in patients with metastatic colorectal carcinoma treated in a Phase II randomized trial comparing bevacizumab (Avastin, Genentech, South San Francisco, CA) plus 5‐fluorouracil/leucovorin (5‐FU/LV) with 5‐FU/LV alone. METHODS At least one circulating D‐dimer level was evaluable in 98 of the 104 previously untreated patients with metastatic colorectal carcinoma in the current trial. Plasma D‐dimer levels were determined using a quantitative immunoassay kit at enrollment, before each treatment, and at the time of trial completion or disease progression. RESULTS At trial enrollment, 86 of 104 patients (88%) had elevated D‐dimer levels (> 20 ng/mL), and 86 of 102 patients (84%) had elevated carcinoembryonic antigen (CEA) levels (> 3 ng/mL). Baseline D‐dimer levels were correlated with the following baseline characteristics: CEA (Pearson coefficient, 0.31; P = 0.002), albumin levels (Pearson coefficient, −0.32; P = 0.002), tumor burden (Pearson coefficient, 0.30; P = 0.003), and number of metastatic sites (Pearson coefficient, 0.21; P = 0.04). At the time of progression, plasma D‐dimer levels reached a maximum postbaseline value in 51 of 61 patients (84%), whereas the CEA level was at its maximum postbaseline value in 39 of 55 patients (71%). Baseline D‐dimer levels were a strong predictor of overall survival on univariate analysis (P = 0.008) and multivariate analysis (P = 0.03). Overall, treatment with bevacizumab (5 mg/kg) and baseline D‐dimer levels were the only predictors of overall survival (P < 0.05). CONCLUSIONS The current study indicates that fibrin remodeling is an important prognostic feature in metastatic colorectal carcinoma. D‐dimer levels should be incorporated into prognostic models, and D‐dimer may represent a useful biomarker for patients treated with antiangiogenic agents. Cancer 2004. © 2004 American Cancer Society.

The effect of anti-VEGF therapy on immature myeloid cell and dendritic cells in cancer patients

“…CEC were defined as CD45 − /Flk + / CD15 − and CEP as CD45 − /Flk + /CD133 + [21,22]. D-dimer, VEGF, uPA, and PAI-1 analyses were performed on platelet-depleted plasma using commercially available ELISA kits [23][24][25][26].…”

Evaluating the Older Patient with Cancer: Understanding Frailty and the Geriatric Assessment

“…For example, elevated CRP has been associated with poorer survival in patients with localized renal cell carcinoma, and high D-dimer has been shown to predict poorer survival and disease progression in patients with metastatic colorectal cancer. 107,108 In addition, IL-6 may be associated with a poorer prognosis in patients with breast cancer, perhaps by upregulating levels of angiogenic mediators such as vascular endothelial growth factor. 109 Elevated IL-6 has also been linked to worsened clinical outcome in patients with advanced non-small cell lung cancer, and may be useful in differentiating hormone-refractory prostate cancer from hormone-sensitive disease or benign prostatic conditions.…”

The Efficacy of Additional Bevacizumab to Cytotoxic Chemotherapy Regimens for the Treatment of Colorectal Cancer: An Updated Meta-Analysis for Randomized Trials

“…Two trials 22,23 underwent FLU + LEU based chemotherapy, with 349 patients involved; 3 trials 10,25-29 underwent IFL-based chemotherapy, with 1,249 patients involved; 3 trials 15,[30][31][32] underwent FOLFOX based chemotherapy, with 3,834 patients involved; 1 trial underwent CAP based 33,34 chemotherapy, with 313 patients involved; 1 trial 35 underwent both CAP + OXA based and FOLFOX based chemotherapy, with 700 patients involved, respectively. Seven trials 10,15,[22][23][24][25][26][27][30][31][32] were completed in USA, the other three trials were completed in Greece, 28 China 29 and Australia, 33,34 respectively. In meta-analyses done for OS and PFS when comparing targeted agent-BEV added to CTX versus CTX alone in the treatment of CRC, BEV is associated with evidently decreased HR [ Fig.…”

“…[26][27][28]34 But D-dimer may represent a useful biomarker for patients treated with antiangiogenic agents, though strongly correlated with OS, but not PFS. 23 In conclusion, BEV, acting as a targeted and antiangiogenic cancer therapeutic agent, is of efficacy and feasibility in adjuvant to CTX. However, the pros and cons should be considered since the generation of benefits is at the cost of toxicity.…”

“…35 As aforementioned, the additional benefits of BEV were not consistent across trials. As for OS, no efficacy of additional BEV to CTX could be identified in several trials, including FLU + LEU, 22,23 IFL, 10 FOLFOX4, 30 and CAP 29,30 based chemotherapy regimens. However, after being stratified based on the CTX, the addition of BEV to FLU + LEU and FOLFOX based chemotherapy showed evident efficacy; its additional benefit was also evident in IFL-based chemotherapy after ignoring the trial 10 leading greatly heterogeneity, suggesting that prior surgery treatment for CRC maybe a main confounding factor; as for CAP-based chemotherapy regimens, both trials 29,30 identified no additional benefits of BEV.…”