The Clinical Efficacy Of Bevacizumab In The First-line Treatment Of Metastatic Colorectal Cancer

Objective:To evaluate the efficacy and toxicities of bevacizumab combined with chemotherapy in the first-line treatment of metastatic colorectal cancer,and analyze the associations between bevacizumab-related hypertension, baseline LDH levels, baseline CA19-9levels and response to bevacizumab.Methods:A total of55patients with metastatic colorectal cancer at the department of medical oncology in Dalian Medical College Hospital from August2010to April2012were included. Chemotherapy alone group of28patients recive mFOLFOX7regimen (16patients) or XELOX regimen (12patients), bevacizumab combined with chemotherapy group27patients recive bevacizumab combined with mFOLFOX7regimen (13patients) or XELOX regimen (14patients). All patients recive CT examination every two cycles, evaluate the efficacy and toxicities.Response rate, disease control rate, progression-free suivival and overall survival were ananlyzed retrospctively. The response to treatment was evaluated accrding to the RECIST1.0criteria,and toxicities were evaluated using CTCAE v3.0(common terminology criteria for adverse events version3.0).Subgroup analyses were performed to investigate the impact of the concurrent chemotherapy regimen, duration of bevacizumab treatment, bevacizumab-related hypertension, baseline LDH levels, baseline CA19-9levels on bevacizumab response.Statistical analyses were carried out using Chi-Square, Kaplan-Meier method, log-rank test.Results:1.To contrast bevacizumab combined with chemotherapy with chemotherapy alone in the first-line treatment of metastatic colorectal cancer, the difference of DCR、PFS、 OS were statistically significant, the difference of ORR was not statistically significant. The addition of bevacizumab increased DCR (96.30%vs75.00%), prolonged both median PFS (8.9months vs5.9months) and median OS (20.8months vs16.0).2. There were not statistically significant difference in the ORR, DCR, median PFS or OS time between the FOLFOX-bevacizumab and FOLFIRI-bevacizumab subgroups.3.①Patients with normal baseline CA19-9levels compare with elevated baseline CA19-9levels, the difference of OS was statistically significant, the differences of ORR, DCR, PFS were not statistically significant, and the median OS (20.0months vs16.2months) was longer.②In the elevated baseline CA19-9levels patients, chemotherapy combined with bevacizumab compared with chemotherapy alone, the differences of PFS, OS were statistically significant, the differences of ORR, DCR were not statistically significant. In the elevated baseline CA19-9levels patients, median PFS (9.6months vs4.7months) and median OS (20.0months vs15.5months) were significantly increasing with bevacizumab than without it. In the normal baseline CA19-9levels patients, the result of ORR, DCR, PFS and OS were not statistically significant.4. In the bevacizumab combined with chemotherapy group,the patients of normal baseline LDH compared with high baseline LDH, the differences of PFS, OS were statistically significant,the median PFS (9.4months and7.0months) and median OS (21months and17.6months) were longer.5.The occurrence of bevacizumab-induced hypertension in the first-line treatment of metastatic colorectal cancer patients was highly associated with improvements in median PFS (10.0months vs.8.6months) and median OS (22months vs.20months), as compared to patients without hypertension, was statistically significant difference. The differences of ORR and DCR were not statistically significant.6. To contrast bevacizumab combined with chemotherapy with chemotherapy alone in the first-line treatment of metastatic colorectal cancer, the differences of adverse reactions, for example, gastrointestinal reactions, bone marrow suppression, liver damage, neurotoxicity, bleeding, were not statistically significant, bevacizumab-induced hypertension and proteinuria were statistically significant.Conclusion:(1)The efficacy of bevacizumab combined with chemotherapy in the first-line treatment of metastatic colorectal cancer was better than chemotherapy alone.(2)There were no significant efficacy differences between the mFOLFOX7-bevacizumab regimen and FOLFIRI-bevacizumab regimen in the first-line treatment of metastatic colorectal cancer.(3) Elevated CA19-9level was a poor prognostic factor compared with normal CA19-9levels. Bevacizumab exhibits better clinical activity for high CA19-9than normal baseline CA19-9.(4) High LDH were associated with poor prognosis in the Bevacizumab treatment of mCRC patients.(5)The occurrence of bevacizumab-induced hypertension was associated with improvements in efficacy, as compared to patients without hypertension, Bevacizumab-induced hypertension may represent a prognostic factor in mCRC patients with bevacizumab.(6) On the basis of chemotherapy plus bevacizumab, is well tolerated and does not significantly increase the side effects of chemotherapy.