Medical oncology
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The aim of this study was to evaluate coagulation disorders in patients with metastatic colorectal cancer treated with bevacizumab by using rotation thrombelastogram (ROTEM(®)) and correlate ROTEM(®) parameters with routine coagulation tests. A total of 18 colorectal cancer patients who received bevacizumab combined with chemotherapy were included. There was no statistically significant difference between results of platelet count, prothrombin time (PT) and activated partial thromboplastin time (APTT), fibrinogen, and D-Dimer obtained at baseline and on day 1 of chemotherapy cycles 4, 8, and 12. ⋯ Platelet count showed a positive correlation with MCF in INTEM (r = 0.627) and EXTEM (r = 0.699) assays while showed a negative correlation with CFT in EXTEM (r = -603). There was a significant negative correlation between fibrinogen levels and CFT in INTEM (r = -0.617) and EXTEM (r = -0.512). Our data demonstrated the value of TEG over conventional coagulation tests in evaluating antiangiogenesis agents-induced coagulation disorders.
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Lapatinib is a dual tyrosine kinase inhibitor (TKI) that has a considerable efficacy in ErbB2-positive metastatic breast cancer (MBC). Previous studies revealed that TKIs caused cardiotoxicity in approximately 10 % of the patients. This study assessed the cardiac safety of lapatinib in women with ErbB2-positive MBC. ⋯ According to our findings, lapatinib was safe and well tolerated and has a low incidence of cardiac side effects. Therefore, it seemed that cardiotoxicity was not a class effect of TKIs. However, despite the absence of clinically significant adverse cardiac effects under lapatinib therapy, the incidence of cardiotoxicity reported in our study was higher than previous lapatinib studies.
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The efficacy of bevacizumab combined with infusional 5-fluorouracil/leucovorin (5-FU/LV) plus irinotecan (FOLFIRI) as the second-line treatment for metastatic colorectal cancer (mCRC) has not been fully clarified, although bevacizumab combined with infusional 5-FU/LV plus oxaliplatin (FOLFOX) in the second-line setting has demonstrated a survival benefit. We investigated the efficacy of bevacizumab plus FOLFIRI in mCRC patients who failed oxaliplatin-containing regimens without bevacizumab. Patients who received bevacizumab plus FOLFIRI or bevacizumab plus FOLFOX as second-line chemotherapy between July 2007 and March 2008 were registered (trial registration: UMIN000001547). ⋯ Overall response rates were 25 and 29%, respectively. The most common grade≥3 bevacizumab-related adverse events were hypertension (5.0%) and bleeding (3.8%). FOLFIRI+BV after OX/FU showed comparable efficacy to FOLFOX+BV after IRI/FU.
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Sequential therapy is a standard strategy used to overcome the limitations of targeted agents in metastatic renal cell carcinoma. It remains unclear whether a mammalian target of rapamycin (mTOR) inhibitor is a more effective second-line therapy after first-line vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI) has failed than the alternative, VEGF TKI. A clinical database was used to identify all patients with renal cell carcinoma who failed at first-line VEGF TKI and then treated with second-line VEGF TKI or mTOR inhibitors in the Asan Medical Center. ⋯ Overall survival was 10.6 months for the VEGF TKI group and 8.2 months for the mTOR inhibitor group (HR = 0.98, 95 % CI 0.57-1.68, P = 0.94). The two groups did not differ significantly in terms of disease control rate (51 % for VEGF TKI and 59 % for mTOR inhibitor, P = 0.75). Second-line VEGF TKI seems to be as effective as mTOR inhibitors and may be a viable option as a second-line agent after first-line anti-VEGF agents have failed.
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A disintegrin and metalloproteinase-17 (ADAM17, also named as tumor necrosis factor-alpha-converting enzyme) is a member of the ADAM family. Of all ADAMs, the strongest evidence for a role in malignancy exists for ADAM17. Especially, it has been demonstrated that ADAM17 expression was significantly increased in human gastric cancer. ⋯ Furthermore, multivariate analysis suggested that lymph node metastases, distant metastases, TNM stage, and ADAM17 expression were independent prognostic indicators for gastric cancer. Our data suggest for the first time that the increased expression of ADAM17 in gastric cancer is associated significantly with aggressive progression and poor prognosis. ADAM17 may be an important molecular marker for predicting the carcinogenesis, progression, and prognosis of gastric cancer.