Combining trifluridine, tipiracil with bevacizumab to treat refractory metastatic colorectal cancer
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Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le |
Posted on May 31st, 2023
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After first diagnosed with metastatic colorectal cancer, the patients will generally be treated with a wide variety of chemotherapy. However, disease still progressed in some of the patients; these cases are considered to be refractory. The combination of trifluridine and tipiracil had been proven to be an useful tool for treating metastatic colorectal cancer. Bevacizumab, a VEGF inhibitor, is another therapy that has clear clinical benefits in slowing down disease progression. Thus, a study was performed to assess the effectiveness of combining bevacizumab with trifluridine and tipiracil in treating refractory metastatic colorectal cancer.
The clinical study included 246 adult patients who have been diagnosed with unresectable adenocarcinoma in the colon or rectum. They have been previously treated with two of the following chemotherapy: fluoropyrimidine, irinotecan, oxaliplatin, anti-VEGF monoclonal antibody, anti-EGFR monoclonal antibody. The median age of the trial participants were between 62 and 64 years old, and they were stratified by their RAS mutation status and their length of disease. These patients were randomly assigned to receive oral trifluridine-tipiracil at a dose of 35 mg per square meter of body-surface area twice a day or the trifluridine-tipiracil treatment with intravenous bevacizumab at a dose of 5 mg per kilogram of body weight. The treatment was administered following a 28-day cycle; trifluridine-tipiracil on from day 1 to day 5 and through day 8 to day 12; bevacizumab was infused on day 1 and day 15. The researchers found that the median survival time in those who were treated with the combination of trifluridine-tipiracil and bevacizumab was 10.8 months; this was significantly longer than the 7.5 months of the trifluridine-tipiracil group. This means that the combination of trifluridine-tipiracil and bevacizumab helps reduce the risk of death by 39%. In addition, the combination helps significantly delay disease progression. Patients treated with the combination of trifluridine-tipiracil and bevacizumab have a 56% less risk of tumor development than their counterparts.
The clinical benefit of the combination treatment can be explained by the cytotoxic effect of the nucleic acid analogue, trifluridine, which stops the proliferation and eliminates the tumor cells. Tipiracil serves as a thymidine phosphorylase inhibitor which increases the biological half-life of trifluridine. In addition, the VEGF inhibitor, bevacizumab, suppresses the angiogenesis effect which would reduce the metastasis of tumor cells. Despite the additional effect of bevacizumab, there was no difference in the rate of adverse events between the two treatment groups. Neutropenia, nausea, and anemia are the most frequently reported events.
The clinical study included 246 adult patients who have been diagnosed with unresectable adenocarcinoma in the colon or rectum. They have been previously treated with two of the following chemotherapy: fluoropyrimidine, irinotecan, oxaliplatin, anti-VEGF monoclonal antibody, anti-EGFR monoclonal antibody. The median age of the trial participants were between 62 and 64 years old, and they were stratified by their RAS mutation status and their length of disease. These patients were randomly assigned to receive oral trifluridine-tipiracil at a dose of 35 mg per square meter of body-surface area twice a day or the trifluridine-tipiracil treatment with intravenous bevacizumab at a dose of 5 mg per kilogram of body weight. The treatment was administered following a 28-day cycle; trifluridine-tipiracil on from day 1 to day 5 and through day 8 to day 12; bevacizumab was infused on day 1 and day 15. The researchers found that the median survival time in those who were treated with the combination of trifluridine-tipiracil and bevacizumab was 10.8 months; this was significantly longer than the 7.5 months of the trifluridine-tipiracil group. This means that the combination of trifluridine-tipiracil and bevacizumab helps reduce the risk of death by 39%. In addition, the combination helps significantly delay disease progression. Patients treated with the combination of trifluridine-tipiracil and bevacizumab have a 56% less risk of tumor development than their counterparts.
The clinical benefit of the combination treatment can be explained by the cytotoxic effect of the nucleic acid analogue, trifluridine, which stops the proliferation and eliminates the tumor cells. Tipiracil serves as a thymidine phosphorylase inhibitor which increases the biological half-life of trifluridine. In addition, the VEGF inhibitor, bevacizumab, suppresses the angiogenesis effect which would reduce the metastasis of tumor cells. Despite the additional effect of bevacizumab, there was no difference in the rate of adverse events between the two treatment groups. Neutropenia, nausea, and anemia are the most frequently reported events.