Relationship Between Safety and Cumulative Bevacizumab Dose in Patients With Metastatic Colorectal Cancer Who Received Long-term Bevacizumab Treatment.

ABSTRACT

BACKGROUND/AIM: Bevacizumab-based chemotherapy is the standard treatment for metastatic colorectal cancer (mCRC) but has several specific adverse events. The cumulative bevacizumab dose (CBD) increases with long-term treatment as it is often used beyond the first disease progression, based on existing evidence. However, the association between CBD and the frequency and severity of adverse events in mCRC patients who received bevacizumab for long-term treatment remains unclear. PATIENTS AND METHODS: Among the mCRC patients who received bevacizumab-based chemotherapy between March 2007 and December 2017 at the University of Tsukuba Hospital, those who continued treatment for more than 2 years were eligible for the study. The onset and worsening of proteinuria, hypertension, bleeding, and thromboembolic events were assessed to determine their relationship with CBD. RESULTS: Of the 109 patients who received bevacizumab-based chemotherapy, 24 were included in the study. Grade 3 proteinuria was observed in 21 (88%) and 9 (38%) patients. The severity of proteinuria markedly increased after administering >100 mg/kg of CBD and progressed to grade 3 at concentrations exceeding 200 mg/kg. Thromboembolic events were observed in three (13%) patients, and two of them developed acute myocardial infarction after receiving a CBD of >300 mg/kg. Grade 2 or higher hypertension and grade 1 bleeding were observed in 9 (38%) patients and in 6 (25%) patients, respectively, regardless of the CBD. CONCLUSION: Proteinuria and thromboembolic events occurred and worsened in mCRC patients when the bevacizumab dose exceeded the threshold dose.