Audit on incidences of Bevacizumab induced Hypertension as a Clinical Biomarker of Antitumor activity in day care Oncology at a Tertiary care hospital, Karachi, Pakistan

Hypertension is not frequently observed during treatment with bevacizumab in our study. Hypertension of all grades has been observed in up to 36% of patients seen in western population treated with bevacizumab ^(11). Low levels of nitric oxide are present in the vessels to maintain a balance between vasodilation and vasoconstriction. The synthesis and release of nitric oxide by the endothelial cells of the vasculature are modulated in part by VEGF-A and fibroblast growth factor^.(12) if we compare our study with international studies incidence of hypertension is not frequent in our population only twelve patients out of fifty-seven patients developed grade I hypertension. Hypertension ranges of both systolic and diastolic in twelve patients recorded out of fifty-seven patients with grade 1 hypertension who received bevacizumab as shown in table- 2

Grade 1 hypertension was frequently followed by blood pressure elevations, suggesting that detecting grade 1 hypertension could allow identification of patients requiring further antihypertensive therapy. This single‐centre, observational prospective study was designed to compare various methods, readings of measurement and grading in patients receiving bevacizumab‐based chemotherapy. However, home‐based blood pressure monitoring twice‐daily and this self‐measurement of blood pressure check at home identified and seen that more patients developing hypertension at home than in‐clinic measurements. This difference was significant for all‐grade hypertension, but did not translate for grade ≥2 hypertension, suggesting that home‐based blood pressure monitoring is useful to detect grade 1 European Society of Hypertension guidelines (ESH), hypertension suggesting that detecting grade 1 hypertension could allow identification of patients requiring further antihypertensive therapy.

In another observational study done in western population, the incidence of hypertension occurring at any time during the treatment period was examined in the 39 patients who received >12 cycles of bevacizumab. Twenty‐eight patients (71.8%; 99% CI, 53.2%–90.4%) developed grade ≥1 hypertension during the treatment period, suggesting that prolonged exposure to bevacizumab might increase the risk for developing hypertension. ⁽¹³⁾

Taken together, these findings from the prospective part of the study suggest that home‐based daily blood pressure assessment was the more reliable method to detect bevacizumab‐induced hypertension, whereas grading according to the European Society of Hypertension guidelines (ESH) criteria was more sensitive in detecting early BP elevation.

Furthermore, a high proportion of patients (71.8%) who received ≥12 cycles of bevacizumab developed hypertension; a finding consistent with the knowledge that the risk for developing bevacizumab associated hypertension appears constant over time ^(14). The cumulative dose received was strongly correlated with the occurrence of hypertension, whereas a history of hypertension was not present. This lack of association could be explained using antihypertensive agents in these patients.

Furthermore, the potential correlation between antitumor activity and the development of hypertension during bevacizumab treatment was examined. In contrast with previous reports no correlation between the development of hypertension occurring at any time during bevacizumab therapy and the response rate was seen. ⁽¹⁵⁾This analysis indicated statistically higher response rates in patients who developed very early ≤42 days of treatment hypertension grade ≥1 according to the European Society of Hypertension guidelines (ESH) criteria^{. (16)} In colorectal and pancreatic cancer patients receiving bevacizumab‐based chemotherapy although these observations examined hypertension occurring within 56 days of treatment. ⁽¹⁷⁾