Clinical monitoring and blood samples
hypertension
ADVERSE EVENT, DISEASE PROGRESSION, TUMOR PROGRESSION, BLOOD, HYPERTENSION
In accordance with Common Terminology Criteria for Adverse Events (CTCAE) (version 3.0), the appearance and severity of hypertension were graded at baseline, Week 1, then every 4 weeks until tumor progression. Briefly, the CTCAE grades for hypertension are defined as follows: Grade 1 hypertension is defined as a transient increase in diastolic blood pressure > 20 mmHg (diastolic) or a total blood pressure > 150/100; Grade 2 hypertension is defined as recurrent or symptomatic increases in diastolic blood pressure > 20 mmHg with the potential requirement of additional monotherapy; and finally, Grade 3 hypertension is defined as a recurrent increase in diastolic blood pressure > 20 mmHg in combination with a required administration of one or more therapeutic interventions.Blood was collected at baseline, 2 weeks, 4 weeks and then every 4 weeks until disease progression. Plasma for metabolomic analysis was collected at baseline (prior to treatment initiation), and during the first 12 weeks after treatment (Weeks 1, 4, and 12) in K2‐EDTA lavender top tubes (Thermo Fisher Scientific). Patients were not required to fast. Samples were processed within 2 h of collection, then stored at −80°C prior to analysis. For metabolomic studies, 76 patients were studied (Figure 