How to manage hypertension in a patient with elevated blood pressure (160/104 mmHg) undergoing chemotherapy with pemetrexed, bevacizumab (Avastin), and cisplatin?

Management of Hypertension (160/104 mmHg) During Bevacizumab-Based Chemotherapy

Omit the bevacizumab dose immediately and initiate antihypertensive therapy with amlodipine 5 mg daily, as the clinic blood pressure of 160/104 mmHg meets the threshold for withholding bevacizumab until blood pressure is controlled below 160/100 mmHg. 1

Immediate Action Required

• Withhold bevacizumab at this visit since clinic BP is ≥160/100 mmHg 1
• Arrange ambulatory blood pressure monitoring (ABPM) or home blood pressure monitoring (HBPM) over at least 4 consecutive days (ignoring day 1 measurements) to confirm sustained hypertension 1
• Continue pemetrexed and cisplatin as scheduled, as hypertension is specifically a bevacizumab-related adverse effect 2, 3

Antihypertensive Treatment Algorithm

For Antihypertensive-Naive Patients:

• Start amlodipine 5 mg daily immediately, which is considered safe and efficient for bevacizumab-associated hypertension 1
• Reassess BP with ABPM/HBPM after at least 2 weeks 1
• If ABPM/HBPM remains ≥150/95 mmHg after 2 weeks, add an ACE inhibitor (e.g., perindopril 2 mg daily) OR an ARB (e.g., losartan 50 mg daily) 1
• If still uncontrolled, add indapamide 2.5 mg daily as third-line therapy 1

For Patients Already on Antihypertensives:

• Step up treatment in accordance with standard hypertension guidelines until clinic BP falls below 160/100 mmHg 1
• Consider adding spironolactone 25 mg daily if already on three drugs, monitoring serum potassium and renal function within 1-2 weeks 4

Criteria for Restarting Bevacizumab

• Restart bevacizumab only when clinic BP is <160/100 mmHg AND/OR ABPM/HBPM is <150/95 mmHg 1
• When there is discrepancy between clinic and ABPM/HBPM readings (>20/10 mmHg), prioritize ABPM/HBPM values for clinical decisions 1
• Continue pemetrexed and cisplatin during the bevacizumab hold period 3

Ongoing Monitoring Protocol

• Measure BP before each bevacizumab infusion to determine if treatment can proceed 1
• Encourage twice-daily home BP monitoring once antihypertensive treatment is initiated 1
• Monitor blood pressure every 2-3 weeks during bevacizumab treatment per FDA labeling 2
• Recheck BP within 2-4 weeks after any medication adjustment 4

Critical Thresholds and Actions

If BP ≥180 systolic or ≥110 diastolic:

• Omit bevacizumab dose immediately 1
• Initiate or intensify antihypertensive therapy 1
• Reassess with ABPM/HBPM after at least 2 weeks 1

If hypertensive crisis or encephalopathy develops:

• Permanently discontinue bevacizumab per FDA labeling 2
• Arrange emergency admission for in-patient treatment 1

Important Clinical Considerations

• Pre-existing hypertension predicts more pronounced BP elevation during bevacizumab therapy, with median systolic increases of 10.85 mmHg versus 2.69 mmHg in normotensive patients 5
• BP increases occur early, typically within the first 6 weeks of bevacizumab therapy 5
• Hypertension may be a biomarker of VEGF pathway inhibition and correlates with improved outcomes (median OS 25.8 vs 11.7 months in patients who develop hypertension) 6
• The incidence of grade 3-4 hypertension with bevacizumab ranges from 5-18% across clinical studies 2
• In the specific regimen of cisplatin/pemetrexed/bevacizumab, grade 3 hypertension occurred in 8% of patients 3

Care Coordination

• Initiate hypertension management in the oncology unit whenever possible 1
• Communicate with primary care team via letter or chemotherapy record booklet, specifying treatment goals (clinic BP <160/100 mmHg) 1
• Consider referral to hypertension specialist if BP remains ≥160/100 mmHg on ≥3 optimized drugs or with multiple drug intolerances 1, 4

Common Pitfalls to Avoid

• Do not continue bevacizumab when clinic BP is ≥160/100 mmHg, even if the patient feels well, as this increases risk of serious cardiovascular complications 1, 2
• Do not use IV antihypertensives for bevacizumab-induced hypertension without end-organ damage, as precipitous BP drops can cause ischemic complications 4
• Monitor for proteinuria concurrently, as bevacizumab can cause renal injury with proteinuria in 0.7-7% of patients (grade 3-4) 2
• Continue monitoring BP at regular intervals even after discontinuing bevacizumab, as hypertension typically resolves but may take months 1