Additional Side Effects When Adding Bevacizumab to Cisplatin-Pemetrexed in Pleural Mesothelioma
When adding bevacizumab to cisplatin-pemetrexed in the second cycle, expect primarily hypertension (23% grade 3+), thrombotic events (6% grade 3-4), and epistaxis (37% grade 1-2), with an overall increase in grade 3-4 toxicity from 62% to 71%. 1
Most Common Additional Side Effects
The MAPS trial, which established bevacizumab's role in mesothelioma, provides the definitive safety profile for this triplet regimen:
Cardiovascular Toxicities
- Hypertension is the most significant new toxicity, occurring as grade 3+ in 23-25% of patients receiving bevacizumab versus 0% with chemotherapy alone 1
- Blood pressure monitoring and antihypertensive management will be essential throughout treatment 1
Thrombotic Complications
- Grade 3-4 thrombotic events increase from 1% to 6% with bevacizumab addition 1
- This includes deep vein thrombosis and intra-abdominal thrombosis 1
Bleeding Events
- Epistaxis (nosebleeds) occurs in 37.4% of patients (mostly grade 1-2) versus 6.3% with chemotherapy alone 1
- While usually mild, this is a characteristic bevacizumab side effect 1
Renal Toxicity
- Grade 3 proteinuria occurs in 3.1% of patients versus 0% without bevacizumab 1
- Regular urine protein monitoring is required 1
Overall Toxicity Profile
- Total grade 3-4 adverse events increase from 62% to 71% with bevacizumab addition 1
- Treatment discontinuation due to toxicity increases from 6% to 24.3% in the bevacizumab arm 1
- Importantly, there was no detriment to quality of life despite increased toxicity 1
Existing Side Effects That May Worsen
Your patient's current fatigue and loss of appetite may be compounded by:
- Fatigue: Can worsen with bevacizumab, though not specifically quantified as a new toxicity in mesothelioma trials 2
- Gastrointestinal symptoms: Nausea and constipation remain common (85.7% and 71.4% respectively in Japanese safety study) 3
Critical Safety Considerations
Absolute Contraindications to Bevacizumab
Bevacizumab should NOT be used if your patient has: 1
- Performance status ≥2
- Age >75 years
- Substantial cardiovascular comorbidity or history of stroke/TIA
- Uncontrolled hypertension
- Active bleeding or clotting risk
- Current use of therapeutic anticoagulation at curative doses
Important Clinical Context
The MAPS trial specifically excluded patients with significant cardiovascular history, and 97% of enrolled patients had excellent performance status (0-1) 1. This careful patient selection likely contributed to the manageable toxicity profile. Given the high frequency of cardiovascular comorbidity in mesothelioma patients, careful screening is essential before adding bevacizumab 1.
Monitoring Requirements
When initiating bevacizumab, implement:
- Regular blood pressure monitoring at each visit 1
- Urine protein checks (dipstick or quantitative) 1
- Assessment for bleeding symptoms 1
- Vigilance for signs of thrombosis 1
Survival Benefit Context
Despite these additional toxicities, bevacizumab provides a meaningful survival benefit of 2.7 months (median OS 18.8 vs 16.1 months, HR 0.77, p=0.0167) 1, which both NCCN and ASCO guidelines support as clinically significant 1.