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Updated: Jul 1, 2026
Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
Phase I study of cetuximab, erlotinib, and bevacizumab in patients with advanced solid tumors
Chia-Chi Lin1, Emiliano Calvo, Kyriakos P Papadopoulos
1Institute for Drug Development, Cancer Therapy and Research Center, San Antonio, TX, USA.
Background:
Complex interrelationships exist between the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) receptor pathways. EGFR activation elicits cell proliferation and increased VEGF expression. To maximally inhibit EGFR and then downstream VEGF activity, this phase I study was initiated to determine the maximum tolerated dose (MTD) of erlotinib with fixed-dose cetuximab, and then combine with bevacizumab in patients with advanced malignancies.
Patients And Methods:
Patients with advanced malignancies likely to express EGFR were treated with a full dose of cetuximab intravenous weekly, combined with various doses of oral erlotinib daily (Part 1). Once the MTD was determined in Part 1, escalating doses of bevacizumab were administered intravenously biweekly (Part 2).
Results:
Forty patients were enrolled and received 155 courses over four dose levels. In Part 1, dose-limiting grade 3 rash occurred in two patients administered with erlotinib at 100 mg daily, and the MTD of erlotinib for this combination was 50 mg daily with standard-dose cetuximab (11 patients treated). Other adverse events included rash, diarrhea, fatigue, and hypomagnesemia. In Part 2, bevacizumab at 10 mg/kg intravenous every 2 weeks was safely added, with additional nondose-limiting headache, proteinuria, and hypertension. There was one partial response in a patient with renal cell carcinoma. Durable stable disease was observed in five patients for 6-11 months.
Conclusions:
The MTD for Part 1 was 50 mg daily of erlotinib combined with standard cetuximab. Bevacizumab at 10 mg/kg biweekly can be safely administered with the MTD for erlotinib and cetuximab combination.
Insights
The maximum tolerated dose (MTD) of erlotinib combined with cetuximab was 50 mg daily. This combination, along with bevacizumab, was safely administered in patients with advanced malignancies.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Complex interplay exists between epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) receptor pathways.
- EGFR activation promotes cell proliferation and upregulates VEGF expression.
- Targeting both EGFR and VEGF pathways may offer enhanced anti-cancer effects.
Purpose of the Study:
- Determine the maximum tolerated dose (MTD) of erlotinib in combination with a fixed dose of cetuximab.
- Evaluate the safety and tolerability of adding bevacizumab to the erlotinib-cetuximab combination.
- Assess the efficacy of this combination therapy in patients with advanced malignancies.
Main Methods:
- Phase I clinical trial design.
- Part 1: Escalating doses of oral erlotinib daily with weekly intravenous cetuximab to determine MTD.
- Part 2: Addition of escalating doses of intravenous bevacizumab biweekly to the MTD combination.
Main Results:
- The MTD of erlotinib was determined to be 50 mg daily when combined with standard-dose cetuximab.
- Grade 3 rash was the dose-limiting toxicity in Part 1.
- Bevacizumab at 10 mg/kg biweekly was safely added in Part 2, with manageable adverse events including headache and hypertension.
- One partial response in renal cell carcinoma and durable stable disease in five patients were observed.
Conclusions:
- The MTD for the combination of erlotinib and cetuximab is 50 mg daily.
- Bevacizumab can be safely administered at 10 mg/kg biweekly with the MTD erlotinib-cetuximab regimen.
- This combination therapy shows potential in managing advanced malignancies.
