Phase II trial of pemetrexed and bevacizumab in patients with recurrent or metastatic head and neck cancer Full Text
Journal of Clinical Oncology, 03/03/2011  Clinical Article

Argiris A et al. – The addition of bevacizumab to pemetrexed resulted in promising efficacy outcomes in SCCHN. Bleeding events were frequent but some may have been due to natural history of disease. Polymorphisms in MTHFR may offer potential for treatment individualization.

• Patients with previously untreated, recurrent, or metastatic SCCHN treated with pemetrexed 500 mg/m2 and bevacizumab 15 mg/kg given intravenously every 21 days with folic acid and B12 supplementation until disease progression
• Primary end point TTP
• DNA isolated from whole blood samples for detection of polymorphisms in thymidylate synthase, methylenetetrahydrofolate reductase (MTHFR), and VEGF

• 40 patients
• Median TTP 5 months, and median OS 11.3 months
• In 37 evaluable patients, ORR 30%, including CRR of 5%, and disease control rate 86%
• Grade 3 to 5 bleeding events occurred in 6 patients (15%): 4 grade 3, and 2 fatal
• Other serious toxicities in 10% or more of patients included neutropenia (10%) and infection (12.5%)
• 1 patient died of sepsis after receiving 8 cycles of therapy
• MTHFR A1298C (rs1801131) single nucleotide polymorphisms, homozygote patients with AA had worse OS (P = .034)