Combining the widely used cancer drug bevacizumab with standard chemoradiation therapy is safe and could prolong survival in patients with advanced nasopharyngeal carcinoma, according to a new phase 2 trial published Online First in The Lancet Oncology. The results indicate that bevacizumab might be more effective at preventing the spread of nasopharyngeal carcinoma to other parts of the body, the most common cause of death in patients with advanced disease.
The introduction of intensity-modulated radiotherapy (IMRT) resulted in local tumour control rates of greater than 90% for patients with nasopharyneal carcinoma. However, the disease has the highest rate of metastases among head and neck cancers, and within 4-5 years spreads to distant organs in around 30% of patients.
Bevacizumab is a monoclonal antibody that blocks vascular endothelial growth factor (VEGF-A) which is associated with poor prognosis in head and neck cancers, and is overexpressed in around two-thirds of patients with nasopharyngeal carcinoma. Bevacizumab has been shown to improve response rates, disease-free, progression-free, and overall survival in many types of advanced cancer including colorectal cancer, renal cell cancer, and non-small cell lung cancer.
Here, Nancy Lee from Memorial Sloan-Kettering Cancer Center, New York, USA, and colleagues from the Radiation Therapy Oncology Group (RTOG) report the results of a phase 2 trial testing the addition of bevacizumab to chemoradiation, the usual treatment for patients with nasopharyneal carcinoma.
The study included 46 previously untreated patients with locoregionally advanced nasopharyneal carcinoma from 19 centres in North America and Hong Kong. Bevacizumab was added to the concurrent and adjuvant phases of chemotherapy with cisplatin and fluorouracil. The new combination treatment resulted in over 90% of patients surviving 2 years with no distant metastases and 75% of patients without the disease getting worse.
The bevacizumab regimen did not appear to significantly increase toxicity or affect compliance with treatment compared to that seen historically with standard chemoradiotherapy alone.
No grade 3 to 4 bleeding or deaths were reported, but 9 (20%) patients experienced treatment-related grade 1 to 2 bleeding. The most common grade 3 or higher adverse events were blood or bone marrow related complications and acute mucositis (painful inflammation of mucous membranes in mouth).
The authors say: "The addition of bevacizumab to chemoradiation for nasopharyneal carcinoma is feasible and…it causes no major compromise in the delivery of standard chemoradiation…and might delay the progression of subclinical distant disease."
They add: "Although the addition of bevacizumab did not seem to result in any unusual grade 3-4 events, toxicity was still substantial overall and compliance to protocol treatment was not ideal…So further research is needed to identify those at risk of distant metastasis and hence those who might benefit most from additional bevacizumab."
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Journal
The Lancet Oncology