Early Trial Supports Bevacizumab in Head and Neck Cancer

MIAMI BEACH – Bevacizumab added to docetaxel and definitive radiotherapy was an effective and safe non–platinum-based regimen for locoregionally advanced squamous cell carcinoma of the head and neck in a small phase II trial that was presented at the annual meeting of the American Society for Radiation Oncology.

The disease-free survival rate at 2 years (the primary end point) was 75% among 28 patients who had completed the full course of chemoradiation in the phase II study, said Dr. Nicholas Galanopoulos of University Hospitals Seidman Cancer Center in Cleveland. In this as-treated population, 85% of patients were alive at 2 years, locoregional control was achieved in 85% of patients, and 81.5% were free of distant metastases at 2 years.

The numbers were slightly lower when two additional patients who dropped out of the study (one for unspecified reasons and one who developed aspiration pneumonia and was hospitalized) were included in an intention-to-treat analysis. Among all 30 patients, the disease-free survival rate at 2 years was 63% and overall survival was 72%, although locoregional control and distant-metastasis-free rates remained unchanged at 85% and 81.5%, respectively.

"Future trials of concurrent chemoradiotherapy with or without bevacizumab are justified for local-regionally advanced head and neck cancer," Dr. Galanopoulos said.

The rationale for trying bevacizumab (Avastin) in chemoradiation regimens for head and neck tumors is based on its demonstrated ability to inhibit endothelial cell proliferation and blood vessel formation, and to increase radiosensitivity of tumors when administered concurrently with radiation, he noted.

In all, 30 treatment-naive patients (26 men, 4 women) with locally advanced stage III (6 patients) or IV (24 patients) squamous cell carcinoma of the head and neck were enrolled. The patients had good performance status and a life expectancy greater than 12 weeks.

They received 70.2 Gy radiation in 1.8-Gy fractions, docetaxel (Taxotere) 20 mg/m² per week, and bevacizumab 5 mg/kg every 2 weeks, with bevacizumab continued for up to 1 year following chemoradiation (median, 7 months).

"Future trials of concurrent chemo-radiotherapy with or without bevacizumab are justified for local-regionally advanced head and neck cancer."

Results were reported as of a median follow-up of 24.4 months.

Adjuvant bevacizumab was stopped 4 weeks before surgery in those patients who required neck dissection, and the drug was discontinued in three patients (one for radiation necrosis of the larynx requiring laryngectomy, one for severe pharyngoesophageal stenosis, and one for hemorrhagic cholecystits requiring cholecystectomy).

Major toxicities associated with the regimen included grade 4 bleeding in two patients (the episode of hemorrhagic cholecystitis already noted), and one oropharyngeal hemorrhage in field during chemoradiation.

Late grade 3 or 4 dysphagia occurred in 7 of 19 patients who had been treated with 3-D conformal radiation therapy, but in none of 11 patients who received intensity-modulated radiation (P less than .05). Patients with laryngeal primary tumors were more likely to develop serious late dysphagia, compared with patients with oropharyngeal primaries (58%% vs. 15%; P less than .05).

The study was funded in part by grants from the National Institutes of Health, Genentech, and Sanofi-Aventis. Dr. Galanopoulos reported having no relevant financial disclosures. Coauthor Dr. Panayiotis Savvides disclosed receiving research grants or support from Genentech and Sanofi-Aventis.

MIAMI BEACH – Bevacizumab added to docetaxel and definitive radiotherapy was an effective and safe non–platinum-based regimen for locoregionally advanced squamous cell carcinoma of the head and neck in a small phase II trial that was presented at the annual meeting of the American Society for Radiation Oncology.

The disease-free survival rate at 2 years (the primary end point) was 75% among 28 patients who had completed the full course of chemoradiation in the phase II study, said Dr. Nicholas Galanopoulos of University Hospitals Seidman Cancer Center in Cleveland. In this as-treated population, 85% of patients were alive at 2 years, locoregional control was achieved in 85% of patients, and 81.5% were free of distant metastases at 2 years.

The numbers were slightly lower when two additional patients who dropped out of the study (one for unspecified reasons and one who developed aspiration pneumonia and was hospitalized) were included in an intention-to-treat analysis. Among all 30 patients, the disease-free survival rate at 2 years was 63% and overall survival was 72%, although locoregional control and distant-metastasis-free rates remained unchanged at 85% and 81.5%, respectively.

"Future trials of concurrent chemoradiotherapy with or without bevacizumab are justified for local-regionally advanced head and neck cancer," Dr. Galanopoulos said.

The rationale for trying bevacizumab (Avastin) in chemoradiation regimens for head and neck tumors is based on its demonstrated ability to inhibit endothelial cell proliferation and blood vessel formation, and to increase radiosensitivity of tumors when administered concurrently with radiation, he noted.

In all, 30 treatment-naive patients (26 men, 4 women) with locally advanced stage III (6 patients) or IV (24 patients) squamous cell carcinoma of the head and neck were enrolled. The patients had good performance status and a life expectancy greater than 12 weeks.

They received 70.2 Gy radiation in 1.8-Gy fractions, docetaxel (Taxotere) 20 mg/m² per week, and bevacizumab 5 mg/kg every 2 weeks, with bevacizumab continued for up to 1 year following chemoradiation (median, 7 months).

"Future trials of concurrent chemo-radiotherapy with or without bevacizumab are justified for local-regionally advanced head and neck cancer."

Results were reported as of a median follow-up of 24.4 months.

Adjuvant bevacizumab was stopped 4 weeks before surgery in those patients who required neck dissection, and the drug was discontinued in three patients (one for radiation necrosis of the larynx requiring laryngectomy, one for severe pharyngoesophageal stenosis, and one for hemorrhagic cholecystits requiring cholecystectomy).

Major toxicities associated with the regimen included grade 4 bleeding in two patients (the episode of hemorrhagic cholecystitis already noted), and one oropharyngeal hemorrhage in field during chemoradiation.

Late grade 3 or 4 dysphagia occurred in 7 of 19 patients who had been treated with 3-D conformal radiation therapy, but in none of 11 patients who received intensity-modulated radiation (P less than .05). Patients with laryngeal primary tumors were more likely to develop serious late dysphagia, compared with patients with oropharyngeal primaries (58%% vs. 15%; P less than .05).

The study was funded in part by grants from the National Institutes of Health, Genentech, and Sanofi-Aventis. Dr. Galanopoulos reported having no relevant financial disclosures. Coauthor Dr. Panayiotis Savvides disclosed receiving research grants or support from Genentech and Sanofi-Aventis.

MIAMI BEACH – Bevacizumab added to docetaxel and definitive radiotherapy was an effective and safe non–platinum-based regimen for locoregionally advanced squamous cell carcinoma of the head and neck in a small phase II trial that was presented at the annual meeting of the American Society for Radiation Oncology.

The disease-free survival rate at 2 years (the primary end point) was 75% among 28 patients who had completed the full course of chemoradiation in the phase II study, said Dr. Nicholas Galanopoulos of University Hospitals Seidman Cancer Center in Cleveland. In this as-treated population, 85% of patients were alive at 2 years, locoregional control was achieved in 85% of patients, and 81.5% were free of distant metastases at 2 years.

The numbers were slightly lower when two additional patients who dropped out of the study (one for unspecified reasons and one who developed aspiration pneumonia and was hospitalized) were included in an intention-to-treat analysis. Among all 30 patients, the disease-free survival rate at 2 years was 63% and overall survival was 72%, although locoregional control and distant-metastasis-free rates remained unchanged at 85% and 81.5%, respectively.

"Future trials of concurrent chemoradiotherapy with or without bevacizumab are justified for local-regionally advanced head and neck cancer," Dr. Galanopoulos said.

The rationale for trying bevacizumab (Avastin) in chemoradiation regimens for head and neck tumors is based on its demonstrated ability to inhibit endothelial cell proliferation and blood vessel formation, and to increase radiosensitivity of tumors when administered concurrently with radiation, he noted.

In all, 30 treatment-naive patients (26 men, 4 women) with locally advanced stage III (6 patients) or IV (24 patients) squamous cell carcinoma of the head and neck were enrolled. The patients had good performance status and a life expectancy greater than 12 weeks.

They received 70.2 Gy radiation in 1.8-Gy fractions, docetaxel (Taxotere) 20 mg/m² per week, and bevacizumab 5 mg/kg every 2 weeks, with bevacizumab continued for up to 1 year following chemoradiation (median, 7 months).

"Future trials of concurrent chemo-radiotherapy with or without bevacizumab are justified for local-regionally advanced head and neck cancer."

Results were reported as of a median follow-up of 24.4 months.

Adjuvant bevacizumab was stopped 4 weeks before surgery in those patients who required neck dissection, and the drug was discontinued in three patients (one for radiation necrosis of the larynx requiring laryngectomy, one for severe pharyngoesophageal stenosis, and one for hemorrhagic cholecystits requiring cholecystectomy).

Major toxicities associated with the regimen included grade 4 bleeding in two patients (the episode of hemorrhagic cholecystitis already noted), and one oropharyngeal hemorrhage in field during chemoradiation.

Late grade 3 or 4 dysphagia occurred in 7 of 19 patients who had been treated with 3-D conformal radiation therapy, but in none of 11 patients who received intensity-modulated radiation (P less than .05). Patients with laryngeal primary tumors were more likely to develop serious late dysphagia, compared with patients with oropharyngeal primaries (58%% vs. 15%; P less than .05).

The study was funded in part by grants from the National Institutes of Health, Genentech, and Sanofi-Aventis. Dr. Galanopoulos reported having no relevant financial disclosures. Coauthor Dr. Panayiotis Savvides disclosed receiving research grants or support from Genentech and Sanofi-Aventis.