A phase 2 study of bevacizumab with cisplatin plus intensity‐modulated radiation therapy for stage III/IVB head and neck squamous cell cancer

Abstract

BACKGROUND: For patients with stage III through IVB head and neck squamous cell carcinoma (HNSCC), concurrent high-dose cisplatin plus radiation therapy is a widely accepted standard of care. HNSCC tumors that express high levels of vascular endothelial growth factor have been associated with a worse prognosis, and bevacizumab may sensitize tumors to cisplatin and radiation. METHODS: Planned treatment consisted of definitive intensity-modulated radiation therapy (IMRT) (total, 70 grays) with concurrent cisplatin (50 mg/m 2 on days 1, 2, 22, 23, 43, and 44) and bevacizumab (15 mg/kg on days 1, 22, and 43). The primary endpoint was 2-year progression-free survival (PFS), and overall survival (OS) was a secondary endpoint. RESULTS: Forty-two previously untreated patients (34 men and 8 women; median age, 55 years; range, 27-75 years) with stage III through IV HNSCC without distant metastasis (oropharyngeal carcinoma, 39 patients; laryngeal carcinoma, 3 patients) were treated. Human papillomavirus (HPV) status by was determined by in situ hybridization (HPV positive, 16 patients; HPV negative, 14 patients, unknown HPV status, 12 patients). The toxicities (determined according to version 3.0 of Common Terminology Criteria for Adverse Events Common) that were experienced by all patients (any grade) were mucositis, lymphopenia, leukopenia, throat pain, fatigue, and anemia. There were 2 treatment-related deaths, including 1 sudden death and 1 death from aspiration pneumonia. The median follow-up was approximately 31.8 months (range, <3 to 51 months). The 2-year PFS rate was 75.9% (95% confidence interval, 63.9%-90.1%), and the 2-year OS rate was 88% (95% confidence interval, 78.6%-98.4%). Among 32 patients for whom post-treatment Head and Neck Performance Status Scores were obtained (median, 5.6 months after completing radiation therapy), scores of 100 for eating, speech, and diet, respectively, were recorded among 75%, 84%, and 50% of patients. BACKGROUND: The addition of bevacizumab to high-dose cisplatin plus IMRT did not appear to increase toxicity to unacceptable levels among patients with HNSCC, and the efficacy results were encouraging. Cancer 2012;118:5008-14.

Does Imaging αvβ3 Integrin Expression with PET Detect Changes in Angiogenesis During Bevacizumab Therapy?

“…Bevacizumab therapy has recently been shown to improve survival of patients with metastatic squamous cell carcinoma of the cervix in randomized phase III trials (18). For head and neck squamous cell carcinoma, phase II studies have shown promising data for the addition of bevacizumab to chemotherapy and chemoradiotherapy (19,20). Hence, the use of bevacizumab for therapy of squamous cell carcinomas is likely to increase in the future.…”

Immunotherapy for Head and Neck Squamous Cell Carcinoma

“…In HNSCC, it has been evaluated for use in a variety of studies in combination with other therapeutic strategies including radiation, various chemotherapeutic medications, and other immunotherapeutics including cetuximab 48-53 . Most recently, a phase II study of the addition of Bevacizumab to Cisplatin plus intensity modulated radiation therapy (IMRT) did not show any significant increase in toxicity, with a 2 year PFS rate of 76% and overall survival rate of 88% 54 . With the addition of Cetuximab to the above regimen, the same authors showed an improved progression free survival to 89% and overall survival to 93% 55 .…”

Emerging drugs for head and neck cancer

“…Bevacizumab is a humanized anti-VEGF mAb that binds to all five isoforms of VEGF [98], reducing the total amount of circulating VEGF. A Phase II trial showed that the addition of bevacizumab to cisplatin plus IMRT did not increase toxicity in LA-HNSCC [99]. In another Phase II trial, combination of bevacizumab with cetuximab was well-tolerated and showed some activity in 46 R/M HNSCC patients [100].…”