A randomized phase II study of 5-fluorouracil, hydroxyurea, and twice-daily radiotherapy compared with bevacizumab plus 5-fluorouracil, hydroxyurea, and twice-daily radiotherapy for intermediate-stage and T4N0-1 head and neck cancers

Salama, Joseph K.; Haraf, Daniel J.; Stenson, K.; Blair, Elizabeth A.; Witt, Mary Ellyn; Williams, R.; Kunnavakkam, Rangesh; Cohen, Ezra E.W.; Seiwert, Tanguy Y.; Vokes, Everett E.

doi:10.1093/annonc/mdq736

Cited by 58 publications

(39 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Two thirds of their study population had received prior irradiation. A subsequent phase II study comparing FHX versus FHX plus bevacizumab in stage II-III and select patients with T4N0-1 HNC had 3 patients (16%) in the experimental arm requiring multiple surgeries for poor wound healing (26). Whether these rates would be lower in the setting of conventional once daily RT or with different concurrent chemotherapy agents is unknown and warrants further investigation in the context of clinical trials.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Prospective Trial of Synchronous Bevacizumab, Erlotinib, and Concurrent Chemoradiation in Locally Advanced Head and Neck Cancer

Yoo

Kirkpatrick

Craciunescu

et al. 2012

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: We assessed the safety and efficacy of synchronous VEGF and epidermal growth factor receptor (EGFR) blockade with concurrent chemoradiation (CRT) in locally advanced head and neck cancer (HNC).Experimental Design: Newly diagnosed patients with stage III/IV HNC received a 2-week lead-in of bevacizumab and/or erlotinib, followed by both agents with concurrent cisplatin and twice daily radiotherapy. Safety was assessed using Common Toxicity Criteria version 3.0. The primary efficacy endpoint was clinical complete response (CR) rate after CRT.Results: Twenty-nine patients enrolled on study, with 27 completing therapy. Common grade III toxicities were mucositis (n ¼ 14), dysphagia (n ¼ 8), dehydration (n ¼ 7), osteoradionecrosis (n ¼ 3), and soft tissue necrosis (n ¼ 2). Feeding tube placement was required in 79% but no patient remained dependent at 12-month posttreatment. Clinical CR after CRT was 96% [95% confidence interval (CI), 82%-100%]. Median follow-up was 46 months in survivors, with 3-year locoregional control and distant metastasis-free survival rates of 85% and 93%. Three-year estimated progression-free survival, diseasespecific survival, and overall survival rates were 82%, 89%, and 86%, respectively. Dynamic contrast enhanced MRI (DCE-MRI) analysis showed that patients who had failed had lower baseline pretreatment median K trans values, with subsequent increases after lead-in therapy and 1 week of CRT. Patients who did not fail had higher median K trans values that decreased during therapy.Conclusions: Dual VEGF/EGFR inhibition can be integrated with CRT in locally advanced HNC, with efficacy that compares favorably with historical controls albeit with an increased risk of osteoradionecrosis. Pretreatment and early DCE-MRI may prospectively identify patients at high risk of failure.

show abstract

Section: Discussionmentioning

confidence: 99%

“…The addition of single-agent bevacizumab to CRT in patients with treatment-na€ ve nonmetastatic HNC was examined by Salama and colleagues as described earlier (26). The study was terminated early after 26 patients, due to unexpected locoregional progression in 4 of 5 T4N0-1 patients treated with bevacizumab and FHX.…”

Section: Discussionmentioning

confidence: 99%

Prospective Trial of Synchronous Bevacizumab, Erlotinib, and Concurrent Chemoradiation in Locally Advanced Head and Neck Cancer

Yoo

Kirkpatrick

Craciunescu

et al. 2012

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…However 11.6% and 9.3% patients with fistula and ulceration/tissue necrosis respectively underline the concern about the side effects of the treatment [22]. Moreover these favourable outcomes were not confirmed by the phase II trial [23].…”

Section: Seiwert Et Al Reported Enthusiastic Results Of the Combinatmentioning

confidence: 95%

Angiogenesis in Head and Neck Cancer

EG¹

2014

J Cancer Sci Ther

View full text Add to dashboard Cite

Locally advanced Head and Neck Squamous Cell Carcinoma (HNC) is a challenging disease for the lack of effective therapies even in the era of molecular medicine (the five-year survival does not exceed 40%). For patients with metastatic and recurrent HNC the standard treatment is the combination of Cetuximab/Platinum and Fluorouracil but median overall survival rate for this population remains lower than 11%. The main reasons of these disappointing outcomes include acquired drug resistance, anti Epidermal growth factors variants, epithelial to mesenchymal transition and tumor hypoxia.Angiogenesis plays a crucial role in HNSCC development and proliferation. Drugs may interfere with the angiogenic process via different mechanisms and there is a sound rationale for combining anti-angiogenic agents with chemotherapy or multiple anti-angiogenic strategies. Promising preclinical results with angiogenic inhibitors have engendered a number of trials, but until now there are not yet conclusive data on the value of anti-angiogenic therapy in HNC.

show abstract

“…Results of a follow-up phase II randomized study by the same group have been reported by Salama et al in which the BFHX regimen was compared to the prior FHX regimen (Salama et al, 2011). In this study, 26 patients with intermediate stage III-IV patients (excluding N2-N3 stage) were enrolled.…”

Section: Bevacizumab and Chemoradiotherapymentioning

confidence: 82%

Novel Chemoradiotherapy Regimens Incorporating Targeted Therapies in Locally Advanced Head and Neck Cancers

Rathore¹

2012

Head and Neck Cancer

View full text Add to dashboard Cite

A forest plot analysis was done to assess whether certain patient groups benefitted with the addition of cetuximab to RT. In this analysis, factors which were associated with a potential increased benefit included presence of oropharyngeal tumors, concomitant boost RT, early T stage (T1-T3), high Karnofsky performance score (90%-100%), male sex, and age < 65 years. These results are provocative but given that the trial was not powered for this subgroup analysis, they should be interpreted with caution.Patients who received cetuximab commonly developed an acneiform rash (83.7%); the severity of the rash was grade 3-4 in 16.8% patients. Infusion-related reactions were also seen in 15.4% patients; in 3.9% patients these were of grade 3/4 severity. However, in-field toxicities, such as mucositis, dermatitis, and dysphagia did not significantly increase with the addition of cetuximab to RT. Quality-of-life parameters were not adversely affected by the addition of cetuximab. This study allowed different RT fractionation regimens which may have impacted results and survival outcomes.

show abstract

A randomized phase II study of 5-fluorouracil, hydroxyurea, and twice-daily radiotherapy compared with bevacizumab plus 5-fluorouracil, hydroxyurea, and twice-daily radiotherapy for intermediate-stage and T4N0-1 head and neck cancers

Abstract: Locoregional progression seen in T4N0-1 tumors treated with BFHX was unexpected and led to study termination. The addition of bevacuzimab to chemoradiotherapy for HNSCC should be limited clinical trials.

Cited by 58 publications

References 12 publications

Prospective Trial of Synchronous Bevacizumab, Erlotinib, and Concurrent Chemoradiation in Locally Advanced Head and Neck Cancer

Prospective Trial of Synchronous Bevacizumab, Erlotinib, and Concurrent Chemoradiation in Locally Advanced Head and Neck Cancer

Angiogenesis in Head and Neck Cancer

Novel Chemoradiotherapy Regimens Incorporating Targeted Therapies in Locally Advanced Head and Neck Cancers

Contact Info

Product

Resources

About