期刊
EUROPEAN JOURNAL OF CANCER
卷 50, 期 8, 页码 1422-1429出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2014.02.003
关键词
Anti-angiogenic therapy; Chemotherapy; Combination chemotherapy; Epidermal growth factor receptor (EGFR) inhibition; Molecularly targeted therapy; Pancreatic cancer
类别
资金
- Royal Marsden Hospital National Health Service (NHS) Foundation Trust
- National Institute for Health Research (NIHR) Biomedical Research Centre
- Hoffmann-La Roche
- National Institute for Health Research [NF-SI-0507-10161] Funding Source: researchfish
Background: Preclinical data support the combined inhibition of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways in the treatment of pancreatic cancer. Following a dose finding phase I study the efficacy and toxicity of a four-drug regimen utilising the cytotoxic doublet of gemcitabine and capecitabine (Gem-Cap), with the biological doublet of erlotinib and bevacizumab were further assessed in patients with advanced pancreatic cancer. Patients and methods: In a phase II expansion cohort, patients with chemonaive locally advanced or metastatic pancreatic cancer received gemcitabine (1000 mg/m(2) D1, 8, 15), capecitabine (1400 mg/m(2) D1-21), erlotinib (100 mg daily) and bevacizumab (5 mg/kg D1, 15) every 28 days. The primary endpoint was radiological response rate by response evaluation criteria in solid tumours (RECIST). Computed tomography (CT) assessment was performed every 8 weeks. Consolidation radiotherapy was considered in locally advanced patients following six cycles of treatment. Results: In total 44 patients (phases I & II) were recruited. The median cycles delivered were 6 (range 1-16). Confirmed radiological responses were seen in 23% (95% confidence interval (CI): 11-38%) of patients. The median progression-free and overall survival for the entire cohort was 8.4 and 12.6 months, respectively. In patients with metastatic disease the median overall survival was 10.1 months. Common grade 3/4 toxicities were; neutropenia 52%, lethargy 32%, diarrhoea 18% and hand-foot syndrome 18%. Conclusion: The combination of gemcitabine, capecitabine, erlotinib and bevacizumab was feasible with a manageable toxicity profile and demonstrated encouraging efficacy data in a good performance status population. (C) 2014 Elsevier Ltd. All rights reserved.
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