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A phase I study evaluating the role of the anti-epidermal growth factor receptor (EGFR) antibody cetuximab as a radiosensitizer with chemoradiation for locally advanced pancreatic cancer
- Source :
- Cancer Chemotherapy and Pharmacology. 67:891-897
- Publication Year :
- 2010
- Publisher :
- Springer Science and Business Media LLC, 2010.
-
Abstract
- (1) To determine the safety of the epidermal growth factor receptor (EGFR) antibody cetuximab with concurrent gemcitabine and abdominal radiation in the treatment of patients with locally advanced adenocarcinoma of the pancreas. (2) To evaluate the feasibility of pancreatic cancer cell epithelial-mesenchymal transition (EMT) molecular profiling as a potential predictor of response to anti-EGFR treatment.Patients with non-metastatic, locally advanced pancreatic cancer were treated in this dose escalation study with gemcitabine (0-300 mg/m(2)/week) given concurrently with cetuximab (400 mg/m(2) loading dose, 250 mg/m(2) weekly maintenance dose) and abdominal irradiation (50.4 Gy). Expression of E-cadherin and vimentin was assessed by immunohistochemistry in diagnostic endoscopic ultrasound fine-needle aspiration (EUS-FNA) specimens.Sixteen patients were enrolled in 4 treatment cohorts with escalating doses of gemcitabine. Incidence of grade 1-2 adverse events was 96%, and incidence of 3-4 adverse events was 9%. There were no treatment-related mortalities. Two patients who exhibited favorable treatment response underwent surgical exploration and were intraoperatively confirmed to have unresectable tumors. Median overall survival was 10.5 months. Pancreatic cancer cell expression of E-cadherin and vimentin was successfully determined in EUS-FNA specimens from 4 patients.Cetuximab can be safely administered with abdominal radiation and concurrent gemcitabine (up to 300 mg/m(2)/week) in patients with locally advanced adenocarcinoma of the pancreas. This combined therapy modality exhibited limited activity. Diagnostic EUS-FNA specimens could be analyzed for molecular markers of EMT in a minority of patients with pancreatic cancer.
- Subjects :
- Male
Oncology
Cancer Research
medicine.medical_treatment
Cetuximab
Toxicology
Deoxycytidine
EGFR Antibody
Cohort Studies
Antineoplastic Combined Chemotherapy Protocols
Pharmacology (medical)
Epidermal growth factor receptor
Aged, 80 and over
biology
Antibodies, Monoclonal
Middle Aged
Cadherins
Combined Modality Therapy
ErbB Receptors
Gene Expression Regulation, Neoplastic
Survival Rate
medicine.anatomical_structure
Female
Pancreas
medicine.drug
Adult
medicine.medical_specialty
Radiosensitizer
Epithelial-Mesenchymal Transition
Biopsy, Fine-Needle
Antineoplastic Agents
Adenocarcinoma
Antibodies, Monoclonal, Humanized
Article
Internal medicine
Pancreatic cancer
medicine
Humans
Vimentin
Aged
Pharmacology
Dose-Response Relationship, Drug
business.industry
Gene Expression Profiling
medicine.disease
Gemcitabine
Pancreatic Neoplasms
Radiation therapy
biology.protein
Feasibility Studies
business
Subjects
Details
- ISSN :
- 14320843 and 03445704
- Volume :
- 67
- Database :
- OpenAIRE
- Journal :
- Cancer Chemotherapy and Pharmacology
- Accession number :
- edsair.doi.dedup.....db78e37af77b70698d4d2af4d821932a