Phase II Trial of Cetuximab and Conformal Radiotherapy Only in Locally Advanced Pancreatic Cancer with Concurrent Tissue Sampling Feasibility Study.
BACKGROUND
Preclinical data have indicated the anti-epidermal growth factor receptor (EGFR) agent cetuximab (Erbitux) as a radiosensitizer in pancreatic cancer, but this has not been specifically addressed in a clinical study. We report the results of an original study initiated in 2007, where cetuximab was tested with radiotherapy (RT) alone in locally advanced pancreatic cancer in a phase II trial (PACER).


METHODS
Patients (n = 21) received cetuximab loading dose (400 mg/m(2)) and weekly dose (250 mg/m(2)) during RT (50.4 Gy in 28 fractions). Toxicity and disease response end point data were prospectively assessed. A feasibility study of on-trial patient blood and skin sampling was incorporated.


RESULTS
Treatment was well tolerated, and toxicity was low; most patients (71%) experienced acute toxicities of grade 2 or less. Six months posttreatment, stable local disease was achieved in 90% of evaluable patients, but only 33% were free from metastatic progression. Median overall survival was 7.5 months, and actuarial survival was 33% at 1 year and 11% at 3 years, reflecting swift metastatic progression in some patients but good long-term control of localized disease in others. High-grade acneiform rash (P = .0027), posttreatment stable disease (P = .0059), and pretreatment cancer antigen 19.9 (CA19.9) level (P = .0042) associated with extended survival. Patient skin and blood samples yielded sufficient RNA and good quality protein, respectively.


CONCLUSIONS
The results indicate that cetuximab inhibits EGFR-mediated radioresistance to achieve excellent local control with minimal toxicity but does not sufficiently control metastatic progression in all patients. Translational studies of patient tissue samples may yield molecular information that may enable individual treatment response prediction.
Academic Department of Radiation Oncology, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, United Kingdom ; The Christie National Health Service (NHS) Foundation Trust, Manchester, United Kingdom.
Agata I
AI
Rembielak
Academic Department of Radiation Oncology, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, United Kingdom ; The Christie National Health Service (NHS) Foundation Trust, Manchester, United Kingdom.
Pooja
P
Jain
Academic Department of Radiation Oncology, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, United Kingdom ; The Christie National Health Service (NHS) Foundation Trust, Manchester, United Kingdom.
Andrew S
AS
Jackson
Academic Department of Radiation Oncology, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, United Kingdom ; Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
Melanie M
MM
Green
Academic Department of Radiation Oncology, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, United Kingdom.
Gillian R
GR
Santorelli
Academic Department of Radiation Oncology, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, United Kingdom ; The Christie National Health Service (NHS) Foundation Trust, Manchester, United Kingdom.
Gillian A
GA
Whitfield
St James' Institute of Oncology, Leeds, United Kingdom.
Adrian
A
Crellin
North Wales Cancer Treatment Centre, Betsi Cadwaladr University Health Board, Rhyl, United Kingdom.
Angel
A
Garcia-Alonso
St James' Institute of Oncology, Leeds, United Kingdom.
Ganesh
G
Radhakrishna
Academic Department of Radiation Oncology, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, United Kingdom.
James
J
Cullen
The Christie National Health Service (NHS) Foundation Trust, Manchester, United Kingdom.
M Ben
MB
Taylor
The Christie National Health Service (NHS) Foundation Trust, Manchester, United Kingdom.
Ric
R
Swindell
Academic Department of Radiation Oncology, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, United Kingdom.
Catharine M
CM
West
Academic Department of Radiation Oncology, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, United Kingdom ; The Christie National Health Service (NHS) Foundation Trust, Manchester, United Kingdom.
Juan
J
Valle
Academic Department of Radiation Oncology, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, United Kingdom ; Imanova Centre for Imaging Sciences, Hammersmith Hospital, London, United Kingdom.
Azeem
A
Saleem
Academic Department of Radiation Oncology, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, United Kingdom ; Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
Patricia M
PM
Price