A phase I study of cetuximab in combination with gemcitabine and radiation for locally advanced pancreatic cancer.
BACKGROUND
Cetuximab is a monoclonal antibody against the epidermal growth factor receptor (EGFR). The primary goal of this phase I study was to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of gemcitabine when combined with cetuximab plus radiation in patients with locally advanced pancreatic cancer.


METHODS
Patients with locally unresectable adenocarcinoma of the pancreas were treated with gemcitabine (200 mg/m(2)/week before dose escalation) plus cetuximab (400 mg/m(2) loading dose, 250 mg/m(2) weekly maintenance dose) concurrent with radiation (50.4 Gy).


RESULTS
Nine patients were enrolled in the study. One withdrew due to declining performance status before receiving any therapy. Grade 4 allergic reactions to cetuximab caused the withdrawal of 2 patients. Another patient had elevated liver function test results and a stroke after his loading dose of cetuximab. Grade 3 or 4 toxicity developed in 3 of the remaining 5 patients treated with the level 1 dose. Therefore, no further dose escalations were planned. Grade 3 toxicities included nausea, vomiting, ileus, and pneumonitis. One patient had grade 4 diarrhea.


CONCLUSIONS
The combination of cetuximab, gemcitabine, and radiation resulted in significant toxicity. A recommended phase II dose could not be determined.
Department of Radiation Oncology.
A Bapsi
AB
Chakravarthy
Chiao Jillian
CJ
Tsai
Nathan
N
O'Brien
A Craig
AC
Lockhart
Emily
E
Chan
Alexander
A
Parikh
Jordan D
JD
Berlin
Nipun
N
Merchant