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.

Patients and 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.