Faculty Collaboration Database

Increased toxicity with gefitinib, capecitabine, and radiation therapy in pancreatic and rectal cancer: phase I trial results. J Clin Oncol 2006 Feb 01;24(4):656-62

Date

02/01/2006

Pubmed ID

16446337

DOI

10.1200/JCO.2005.04.1749

Scopus ID

2-s2.0-33644848522 (requires institutional sign-in at Scopus site)   130 Citations

Abstract

PURPOSE: Overexpression of epidermal growth factor receptor (EGFR) has been associated with aggressive tumor phenotypes, chemotherapy, and radiation resistance, as well as poor survival in preclinical and clinical models. The EGFR inhibitor gefitinib potentiates chemotherapy and radiation tumor cytotoxicity in preclinical models, including pancreatic and colorectal cancer. We initiated two phase I trials assessing the combination of gefitinib, capecitabine, and radiation in patients with localized pancreatic and rectal cancer.

PATIENTS AND METHODS: Patients with pathologically confirmed adenocarcinoma of the pancreas and rectum were eligible. Pretreatment staging included computed tomography, endoscopic ultrasound, and surgical evaluation. Patients received 50.4 Gy of external-beam radiation therapy to the tumor in 28 fractions. Capecitabine and gefitinib were administered throughout the radiation course. Following completion, patients were restaged and considered for resection. Primary end points included determination of dose-limiting toxicity (DLT) and a phase II dose; secondary end points included determination of non-DLTs and preliminary radiographic and pathologic response rates.

RESULTS: Ten patients were entered in the pancreatic study and six in the rectal study. DLT was seen in six of 10 patients in the pancreatic study and two of six patients in the rectal study. The primary DLT in both studies was diarrhea. Two patients developed arterial thrombi.

CONCLUSION: The combination of gefitinib, capecitabine, and radiation in pancreatic and rectal cancer patients resulted in significant toxicity. A recommended phase II dose was not determined in either of our studies. Further investigation with this combination should be approached with caution.

Author List

Czito BG, Willett CG, Bendell JC, Morse MA, Tyler DS, Fernando NH, Mantyh CR, Blobe GC, Honeycutt W, Yu D, Clary BM, Pappas TN, Ludwig KA, Hurwitz HI

Author

Kirk A. Ludwig MD Chief, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Aged
Aged, 80 and over
Antimetabolites, Antineoplastic
Antineoplastic Combined Chemotherapy Protocols
Capecitabine
Chemotherapy, Adjuvant
Deoxycytidine
ErbB Receptors
Female
Fluorouracil
Humans
Male
Middle Aged
Neoplasm Staging
Pancreatic Neoplasms
Quinazolines
Radiotherapy, Adjuvant
Rectal Neoplasms