Gefitinib and celecoxib in advanced metastatic gastrointestinal tumors: a pilot feasibility study.
BACKGROUND
This pilot, open-label study examined the safety and tolerability (primary objective) and efficacy (secondary objective) of gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in combination with celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, in patients with advanced or refractory gastrointestinal (GI) tumors of epithelial origin.


METHODS
Patients were administered gefitinib (250 mg/day) plus celecoxib (400 mg twice daily). In the event of toxicity, dose interruptions were permitted and a single celecoxib dose reduction was allowed.


RESULTS
Thirty patients (median age 60 years) with primary colorectal (25 patients), pancreatic (3 patients), esophageal (1 patient), or gall bladder (1 patient) tumors were recruited, 29 of whom had received prior chemotherapy. Adverse events (AEs) were generally mild and consisted mainly of acne, diarrhea, and nausea. Few severe AEs were noted. There were no withdrawals or deaths due to AEs. Dose reductions for celecoxib were reported for five patients, in three cases due to toxicity. Stable disease was confirmed in 12 patients (40%), with progressive disease in 18 patients (60%).


CONCLUSIONS
After study completion, safety issues relating to the long-term use of COX-2 inhibitors have been raised. However, in this pilot study, the combination of gefitinib and celecoxib was generally well tolerated in patients with advanced GI cancer.
University of São Paulo Medical School and Institute of Advances in Medicine, São Paulo, Brazil ;
Nise H
NH
Yamaguchi
Vanderbilt-Ingram Cancer Center, Nashville, TN, USA ;
Ingrid A
IA
Mayer
Hospital Israelita Albert Einstein and Heliopolis Hospital and Clínica de Oncologia Médica, São Paulo, Brazil ;
Artur
A
Malzyner
National Cancer Institute, Rio de Janeiro, Brazil ;
Carlos Jc
CJ
de Andrade
Oncology Department, Hospital das Clinicas, Federal University of Minas Gerais, Belo Horizonte, Brazil ;
Andre M
AM
Murad
ABC Foundation Medical School, ABC São Paulo, Brazil ;
Auro
A
Del Giglio
University of São Paulo School of Medicine, São Paulo, Brazil.
Venancio
V
Alves
Gefitnib; celecoxib; gastrointestinal cancer (GI cancer)