TY - JOUR
T1 - Initial experience combining cyclooxygenase-2 inhibition with chemoradiation for locally advanced pancreatic cancer
AU - Crane, Christopher H.
AU - Mason, Kathy
AU - Janjan, Nora A.
AU - Milas, Luka
PY - 2003/8
Y1 - 2003/8
N2 - Pancreatic cancer is a lethal disease that is resistant to chemotherapy and radiotherapy. Gemcitabine has recently been shown to be an improvement over 5-fluorouracil in patients with advanced disease. It is also a potent radiosensitizer, which has led to the investigation of gemcitabine with concurrent radiotherapy. However, preliminary results indicate that there are significant limitations to this approach in this challenging disease. Pancreatic cancer cells have alterations in many molecular signaling pathways that may be responsible for their resistance to cytotoxic therapy and aggressive behavior. Cyclooxygenase-2 (COX-2) is commonly overexpressed in pancreatic tumors, and preclinical evidence indicates that selective COX-2 inhibition enhances both chemotherapy and radiotherapy response, without affecting normal tissue damage. We have initiated preclinical studies as well as a phase I clinical protocol evaluating the combination of gemcitabine and celecoxib (Celebrex) with radiotherapy. In preclinical studies, celecelecoxib strongly enhanced the antitumor efficacy of chemoradiation. However, preliminary observations from both the preclinical experiments as well as the clinical protocol have revealed more toxicity with this combination than with gemcitabine and radiotherapy alone. These observations require further study, but are cause for concern when combining gemcitabine, radiotherapy, and celecoxib.
AB - Pancreatic cancer is a lethal disease that is resistant to chemotherapy and radiotherapy. Gemcitabine has recently been shown to be an improvement over 5-fluorouracil in patients with advanced disease. It is also a potent radiosensitizer, which has led to the investigation of gemcitabine with concurrent radiotherapy. However, preliminary results indicate that there are significant limitations to this approach in this challenging disease. Pancreatic cancer cells have alterations in many molecular signaling pathways that may be responsible for their resistance to cytotoxic therapy and aggressive behavior. Cyclooxygenase-2 (COX-2) is commonly overexpressed in pancreatic tumors, and preclinical evidence indicates that selective COX-2 inhibition enhances both chemotherapy and radiotherapy response, without affecting normal tissue damage. We have initiated preclinical studies as well as a phase I clinical protocol evaluating the combination of gemcitabine and celecoxib (Celebrex) with radiotherapy. In preclinical studies, celecelecoxib strongly enhanced the antitumor efficacy of chemoradiation. However, preliminary observations from both the preclinical experiments as well as the clinical protocol have revealed more toxicity with this combination than with gemcitabine and radiotherapy alone. These observations require further study, but are cause for concern when combining gemcitabine, radiotherapy, and celecoxib.
KW - Cyclooxygenase-2
KW - Gemcitabine
KW - Pancreatic cancer
KW - Radiotherapy
UR - http://www.scopus.com/inward/record.url?scp=0042575268&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0042575268&partnerID=8YFLogxK
U2 - 10.1097/00000421-200308002-00009
DO - 10.1097/00000421-200308002-00009
M3 - Article
C2 - 12902862
AN - SCOPUS:0042575268
SN - 0277-3732
VL - 26
SP - S81-S84
JO - American Journal of Clinical Oncology: Cancer Clinical Trials
JF - American Journal of Clinical Oncology: Cancer Clinical Trials
IS - 4 SUPPL. 2
ER -