Celecoxib Plus Chemotherapy Promising in Advanced Pancreatic Cancer

March 1, 2004

This special "annual highlights" supplement to Oncology News International is a compilation of some of the major advances in the management of gastrointestinal cancers during 2003–2004, as reported in ONI. Guest editor Dr. James L. Abbruzzesecomments on the reports included herein and discusses advances in the clinical management of GI cancers, with a focus on developments in targeted therapy, newcombinations, adjuvant therapy, and what to watch for in 2004.

NEW YORK-Adding celecoxib(Celebrex) to chemotherapy withgemcitabine (Gemzar) and irinotecan(Camptosar) markedly reduces CA 19-9 and CEA levels in patients with advancedpancreatic cancer, accordingto results of a recent clinical studypresented at the Chemotherapy FoundationSymposium XXI (abstract 62).The majority of patients in the small,nonrandomized investigation have hadstable disease and many had decreasedpain leading to decreased use of narcotics,said Allan Lipton, MD, professorof medicine and oncology, MiltonS. Hershey Medical Center, Penn StateCollege of Medicine, Hershey, Pennsylvania.Toxicities were acceptable andincluded neutropenia, anemia, diarrhea,and leg edema."From this early analysis of this relativelysmall experience, chemotherapyplus Celebrex is a promising combinationfor inoperable pancreaticcancer," Dr. Lipton said. "At this point,we have a projected median survivalof at least 6-plus months fromthe patients who are continuing ontherapy."More than 90% of patients withpancreatic cancer overexpress theCOX-2 enzyme, providing a firm rationalefor adding a COX-2-specificnonsteroidal anti-inflammatory drug(NSAID) to chemotherapy, he said.Moreover, COX-2 inhibitors havebeen shown in vitro to arrest the growthof pancreatic cancer cells and, in separateinvestigations, appear to enhancethe cytotoxic effect of gemcitabine onthose cells.Dr. Lipton and his colleaguessought to determine the response rateof gemcitabine, irinotecan, and celecoxibin patients with previously untreatedmetastatic or locally advanced(unresectable) pancreatic adenocarcinoma.Secondarily, they are evaluatingduration of response, progressionfreesurvival, overall survival, pain,quality of life, and toxicity.The treatment schedule under investigationincludes IV gemcitabine1,000 mg/m2 and IV irinotecan 100mg/m2 on days 1 and 8 every 3 weeks,along with celecoxib 400 mg orallytwice daily. Evaluations include CA19-9, CEA, pain, and quality of lifeeach cycle, along with CT scan everytwo cycles.So far, the researchers have entered14 patients (median age, 56 years),including 7 with localized inoperabledisease and 7 with metastatic disease.Study Results
Clinical responses to date includeone partial response (11 months) in apatient who started with localized inoperabledisease. In addition, 11 patientshave had stable disease for 4 to12 months; of those patients, 4 haveprogressed so far, including 1 patientwith localized disease and 3 with metastaticdisease.There has been one early drug toxicityand death in this trial, Dr. Liptonsaid. This was an elderly patient whodeveloped severe diarrhea and expiredat a local hospital. Another patientwas inevaluable 5 days into therapybecause of bile duct obstruction thatdeveloped due to disease, not therapy."Encouragingly, nine of nine patientswho began treatment with abdominalpain had improvement intheir symptoms and decreased narcoticsusage," Dr. Lipton said.Also encouraging, according to theresearcher, is the time course of CA19-9: The median decrease in CA 19-9 was over 90% in this patient population;this marked decrease was evidentas early as two cycles of therapy andcontinued over the rest of the courseof treatment. The CEA levels were alsodecreased in this treatment group(about 50% median decrease overtime), occurring somewhat later thanthe decrease in CA 19-9.Toxicity was that expected of thechemotherapy and included four casesof neutropenia (one grade 3, andone grade 4) and two cases of anemia(one grade 3). Six patients experienceddiarrhea, three had edema, andone developed grade 3 deep-veinthrombosis."Hopefully, this study will continueto accrue patients up to the projectednumber of 20," Dr. Lipton said. "Itis my opinion, at this point, that theseresults might merit enlargement of thisstudy into a phase III trial of Celebrex/chemotherapy vs chemotherapyalone."