Celecoxib Plus Chemotherapy Promising in Advanced Pancreatic Cancer

NEW YORK-Adding celecoxib(Drug information on celecoxib) (Celebrex) to chemotherapy with gemcitabine(Drug information on gemcitabine) (Gemzar) and irinotecan(Drug information on irinotecan) (Camptosar) markedly reduces CA 19- 9 and CEA levels in patients with advanced pancreatic cancer, according to results of a recent clinical study presented at the Chemotherapy Foundation Symposium XXI (abstract 62). The majority of patients in the small, nonrandomized investigation have had stable disease and many had decreased pain leading to decreased use of narcotics, said Allan Lipton, MD, professor of medicine and oncology, Milton S. Hershey Medical Center, Penn State College of Medicine, Hershey, Pennsylvania. Toxicities were acceptable and included neutropenia, anemia, diarrhea, and leg edema. "From this early analysis of this relatively small experience, chemotherapy plus Celebrex is a promising combination for inoperable pancreatic cancer," Dr. Lipton said. "At this point, we have a projected median survival of at least 6-plus months from the patients who are continuing on therapy." More than 90% of patients with pancreatic cancer overexpress the COX-2 enzyme, providing a firm rationale for adding a COX-2-specific nonsteroidal anti-inflammatory drug (NSAID) to chemotherapy, he said. Moreover, COX-2 inhibitors have been shown in vitro to arrest the growth of pancreatic cancer cells and, in separate investigations, appear to enhance the cytotoxic effect of gemcitabine on those cells. Dr. Lipton and his colleagues sought to determine the response rate of gemcitabine, irinotecan, and celecoxib in patients with previously untreated metastatic or locally advanced (unresectable) pancreatic adenocarcinoma. Secondarily, they are evaluating duration of response, progressionfree survival, overall survival, pain, quality of life, and toxicity. The treatment schedule under investigation includes IV gemcitabine 1,000 mg/m² and IV irinotecan 100 mg/m² on days 1 and 8 every 3 weeks, along with celecoxib 400 mg orally twice daily. Evaluations include CA 19-9, CEA, pain, and quality of life each cycle, along with CT scan every two cycles. So far, the researchers have entered 14 patients (median age, 56 years), including 7 with localized inoperable disease and 7 with metastatic disease. Study Results
Clinical responses to date include one partial response (11 months) in a patient who started with localized inoperable disease. In addition, 11 patients have had stable disease for 4 to 12 months; of those patients, 4 have progressed so far, including 1 patient with localized disease and 3 with metastatic disease. There has been one early drug toxicity and death in this trial, Dr. Lipton said. This was an elderly patient who developed severe diarrhea and expired at a local hospital. Another patient was inevaluable 5 days into therapy because of bile duct obstruction that developed due to disease, not therapy. "Encouragingly, nine of nine patients who began treatment with abdominal pain had improvement in their symptoms and decreased narcotics usage," Dr. Lipton said. Also encouraging, according to the researcher, is the time course of CA 19-9: The median decrease in CA 19- 9 was over 90% in this patient population; this marked decrease was evident as early as two cycles of therapy and continued over the rest of the course of treatment. The CEA levels were also decreased in this treatment group (about 50% median decrease over time), occurring somewhat later than the decrease in CA 19-9. Toxicity was that expected of the chemotherapy and included four cases of neutropenia (one grade 3, and one grade 4) and two cases of anemia (one grade 3). Six patients experienced diarrhea, three had edema, and one developed grade 3 deep-vein thrombosis. "Hopefully, this study will continue to accrue patients up to the projected number of 20," Dr. Lipton said. "It is my opinion, at this point, that these results might merit enlargement of this study into a phase III trial of Celebrex/ chemotherapy vs chemotherapy alone."