Pilot study of celecoxib and infusional 5‐fluorouracil as second‐line treatment for advanced pancreatic carcinoma

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Abstract
BACKGROUND: Cyclooxygenase‐2 (COX‐2) is up‐regulated frequently and may constitute a promising therapeutic target in patients with pancreatic ductal adenocarcinoma (PDAC).METHODS: Patients with advanced PDAC who had progressive disease after gemcitabine‐based chemotherapy were eligible for this pilot study. Treatment was comprised of oral celecoxib (400 mg twice daily) and protracted intravenous (i.v.) infusion 5‐fluorouracil (5‐FU) (200 mg/m2 per day), both given continuously for a maximum of 9 treatment months, in the absence of disease progression or unacceptable toxicity. Patients were examined weekly for toxicity and were restaged every 6–8 weeks for tumor assessment.RESULTS: Seventeen patients entered the study. Asymptomatic transaminase elevation was the most common toxicity and reached NCI‐CTC (version 3.0) Grade 3–4 in 4 of 133 treatment weeks. No other hematologic or nonhematologic toxicity > Grade 2 was observed. Four patients discontinued celecoxib due to upper gastrointestinal tract toxicity. Two confirmed partial responses (durations of 23 weeks and 68 weeks, respectively) and 2 patients with stable disease (durations of 10 weeks and 13 weeks, respectively) were observed for an overall response rate of 12% (95% confidence interval, 0–27%) in the intent‐to‐treat population. A significant decrease (≥ 50%) in serum CA 19.9 levels was observed in 3 of 9 evaluable patients. The median time to disease progression was 8 weeks, and the median overall survival was 15 weeks.CONCLUSIONS: The combination of oral celecoxib and 5‐FU by protracted i.v. infusion was found to be feasible and well tolerated, and was capable of inducing durable objective responses, even in patients with far advanced, gemcitabine‐resistant/refractory PDAC. Further exploration of COX‐2 inhibitor/fluropyrimidine combinations is warranted. Cancer 2004. © 2004 American Cancer Society.