Article

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

Divisions of Medical Oncology "A" and "C", Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
Cancer (impact factor: 4.77). 08/2004; 101(1):133-8. DOI:10.1002/cncr.20338
Source: PubMed

ABSTRACT Cyclooxygenase-2 (COX-2) is up-regulated frequently and may constitute a promising therapeutic target in patients with pancreatic ductal adenocarcinoma (PDAC).
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/m(2) 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.
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 (> or = 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.
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.

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Keywords

133 treatment weeks
 
2 patients
 
9 evaluable patients
 
9 treatment months
 
95% confidence interval
 
Asymptomatic transaminase elevation
 
common toxicity
 
COX-2 inhibitor/fluropyrimidine combinations
 
gemcitabine-resistant/refractory PDAC
 
inducing durable objective responses
 
nonhematologic toxicity
 
oral celecoxib
 
pancreatic ductal adenocarcinoma
 
partial responses
 
promising therapeutic target
 
significant decrease
 
stable disease
 
tumor assessment
 
unacceptable toxicity
 
upper gastrointestinal tract toxicity