Gemcitabine (Gem) plus celecoxib in advanced pancreatic carcinoma: a phase II study

Abstract

4103 Background: GEM is the most active single agent in the treatment of pancreatic carcinoma. Celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor. Recent studies in human pancreatic tumor cell lines suggest an involvement of COX-2 in the control of tumor-dependent angiogenesis and provide the rational for inhibition of the COX pathway as an effective therapeutic approach for pancreatic cancer. The aim of this study is to evaluate the toxicity, safety and efficacy of this combination regimen. Methods: From January 2001 to July 2002, 32 consecutive patients (18 male/14 female) entered the trial. Median age was 63 years (range 48–76), median PS 1 (range 0–2); 22 patients (pts) were metastatic, 10 pts had locally advanced disease. Median basal CA19.9 value was 747 U/mL (range 1–50000). A total number of 210 cycles (median 6,5 per patient; range 2–12) were administered. The schedule consisted of GEM 1000 mg/m2 (as a 30 minutes iv infusion) on days 1,8 every 3 weeks and Celecoxib 400 mg bid. Results: Grade 3 NCI-CTC haematological toxicity was neutropenia in 9% of pts. Neither grade 4 neutropenia nor grade 3–4 thrombocytopenia were observed. Grade 3 non-haematological toxicity was as follows: hepatic toxicity 9%, nausea 3%. Although the high dose of celecoxib, neither gastric toxicity nor renal failure were observed. Only 3 pts (9%) had a minimum creatinine increase. Clinical benefit was obtained in 46% of pts, 38% had no basal pain and 16% didn't achieve any symptom control. Median survival was 9,1 months; 1-year survival rate was 36%. Conclusions: The goals we achieved with celecoxib-GEM combination are very low toxicity, good quality of life and improved overall survival. Accrual is ongoing. No significant financial relationships to disclose.