A phase II trial of raltitrexed (Tomudex®) in advanced pancreatic and biliary carcinoma

Purpose: To evaluate the impact of raltitrexed (Tomudex(R)) on the quality of life in a multicenter, phase 11 study in advanced pancreatic and biliary carcinomas. Patients and Methods: Forty-six patients with advanced, histologically proven pancreatic (n = 37, 80.4%) or biliary (n = 9, 19.6%) carcinoma received 3 mg/m(2) raltitrexed intravenously once every 3 weeks. For the quality of life assessments, EORTC QLQ-C30 was used, and the evaluation of the clinical benefit was performed according to the 4 criteria of the clinical benefit response. All patients were assessed for safety, and 41 patients were evaluable for objective response. Results: Patients (63% male/37% female) had a mean age of 61.2 years, 71.7% had a PS of 0-1, 78.3% had metastatic disease, and 63% had at least 2 tumoral sites. A total of 176 cycles were administered with a mean of 4 cycles per patient (range 1-12). Three out of 43 patients evaluable for EORTC QLQ-C30 (7.0%; Cl-95% 1.4-19.0%) had a quality of life improvement. Thirty-two patients fulfilled the 4 criteria required to evaluate the clinical benefit response; 5 were responders (15.6%; Cl-95% 5.3-32.8%); 1 patient was a good responder based on both the EORTC questionnaire and the clinical benefit response. Forty-one patients were assessable for response, 3 responded to treatment (response rate: 6.5%; Cl-95% 1.3-17.9%). Median survival was 4.6 months (Cl-95% 2.9-8.2 months), the 1-year survival rate was 21.8%. The most common grade 3-4 toxicities were neutropenia (8%), leukopenia (8%), thrombopenia (6%), anemia (6%), liver enzyme elevations (11%), asthenia (9%), vomiting (9%), abdominal pain (7%), and phlebitis (6%). One treatment-related death occurred (neutropenic sepsis). Conclusion: Raltitrexed appeared to be generally well tolerated and showed a clinical benefit response and/or quality of life improvement in a limited number of patients. Copyright (C) 2005 S. Karger AG, Basel.