The tyrosine kinase inhibitor imatinib fails to inhibit pancreatic cancer progression

Imatimb targets KIT and platelet-derived growth factor receptors (PDGFR) and is highly effective in the treatment of CML and GIST patients. Pancreatic cancers express KIT and PDGFRs. Therefore, 26 patients with unresectable pancreatic cancer were randomized to either gemcitabine (1000 mg/m 2 weekly) or imatimb (2 X 400 mg po) treatment daily. Pancreatic adenocarcinoma was confirmed histologically and expression of KIT and PDGFR beta was determined immunohistochemically in the biopsy specimens. Quality of life was assessed with two standard questionnaires. No objective responses were seen in either group. Median time to progression was 77 and 29 days (P = 0.411) and median survival time was 140 and 60 days (P = 0.517) for gemcitabine and imatinib, respectively. Survival and treatment responses were independent of KIT and PDGFR beta expression in patients treated with imatimb. Grade 3/4 toxicities of imatinib treatment were anemia, elevated liver enzymes, vomiting, and dyspnea. Patients treated with imatinib reported diarrhoea and/or altered bowel function more frequently, which were treatable symptomatically. Quality of life was similar in both groups. In this small series of pancreatic cancer patients, treatment with imatimb was not associated with a significant control of cancer progression. (c) 2005 Elsevier Ireland Ltd. All rights reserved.