The tyrosine kinase inhibitor imatinib fails to inhibit pancreatic cancer progression.
Imatinib 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/m2 weekly) or imatinib (2x400 mg po) treatment daily. Pancreatic adenocarcinoma was confirmed histologically and expression of KIT and PDGFRbeta 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 PDGFRbeta expression in patients treated with imatinib. 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 imatinib was not associated with a significant control of cancer progression.
Chen
Jie
J
Department of Gastroenterology, Hepatology, and Infectious Diseases, Otto-von-Guericke University, Leipzigerstr. 44, D-39120 Magdeburg, Germany.
Röcken
Christoph
C
Nitsche
Barbara
B
Hosius
Christian
C
Gschaidmeier
Harald
H
Kahl
Stefan
S
Malfertheiner
Peter
P
Ebert
Matthias P A
MP
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010879:Piperazines / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011743:Pyrimidines / Q000627:therapeutic use*; D011788:Quality of Life; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D011795:Surveys and Questionnaires; D015996:Survival Rate; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D003841:Deoxycytidine; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit; D017479:Receptors, Platelet-Derived Growth Factor; D000093542:Gemcitabine