Gemcitabine treatment enhances the activity of deoxycytidine kinase in periferial lymphocytes of patients with pancreatic cancer

Introduction: Gemcitabine (2', 2'-difluorodeoxycytidine, dFdC) has shown significant preclinical and clinical activity against several human solid tumors, including pancreatic cancer. Deoxycytidine kinase (dCK) is the key enzyme in the bioactivation of gemcitabine. In the present work the activity of dCK prior to and following gemcitabine treatment in patients with advanced pancreatic cancer has been evaluated. Methods: 11 patients with verified pancreatic cancer were treated with gemcitabine (1000mg/m2 in 30 minutes) plus 5-fluorouracil (600mg/m2 in 120 minutes) modulated with folinic acid, once a week throughout 7 weeks. PBMC were isolated prior to the first cycle of gemcitabine administration and 1.5 and 20 hours later, respectively. The sampling procedure was repeated 8–9. dCK enzyme activity was determined from the crude extracts of mononuclear cells. Results: The basal mean dCK activity of the PMBC of 11 patients was 20.5 pmol/min/mg protein [100%]. Enzyme activity was increased to 31.3 pmol/min/mg protein [153%] 1.5 hours after the end of gemcitabine infusion and it was still elevated 20 hours following drug administration (23.7 pmol/min/mg protein, [115%]). At weeks 8–9 of chemotherapy, the mean elevation in dCK activity measured after 1,5 hours was only 33%. Conclusions: Gemcitabine treatment led to a marked upregulation of dCK activity in the mononuclear cells of patients suffering from advanced pancreatic cancer. This effect might reflect the enhanced sensitivity of the cancer cells towards gemcitabine chemotherapy.