1. ¹Department of Oncology and Hematology, Division of Medical Oncology, University of Modena and Reggio Emilia, Via del Pozzo71, Modena 41100, Modena, Italy
2. ²Division of Pharmacology and Chemotherapy, University Hospital, Pisa, Italy
3. ³Division of Medical Oncology, University Hospital, Pisa, Italy
4. ⁴Division of Surgery, University Hospital, Pisa, Italy

Correspondence: Dr C Bengala, E-mail: bengala.carmelo@policlinico.mo.it

Received 21 April 2005; Accepted 23 May 2005; Published online 28 June 2005.

Abstract

This study aimed to define the maximum-tolerated dose (MTD) of fixed dose rate (FDR) of gemcitabine (2'-2'-difluorodeoxycitidine) infusion with circulating haemopoietic progenitor support and to evaluate the activity of the treatment. Secondary end points were pharmacokinetic of gemcitabine and difluorodeoxyuridina (dFdU) measured at first course and the activity andexpression profile of cytidine deaminase (CdA) on circulating mononuclear cells. Patients with advanced pancreatic carcinoma received escalating dose of gemcitabine 10 mg m^-2 min^-1 every 2 weeks with circulating haemopoietic progenitor support. First dose level was 3000 mg m^-2 and the doses were increased by 500 mg m^-2 until MTD. In all, 23 patients were enrolled. Toxicities were mild or moderate; the only patient treated at 7000 mg m^-2 died because of toxicity; therefore; the MTD was established at 6500 mg m^-2. The overall response rate was 22.2%. The AUC of gemcitabine showed a dose-dependent increase, while the AUC of dFdU reached a plateau at 4500 mg m^-2. A significant relationship was found between the AUC of dFdU and CdA expression and activity (P<0.05). Moreover, progression rate and survival were significantly related to CdA expression and activity levels. The activity of high-dose gemcitabine is not superior to that reported with less intensive FDR schedules. The predictive role of CdA expression and activity on outcome deserves further investigation.