© 2006 European Society for Medical Oncology
symposium article |
Pharmacokinetic evaluation of gemcitabine and 2',2'-difluorodeoxycytidine-5'-triphosphate after prolonged infusion in patients affected by different solid tumors
1 Department of Science and Drug Technology, University of Turin; 2 Medical Oncology Dept., S. Giovanni A.S. Hospital, Turin, Italy
* Correspondence to: Department of Science and Drug Technology, University of Turin, Corso Raffaello 31, 10125 Turin, Italy. E-mail: luigi.cattel{at}unito.it
Background: The study determined pharmacokinetic parameters, toxicity profile and preliminary clinical activity of gemcitabine administered i.v. at different infusion rates in patients with a range of solid tumors.
Patients and methods: Twenty patients were enrolled for both pharmacokinetic and clinical studies. Gemcitabine 300 mg/m2 was administered during 1 h, 2 h or 3 h, and as a conventional dose of 1000 mg/m2 during 30 min infusion. Administration was on days 1, 8 and 15 every 4 weeks.
Results: Patients were randomly assigned to one of the four arms. After 30 min infusion of 1000 mg/m2 gemcitabine the plasma concentration remained above the saturation level of 10–20 µM, whereas after 1, 2 or 3 h infusion 300 mg/m2 gemcitabine it remained below the saturation level for most of the time (being in the range 2.5–10 µM). Gemcitabine triphosphate was determined in the four arms in white blood cells; for infusion times from 0.5 to 3 h there was a progressive enhancement of gemcitabine triphosphate levels. In all evaluable patients the toxicity was mild, myelosuppression being the main toxicity. No grade 3 or 4 toxicities occurred. Clinical response was similar in patients receiving 300 mg/m2 gemcitabine in 2 and 3 h and in the 1000 mg/m2 arm.
Conclusions: 300 mg/m2 gemcitabine during 3 h infusion produced the highest accumulation of gemcitabine triphosphate. Thus, to achieve the highest possible gemcitabine triphosphate level, prolonged infusion time would appear to be more important than a high dose administered as a short infusion. However, there was no substantial difference in toxicity or antitumoral activity in the all different patient groups.
Key words: gemcitabine, gemcitabine prolonged infusion, gemcitabine triphosphate, pharmacokinetics
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