Original Article · Originalarbeit

Pharmacokinetics of Gemcitabine Combined with Trastuzumab in Patients with Advanced Breast Cancer
M. Czejka^a,c; E. Ostermann^b; L. Muric^a; D. Heinz^a; J. Schueller^b,c

^aDepartment für Klinische Pharmazie und Diagnostik der Universität Wien, ^bAbteilung für Innere Medizin und Onkologie, Krankenanstalt Rudolfstiftung, ^cAustrian Society of Applied Pharmacokinetics, Wien, Austria

Onkologie 2005;28:318-322
(DOI: 10.1159/000085596)

  Summary

Background: Combining the monoclonal antibody trastuzumab (TMAB) with chemotherapy is a new strategy in treatment of advanced breast cancer in HER+++ overexpressing patients. Patients and Methods: The disposition of gemcitabine has been investigated in 8 breast cancer patients (prospective cross-over design). Gemcitabine was administered as a 30-min i.v. infusion (1,000 mg/m2 in 250 ml) on day 1 weekly for 3 weeks. On day 2 TMAB was infused with a loading dose of 4 mg/kg (90-min infusion) followed by a weekly maintenance dose of 2 mg/kg (30-min infusion). Pharmacokinetic analysis was performed after the first (= MONO) and after the third gemcitabine infusion (= TMAB). Results: Cmax was 22.2 µg/ml (tmax = 24 min) in the MONO and 24.6 µg/ml (tmax = 23 min) in the TMAB schedule. Gemcitabine distributed rapidly from plasma within a few minutes and was eliminated with a t1/2el of about 80 min in both arms of the study. The metabolite difluorodeoxyuridine (dFdU) appeared in plasma with t1/2appin = 12.8 min (MONO) or t1/2appin = 10.2 min (TMAB) reaching a mean peak concentration of 35.9 µg/ml (MONO) or 30.4 µg/ml (TMAB), respectively. Conclusion: The results gave evidence that TMAB does not affect the disposition of gemcitabine.

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