Pharmacokinetics of gemcitabine combined with trastuzumab in patients with advanced breast cancer.

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/m(2) 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 microg/ml (t(max) = 24 min) in the MONO and 24.6 microg/ml (t(max) = 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 microg/ml (MONO) or 30.4 microg/ml (TMAB), respectively.
Conclusion: The results gave evidence that TMAB does not affect the disposition of gemcitabine.