Plasma and tissue pharmacokinetics of epirubicin and Paclitaxel in patients receiving neoadjuvant chemotherapy for locally advanced primary breast cancer.
The objective of the study was to assess individual distribution of antineoplastic drugs into the tumor. Twelve advanced-stage primary breast cancer patients with neoadjuvant epirubicin+paclitaxel chemotherapy were studied. Plasma concentrations of epirubicin and paclitaxel were monitored for 24 h. Epirubicin concentrations in subcutaneous and tumor tissues were measured using microdialysis up to 12 h postdose. Epirubicin concentrations were described by a compartmental population pharmacokinetic model (NONMEM). Noncompartmental analysis was used for paclitaxel. Plasma pharmacokinetics corresponded to published data. Mean epirubicin exposure in the tumor and in subcutaneous tissue was very similar, but tissue Cmax and area under the curve values reached only (means) 1% and 11%, respectively, of plasma values. Epirubicin doses were significantly correlated to tumor exposure irrespective of body surface area. There is no specific barrier for epirubicin to reach primary breast cancer tumors.
Hunz
M
M
Department of Pharmacology, Clinical Pharmacology, University of Cologne, Cologne, Germany.
Jetter
A
A
Warm
M
M
Pantke
E
E
Tuscher
M
M
Hempel
G
G
Jaehde
U
U
Untch
M
M
Kurbacher
C
C
Fuhr
U
U
D000273:Adipose Tissue / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015251:Epirubicin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D017551:Microdialysis; D017239:Paclitaxel / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D015251:Epirubicin; D017239:Paclitaxel