Pharmacologic study of 3-hour 135 mg M-2 paclitaxel in platinum pretreated patients with advanced ovarian cancer.
Paclitaxel (Taxol(R)) is an active agent in platinum-refractory ovarian cancer. Since the available pharmacokinetic data of 135 mg m-2 paclitaxel administered by 3-h infusion are scarce and fragmented, we now describe a comprehensive pharmacologic study in a group of 13 patients who were pretreated with platinum for advanced ovarian cancer. The mean paclitaxel AUC was 10.3+/-2.4 h micromol l-1 (range 6.8-13.9 h micromol l-1). Quantification of the two major paclitaxel metabolites, 6alpha-hydroxypaclitaxel and 3'-p-hydroxypaclitaxel yielded AUCs of 0.44+/-0.30 h micromol l-1 and 0.31+/-0.20 h micromol l-1, respectively. The AUC of 3'-p-hydroxypaclitaxel was significantly different from that of patients with an altered hepatic function. The administration of 135 mg m-2 single-paclitaxel was safe, and the toxicities observed at higher doses in earlier studies were absent in this study. This is important, because the schedule and paclitaxel dose of 135 mg m-2 given by a 3-h infusion is expected to be used more frequently in combination with other cytotoxic agents with the aim of improving efficacy.
Department of Medical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan, The Netherlands.
V R
VR
Panday
M T
MT
Huizing
L J
LJ
van Warmerdam
R C
RC
Dubbelman
I
I
Mandjes
J H
JH
Schellens
W W
WW
Huinink
J H
JH
Beijnen
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
D000972:Antineoplastic Agents, Phytogenic; D009944:Organoplatinum Compounds; D017239:Paclitaxel