Clinical trial and pharmacokinetic study of combination paclitaxel and carboplatin in patients with epithelial ovarian cancer.
OBJECTIVE
To determine the recommended dose of paclitaxel in chemotherapy used in combination with carboplatin, and to examine the pharmacokinetic parameters of paclitaxel and carboplatin in Japanese patients with epithelial ovarian cancer.


METHODS
The study group comprised 18 patients (median age 53 years, range 30-67 years) who received a total of 28 courses of first-line chemotherapy. The paclitaxel levels were set at 150 mg/m(2) ( n=5), 175 mg/m(2) ( n=6) and 200 mg/m(2) ( n=7), with the fixed dose of carboplatin at AUC 5. The plasma concentrations of paclitaxel in 28 courses and platinum in 23 courses were measured to determine the in vivo pharmacokinetics parameters.


RESULTS
The nadir of neutrophils in the paclitaxel 200 mg/m(2) group was significantly lower ( P<0.05) than in the 150 and 175 mg/m(2) groups. Of seven patients in the paclitaxel 200 mg/m(2) group, one had grade 3 myalgia, another grade 3 neuropathy, and two grade 4 neutropenia. Paclitaxel AUC and the peak level tended to be dose-dependent, clearly indicating a two-phase disappearance. Further, the paclitaxel dosage and paclitaxel AUC were also dose-dependent. Using a limited sampling protocol for carboplatin, the carboplatin AUC was found to change little in relation to the paclitaxel dosage.


CONCLUSIONS
Based on the results of this clinical trial and pharmacokinetic study, 175 mg/m(2) of paclitaxel as a 3-h infusion in combination with carboplatin AUC 5 can be considered as the recommended dose for Japanese ovarian cancer patients.
Yamamoto
Ritsu
R
Department of Obstetrics and Gynecology, Hokkaido University School of Medicine, Kita-15, Nishi-7, Kita-Ku, Sapporo, 060-8638, Japan. rityam@med.hokudai.ac.jp
Kaneuchi
Masanori
M
Nishiya
Masashi
M
Todo
Yukiharu
Y
Takeda
Mahito
M
Okamoto
Kazuhira
K
Negishi
Hiroaki
H
Sakuragi
Noriaki
N
Fujimoto
Seiichiro
S
Hirano
Takeshi
T
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002277:Carcinoma / Q000188:drug therapy* / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007970:Leukopenia / Q000139:chemically induced; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000601:surgery; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D016190:Carboplatin; D017239:Paclitaxel