Optimal doses of paclitaxel and carboplatin combination chemotherapy for ovarian cancer: a phase I modified continual reassessment method study.
BACKGROUND
A multicenter, phase I study of combination therapy with paclitaxel and carboplatin for epithelial ovarian cancer was conducted to determine the safety and recommended dosages for Japanese women.


METHODS
Paclitaxel was administered intravenously over a 3-h period, followed by carboplatin administered intravenously over a 1.5-h period. A modified continual reassessment method (mCRM) was used in two treatment arms to establish the maximum tolerated dose (MTD) and recommended doses of the combination. In group A, the dose of paclitaxel (175 mg/m2) was constant and the dose of carboplatin was increased from 4 to 7 in terms of the target area under the plasma concentration-versus-time curve (AUC). In group B, the dose of carboplatin was constant (AUC 6) and paclitaxel was administered at two dose levels (160 and 175 mg/m2). In both groups, the carboplatin dose was limited to a maximum of 800 mg/body for each administration.


RESULTS
Because the calculated probability of toxicity was greatest at a dose of paclitaxel 175 mg/m2 and carboplatin AUC 7, this dose was designated the MTD in group A. Based on this result, treatment in group B was initiated at doses of paclitaxel of 160 mg/m2 and carboplatin AUC 6. While the dose of paclitaxel was escalated to 175 mg/m2, the safety of the combination was confirmed. The most frequent adverse effect was neutropenia, which resolved promptly with the appropriate use of granulocyte-colony stimulating factor (G-CSF). No other severe hematologic or nonhematologic toxicities were observed.


CONCLUSIONS
Our study demonstrated that the recommended dose for this combination regimen should be paclitaxel 175 mg/m2 plus carboplatin AUC 6 (maximum dose, 800 mg/body).
Kuzuya
K
K
Department of Gynecology, Aichi Cancer Center Hospital, 1-1 Kanoko-den, Chikusa-ku, Nagoya 464-8681, Japan. 105182@acc.pref.aichi.jp
Ishikawa
H
H
Nakanishi
T
T
Kikkawa
F
F
Nawa
A
A
Fujimura
H
H
Iwase
A
A
Arii
Y
Y
Kawai
M
M
Hattori
S
S
Sakakibara
K
K
Sasayama
E
E
Furuhashi
Y
Y
Suzuki
T
T
Mizutani
S
S
D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy*; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage; D018269:Carcinoma, Endometrioid / Q000188:drug therapy*; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D016896:Treatment Outcome
D016179:Granulocyte Colony-Stimulating Factor; D016190:Carboplatin; D017239:Paclitaxel