In vitro evaluation of dose-response curve for paclitaxel in breast cancer.
BACKGROUND
The dose-response curve for anticancer agents cannot be evaluated by studying patients directly. To investigate individual differences in the dose-response curve for paclitaxel in breast cancer, we utilized the histoculture drug response assay (HDRA) technique.


METHODS
Twenty specimens obtained from breast cancer patients who underwent surgical resection were used in this study. The inhibition rates of paclitaxel at several concentrations were measured and fitted to a sigmoid dose-response curve, using non-linear least squares analysis with the fitting equation y=A(1-1/(1+exp(B(x-log(C))))), where A denotes maximal response; B, slope factor; and C, ED50.


RESULTS
A dose-response curve was obtained in all tumors. The mean value (+/-SD) of maximum response, slope factor, and ED50 were 90.2+/-5.5%, 9.4+/-4.3, and 36.8+/-17.2 microg/ml, respectively. The slope factor was higher in nuclear grade 3 tumors compared with nuclear grade 1 and 2 tumors.


CONCLUSIONS
An individual dose-response curve for paclitaxel in breast cancer can be obtained using the HDRA technique. Nuclear grade 3 tumors appeared to have more uniform chemosensitivity to paclitaxel compared with nuclear grade 1 and 2 tumors.
Yoshimasu
Tatsuya
T
Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, 641-8509, Japan. yositatu@wakayama-med.ac.jp
Oura
Shoji
S
Hirai
Issei
I
Tamaki
Takeshi
T
Kokawa
Yozo
Y
Ota
Fuminori
F
Nakamura
Rie
R
Shimizu
Yukio
Y
Kawago
Mitsumasa
M
Hirai
Yoshimitsu
Y
Naito
Koma
K
Kiyoi
Megumi
M
Tanino
Hirokazu
H
Okamura
Yoshitaka
Y
Furukawa
Tomoko
T
D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary / Q000601:surgery; D002288:Adenocarcinoma, Mucinous / Q000188:drug therapy / Q000556:secondary / Q000601:surgery; D002293:Adenocarcinoma, Scirrhous / Q000188:drug therapy / Q000556:secondary / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D017239:Paclitaxel / Q000008:administration & dosage*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel