In vitro measurement of chemosensitivity of human small cell lung and gastric cancer cell lines toward cell cycle phase-nonspecific agents under the clinically equivalent area under the curve.
BACKGROUND
Based on the previous finding that cell killing effects of cell cycle phase-nonspecific agents depend on the concentration-time product (C x T) or the area under the curve (AUC), the authors investigated in vitro cytotoxic effects of nimustine hydrochloride (ACNU) and mitomycin C (MMC) under an experimental condition in which the assay AUC was equivalent to their clinically achievable AUC.


METHODS
The cytotoxic effects of these agents on human cancer cell lines, consisting of 9 small cell lung carcinomas (SCLC) and 10 gastric cancers, were measured by a tetrazolium-based colorimetric assay (MTT assay).


RESULTS
These cell lines individually responded to ACNU and MMC in this assay condition. When the authors considered 60% or greater cell kill to be effective, the in vitro response rates of SCLC to ACNU and MMC were 22% (two of nine carcinomas) and 67% (six of nine carcinomas), respectively. The response rates of gastric cancer to ACNU and MMC were 10% (1 of 10 carcinomas) and 40% (4 of 10 carcinomas), respectively. Except for the response of SCLC to ACNU, these in vitro response rates corresponded well to the clinical rates (SCLC to ACNU and MMC, 47% [14 of 30 carcinomas] and 50% [17 of 34 carcinomas], respectively; gastric cancer to ACNU and MMC, 11% [4 of 37 carcinomas] and 30% [63 of 211 carcinomas], respectively).


CONCLUSIONS
These results suggest that the introduction of the clinically equivalent AUC to the in vitro chemosensitivity test for cell cycle phase-nonspecific agents may improve its clinical predictability.
Mitsuhashi
Y
Y
Bioscience Research Laboratories, Sankyo Co. Ltd., Tokyo, Japan.
Inaba
M
M
Sugiyama
Y
Y
Kobayashi
T
T
D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008937:Mitomycins / Q000494:pharmacology; D015376:Nimustine / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D008937:Mitomycins; D015376:Nimustine