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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
Author(s) -
Mitsuhashi Yoshihiro,
Lnaba Makoto,
Sugiyama Yuichi,
Kohayashi Tomowo
Publication year - 1992
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19921115)70:10<2540::aid-cncr2820701024>3.0.co;2-2
Subject(s) - medicine , chemosensitivity assay , in vitro , cancer , cell , cell culture , cancer research , cell cycle , cytotoxic t cell , pathology , lung cancer , mitomycin c , large cell , cancer cell , carcinoma , adenocarcinoma , biology , surgery , biochemistry , genetics
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.