A Phase I Trial of A Combination of Cisplatin and Carboplatin in Advanced Non-Small Cell Lung Cancer. An Intensification of Platinum Dose by A Combination of Two Platinum Cmpounds.

The log/log relationship between the IC50 of cisplatin or carboplatin and the exposure time, determined by human tumor clonogenic assay (HTCA) and MTTAI (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay with additional incubation) using PC-14 cells, exhibited a straight line with a slope of -1, indicating that both drugs have AUC-dependent cytotoxicity (AUC, area under the c/t curve). The combined effect of cisplatin and carboplatin was estimated by the median-effect analysis using HTCA, and it was additive when the AUC ratio (AUC of free platinum from carboplatin/that from cisplatin) was low (3.2, 6.5 or 13.1 in each of PC-7, PC-9, PC-14, H-69, and K562). However, it was significantly worse at a higher AUC ratio (19.5 in PC-7, PC-9, and PC-14). The log/log relationship of each drug, determined by MTTAI using human bone marrow cells, showed that each drug exerts an AUC-dependent cytotoxicity on marrow granulocytes. When cisplatin and carboplatin were combined at an AUC ratio of 14, the therapeutic index was significantly better than that of carboplatin alone and less than that of cisplatin alone using K562, PC-9 and PC-14, indicating the usefulness of this combined therapy for tumor cells with high sensitivity to platinum compounds at this AUC ratio.

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In vitro investigation of a combination of two drugs, cisplatin and carboplatin, as a function of the area under thec/t curve

Kobayashi

Kudoh

Takemoto

et al. 1995

J Cancer Res Clin Oncol

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A Phase I Trial of A Combination of Cisplatin and Carboplatin in Advanced Non-Small Cell Lung Cancer. An Intensification of Platinum Dose by A Combination of Two Platinum Cmpounds.

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In vitro investigation of a combination of two drugs, cisplatin and carboplatin, as a function of the area under thec/t curve

In vitro investigation of a combination of two drugs, cisplatin and carboplatin, as a function of the area under thec/t curve

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