Docetaxel and gemcitabine activity in NSCLC cell lines and in primary cultures from human lung cancer

The activity of the following drugs was investigated in two established NSC LC cell lines: docetaxel, gemcitabine, vinorelbine, paclitaxel, doxorubicin (0.01, 0.1, 1 mu g ml(-1)), cisplatin, ifosfamide (1, 2, 3 mu g ml(-1)) an d carboplatin (2, 4, 6 mu g ml(-1)). The cytotoxic activity was evaluated b y the sulphorhodamine B assay. The two most active drugs, docetaxel and gem citabine, used singly and in association, were investigated as a function o f treatment schedule. The sequence docetaxel-->gemcitabine produced only a weak synergistic interaction in RAL but a strong synergism in CAEP cells. T he synergistic interaction increased in both cell lines after a 48-h washou t between the drug administrations. Flow cytometric analysis showed that in docetaxel-->gemcitabine sequence, docetaxel produced a block in G2/M phase and, after 48 h, provided gemcitabine with a large fraction of recovered s ynchronized cells in the G1/S boundary, which is the specific target phase for gemcitabine. Conversely, simultaneous treatment induced an antagonistic effect in both cell lines, and the sequential scheme gemcitabine-->docetax el produced a weak synergistic effect only in RAL cells. Moreover, the syne rgistic interaction disappeared when washout periods of 24 or 48 h between two drug administrations were adopted. The synergistic activity of docetaxe l--> 48-h washout-->gemcitabine was confirmed in 11 of 14 primary cultures, which represents an important means of validating experimental results bef ore translating them into clinical practice. (C) 1999 Cancer Research Campa ign.