DIFFERENTIAL ACTIVITY OF CREMOPHOR EL AND PACLITAXEL IN PATIENTS TUMOR-CELLS AND HUMAN CARCINOMA CELL-LINES IN-VITRO

BACKGROUND. Previous studies indicate that Cremophor EL (CEL), the exc ipient for Taxol, a clinical preparation of paclitaxel, has biologic p roperties per se. METHODS. The cytotoxic activity of Taxol and its sol vents CEL/ethanol, paclitaxel in ethanol, and 14 other cytotoxic drugs was investigated in vitro in 10 human carcinoma cell lines and 183 tu mor samples from patients with tumors of various types. Cytotoxicity w as determined by the fluorometric microculture cytotoxicity assay. RES ULTS. In the cell lines, Taxol was generally more active than paclitax el; this may have been due to an additive effect of the diluent. This activity was pronounced in sublines expressing tubulin-associated and P-glycoprotein-mediated drug resistance, indicating involvement of the se mechanisms in paclitaxel resistance and their modulation by CEL. Ta xol and paclitaxel were highly cross-resistant to other tubulin-active agents, whereas the low cytotoxic effect of CEL seemed unrelated to o ther drugs. In the samples from patients, Taxol was less active than i n the cell lines but showed a differential activity that corresponded reasonably well with that in the clinic. CEL and Taxol were similarly active, indicating that paclitaxel did not add substantially to the ac tivity of Taxol. CONCLUSIONS, Whereas the cell line data clearly confi rmed the well-known properties of paclitaxel, a more valid model using tumor cells from patients demonstrated that CEL significantly contrib utes to the efficacy of Taxol in vitro. The clinical relevance of this finding remains to be elucidated. (C) 1997 American Cancer Society.