Anaplastic thyroid carcinoma (ATC) has a rapidly fatal course in the mostly elderly patients with a median survival after diagnosis of 4-12 months. Activity of commonly used
chemotherapy (
doxorubicin) is low, thus more active compounds need to be introduced into the therapeutic concept of ATC. Recently, based on preclinical data Ain et al. conducted a clinical phase II study with
paclitaxel 96 h infusion in ATC achieving a promising response rate of 53%. To further improve therapeutic options in ATC, we evaluated the activity of
topotecan,
oxaliplatin,
vinorelbine,
gemcitabine and
paclitaxel in comparision to
cisplatin and
doxorubicin (1 and 96 h drug exposure) alone or in combination in the ATC cell lines SW1736 and 8505C. IC50 values were determined by the
sulforhodamine B assay, potential clinical activity was estimated by relative antitumor activity (RAA) and drug interaction was analyzed using a parametric response surface approach (Greco model) of the Loewe additivity. Duration of drug effect was estimated by regrowth kinetics. We found
paclitaxel,
vinorelbine and
gemcitabine active in ATC with RAA (1 h drug exposure) ranging from 86 to 454, 15 to 17 and 31 to 140, respectively. The activity of
doxorubicin and
cisplatin was moderate with RAA ranging from 1.4 to 2.2 and 0.2 to 0.3, respectively. Combined drug exposure of
gemcitabine/
paclitaxel and
gemcitabine/
vinorelbine was synergistic with a Loewe index > 0. However, these results did not reach statistical significance with p > 0.05. At clinically relevant drug concentrations
paclitaxel,
gemcitabine and
vinorelbine but not
oxaliplatin exerted a sustained growth inhibition after cessation of drug exposure for the complete assay time of 15 days. In conclusion,
paclitaxel,
gemcitabine and
vinorelbine but not
topotecan or
oxaliplatin appeared to be active in
anaplastic thyroid carcinoma based on RAA or growth delay at clinically relevant drug concentrations. Combinations of
vinorelbine/
gemcitabine and
paclitaxel/
gemcitabine exerted a trend to synergy. Thus, further evaluation of
paclitaxel,
vinorelbine and
gemcitabine alone or in combination with ATC seems warranted.