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Cytotoxic Activity of Camptothecin and Paclitaxel in Newly Established Continuous Human Medullary Thyroid Carcinoma Cell Lines

Section of Endocrine Surgery (K.K., M.S., C.S., C.P., G.P., B.N.), Division of Experimental Surgery (G.H.), Department of Surgery, Division of General Surgery, and Department of Internal Medicine I/Oncology (M.R.), and Section of Clinical Biometrics (M.M.), Department of Medical Computer Sciences, University of Vienna Medical School, A-1090 Vienna, Austria; Children’s Cancer Research Institute (A.W.), St. Anna Children’s Hospital, A-1090 Vienna, Austria; and Department of Pathophysiology (V.S., R.P.), University of Graz Medical School, A-8010 Graz, Austria

Address all correspondence and requests for reprints to: Klaus Kaczirek, M.D., Section of Endocrine Surgery, Department of Surgery, Division of General Surgery, University of Vienna, Medical School, Währinger Gürtel 18-20, A-1090 Vienna, Austria. E-mail: klaus.kaczirek{at}akh-wien.ac.at.

At the time of diagnosis, more than one quarter of patients with medullary thyroid carcinoma (MTC) has distant metastases. Only few of these patients can be cured by surgery. Standard chemotherapy is characterized by low response rates and short response time. The establishment of eight human MTC cell lines provides a new basis for in vitro investigation of cytotoxic drugs. Camptothecin (CPT) and paclitaxel, which never have been investigated in the treatment of MTC, were tested for their cytotoxic profile in comparison with the clinically ineffective dacarbazine.

Eight MTC cell lines were established from seven patients with MTC. IC₅₀ values were calculated from dose-response relationships using cell counts and a formazan dye assay (WST-1).

IC₅₀ values were 3.5 ± 1.2 nmol/liter for CPT and 8.2 ± 1.9 nmol/liter for paclitaxel. Dacarbazine showed no reduction of cell proliferation at concentrations 10-fold higher than clinically achievable.

Given peak plasma concentrations of 65 ± 20 nmol/liter for CPT and 1 µmol/liter for paclitaxel, these promising in vitro results provide a basis for the performance of clinical trials in patients with advanced MTC.

This work was supported by the Hochschul Jubiläumsfond H-144/2001 of the University of Vienna.

Abbreviations: CPT, Camptothecin; DTIC, dacarbazine; 5-FU, 5-fluorouracil; MTC, medullary thyroid carcinoma.

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