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

Abstract

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. IC(50) values were calculated from dose-response relationships using cell counts and a formazan dye assay (WST-1). IC(50) 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 micro mol/liter for paclitaxel, these promising in vitro results provide a basis for the performance of clinical trials in patients with advanced MTC.

Medullary Thyroid Cancer: Molecular Biology and Novel Molecular Therapies

“…However, there are no further studies available regarding this treatment regimen. In a human MTC cell line study, camptothecin and paclitaxel were evaluated [145]. Although promising results were provided, these drugs have not so far been used in patients with MTC.…”

Oxaliplatin (Eloxatin™) Plus Irinotecan Combination Chemotherapy Found Effective in Refractory Metastatic Insular Thyroid Carcinoma

“…Oxaliplatin, which is a 1,2 diaminocyclohexane platinum compound, and irinotecan (CPT-11), which is a topoisomerase I inhibitor, are two new cytotoxic compounds with dissimilar mechanisms of action, overlapping antitumour activity and in vitro synergy (21,22). They have been found active in the treatment of advanced colorectal cancer and are being tested in a number of solid tumors especially while irinotecan has shown activity against human medullary thyroid carcinoma cell lines (23)(24)(25). We decided to treat this young woman with oxaliplatin plus irinotecan combination, considering the favorable characteristics of this regimen, which include low hematologic toxicity, synergy and convenience of administration.…”

The Role of Cell Lines in the Study of Neuroendocrine Tumors

“…In order to try to evaluate the possible effect of different chemotherapeutic agents on MTC in vitro, eight continuous human MTC cell lines representing different local tumor stages, growth dynamics, immunocytochemical characteristics, ages of patients, and sporadic or hereditary forms have been established from 7 patients with MTC [111]. The cells have been found to be sensitive to the cytotoxic/cytostatic effects of camptothecin and paclitaxel and resistant to dacarbazine.…”