Kim, Seok-Mo1; Kim, Soo Young1; Park, Ki-Cheong; ; Kim, Bup-Woo1; Lee, Yong Sang1; Chang, Hang-Seok1; Park, Cheong Soo1
1 Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
Background: In the past 10 years, several tyrosine-kinase inhibitor have been tested for the treatment of progressive thyroid cancer. At present, two different TKIs (Lenvatinib and Sorafenib) were recently approved by both US FDA and European Medicine Agency. Until now, the duration of TKI response is not durable and resistance will arrive sooner or later. The goal of this study was to investigate the effect of a new treatment regimen, where a switching interval treatment between levantinib and sorafenib is given.
Methods: Three progressive thyroid cancer cell lines (Sorafenib resistant cell line, aggressive PTC cell line, cell lines from a patient with 10 times recurrence) were exposed to Sorafenib and then switched to Lenvatinib in a 5 days interval. This treatment was repeated twice. Cell viability was determined by MTT assay.
Results: In Sorafenib resistant cell line, Lenvatinib treatment, given after Sorafenib treatment, was effective in controlling tumor growth. A repeated treatment with Lenvatinib after an interval of Sorafenib treatment, efficacy was observed second time. In refractory cell lines compared to control cell lines, Sorafenib could inhibit cell growth, and switching to Lenvatinib showed bigger treatment effect. Repeating Sorafenib treatment, a slower cell growth than in control cell lines was observed. Another switching to Lenvatinib interaval treatment showed that cells were still affected by Lenvatinib treatment.
Conclusions: A switching interval therapy of both Lenvatinib and Sorafenib may have an effect in progressive thyroid cancer, which enables to escape resistance mechanism in tyrosine kinase pathway.