Novel Chemotherapeutic Combination in MTC Exhibits Promising Results

A combination of 2 chemotherapeutic drugs, cisplatin and sorafenib, could perform better than monotherapy in patients with medullary thyroid carcinoma (MTC), especially those with metastasis, according to a study recently published in Biomedicines.

“In this study, we aimed to investigate whether aggressive MTC can be suppressed via the induction of cytochrome c-mediated apoptosis in response to the combinational anticancer treatment of cisplatin and sorafenib at a low dose compared to each agent administered alone,” the authors wrote.

This experimental, retrospective research used 3 patient-derived MTC cell lines: YUMC-M1, -M2, and -M3. YUMC-M1 was obtained from a 24-year-old woman with stage II MTC who underwent total thyroidectomy with central compartment dissection and bilateral modified lateral neck dissection. She remained without recurrence or metastasis at the 71-month follow-up.

YUMC-M2 was from a 19-year-old woman with stage IVa MTC and a RET gene mutation who underwent a total thyroidectomy, modified radical neck dissection, and left adrenalectomy due to pheochromocytoma. At her 76-month follow-up, she had no metastasis, although serum calcitonin levels did not normalize.

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Finally, YUMC-M3 was obtained from a 57-year-old man with stage IVa MTC and metastasis to the lung and lymph nodes; despite undergoing total thyroidectomy, bilateral modified radical neck dissection, mediastinal dissection, and lymph node dissection, the metastasis progressed. Treatment was then initiated with vandetanib.

The researchers assessed the behavior of each cell line after the administration of cisplatin and sorafenib, alone and together. The combination of both drugs achieved a lower half-maximal inhibitory concentration (IC50) than each drug separately in all 3 cell lines.

Cisplatin monotherapy had an IC50 of 9.08, 8.64, and 10.11 in YUMC-M1, -M2, and -M3, respectively. Sorafenib alone showcased an IC50 of 7.82, 7.04, and 10.28 in YUMC-M1, -M2, and -M3, respectively. Lastly, the combination of both agents attained an IC50 of 5.54, 4.87, and 6.11 in YUMC-M1, -M2, and -M3, respectively.

These results may support this novel chemotherapeutic regimen for the treatment of patients with MTC, especially those with metastatic disease, in whom the current 10-year survival is about 20%.

“In these research findings, the combinational anticancer consequences of the cisplatin and sorafenib were more capable at low doses of each agent alone against patient-derived metastatic MTC,” the study authors concluded.

Reference

Yun HJ, Lim JH, Kim SY, Kim SM, Park KC. Discovery of pharmaceutical composition for prevention and treatment in patient-derived metastatic medullary thyroid carcinoma model. Biomedicines. 2022;10(8):1901. doi:10.3390/biomedicines10081901