Revisiting the Role of Chemotherapy in Advanced Medullary Thyroid Carcinoma: A Case Report and Review of the Literature

BACKGROUND: Chemotherapy has been always considered scarcely or completely ineffective in the treatment of metastatic and progressive MTC. CASE REPORT: We report the case of a 45-year-old man who underwent total thyroidectomy and lymphadenectomy in May 2023 for bilateral MTC with extrathyroidal extension and 2/23 metastatic lymph nodes. Germline and somatic RET genetic analysis were negative. From July 2023 to February 2024 tumour markers progressively increased and a 18F-DOPA PET/CT revealed metastases in the cervical region and mediastinal inlet. Therefore, cabozantinib was started, obtaining a partial response, but after 1 year of treatment disease progression at the cervicomediastinal level was documented, despite dosage increase. Thus, an off-label treatment with lenvatinib was started, achieving a transient stabilization. In October 2025, a further disease progression was diagnosed. The patient started off-label chemotherapy consisting of 5-fluorouracil (5-FU) 400 mg/m2 intravenous (IV) bolus, followed by 5-FU 2400 mg/m2 as a 48-hour infusion, combined with dacarbazine 800 mg/m2 IV in 30 minutes, every 14 days for the first month and then every 21 days for the following months. Chemotherapy was very well tolerated. At the last visit, after 17 cycles, tumour markers returned to the normal range (CA 19-9 22.9 kU/L, CEA 2.5 μg/L) and PET/CT scanning showed a complete response. CONCLUSION: In conclusion, this case shows that, although treatment with multikinase inhibitors is actually the first choice for advanced RET-wild-type MTC, conventional chemotherapy can be effective at least in some patients and should always be considered, especially in case of failure of other approaches.