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Radiation Therapy Plus TKIs for Medullary Thyroid Cancer: Preclinical Study Findings

By: Sarah Campen, PharmD
Posted: Tuesday, July 21, 2020

Combining irradiation with a tyrosine kinase inhibitor (TKI) appears to be more effective than irradiation alone in the treatment of medullary thyroid cancer in mice models, according to a preclinical trial published in PLOS One. “The animals in the combination therapy groups showed the largest reduction in tumor volume and the longest time to tumor progression,” stated Eva Forssell-Aronsson, PhD, of Sahlgrenska University Hospital, Gothenburg, Sweden, and colleagues.

In this study, mice carrying patient-derived GOT2 medullary thyroid tumors were treated with external-beam radiotherapy and/or one of the two TKIs recently approved for systemic treatment of metastatic medullary thyroid cancer—vandetanib or cabozantinib. The treatment doses were chosen to give a “moderate effect” as monotherapy; this was to detect any increased therapeutic effect from the combination therapy.

An antitumor effect was observed in mice receiving external-beam radiotherapy or TKI monotherapy compared with controls. However, the largest reduction in tumor volume was achieved with combination therapy, with a 70% to 75% reduction within 2 weeks of starting treatment. The slowest regrowth was also seen in the combination-therapy group; after about 20 days, 100% of the mice treated with external-beam radiotherapy monotherapy experienced disease progression, compared with 50% of the mice treated with cabozantinib monotherapy and just 20% of the mice given the combination therapy.

Because overexpression of somatostatin receptors is common in medullary thyroid cancer, the authors suggested patients may also benefit from treatment with radiolabeled somatostatin analogs, such as Lu-177 octreotate or Y-90 octreotide. “It is likely this increased effect would also be achieved if Lu-177 octreotate treatment, instead of external-beam radiotherapy, is used in combination with TKIs,” they concluded.

Disclosure: The study authors reported no conflicts of interest.

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