Capecitabine therapy for refractory metastatic thyroid carcinoma: A case series

Objective: There are few effective therapies for metastatic medullary (MTC) or radioiodine-resistant follicular thyroid carcinomas (FTC). We report a single institution's experience with capecitabine, a thymidylate synthase (TS) inhibitor, in the treatment of MTC and FTC. Design: We retrospectively analyzed five cases of metastatic thyroid carcinoma, three MTCs and two radioiodine-resistant FTCs, treated with capecitabine alone or in combination with other chemotherapeutics. Patients were selected for treatment based on low tumor TS immunohistochemical staining (<= 5%). Staining for thymidylate phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) was also performed. Therapeutic response was assessed by imaging studies and serum tumor markers: calcitonin and carcinoembryonic antigen (MTC), and thyroglobulin (FTC). Main outcome: Two of three patients with MTC had stable disease or disease regression on capecitabine. One of these patients had a 90% reduction in calcitonin and stabilization by imaging that lasted 4 years. Both patients with FTC initially had stable disease on capecitabine. One patient, who was treated with capecitabine in combination first with doxorubicin and then etoposide, had an initial decrease in tumor burden, followed by stable disease for 2.8 years. The second patient had stable disease, but capecitabine was discontinued after 11 months because of hand/foot syndrome. Conclusions: This series demonstrates promising results for the use of capecitabine in treatment of MTC and radioiodine-resistant FTC, for which there is a limited repertoire of therapeutic agents. Larger studies are needed to confirm these findings and to establish the role of fluoropyramidine metabolism markers in predicting response.