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.


METHODS
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 (< or =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).


RESULTS
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.
Gilliam
Lisa K
LK
Divisions of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, Washington 98195, USA. lgilliam@u.washington.edu
Kohn
Aimee D
AD
Lalani
Tasneem
T
Swanson
Paul E
PE
Vasko
Vasyl
V
Patel
Aneeta
A
Livingston
Robert B
RB
Pickett
Cheryl A
CA
D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000069287:Capecitabine; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007457:Iodine Radioisotopes / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012189:Retrospective Studies; D013939:Thymidine Phosphorylase / Q000378:metabolism; D013954:Thyroglobulin / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000188:drug therapy*
D000964:Antimetabolites, Antineoplastic; D002272:Carcinoembryonic Antigen; D007457:Iodine Radioisotopes; D003841:Deoxycytidine; D000069287:Capecitabine; D013954:Thyroglobulin; D042943:Dihydrouracil Dehydrogenase (NADP); D013939:Thymidine Phosphorylase; D005472:Fluorouracil