Hematologic toxicity in patients treated with sunitinib for advanced thyroid cancer.
BACKGROUND
Although thyroid carcinoma is more indolent than other solid tumors, distant metastatic disease due to differentiated thyroid carcinoma (DTC) and medullary thyroid carcinoma (MTC) is often refractory to treatment and thus a challenge for clinicians. New agents such as tyrosine kinases inhibitors have been introduced recently for therapy of metastatic thyroid cancer but they have toxic side effects as well as therapeutic benefits. The objective of this study was to determine the hematologic toxicities of sunitinib, a multiple receptor tyrosine kinases inhibitor, when used to treat progressive, advanced DTC and MTC.


METHODS
Six patients with DTC and four with MTC who were treated with sunitinib were retrospectively studied for short-term hematological toxicities related to red cell and platelet mass and the major leukocyte series.


RESULTS
Before the start of sunitinib treatment, 5 of 10 patients (50%) received external beam radiation therapy and 6 of 10 (60%) had hematologic abnormalities. During sunitinib treatment, some grade of neutropenia was noted in 6 of 10 patients (60%), anemia in 1 of 10 (10%), thrombocytopenia in 7 of 10 (70%), and lymphocytopenia in 4 of 10 (40%). Monocytopenia was present in all 10 patients. Considering grades 3 and 4 hematologic toxicities, neutropenia was noted in 2 of 10 (20%), anemia in 1 of 10 (10%), and thrombocytopenia in 1 of 10 (10%). There was no grade 3 or 4 lymphocytopenia, but we noted a 52.4% (+/-17.47% standard deviation) decrease in monocyte counts. All patients had macrocytosis, despite normal circulating folate and cobalamin levels. In one patient with DTC, sunitinib had to be permanently discontinued because of hematological toxicity.


CONCLUSIONS
Despite the fact that most patients with DTC had received large doses of radioiodine and some had received external beam radiation therapy, both of which have myelosuppressive potential, treatment with sunitinib was well tolerated in most patients with DTC as well as in the patients with MTC. These results are encouraging, but, as our series was small and did not evaluate efficacy, more extensive studies in DTC and MTC are needed to determine the possible roles of sunitinib in these very different tumors.
Gkountouvas
Anastasios
A
Department of Endocrinology and Metabolism, Metaxa Cancer Hospital, Piraeus, Greece. gkountouvas@yahoo.com
Kostoglou-Athanassiou
Ifigeneia
I
Veniou
Eirini
E
Repousis
Panagiotis
P
Ziras
Nikolaos
N
Kaldrimidis
Philippos
P
D000328:Adult; D000368:Aged; D018276:Carcinoma, Medullary / Q000188:drug therapy*; D002454:Cell Differentiation; D003131:Combined Modality Therapy; D004791:Enzyme Inhibitors / Q000009:adverse effects*; D005260:Female; D006413:Hematopoietic System / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009503:Neutropenia / Q000139:chemically induced; D011758:Pyrroles / Q000009:adverse effects*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D000077210:Sunitinib; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000473:pathology
D004791:Enzyme Inhibitors; D007211:Indoles; D011758:Pyrroles; D020794:Receptor Protein-Tyrosine Kinases; D000077210:Sunitinib