A previous GIST study suggested that Sutent has an anti-thyroidal effect. The study looked at thyroid function in 42 patients with GIST who had received Sutent for a median of 37 weeks (range, 10-167). These authors reported that 62% of patients developed abnormal thyroid stimulating hormone (TSH) concentrations and 36% developed persistent hypothyroidism. The risk of developing hypothyroidism increased with increasing duration of therapy. These authors speculated that Sutent causes thyroiditis through follicular apoptosis. They also suggested that Sutent might be effective therapy for advanced thyroid cancer. A 2008 abstract, not yet published as a peer-reviewed article, concluded: “In patients with refractory DTC or MTC who have evidence of progressive disease, sunitinib at the 50 mg 4/2 schedule is able to induce responses or disease stabilization in the great majority.”
Sunitinib is in a phase II trial. This NCT00381641 phase II trial is studying the side effects and how well sunitinib works in treating patients with thyroid cancer that did not respond to iodine I 131 (radioactive iodine) and cannot be removed by surgery. This is an open-label, parallel-group, cohort, multicenter study. Patients are assigned to 1 of 2 cohorts according to type of thyroid cancer (medullary vs well-differentiated). Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for 2 years.
Objectives are to determine the response rate to sunitinib malate in patients with iodine-refractory, unresectable well-differentiated thyroid cancer (WDCT) or medullary thyroid cancer (MTC) who have evidence of disease progression within the past 6 months, determine the toxicity of this drug in these patients, determine the duration of response, progression-free survival, and overall survival of patients with WDTC or MTC treated with this drug.
Another trial, although not in papillary cancer, is: Thyroid Cancer and Sunitinib (THYSU, NCT00510640 . The objective of the trial is to determine the objective tumor response rate (efficacy) in patients with locally advanced or metastatic anaplastic, differentiated or medullary thyroid carcinoma treated with sunitinib; a secondary objective is to evaluate the safety of sunitinib in these patients.
The THYSU trial is a phase II, French multi-center study. This trial’s plan is to enroll 75 patients with locally advanced or metastatic anaplastic, differentiated or medullar thyroid carcinoma. There are other ongoing trials. IN 2009, NCCN added the recommendation to consider commercially available, small molecule kinase inhibitors such as sorafenib (Nexavar(R), Bayer) or sunitinib (Sutent(R), Pfizer, Inc.) in the treatment of metastatic papillary carcinoma, follicular carcinoma, Hurthle cell carcinoma, or medullary carcinoma. Its primary recommendation for these patients is to investigate a clinical trial, but if one is not available or appropriate; data from clinical trials have shown that small molecule kinase inhibitors such as sorafenib and sunitinib can be effective
E. E. Cohen, B. M. Needles, K. J. Cullen, S. J. Wong, J. L. Wade, S. P. Ivy, V. M. Villaflor, T. Y. Seiwert, K. Nichols, E. E. Vokes Phase 2 study of sunitinib in refractory thyroid cancer.
J Clin Oncol 26: 2008 (May 20 suppl; abstr 6025)
Desai J, Yassa L, Marqusee E, et al. Hypothyroidism after sunitinib treatment of patients with gastrointestinal stromal tumors. Annals of Internal Medicine 2006;145:660-664.