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Phase II trial of continuous dosing of sunitinib in advanced, FDG-PET avid, medullary thyroid carcinoma (MTC) and well-differentiated thyroid cancer (WDTC)
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2009
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Metronomic ChemotherapyNeuro-oncologyOncologyAggressive Thyroid CancerRadiopharmaceutical TherapyNuclear MedicineCancer ResearchMolecular OncologyRadiologyPhase Ii TrialRadionuclide TherapyResponse RateCancer TreatmentPharmacologyTumor MicroenvironmentContinuous DosingFdg-pet AvidThyroid DiseaseImmune Checkpoint InhibitorThyroid HormoneMedicineThyroid Cancer
6056 Background: Due to the low efficacy of chemotherapy in progressive, WDTC and MTC, novel treatment approaches are needed. Thyroid cancers have elevated levels of vascular endothelial growth factor and higher microvessel density than normal thyroid tissue. Sunitinib inhibits several tyrosine kinase receptors involved in angiogenesis as well as the RET kinase frequently mutated in thyroid cancer. Here we report the results of a phase II trial investigating the use of continuous dosing sunitinib in patients with metastatic WDTC and MTC. Methods: Patients were eligible for enrollment if they had metastatic, iodine-refractory WDTC or MTC. To target those patients with more aggressive thyroid cancer, enrollment was limited to FDG-PET avid disease. Sunitinib was administered at 37.5 mg po qday on a continuous basis. Planned sample size is 35 patients. The primary end-point is response rate per RECIST criteria. Secondary end-points include FDG-PET response rate (defined as 20% reduction from baseline SUV) after 7 days of treatment, toxicity, overall survival, duration of response, and time to progression. Results: To date 33 patients have been enrolled (7 MTC:26 WDTC), and 29 patients have been evaluated for disease response. Median time on study is 7.5 months. Response rates to date: CR 7% (2/29), duration of response (9m+ and 14m+), PR 25% (8/29) (median 12 months), SD 48% (14/29) (median 6 months). Rate of disease control at 3 months (SD+PR+CR) 83% (24/29). 15 patients remain on study. Among those who have progressed the median time to progression is 6.5 months. FDG-PET was performed on 22 patients following 7 days of treatment, 36% (8/22) have a PET response. Of these patients 7 have disease control per RECIST criteria. Grade 3 toxicities seen in more than one patient include: anemia (2/33), fatigue (4/33), neutropenia (12/33), hand/foot syndrome (4/33), diarrhea (5/33), and leukopenia (11/33). One patient on lovenox therapy died of gastrointestinal bleeding. Conclusions: Continuous dosing of sunitinib is active (disease control rate 83%) in patients with high risk, metatstatic WDTC and MTC, as defined by FDG-PET avid disease. [Table: see text]