Treatment with Tyrosine Kinase Inhibitors for Patients with Differentiated Thyroid Cancer: the M. D. Anderson Experience

• Published in: The journal of clinical endocrinology and metabolism 2010-06, Vol.95 (6), p.2588-2595
• Main Authors: Cabanillas, Maria E., Waguespack, Steven G., Bronstein, Yulia, Williams, Michelle D., Feng, Lei, Hernandez, Mike, Lopez, Adriana, Sherman, Steven I., Busaidy, Naifa L.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Benzenesulfonates - administration & dosage; Benzenesulfonates - therapeutic use; Biological and medical sciences; Disease Progression; Disease-Free Survival; DNA Mutational Analysis; Endocrinopathies; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Humans; Indoles - administration & dosage; Indoles - therapeutic use; Kaplan-Meier Estimate; Male; Malignant tumors; Medical sciences; Middle Aged; Neoplasm Metastasis; Niacinamide - analogs & derivatives; Off-Label Use; Phenylurea Compounds; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Protein-Tyrosine Kinases - antagonists & inhibitors; Pyridines - administration & dosage; Pyridines - therapeutic use; Pyrroles - administration & dosage; Pyrroles - therapeutic use; Survival Analysis; Thyroglobulin - blood; Thyroid Neoplasms - diagnostic imaging; Thyroid Neoplasms - drug therapy; Thyroid Neoplasms - pathology; Thyroid. Thyroid axis (diseases); Tomography, X-Ray Computed; Treatment Outcome; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2009-1923

Objectives: Until recently, treatment options for patients with progressive, radioactive iodine-resistant differentiated thyroid cancer (DTC) have been limited. In our clinical practice, we have begun to use sorafenib and sunitinib for patients with progressive DTC who are not able or willing to participate in clinical trials. In this paper, we describe the University of Texas M. D. Anderson Cancer Center’s experience with the off-label use of these tyrosine kinase inhibitors for DTC. Methods: Adult patients were included if they had a diagnosis of radioactive iodine-refractory DTC, were treated with single agent sorafenib or sunitinib, and had both baseline and at least one follow-up scan for restaging purposes. All imaging data were collected, as well as the TSH-suppressed thyroglobulin (Tg) levels corresponding to each scan date. The primary endpoints were radiographic response and progression-free survival (PFS). Secondary objectives were tissue-specific radiographic responses and correlation of Tg with overall response. Results: We identified 33 patients from our clinical database. Fifteen patients (nine women, six men) met inclusion criteria, with a median age of 61 yr (range, 38–83 yr). Eight patients had papillary and seven had follicular thyroid carcinoma. Sorafenib was used in 13 and sunitinib in two, including one patient who failed prior sorafenib therapy. All patients had evidence of progressive disease (PD) before start of therapy, with a median PFS of only 4 months. Best response in target lesions was: partial response (PR) in three (20%), stable disease (SD) in nine (60%), and PD in three (20%). Clinical benefit (PR+SD) was 80%. The sunitinib patient previously refractory to sorafenib had a 38% reduction in tumor size. The most noticeable organ-specific response was observed in lung (median change, −22%) compared to lymph nodes (median change, 0%). Pleural disease and nonirradiated bone metastases demonstrated PD. All histological subtypes had similar responses. The median PFS was 19 months. The median overall survival has not yet been reached, but at 2 yr of follow-up, overall survival is 67%. Log Tg correlated with radiographic response (P = 0.0005). Conclusions: Sorafenib and sunitinib appear to be effective in patients with widely metastatic, progressive DTC, with most patients achieving SD or PR, despite having PD at baseline. The most noticeable responses occurred in the lungs in contrast with minimal changes in nodal metastases and P