Table 2.

Prospective studies.

Author	Year	Site	No. of pts	Study details	Results
Sosa et al. [61]	2010	International	80	55 pts were randomized to paclitaxel/carboplatin and fosbretabulin, and 25 patients were randomized to receive paclitaxel and carboplatin only. Pts were followed until they died.	Fosbretabulin was well tolerated with carboplatin and paclitaxel. Improved overall survival (OS) in ATC from 4.1 months to 5.1 months. OS was longer in younger patients <60 yrs increasing from medial of 3.1 months to 10.9 months (HR: 0.38, 95% CI: 0.16, 0.88, P = .0222).
Troch et al. [62]	2010	Austria	6	Standard external beam radiation of 60 gy was combined along with docetaxel at 100 mg fixed dose every 3 wks for a total of six cycles starting within the first week of radiation.	One patient had only completed radiation at the time of the report. Four patients achieved complete remission, and two achieved partial response. After a median followup of 21.5 months (range, 2–40 months), five patients were alive.
Mooney et al. [63]	2009	USA	26	26 patients with biopsy-proven ATC received fosbretabulin at 45 mg/m2.	There was no objective response. Median survival was 4.7 months with 34% and 23% alive at 6 and 12 months, respectively. Median duration of stable disease in seven patients was 12.3 months (range, 4.4–37.9 months). Lower baseline sICAM-1 levels correlated with better event-free survival. Fosbretabulin was well tolerated with grade 3 toxicity in 34% and grade 4 in 4% of patients.
Nagaiah et al. [64]	2009	USA	16	Patients with biopsy-proven ATC who had progressed on cytotoxic chemotherapy with or without radiation were treated with sorafenib 400 mg BID on a 28 day cycle.	2 of the 15 evaluable patients (13%) had partial response, and 4 patients (27%) had stable disease. Median time in study was 2 months. Median duration of PD/SD was 5.1 months, and median duration of survival was 3.5 months.
Koussis et al. [65]	2006	Italy	56	Patients were divided into 3 groups. Group A: 19 patients radiotherapy, total thyroidectomy, and chemotherapy. Cisplatin once a week and by radiation at 36 Gy in 18 fractions over 3 weeks, followed by total thyroidectomy and by further chemotherapy with doxorubicin and bleomycin. Additionally, five patients received weekly docetaxel. Group B: consisted of 19 patients with distant metastasis at diagnosis who received chemotherapy (Platinum-based combination). Group C: consisted of 18 elderly patients in poor general condition; 6 received local radiation, while 12 did not receive any treatment.	Five complete responses were seen in patients from Group A. Four patients had long-term survival (14, 15, 24, and 41 months) with a disease-free survival interval of 6, 8, 11, and 32 months. Median survival rates for Groups A, B, and C was 12, 5.7, and 4 months, respectively.
Wallin et al. [66]	2004	Sweden	22	Hyperfractionated radiotherapy 1.6 Gy × 2 to a total target dose of 46 Gy given preoperatively, 20 mg doxorubicin was administered intravenously once weekly and surgery was carried out 2-3 weeks after the radiotherapy.	17 of these 22 patients were operated. Partial regression in 7 others; the one patient whose tumor failed to respond was treated only once daily. Two patients died of spinal cord necrosis and a third of pneumonitis due to the unexpected increase in radiation toxicity caused by the concurrent administration of doxorubicin. None of these 17 patients got a local recurrence. No survival data.
De Crevoisier et al. [67]	2004	France	30	Hyperfractionated accelerated radiotherapy and total of 6 cycles of doxorubicin/cisplatin was used.	Complete local response was seen in 19 patients. Overall survival at 3 years was 27% and median survival was 10 months. Death was related to local progression in 5% of patients.
Mitchell et al. [68]	2002	USA	28	28 patients with ATC without distant metastases received radiotherapy to the primary tumor and bilateral neck in 1.6 Gy fractions twice daily and 3 days per week, with concurrent doxorubicin 10 mg/m2 weekly. Three histological subsets: anaplastic carcinoma with giant and/or spindle cell features (n = 12); anaplastic carcinoma arising from papillary or follicular carcinoma (n = 8); and undifferentiated (n = 8).	The 3-year actuarial local control, metastasis-free survival, and overall survival rates were 47%, 8%, and 14%, respectively. Followup among the five currently living patients is 82, 27, 4, 3, and 1 months, respectively. Site of first failure was distant in 13 patients and local in 7 patients.
Ain et al. [69]	2000	USA	20	Patients received 96-hour continuous infusion of paclitaxel every 3 weeks for 1 to 6 cycles; the first 7 patients received 120 mg/m2 per 96 hours, and the rest received 140 mg/m2 per 96 hours.	Of the 19 evaluable patients, there was a 53% total response rate (95% confidence interval; 29–76%) including 1 complete response and 9 partial responses (including one off protocol). Nonconventional response criteria.
Busnardo et al. [70]	2000	Italy	39	A total of 16 patients (Group 1) were treated with total thyroidectomy, radiation therapy, and chemotherapy in various orders. Nine patients with distant metastases at diagnosis (Group 2) received chemotherapy; one patient had disappearance of lung metastases and was then treated by total thyroidectomy and further chemotherapy. Group 3 consisted of 14 elderly patients in poor general conditions; 4 of these received local radiation therapy, while the remaining did not receive any treatment.	Median survival rate was 11 month for Group 1. It was 5.7 months for Group 2, and 4 months for Group 3. Multimodality treatment was associated with increased survival. Nine out of 16 patients, who underwent surgery and complementary treatment, had no local progression.
Mitchel et al. [16]	1999	UK	17	Twice-daily radiation for 5 days a week to a total dose of 60.8 Gy in 32 fractions over 20–24 days was given in two or three phases.	Three patients with ATC demonstrated a complete clinical response, and 7 patients achieved a partial response. Five patients had stable disease, and 2 patients died before radiotherapy was completed.
Schlumberger et al. [19]	1991	France	20	Chemotherapy and radiation for patients aging less than 65 years treated with doxorubicin and cisplatin; patients older than 65 years with mitoxantrone and radiation at 17.5 Gy.	Three patients survived more than 20 months; 5 patients had complete local tumor response.
Tennevall et al. [60]	1990	Sweden	16	Hyperfractionated radiotherapy, doxorubicin, and debulking surgery. The radiotherapy was preoperatively administered to a target dose of 30 Gy in 3 weeks, and postoperatively to an additional dose of 16 Gy in 1.5 weeks. 20 mg doxorubicin was used.	Five patients achieved local complete remission, and 3 patients were alive disease-free at 10, 30, and 30 months, respectively, after diagnosis. Only 6 patients succumbed to local failure.
Kim and Leeper [12]	1987	USA	19	Group 2 patients with anaplastic giant and spindle cell carcinoma of the thyroid (n = 19) received doxorubicin (10 mg/m2) before hyperfractionated radiation. Radiation therapy was carried out with a fractional dose of 160 cGy per treatment twice a day for 3 days per week to a total dose of 5760 cGy in 40 days.	Local tumor control rates at 2 years after combined therapy were 77% and 68%, respectively. The median survival time was 4 years for group 1 and 1 year for group 2.