Randomized Safety and Efficacy Study of Fosbretabulin with Paclitaxel/Carboplatin Against Anaplastic Thyroid Carcinoma

<jats:sec> <jats:title>Background:</jats:title> <jats:p>Anaplastic thyroid cancer (ATC), a rare highly vascularized tumor, has a dismal outcome. We conducted an open-label study of doublet carboplatin/paclitaxel chemotherapy with or without fosbretabulin in patients with ATC.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p> Patients were randomly assigned in a 2:1 ratio to 6 cycles of paclitaxel 200 mg/m <jats:sup>2</jats:sup> followed by carboplatin AUC 6 on day 1 every 3 weeks (CP), or these drugs were given on day 2 after fosbretabulin 60 mg/m <jats:sup>2</jats:sup> (CP/fosbretabulin) on days 1, 8 and 15. After 6 cycles, patients on the fosbretabulin arm without progression could continue to receive fosbretabulin on days 1 and 8 of a 3-week schedule until progression. The primary end point was overall survival (OS). </jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p> Eighty patients were assigned (planned, 180) when enrollment was stopped due to rarity of disease and very low accrual. Median OS was 5.2 months [95% confidence interval (CI) 3.1, 9.0] for the CP/fosbretabulin arm ( <jats:italic toggle="yes">n</jats:italic> =55; hazard ratio 0.73 [95% CI 0.44, 1.21]) and 4.0 months [95% CI 2.8, 6.2] for the CP arm ( <jats:italic toggle="yes">n</jats:italic> =25; <jats:italic toggle="yes">p</jats:italic> =0.22 [log rank test]). One-year survival for CP/fosbretabulin versus CP was 26% versus 9%, respectively. There was no significant difference in progression-free survival between the two arms. Grade 1–2 hypertension and grade 3–4 neutropenia were more common with CP/fosbretabulin. There were no significant adverse cardiovascular side effects. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>Although the study did not meet statistical significance in improvement in OS with the addition of fosbretabulin to carboplatin/paclitaxel, it represents the largest prospective randomized trial ever conducted in ATC. The regimen is well tolerated, with AEs and deaths primarily related to ATC and disease progression.</jats:p> </jats:sec>