Randomized safety and efficacy study of fosbretabulin with paclitaxel/carboplatin against anaplastic thyroid carcinoma

Julie A. Sosa, Rossella Elisei, Barbara Jarzab, Jai Balkissoon, Shiao Ping Lu, Chandrasekhar Bal, Shanthi Marur, Ann Gramza, Rami Ben Yosef, Barbara Gitlitz, Bryan R. Haugen, Frank Ondrey, Charles Lu, S. M. Karandikar, Fadlo Khuri, Lisa Licitra, Scot C. Remick

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Abstract

Background: 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. Methods: Patients were randomly assigned in a 2:1 ratio to 6 cycles of paclitaxel 200 mg/m2 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 2 (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). Results: 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 (n=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 (n=25; p=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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)232-240
Number of pages9
JournalThyroid
Volume24
Issue number2
DOIs
StatePublished - Feb 1 2014

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    Sosa, J. A., Elisei, R., Jarzab, B., Balkissoon, J., Lu, S. P., Bal, C., Marur, S., Gramza, A., Yosef, R. B., Gitlitz, B., Haugen, B. R., Ondrey, F., Lu, C., Karandikar, S. M., Khuri, F., Licitra, L., & Remick, S. C. (2014). Randomized safety and efficacy study of fosbretabulin with paclitaxel/carboplatin against anaplastic thyroid carcinoma. Thyroid, 24(2), 232-240. https://doi.org/10.1089/thy.2013.0078