Randomized Safety and Efficacy Study of Fosbretabulin with Paclitaxel/Carboplatin Against Anaplastic Thyroid Carcinoma
- 1 February 2014
- journal article
- research article
- Published by Mary Ann Liebert Inc in Thyroid®
- Vol. 24 (2), 232-240
- https://doi.org/10.1089/thy.2013.0078
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/m2 (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.Keywords
This publication has 24 references indexed in Scilit:
- American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid CancerThyroid®, 2012
- Concurrent doxorubicin and radiotherapy for anaplastic thyroid cancer: A critical re-evaluation including uniform pathologic reviewRadiotherapy and Oncology, 2011
- Anaplastic Thyroid Cancer: A Review of Epidemiology, Pathogenesis, and TreatmentJournal of Oncology, 2011
- Increasing Incidence of Thyroid Cancer in the United States, 1973-2002Jama-Journal Of The American Medical Association, 2006
- Anaplastic thyroid carcinomaCancer, 2005
- Combretastatin A4 phosphate: background and current clinical statusExpert Opinion on Investigational Drugs, 2004
- Phase I Clinical Trial of Weekly Combretastatin A4 Phosphate: Clinical and Pharmacokinetic ResultsJournal of Clinical Oncology, 2003
- Anaplastic thyroid carcinoma: A 50-year experience at a single institutionSurgery, 2001
- In vivo and in vitro evaluation of combretastatin A-4 and its sodium phosphate prodrugBritish Journal of Cancer, 1999
- Treatment of locally advanced thyroid carcinoma with combination doxorubicin and radiation therapyCancer, 1987