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.
Randomized safety and efficacy study of fosbretabulin with paclitaxel/carboplatin against anaplastic thyroid carcinoma / J.A. Sosa, R. Elisei, B. Jarzab, J. Balkissoon, S.-. Lu, C. Bal, S. Marur, A. Gramza, R.B. Yosef, B. Gitlitz, B.R. Haugen, F. Ondrey, C. Lu, S.M. Karandikar, F. Khuri, L. Licitra, S.C. Remick. - In: THYROID. - ISSN 1050-7256. - 24:2(2014), pp. 232-240.
|Titolo:||Randomized safety and efficacy study of fosbretabulin with paclitaxel/carboplatin against anaplastic thyroid carcinoma|
LICITRA, LISA FRANCESCA LINDA (Penultimo)
|Parole Chiave:||combrestatin A4 phosphate; phase-I trial; vascular-targeting agent; A-4 phosphate; combination chemotherapy; natural product; advanced cancer; solid tumors; carboplatin; doxorubicin|
|Settore Scientifico Disciplinare:||Settore MED/06 - Oncologia Medica|
|Data di pubblicazione:||2014|
|Data ahead of print / Data di stampa:||30-mag-2013|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1089/thy.2013.0078|
|Appare nelle tipologie:||01 - Articolo su periodico|