title: Randomized safety and efficacy study of fosbretabulin with paclitaxel/carboplatin against anaplastic thyroid carcinoma.
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/m(2) 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.
authors.affiliation: 1 Department of Surgery, Duke University School of Medicine , Durham, North Carolina.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Sosa
authors.forename: Rossella
authors.initials: R
authors.lastname: Elisei
authors.forename: Barbara
authors.initials: B
authors.lastname: Jarzab
authors.forename: Jai
authors.initials: J
authors.lastname: Balkissoon
authors.forename: Shiao-Ping
authors.initials: SP
authors.lastname: Lu
authors.forename: Chandrasekhar
authors.initials: C
authors.lastname: Bal
authors.forename: Shanthi
authors.initials: S
authors.lastname: Marur
authors.forename: Ann
authors.initials: A
authors.lastname: Gramza
authors.forename: Rami Ben
authors.initials: RB
authors.lastname: Yosef
authors.forename: Barbara
authors.initials: B
authors.lastname: Gitlitz
authors.forename: Bryan R
authors.initials: BR
authors.lastname: Haugen
authors.forename: Frank
authors.initials: F
authors.lastname: Ondrey
authors.forename: Charles
authors.initials: C
authors.lastname: Lu
authors.forename: S M
authors.initials: SM
authors.lastname: Karandikar
authors.forename: Fadlo
authors.initials: F
authors.lastname: Khuri
authors.forename: Lisa
authors.initials: L
authors.lastname: Licitra
authors.forename: Scot C
authors.initials: SC
authors.lastname: Remick
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D013267:Stilbenes / Q000009:adverse effects / Q000627:therapeutic use*; D065646:Thyroid Carcinoma, Anaplastic; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D013267:Stilbenes; C058728:fosbretabulin