title: Retrospective Study of Sirolimus and Cyclophosphamide in Patients with Advanced Differentiated Thyroid Cancers.
abstract: BACKGROUND
  We hypothesize that the combination of an mTOR inhibitor, sirolimus, with a well-known cytotoxic agent, cyclophosphamide, provides a well-tolerated and promising alternative treatment for advanced, differentiated thyroid cancers (DTC).
  
  
  METHODS
  This retrospective review extracted data from patients treated for advanced DTC at the University of Michigan Comprehensive Cancer Center from 1995 through 2013. Fifteen patients treated with combination sirolimus and cyclophosphamide were identified as the sirolimus+cyp group. Seventeen patients treated with standard of care and enrolled in clinical trials were identified as the comparison group.
  
  
  RESULTS
  The one-year progression free survival rate (PFS) was 0.45, 95% CI [0.26, 0.80] in the sirolimus+cyp population and 0.30, 95% CI [0.13, 0.67] in the comparison population. The hazard ratio for PFS from initiation of treatment was 1.47, 95% CI [0.57, and 3.78]. In patients treated as first line, one-year PFS rate was 0.57, 95% CI [0.30, 1.00] in the sirolimus+cyp group and relatively unchanged at 0.29, 95% CI [0.11, 0.74] in the comparison group. The hazard ratio for PFS for first line patients was 1.10, 95% CI[ 0.4, and 3.5]. In patients with 3 or fewer sites of metastases, the one year PFS was 0.58, 95% CI [0.33, 1.00] in the sirolimus+cyp group, and 0.37, 95% CI [0.17, 0.80] in the comparison group. The average number of toxicities was 0.87 in the sirolimus+cyp patients and 1.71 in the comparison group.
  
  
  CONCLUSIONS
  The combination of sirolimus and cyclophosphamide was generally well tolerated with similar progression free survival, highlighting its applicability in patients with limited options.
authors.affiliation: Department of internal Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: Poorni M
authors.initials: PM
authors.lastname: Manohar
authors.affiliation: Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, United States.
authors.forename: Lauren J
authors.initials: LJ
authors.lastname: Beesley
authors.affiliation: Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, United States.
authors.forename: Jeremy Mg
authors.initials: JM
authors.lastname: Taylor
authors.affiliation: Department of Endocrinology, University of Michigan, Ann Arbor, Michigan, United States.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hesseltine
authors.affiliation: Department of Endocrinology, University of Michigan, Ann Arbor, Michigan, United States.
authors.forename: Megan R
authors.initials: MR
authors.lastname: Haymart
authors.affiliation: Department of Endocrinology, University of Michigan, Ann Arbor, Michigan, United States.
authors.forename: Nazanene H
authors.initials: NH
authors.lastname: Esfandiari
authors.affiliation: Department of Computational Medicine and Bioformatics, University of Michigan, Ann Arbor, Michigan, United States.
authors.forename: David A
authors.initials: DA
authors.lastname: Hanauer
authors.affiliation: Department of Oncology, University of Michigan, Ann Arbor, Michigan, United States.
authors.forename: Francis P
authors.initials: FP
authors.lastname: Worden
keywords: Thyroid cancer; advanced differentiated thyroid carcinoma; cyclophosphamide; sirolimus