title: A phase II trial of the BCL-2 homolog domain 3 mimetic AT-101 in combination with docetaxel for recurrent, locally advanced, or metastatic head and neck cancer.
abstract: AT-101 is a BCL-2 Homolog domain 3 mimetic previously demonstrated to have tumoricidal effects in advanced solid organ malignancies. Given the evidence of activity in xenograft models, treatment with AT-101 in combination with docetaxel is a therapeutic doublet of interest in metastatic head and neck squamous cell carcinoma.
  
  
  
  Patients included in this trial had unresectable, recurrent, or distantly metastatic head and neck squamous cell carcinoma (R/M HNSCC) not amenable to curative radiation or surgery. This was an open label randomized, phase II trial in which patients were administered AT-101 in addition to docetaxel. The three treatment arms were docetaxel, docetaxel plus pulse dose AT-101, and docetaxel plus metronomic dose AT-101. The primary endpoint of this trial was overall response rate.
  
  
  
  Thirty-five patients were registered and 32 were evaluable for treatment response. Doublet therapy with AT-101 and docetaxel was well tolerated with only 2 patients discontinuing therapy due to treatment related toxicities. The overall response rate was 11 % (4 partial responses) with a clinical benefit rate of 74 %. Median progression free survival was 4.3 months (range: 0.7-13.7) and overall survival was 5.5 months (range: 0.4-24). No significant differences were noted between dosing strategies.
  
  
  
  Although met with a favorable toxicity profile, the addition of AT-101 to docetaxel in R/M HNSCC does not appear to demonstrate evidence of efficacy.
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA. pswiecic@med.umich.edu.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Swiecicki
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Bellile
authors.affiliation: University of California San Diego Moores Cancer Center, La Jolla, CA, USA.
authors.forename: Assuntina G
authors.initials: AG
authors.lastname: Sacco
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Pearson
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Jeremy M G
authors.initials: JM
authors.lastname: Taylor
authors.affiliation: Department of Mathematics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Trachette L
authors.initials: TL
authors.lastname: Jackson
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Toronto, Toronto, ON, Canada.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Chepeha
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Spector
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Shuman
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Malloy
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Moyer
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: McKean
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: McLean
authors.affiliation: Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA.
authors.forename: Ammar
authors.initials: A
authors.lastname: Sukari
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Wolf
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Avraham
authors.initials: A
authors.lastname: Eisbruch
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Prince
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Bradford
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Carey
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Shaomeng
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Restorative Sciences, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
authors.forename: Jacques E
authors.initials: JE
authors.lastname: Nör
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Francis P
authors.initials: FP
authors.lastname: Worden
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D018572:Disease-Free Survival; D000077143:Docetaxel; D004334:Drug Administration Schedule; D005260:Female; D006072:Gossypol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D006072:Gossypol; C028178:gossypol acetic acid
keywords: AT-101; BH3 mimetic; Docetaxel; Gossypol; Head and neck neoplasms; Metronomic dosing