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

Invest New Drugs. 2016 Aug;34(4):481-9. doi: 10.1007/s10637-016-0364-5. Epub 2016 May 26.


Background: 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 and methods: 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.

Results: 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.

Conclusion: 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.

Keywords: AT-101; BH3 mimetic; Docetaxel; Gossypol; Head and neck neoplasms; Metronomic dosing.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Squamous Cell / drug therapy*
  • Disease-Free Survival
  • Docetaxel
  • Drug Administration Schedule
  • Female
  • Gossypol / administration & dosage
  • Gossypol / adverse effects
  • Gossypol / analogs & derivatives*
  • Gossypol / therapeutic use
  • Head and Neck Neoplasms / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Taxoids / administration & dosage
  • Taxoids / adverse effects
  • Taxoids / therapeutic use*
  • Treatment Outcome


  • Antineoplastic Agents
  • Taxoids
  • Docetaxel
  • Gossypol
  • gossypol acetic acid