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

Overview

Journal Invest New Drugs

Publisher Springer

Specialty Oncology

Date 2016 May 27

PMID 27225873

Citations 15

Authors

Paul L Swiecicki

Emily Bellile

Assuntina G Sacco

Alexander T Pearson

Jeremy M G Taylor

Trachette L Jackson

Douglas B Chepeha

Matthew E Spector

Andrew Shuman

Kelly Malloy

Jeffrey Moyer

Erin McKean

Scott McLean

Ammar Sukari

Gregory T Wolf

Avraham Eisbruch

Mark Prince

Carol Bradford

Thomas E Carey

Shaomeng Wang

Jacques E Nor

Francis P Worden

Affiliations

Soon will be listed here.

Abstract

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.

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