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

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

Paul L Swiecicki  1 , Emily Bellile  2 , Assuntina G Sacco  3 , Alexander T Pearson  2 , Jeremy M G Taylor  2 , Trachette L Jackson  4 , Douglas B Chepeha  5 , Matthew E Spector  2 , Andrew Shuman  2 , Kelly Malloy  2 , Jeffrey Moyer  2 , Erin McKean  2 , Scott McLean  2 , Ammar Sukari  6 , Gregory T Wolf  2 , Avraham Eisbruch  2 , Mark Prince  2 , Carol Bradford  2 , Thomas E Carey  2 , Shaomeng Wang  2 , Jacques E Nör  7 , Francis P Worden  2
Affiliations
Clinical Trial

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

Paul L Swiecicki et al. Invest New Drugs. 2016 Aug.

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.

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

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1. Trial Schema
This figure graphically demonstrates the trial schema employed in this Phase II trial.
Figure 2
Figure 2. Differences in CXCL1 between Groups
This figure illustrates the log change in serum levels of CXCL1 between treatment arms.
Figure 3
Figure 3. Differences in CXCL8 between Groups
This figure illustrates the log change in serum levels of CXCL8 between treatment arms.
See this image and copyright information in PMC

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