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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

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Summary

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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Acknowledgments

The authors thank the many investigators in the University of Michigan Head and Neck Specialized Program of Research Excellence for their contributions to patient recruitment, assistance in data collection and encouragement including Lisa Peterson, MPH, Sonia Duffy, PhD, Joseph Helman, DDS, Jonathan McHugh, MD, Tamara H. Miller, RN, Nancy Rogers, RN, Nancy E. Wallace, RN, Heather Walline, PhD, Brent Ward, DDS, Mary Beth DeRubeis, NP-C, M.S.N., Heidi Mason, NP-C, M.S.N., Leah Shults, RN, and Terri Jobkar, RN.Contract grant sponsor.

This work was supported by the University of Michigan Head and Neck Specialized Program of Research Excellence NIH/NCI P50CA097248 and NIH/NIDCD T32 DC005356, NIH/NIDCR R01-DE023220 (JEN), as well as University of Michigan Cancer Center Core Grant NIH/NCI P3O CA046592.

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Authors and Affiliations

  1. University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA

    Paul L. Swiecicki, Emily Bellile, Alexander T. Pearson, Jeremy M. G. Taylor, Matthew E. Spector, Andrew Shuman, Kelly Malloy, Jeffrey Moyer, Erin McKean, Scott McLean, Gregory T. Wolf, Avraham Eisbruch, Mark Prince, Carol Bradford, Thomas E. Carey, Shaomeng Wang & Francis P. Worden

  2. University of California San Diego Moores Cancer Center, La Jolla, CA, USA

    Assuntina G. Sacco

  3. Department of Mathematics, University of Michigan, Ann Arbor, MI, USA

    Trachette L. Jackson

  4. Department of Otolaryngology-Head and Neck Surgery, University of Toronto, Toronto, ON, Canada

    Douglas B. Chepeha

  5. Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA

    Ammar Sukari

  6. Department of Restorative Sciences, University of Michigan School of Dentistry, Ann Arbor, MI, USA

    Jacques E. Nör

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  1. Paul L. Swiecicki
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Swiecicki, P.L., Bellile, E., Sacco, A.G. et al. 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 34, 481–489 (2016). https://doi.org/10.1007/s10637-016-0364-5

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